lacidipine and Hypertension

Drugs currently known as calcium channel blockers (CCB) were initially called calcium antagonists because of their ability to inhibit calcium-evoked contractions in depolarized smooth muscles. Blocking the entry of calcium reduces the active tone of vascular smooth muscle and produces vasodilatation. This pharmacological property has been the basis for the use of CCBs in the management of hypertension and coronary heart disease. A major question is whether drugs reducing blood pressure have other effects that help prevent the main complications of hypertension, such as atherosclerosis, stroke, peripheral arterial disease, heart failure and end-state renal disease. Experimental studies that focus on this question are reviewed in the present paper.

Topics: Animals; Antioxidants; Atherosclerosis; Calcium Channel Blockers; Calcium Channels; Dihydropyridines; Humans; Hypertension; Oxidative Stress

Lacidipine (Caldine, Lacimen, Lacipil, Midotens, Motens) is a once-daily, orally-administered, lipophilic dihydropyridine calcium antagonist with an intrinsically slow onset of activity, resulting in a lack of reflex tachycardia. It has a long duration of action and a high degree of vascular selectivity. In addition to calcium channel-modulated vasodilation, lacidipine displays antioxidant activity greater than that of other dihydropyridine calcium antagonists. In randomised, well-controlled trials, lacidipine 2-6 mg orally once daily had antihypertensive efficacy similar to that of other long-acting dihydropyridine calcium antagonists, thiazide diuretics, atenolol (a beta-blocker) and enalapril (an ACE inhibitor). Lacidipine was effective in elderly patients (including those with isolated systolic hypertension), African Nigerian patients and patients with concurrent type 2 diabetes mellitus. During long-term treatment for 4 or 5 years in patients with isolated systolic hypertension or essential hypertension, the incidence of cardiovascular events and mortality with lacidipine was similar to that with chlorthalidone or atenolol. The European Lacidipine Study on Atherosclerosis (ELSA), in which 2334 patients with hypertension were randomised to 4 years of therapy with lacidipine 4-6 mg/day or the beta-blocker atenolol 50-100 mg/day, demonstrated significantly lower atherosclerotic progression and plaque formation with lacidipine compared with atenolol in patients completing the full 4 years of the study. Between-group differences in favour of lacidipine for the primary efficacy variable (mean change in carotid artery intima-media thickness) did not reach statistical significance in the intent-to-treat population. The tolerability profile of lacidipine (headache, flushing, pedal oedema, dizziness and palpitations) is similar to that of other dihydropyridine calcium antagonists, but with a lower incidence of peripheral oedema. Data from the ELSA study suggest that the incidence of serious adverse events during long-term lacidipine therapy is similar to that with atenolol.. Lacidipine is an effective, well tolerated, once-daily, oral antihypertensive agent that can be used in a wide variety of patients. As with other members of its class, lacidipine has shown potentially beneficial antiatherosclerotic effects, although definitive data with respect to possible superiority over other drug classes are still required. Therefore, lacidipine is an attractive therapy for the long-term management of essential hypertension.

Topics: Area Under Curve; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Dose-Response Relationship, Drug; Economics, Pharmaceutical; Half-Life; Heart Rate; Humans; Hypertension; Kidney

Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Drug Interactions; Humans; Hypertension; Randomized Controlled Trials as Topic

Similarities and dissimilarities of 3 third generation calcium antagonist (amlodipine, lacidipine and lercanidipine) are presented. Lacidipine is characterized by prolonged antihypertensive action despite its plasma half life is just about 14 hours. Duration of lacidipine effect can be explained by accumulation in lipid bilayer of cellular membranes where it interacts with calcium channels. Pharmacodynamics of lacidipine is discussed in detail as well as experience of its use in hypertension including data of ELSA study which has demonstrated ability of lacidipine to inhibit progression of carotid artery atherosclerosis.

Topics: Antihypertensive Agents; Calcium Channel Blockers; Clinical Trials as Topic; Dihydropyridines; Humans; Hypertension

Topics: Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension

The emphasis on evidence-based medicine and the use of safe, cost-effective therapeutic strategies demands that management decisions be based upon evidence derived from clinical studies. Whilst prospective double blind clinical trials are regarded as the gold standard, there is no doubt that meta-analysis has proved valuable in defining the benefits of antihypertensive therapy. The antihypertensive efficacy of lacidipine has been assessed in a retrospective meta-analysis of a series of clinical studies in which the drug was compared with placebo and all the major classes of antihypertensive agent. All of the studies entered into the meta-analysis were parallel group double blind trials. Efficacy was based upon the reduction in both systolic and diastolic blood pressure and the effect on heart rate at trough immediately prior to dosing during maintenance therapy. In placebo controlled trials a clear dose response relationship was apparent with blood pressure reductions that were significantly greater than that observed with placebo at doses of 2 mg lacidipine and above. In active control trials, diastolic blood pressure reductions of 10-15 mmHg were observed at the end of the monotreatment phases (> 6-8 weeks) with a final reduction of 15-20 mmHg with the efficacy of lacidipine being equivalent to that of the comparator drug. Comparable results were also achieved for the response rates to therapy which varied between 70 and 85% at the end of the monotreatment phase and 82-98 when combination with other antihypertensive agents was permitted. There was no evidence of cardio-acceleration in any of the trials where significant blood pressure reduction was detected. This retrospective analysis in a large population base confirms the documented antihypertensive efficacy of lacidipine and demonstrates the suitability of the drug as a first line antihypertensive agent.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Clinical Trials as Topic; Databases, Factual; Dihydropyridines; Diuretics; Humans; Hypertension

More than 50% of hypertensive patients are aged above 65 years. Physiopathology of essential hypertension is different in the elderly as compared with the young adult. Furthermore, not only are concomitant diseases statistically more frequent in the elderly, but the aging process in itself produces several specific changes in target organs. Several trials have shown that treatment of hypertension in the elderly, including the 'old elderly', is highly beneficial in terms of reduced morbidity and mortality. The therapy used in all these major intervention trials consisted of diuretics and/or beta-blockers. Recently, the Systolic Hypertension in Europe study and the HOT study extended the list of antihypertensive agents with proven beneficial effects on cardiovascular outcomes to dihydropyridine calcium antagonists. Dihydropyridine calcium antagonists, such as lacidipine, have been advocated as first-choice agents for the treatment of hypertension in the elderly on grounds that: a) they may be more active in lowering blood pressure because of the predominantly low renin status in the elderly hypertensives; b) they may be better tolerated because the side effects related to the activation of the sympathetic system may be less frequent as a consequence of the attenuation of baroreflexes during aging; and c) they may have beneficial effects on a variety of concomitant cardiovascular diseases which are frequently present in the elderly. These assumptions are, however, not always proven in the clinical practice. Only well-designed prospective comparative trials may solve this issue. STOP-2, NICS-EH, HYVET, SCOPE and SHELL are acronyms of ongoing clinical trials specifically designed in the elderly hypertensive. The SHELL study assesses the benefits of lacidipine compared with chlortalidone on the prevention of cardiovascular events. The effects of lacidipine (vs atenolol) on the development and progression of carotid atherosclerosis are also being currently investigated in the ELSA study.

Topics: Aged; Antihypertensive Agents; Dihydropyridines; Humans; Hypertension

Calcium antagonists are uniquely suitable for managing hypertension by virtue of their efficacy, metabolic neutrality and their ability to countervail counterregulatory adaptive changes, thereby enhancing blood pressure lowering. Recent evidence has accrued underscoring the concept that calcium antagonists are heterogeneous and consist of chemically dissimilar agents. The difference in formulations and pharmacokinetics affect clinical events including the effect on blood pressure, heart rate and the degree with which sympathetic activity is activated. Lacidipine is a new calcium antagonist that is the prototype of the lipophilic dihydropyridines. Of great importance, lacidipine has a slow onset of vasodilator/antihypertensive effect and does not promote an excessive sympathetic drive. These attributes commend its selection as an antihypertensive agent.

Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension

The evaluation of haemodynamic patterns in hypertensive patients by radionuclide techniques and a tomographic gamma camera has revealed differences between older and younger patients. In younger hypertensive patients, the hyperkinetic state is reflected in an increase in heart rate and, consequently, an increased cardiac index and left ventricular ejection fraction (LVEF) in comparison with normotensive controls. Older hypertensive patients, however, show a different haemodynamic pattern, with reduced systolic and diastolic function at rest compared with normotensive elderly people, and marked depression of cardiac reserve during exercise. Elderly hypertensive patients also show strikingly higher hyperresistance and reduced peripheral perfusion in comparison with younger hypertensive patients. These haemodynamic differences need to be taken into account when considering antihypertensive treatment. In a study in elderly hypertensive patients, lacidipine treatment (4 mg/day for 90 days) produced a significant decrease in total peripheral resistance and blood pressure, together with a reduction in left ventricular (LV) afterload and an increase in cardiac output and LVEF (tending towards normal values). The LV peak filling rate was also increased, and evaluation of systolic and diastolic cardiac reserve during exercise showed positive changes in cardiac performance. The haemodynamic changes with lacidipine were similar to those produced by other long-acting dihydropyridines [nifedipine gastrointestinal therapeutic system (GITS) and nitrendipine], but changes occurring with nisoldipine were less significant. The reduction in left ventricular hypertrophy (LVH) is an obvious goal of antihypertensive therapy, and several studies have demonstrated the effectiveness of lacidipine treatment in decreasing LVH in hypertensive patients. In hypertensive patients with associated LV dysfunction, favourable effects on global parameters of LV function similar to those with amlodipine have been noted with lacidipine. Myocardial blood flow was strikingly increased during lacidipine treatment and coronary resistance was significantly decreased, both at baseline and after maximal vasodilatation with dipyridamole. Thus, lacidipine's vasodilatory and anti-ischaemic profile makes it an appropriate choice for the treatment of hypertension.

Topics: Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular System; Dihydropyridines; Humans; Hypertension

The aim was to review the clinical safety profile of lacidipine with the help of the rather comprehensive datafile of the manufacturer- a novel approach which may be of some value while awaiting the outcome of calcium antagonist treatment in prospective, randomised trials of cardiovascular morbidity and mortality.. This paper includes data from clinical trials finished before 1 January 1995. Since 1985, 50 phase III-IV trials have been performed investigating antihypertensive efficacy in patients with hypertension; 32 were controlled trials with comparison treatment and 18 were open studies of lacidipine treatment.. In all, 16,590 patients received lacidipine; 13,419 in open studies and 3171 in double blind, comparative trials. Altogether, these patients contributed 5 124 person-years (p.y.). Furthermore, active comparative treatment was given to 1810 patients and placebo to 451.. Both fatal and non-fatal cardiovascular events have been estimated. Efficacy (change in blood pressure and heart rate), adverse event rates, and drop-out rates have been compared for the different treatment regimes. Also the reasons for dropping out of studies have been compared. Adverse effects were also analysed as to their time of occurrence and duration.. Blood pressure was lowered by 2-6 mg lacidipine; in the controlled trials from 166/102 to 144/85 mmHg. Heart rate dropped from 75.6 to 74.1 beats per minute. The estimated event rate for a possible myocardial infarction in all studies was 5.46 per 1000 p.y. The fatal (all causes) event rate was 5.27 per 1000 p.y., and the estimated fatal cardiovascular event rate 2.93 per 1 000 p.y. In one long-term study (48 weeks) comprising 2282 patients (1658 p.y.), the observed fatal (all causes) event rate was 4.2 per 1 000 p.y. The overall incidence in the comparative studies of (one or more) adverse events was: for lacidipine 30.3%, other calcium antagonists 43.8%, diuretics 18.7%, beta-receptor blockers 48.7%, ACE inhibitors 10.4%, and placebo 15.7%. The adverse effects of lacidipine were the expected ones, e.g. headache, flushing, pedal oedema, and palpitations.. When analysing the data on file for lacidipine and some comparatory drugs in almost 19000 hypertensive patients we have found lacidipine to be an effective and well tolerated drug with a reasonable adverse profile typical for a calcium antagonist of the dihydropyridine group. Our study has the obvious limitations of a retrospective analysis of data obtained from a large cohort of patients, most of whom received lacidipine for a relatively short period of time. The present results indicate a lower fatal event rate than previously reported in the actively treated hypertensives in Collins' meta-analyses, comprising ten times more person-years than our analysis. Prospective studies with lacidipine focusing on possible reductions of atherosclerosis as well as incidence of cardiovascular disease are required and are well under way.

Topics: Adult; Aged; Blood Pressure; Calcium Channel Blockers; Clinical Trials as Topic; Dihydropyridines; Heart Rate; Humans; Hypertension; Middle Aged

Topics: Antihypertensive Agents; Arteriosclerosis; Clinical Trials as Topic; Dihydropyridines; Humans; Hypertension; Hypertrophy, Left Ventricular; Multicenter Studies as Topic

GUIDELINES ON DRUG SAFETY: Recent European Union draft guidelines for the safety evaluation of drugs intended for long-term use state that during drug development the safety profile of the new compound should be assessed over a period of time consistent with intended usage. This is in reasonable agreement with guidelines prepared by other regulatory authorities. CLINICAL DRUG DEVELOPMENT: Satisfactory preclinical data on a new compound are used to obtain authorization for human testing from the National Committees on Safety of Medicines. Clinical trials are performed in four phases, ranging from phase I studies performed on healthy volunteers (n = 20-50) to postmarketing (phase IV) studies. The latter are of great importance as they cover large patient populations (n = 2000 to > or = 10,000) and allow detection of rare adverse drug reactions. ADVERSE DRUG REACTIONS: Type B reactions are serious, unpredictable reactions to a drug that necessitate treatment withdrawal. Type A reactions are dose-dependent, and represent the majority of adverse reactions. They are often managed by dose reduction rather than drug withdrawal. ADVERSE REACTIONS TO ANTIHYPERTENSIVE AGENTS: Examples of type B adverse reactions to antihypertensives are the cutaneous and ocular reactions to practolol, and angioneurotic oedema associated with angiotensin converting enzyme inhibitors. Lacidipine, a second-generation calcium antagonist, is an example of a modern antihypertensive agent with a favourable safety profile. The adverse reactions associated with lacidipine are mild to moderate and of the A type, the major ones being those typical of calcium antagonists (headache, flushing and pedal oedema due to vasodilation.

Topics: Antihypertensive Agents; Dihydropyridines; Humans; Hypertension; Product Surveillance, Postmarketing

To assess the benefits of the calcium antagonist lacidipine on the prevention of cardiovascular events and the prevention of organ damage in two long-term clinical trials. SYSTOLIC HYPERTENSION IN THE ELDERLY LONG-TERM LACIDIPINE (SHELL) TRIAL: In the SHELL trial, the efficacy of lacidipine-based treatment is to be compared with that of thiazide-like diuretic (chlorthalidone)-based treatment in elderly patients with isolated systolic hypertension. The incidence of cardiovascular mortality and cardiovascular morbidity over a 5-year period are endpoints.. In the ELSA trial, the effects of lacidipine-based treatment and beta-blocker (atenolol)-based treatment on the development and progression of carotid atherosclerosis are to be assessed in hypertensive patients. The primary endpoint of this study is the rate of change in the thickness of the carotid artery wall, measured with B-mode ultrasound.

Topics: Antihypertensive Agents; Arteriosclerosis; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension

Lacidipine is an orally administered calcium channel blocker of the dihydropyridine class, which shows selectivity for vascular smooth muscle over cardiac tissue and has a long duration of action. In studies using ambulatory blood pressure monitoring, lacidipine 2 to 8mg administered once daily in the morning reduced blood pressure over 24 hours, with the reductions being greater during the day than at night in some studies. 77 to 87% of patients with mild to moderate hypertension had their blood pressure controlled by treatment with lacidipine 2 to 8 mg/day for 1 to 4 months in dose-finding studies. When administered once daily, lacidipine 4 to 6 mg was equivalent in antihypertensive efficacy to hydrochlorothiazide 25 to 50 mg/day, atenolol 50 to 100 mg/day, and the prototype calcium channel blocker nifedipine 20 to 40 mg twice daily (sustained-release formulation). The adverse effects of lacidipine are those common to other dihydropyridine calcium channel blockers, and include headache, flushing, ankle oedema, dizziness and palpitations. The long term effects of lacidipine on cardiovascular morbidity and mortality, and possible additional clinical benefits in terms of its antiatherosclerotic effects, are under investigation; the outcome of these studies will be important in defining the future role of this agent in the treatment of hypertension. Thus, available evidence suggests lacidipine provides a further alternative to the dihydropyridine calcium channel blockers currently available for the treatment of essential hypertension.

Topics: Adult; Aging; Animals; Antihypertensive Agents; Calcium Channel Blockers; Cross-Over Studies; Dihydropyridines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Hemodynamics; Humans; Hypertension; Middle Aged; Tissue Distribution

In our recent review of calcium antagonists for the treatment of patients with cardiovascular disease we concluded that most patients could be managed with formulations of one of the original calcium antagonists, verapamil, diltiazem or nifedipine. Experience is greatest with these drugs, and none of the newer alternatives appeared more effective or better tolerated. Lacidipine (Motens-Boehringer Ingelheim) is the latest calcium antagonist to be marketed for the treatment of patients with mild to moderate hypertension. It is licensed for once-daily use without the need for a modified-release formulation; in this respect it resembles amlodipine. The manufacturer of lacidipine claims that its gradual onset of action "cushions the fall in blood pressure" and "cushions against side effects".

Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension

Effects of calcium antagonists on pressor mechanisms: A number of differences have been reported in the variable extent to which calcium antagonists interfere with various pressor mechanisms. In theory, high lipid solubility, membrane-binding characteristics and a prolonged duration of action appear to be requirements for a calcium antagonist to affect mechanisms such as vasodilation, endogenous vasoconstrictor responses, hormone release and natriuretic activity. Reduction in peripheral vascular resistance: A reduction in peripheral vascular resistance is fundamental to the antihypertensive effect not only of calcium antagonists but also of angiotensin converting enzyme inhibitors and alpha 1-adrenoceptor antagonists. However, only the calcium antagonists interfere directly with the pressor responses mediated by both the adrenergic nervous system and the renin-angiotensin system. Mechanism of lacidipine effects: Preliminary results with the new dihydropyridine calcium antagonist lacidipine indicate that it not only has vasodilator activity but that it also interferes with both adrenergic and non-adrenergic endogenous vasoconstrictor mechanisms. This may provide additional potentially beneficial cardiovascular effects, particularly in relation to left ventricular hypertrophy and dysfunction.

Topics: Aldosterone; Angiotensin II; Blood Pressure; Calcium Channel Blockers; Cardiovascular Physiological Phenomena; Cardiovascular System; Dihydropyridines; Humans; Hypertension; Norepinephrine; Vascular Resistance; Vasoconstriction

Importance of L-channels for calcium: Calcium L-channels, the specific target of calcium antagonists, appear to be the receptors for these therapeutic agents. Therefore, the accessibility of these channels/receptors to calcium antagonists is a major determinant of the response to these drugs in cardiovascular disorders, including essential hypertension. As with numerous other drugs, the concentration at the receptor level and its time-course largely determine not only the intensity but also the rate of onset and the duration of the drug's effect. Disadvantages of nifedipine: Within the series of dihydropyridine calcium antagonists, the first compound introduced was nifedipine, a relatively hydrophilic drug. Owing to its hydrophilic character the drug rapidly reaches the receptor, thus explaining the rapid onset of its vasodilator action. Accordingly, reflex tachycardia develops, which is not only triggered by the degree of vasodilation but also by the rapidity of its onset. In addition, nifedipine has a short duration of action, requiring the use of special galenic formulations to allow one dose a day. New dihydropyridine calcium antagonists: In view of the disadvantages of the hydrophilic calcium antagonists, attempts have been made to develop dihydropyridines with a slower onset and a longer duration of action. This may be achieved by drugs which are largely in the ionized state at a physiological pH (e.g. amlodipine) and therefore combine slowly with the receptor and bind firmly to various tissue compartments. Another logical approach is the use of highly lipophilic drugs such as lacidipine. Because of its physicochemical properties, the effect in equilibrium is reached very slowly, after up to 5 h in isolated tissues and after more than 2 h after intravenous administration. Lacidipine appears to slowly enter a lipid compartment surrounding the dihydropyridine binding site, which has to be saturated before an equilibrium effect is reached. In addition, the persistence of the drug in this lipid compartment contributes to its long-lasting vasodilator effect.

Topics: Animals; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Hemodynamics; Humans; Hypertension; In Vitro Techniques; Models, Biological; Nifedipine

Comparison of first- and second-generation calcium antagonists: Despite their diversity of structure, the first-generation calcium antagonists nifedipine, verapamil and diltiazem all have a short elimination half-life and a relatively short duration of action. In contrast, there appears to be wide diversity in these properties among the newer calcium antagonists, which are mostly dihydropyridines. The longer half-life and physicochemical properties of some of the newer agents allow full 24-h blood pressure control. Duration of action of lacidipine: Taken only once a day, lacidipine has proved as potent an antihypertensive agent as slow-release nifedipine administered twice a day. Lacidipine produces a satisfactory fall in blood pressure not only during waking hours but also during sleep at night, as shown by 24-h ambulatory monitoring. Moreover, this blood pressure fall is obtained without any reflex tachycardia or associated side effects. Compared with patients treated with placebo, systolic and mean arterial blood pressure variability (standard deviation) is reduced by lacidipine treatment.. Control of blood pressure using lacidipine once a day meets the criteria proposed by the United States Food and Drugs Administration for antihypertensive drug efficacy and duration of action.

Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Drug Administration Schedule; Half-Life; Humans; Hypertension

Characteristics of three different calcium antagonist groups: Most important calcium antagonists used to treat cardiovascular disease belong to one of three main groups, phenylalkylamines, dihydropyridines and benzothiazepines. The best known drug in each group is verapamil, nifedipine and diltiazem, respectively. Dihydropyridines are predominantly vasodilators, with little or no primary cardiac activity; the tachycardia caused by these compounds is a reflex phenomenon. Verapamil and related drugs are also vasodilators, with an additional depressant effect on atrioventricular conduction, heart rate and contractility. Diltiazem's pharmacodynamic profile and side effects may be considered as intermediate between those of the dihydropyridines and verapamil. Characteristics of new calcium antagonists: Several new calcium antagonists have been introduced in the last few years, virtually all dihydropyridines. Compared with the older generation of calcium antagonists these newer drugs tend to have (1) a longer duration of action; (2) some selectivity for a specific vascular bed, such as resistance, coronary, renal or cerebral vessels; (3) a potentially useful extra component, such as diuretic or anti-atherogenic activity. Newer calcium antagonists described in this review: The newer compounds briefly characterized in this review are amlodipine, felodipine, isradipine, lacidipine, nimodipine, nisoldipine and nitrendipine. New slow-release formulations are also discussed. There is a particular emphasis on lacidipine and its potential for cardiovascular drug therapy.

Topics: Angina Pectoris; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Diltiazem; Humans; Hypertension; Nifedipine; Vasodilator Agents; Verapamil

To compare the vascular effects of lacidipine with those of other calcium antagonists.. A review of published studies.. Experimental studies have shown that for a similar fall in blood pressure, lacidipine increased cardiac contractility while verapamil decreased cardiac contractility. In the rat aorta, the dose of lacidipine required to reduce a calcium-induced contraction by 50% was lower than that of all other calcium antagonists tested except nisoldipine. In human studies, especially, there are inherent limitations in the techniques available to measure regional blood flows under physiological conditions, making it difficult to compare the effects of different antihypertensive drugs. A recent study showed that renal blood flow was increased by lacidipine without any reduction in renal function. As in animals, vital organ perfusion was either preserved or increased. Further, maximal coronary vasodilation was associated with lower coronary resistance values during lacidipine treatment compared with pretreatment values. Another lacidipine study showed increased brachial artery compliance, while a study on the radial artery showed that lacidipine increased the compliance of this artery also.. Lacidipine has vascular selectivity. Although regional blood flows are difficult to measure, due to inherent limitations in the techniques available, the evidence suggests that lacidipine produces vasodilation in essential hypertensive subjects while maintaining or even increasing vital organ perfusion. This appears to be due to a regression of the structural changes that characterize hypertension.

Topics: Animals; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Hemodynamics; Humans; Hypertension

Effects of calcium antagonists on left ventricular hypertrophy: The goals of antihypertensive treatment are to lower systemic blood pressure and to reverse left ventricular hypertrophy. A number of different drugs can induce a decrease in left ventricular mass, some of which are calcium antagonists. In particular, verapamil, diltiazem and a number of dihydropyridines (nifedipine, isradipine, lacidipine) have proved effective in this respect. Left ventricular systolic function: Left ventricular systolic function is often normal at rest in patients with hypertension, but is quite commonly abnormal during exercise. Calcium antagonists therefore do not affect resting systolic function in this category of hypertensive patients. In contrast, in hypertensive patients with heart failure the administration of dihydropyridines improves systolic performance. Left ventricular diastolic function: Isovolumic relaxation and rapid filling are often impaired in patients with hypertension, with or without left ventricular hypertrophy. Verapamil is effective in abolishing this diastolic dysfunction when given intravenously; in contrast, medium-term therapy with calcium antagonists such as diltiazem or dihydropyridines does not improve left ventricular filling properties. However, when antihypertensive therapy achieves a reduction in left ventricular mass, a consistent improvement in diastolic properties occurs.

Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardial Contraction; Ventricular Function, Left

To review the effects of calcium antagonists, and of the new dihydropyridine lacidipine in particular, on the glomerular filtration rate, renal plasma flow, and the sodium to water ratio in hypertensive patients.. Review of published data.. Different studies have shown a wide range of responses to all three subgroups of calcium antagonists in glomerular filtration rates and in renal plasma flows. In some studies there was a reduction and in others a rise in these two renal parameters. The administration of lacidipine was associated with a significant rise in renal plasma flow which disappeared with chronic treatment and no change in the glomerular filtration rate. There are only a few studies on the long-term natriuretic and diuretic effects of calcium antagonists. In the short term, dihydropyridine calcium antagonists appear to produce diuretic and natriuretic effects, but these effects are not seen with verapamil. Lacidipine showed no trend towards sodium and water retention.. Reported differences between calcium antagonists in glomerular filtration and renal plasma flow probably reflect differences in the baseline tone of pre- and postglomerular arterioles. Calcium antagonists do not cause sodium and water retention during chronic therapy. The new dihydropyridine derivative lacidipine lowers blood pressure without reducing renal function or causing sodium and water retention.

Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Renal Circulation; Water-Electrolyte Balance

Renal vascular resistance is increased in essential hypertension, with a consequent reduction in renal plasma flow together with a normal or slightly reduced glomerular filtration rate. Non-specific vasodilators may exacerbate this effect while loop diuretics, beta-blockers, angiotensin converting enzyme inhibitors and calcium antagonists may increase these renal hemodynamic parameters. We studied the effect of lacidipine, a new long-lasting calcium antagonist, on renal hemodynamics in 11 essential hypertensives. Lacidipine (4 mg once a day) acutely increased renal plasma flow without affecting the glomerular filtration rate. A transient, but non-significant, diuresis and natriuresis occurred. After 4 weeks of lacidipine treatment, all the parameters of renal function returned to basal levels. These results suggest that the well known renal effects of calcium antagonists are, at least in part, related to the onset of the antihypertensive effect being more pronounced with compounds such as nifedipine which have a rapid-onset, blood pressure-lowering effect.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Diuretics; Drug Evaluation; Humans; Hypertension; Kidney; Renal Circulation; Vascular Resistance

The effects of calcium antagonists in reducing blood pressure at rest and during exercise were examined in patients with mild-to-moderate essential hypertension. The haemodynamic effects of calcium antagonists were evaluated at rest and during exercise. We also examined 10 patients with mild-to-moderate essential hypertension taking lacidipine, a new dihydropyridine calcium antagonist (4 mg once a day, at 0700 h). Compared with placebo, lacidipine induced significant mean reductions in 24-h blood pressure (P less than 0.001 for systolic blood pressure; P less than 0.002 for diastolic blood pressure). After 24 h, the blood pressure reductions were still significant (P less than 0.02 for systolic blood pressure; P less than 0.04 for diastolic blood pressure). The heart rate did not change. During dynamic exercise, blood pressure at maximal effort was reduced (P less than 0.01 for systolic and diastolic blood pressure) and the external workload reached at the anaerobic threshold was significantly increased (P less than 0.001), but not at maximum effort. Ventilation and tidal volume were similar at both the anaerobic threshold and peak exercise, while oxygen uptake and carbon dioxide production were increased at the anaerobic threshold (P less than 0.02 for carbon dioxide production) but were similar at peak exercise.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Anaerobic Threshold; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Dihydropyridines; Diuretics; Exercise; Exercise Test; Female; Hemodynamics; Humans; Hypertension; Male

Lacidipine is a calcium antagonist of the dihydropyridine group that is highly selective for vascular tissues. It has been tested during the last few years for the treatment of arterial hypertension. We evaluated the clinical position of this calcium antagonist on the basis of clinical results. From the dose-ranging studies carried out to determine the efficacy of lacidipine, it has been shown that the dose range of 2-6 mg of lacidipine given once daily is effective in reducing blood pressure levels. Lacidipine efficacy (4-6 mg/o.d.) also has been compared with that of the diuretic hydrochlorothiazide, the calcium-antagonist nifedipine, and the beta-blocker atenolol in three different clinical trials according to the same protocol. The results indicated that lacidipine, hydrochlorothiazide, nifedipine, and atenolol caused similar reductions both in systolic and diastolic blood pressure after 1 and 2 months of treatment. Similar blood pressure levels were also reached when another antihypertensive agent (atenolol or hydrochlorothiazide) had been added in nonresponders to monotherapy. Heart rate showed a significant decrease only under atenolol treatment, either monotherapy or associated to the previous treatment. In these comparison studies, tolerability was also evaluated. The incidence of side effects during lacidipine treatment was lower than during nifedipine or atenolol treatment, but higher than during hydrochlorothiazide therapy. Lacidipine did not cause any changes in the laboratory parameters evaluated during the 2-month monotherapy period. From a trial conducted in elderly patients, lacidipine 2 and 4 mg/o.d. has been shown to cause similar diastolic blood pressure reduction after 1 month of treatment, the effect being more gradual with the lower dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Calcium Channel Blockers; Dihydropyridines; Female; Humans; Hypertension; Male; Meta-Analysis as Topic

Lacidipine is a new 1,4-dihydropyridine (DHP) that induces a potent calcium antagonistic activity on vascular preparations. It has a markedly slow rate of onset, but its effect is still apparent after 9 h of drug washout. Calcium antagonistic activity has been evaluated on nonvascular smooth muscle, and lacidipine has proved to be more vascular-selective than standard DHP derivatives. In cardiac preparations, the concentrations required to induce negative inotropic effects are approximately 100 times higher than concentrations needed to antagonize calcium-induced contractions in vascular smooth muscle. In addition, lacidipine exhibits antioxidant properties in tests based on the autoperoxidation of rat cerebral cortical membranes. In spontaneously hypertensive rats (SHRs), lacidipine induces a potent and long-acting blood pressure reduction (ED25 = 0.19 mg/kg orally and 0.006 mg/kg intravenously, with durations greater than 12 and 3 h, respectively). In saline-loaded SHRs and at antihypertensive dosages, lacidipine increases urine volume as well as urinary excretion of sodium. In one-clip, two-kidney renal hypertensive dogs, the antihypertensive properties of lacidipine after both oral and intravenous administration were confirmed. The marked vascular selectivity of lacidipine was clearly evident both in pithed rats infused with angiotensin II and in anesthetized dogs, in which preferential and long-lasting coronary and vertebral blood flow increases were also observed.

Topics: Animals; Blood Pressure; Blood Vessels; Calcium Channel Blockers; Dihydropyridines; Dogs; Hypertension; Rabbits; Rats

Selection of the appropriate dose of a new drug for initiation of treatment and then for maintenance is a complicated task. It requires the careful assessment and weighing of benefit vs. risk. A series of studies was carried out with lacidipine to determine the optimal initial dose in a general hypertensive population as well as in special populations in whom the pharmacokinetics may be different. The conclusions of these studies are that (a) in a general adult population, the initial dose should be 4 mg once daily; (b) in the elderly and in those with impaired liver function, the starting dose should be 2 mg once daily; and (c) renal dysfunction does not alter the usual starting dose of 4 mg once daily.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Drug Administration Schedule; Female; Humans; Hypertension; Male; Middle Aged

The circadian rhythm of blood pressure has been shown to be an accurate and repeatable method of characterizing blood pressure over each 24-h period, and probably provides the best index of cardiovascular risk. Many studies have confirmed that these curves can be used to define accurately the duration and degree of antihypertensive effect of drugs, and are not influenced by the administration of placebo. Furthermore, these curves represent an ideal method for testing the efficacy of once-daily drugs. Lacidipine has been tested against these curves in 12 hypertensive patients, and has been shown to be an effective antihypertensive agent throughout the day, with a 24-h duration of action after a single oral dose and without reflex tachycardia.

Topics: Blood Pressure; Calcium Channel Blockers; Circadian Rhythm; Dihydropyridines; Humans; Hypertension

The clinical safety of the new dihydropyridine calcium antagonist lacidipine was assessed in 14 clinical trials, including 1,372 patients treated with lacidipine and 687 treated with an alternative antihypertensive agent. The type and incidence of adverse events seen with lacidipine were characteristic of this class of drug, being mainly those associated with the pharmacologic effect of vasodilation, but with a lower incidence of edema than seen with nifedipine. There were no unexpected adverse effects. Hence, lacidipine is likely to be well accepted in general clinical use. Furthermore, as it has the advantages of a long duration of action and once-daily dosage, the benefit/risk ratio indicates that lacidipine is a suitable agent for the first-line treatment of hypertension across a wide range of patients.

Topics: Adult; Aged; Aged, 80 and over; Calcium Channel Blockers; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged; Safety

Arterial diameter, blood flow, and vascular resistance of the common carotid artery were studied, using a pulsed Doppler system, in patients with uncomplicated sustained essential hypertension compared with age-matched normotensive subjects. In the hypertensive subjects, arterial diameter and blood flow remained close to the normal range while vascular resistance was increased. Following antihypertensive drug treatment with converting enzyme inhibitors, nitrates, or calcium antagonists, dilation of small or large arteries, or both, may be obtained, depending on the administered compound. Calcium blockade by lacidipine produced a predominantly carotid arteriolar dilation with no change in arterial diameter, suggesting independent consequences on cerebral circulation and baroreflex mechanisms.

Topics: Calcium Channel Blockers; Carotid Arteries; Cerebrovascular Circulation; Dihydropyridines; Humans; Hypertension; Pressoreceptors; Vasodilation

Whether increased serum uric acid (SUA) favours resistance to antihypertensive drugs is not clear.. The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind, multicenter trial comparing the effects of a 4-year treatment with either lacidipine or atenolol on progression of carotid atherosclerosis in patients with moderate hypertension. SUA was assessed at randomization and at the study end, office blood pressure (BP) was measured at each titration visit and every 6 months thereafter, ambulatory BP was measured at randomization and every year thereafter.. No difference was found in office and ambulatory BP reduction achieved after 1 and 4 years of treatment in baseline SUA tertiles. This was the case for both treatments. The percentage of patients with controlled office BP (<140/90 mmHg) after 1 year (36.5, 34.2 and 33.8%, P = 0.56) and 4 years (39.9, 39.4 and 38%, P = 0.82) was not different in SUA tertiles. Similar results were obtained basing the analysis on the control of ambulatory BP (<130/80 mmHg) or when data were analyzed taking into account SUA extreme values (≥7 and <3.5 mg/dl). The average and percentage changes of SUA (baseline-study end) were not different between patients who achieved or did not achieve office BP control (5.31 ± 1.26 vs. 5.4 ± 1.29 mg/dl, P = 0.22 e 0.13 ± 0.33 vs. 0.13 ± 0.68, P = 0.87, respectively). This was the case also for control of ambulatory BP.. In the ELSA study, SUA levels do not affect the responsiveness to antihypertensive treatment.

Topics: Antihypertensive Agents; Atenolol; Atherosclerosis; Blood Pressure; Carotid Artery Diseases; Dihydropyridines; Disease Progression; Double-Blind Method; Drug Resistance; Female; Humans; Hypertension; Male; Middle Aged; Uric Acid

Obesity is becoming one of the leading risk factors of coronary heart disease, hypertension, cerebrovascular disease. Despite the presence of a large number of antihypertensive agents and scientific substantiation of antihypertensive treatment principles it would be wrong to assume that the problem is completely solved. Development of endothelial dysfunction is one of the key pathogenic mechanisms in hypertension. This process is proven to have contributed by immune inflammation activation which is mediated by pro-inflammatory cytokines and oxidative stress.. To investigate the additional benefits of the combined antihypertensive therapy with lacidipine and candesartan on the basis of studying their antioxidant properties, impact on endothelial function and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity.. A combination of a calcium channel blocker and angiotensin receptor blocker (lacidipine 2 mg, 4 mg, and candesartan 4mg, 8mg, 16mg) was prescribed to 30 patients with essential hypertension of grades 1-3, 30 to 65 years old (mean age - 54.7 ± 5.8 years), who previously have not been receiving regular antihypertensive therapy.. During the course of combined antihypertensive therapy with lacidipine and candesartan, a significant reduction in i-NOS activity, TNF-α to its type I soluble receptor ratio (TNF- α/sTNF-αRI), and oxidative stress marker - 8-iso-PgF2α has been observed. Activity of e-NOS, levels of SOD and catalase, in contrast, have increased by the end of observation period.. The improvement of endothelial function due to lower level of oxidative stress and a significant decrease of immune activation has been observed in hypertensive patients with overweight and obesity under the influence of combined antihypertensive therapy with lacidipine and candesartan.

Topics: Adult; Aged; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Case-Control Studies; Dihydropyridines; Dinoprost; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Obesity; Tetrazoles; Tumor Necrosis Factor-alpha

Recent studies have reported that in patients under antihypertensive treatment visit-to-visit (or long-term) variability of clinic BP within a given patient has an independent prognostic significance. Partly based on between-patient dispersion of BP values during treatment (interindividual variability) it has also been reported that long-term clinic BP variability is greater for β-blocker than for calcium antagonist and other types of treatment.. To measure visit-to-visit intraindividual variations of both clinic and 24-h mean BP in the hypertensive patients of the European Lacidipine Study on Atherosclerosis (ELSA) trial treated for 4 years with either atenolol or lacidipine, and to check whether interindividual clinic and 24-h BP variabilities during treatment can really be considered a surrogate of intraindividual variabilities in exploring differences between β-blocker and calcium antagonist treatments.. Long-term intraindividual BP variability was defined as the coefficient of variation of the average systolic or diastolic values of clinic and 24-h BP measured at each visit throughout the treatment period. Patients in whom at least seven clinic (6-month intervals) or at least three (yearly intervals) 24-h values were available from the end of the drug titration phase to the end of the study were considered.. Visit-to-visit 24-h SBP/DBP variabilities were 20-25% smaller than, and loosely correlated with clinic BP variability (r(2) < 0.022). There was also a very limited relationship (r (2)< 0.026) between visit-to-visit and within 24-h ambulatory BP variabilities, the latter being two to three times greater than the former. Visit-to-visit intraindividual clinic SBP variability was only slightly lower on calcium antagonist than on β-blocker treatment but little or no between-treatment difference was found for visit-to-visit clinic DBP and ambulatory SBP/DBP particularly in patients under monotherapy throughout the study. Interindividual BP variability was markedly greater than the intra-individiual one of which it did not precisely reflect the treatment-induced changes.. In mild-to-moderate hypertensive patients, visit-to-visit BP variability does not differ substantially between β-blocker and calcium antagonist treatment. Major discrepancies exist between visit-to-visit BP variability as quantified by 24-h vs. clinic BP, making investigation of which of these indices is clinically more relevant important. Interindividual BP variability during treatment shows marked quantitative differences with intraindividual BP variability questioning whether its use can accurately reflect individual BP variations from one visit to another.

Topics: Antihypertensive Agents; Blood Pressure; Dihydropyridines; Double-Blind Method; Europe; Humans; Hypertension

In high-cardiovascular-risk treated hypertensive patients, the incidence of cardiovascular events has been reported to relate to visit-to-visit blood pressure (BP) variability. We investigated whether visit-to-visit BP variability is prognostically important in treated mildly to moderately hypertensive patients in whom treatment aims at avoiding events but also at preventing or delaying progression of organ damage.. We analyzed the pooled data from the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind 4-year trial of the effect of lacidipine or atenolol on echographic carotid intima-media thickness. Visit-to-visit BP variability was assessed by the coefficient of variation or the SD of the mean on-treatment systolic BP (SBP) obtained at 6- (clinic BP) and 12- (24 hours BP) month intervals, respectively (1521 and 1264 patients, respectively). In a multivariable linear regression model, mean on-treatment clinic or 24-hour SBP, but not SBP coefficient of variation or SD, was associated with end-of-treatment carotid intima-media thickness. Intima-media thickness increased progressively from the lowest to highest quartile of mean on-treatment clinic or 24-hour SBP (adjusted P for trend=0.046 and 0.048) but not along similar quartiles of SBP coefficient of variation or SD. In a multivariable logistic regression model, mean BP, but not variability, was associated with cardiovascular outcomes.. In mildly to moderately hypertensive patients, carotid intima-media thickness and cardiovascular outcomes were related to the mean clinic or ambulatory SBP achieved by treatment but not to on-treatment visit-to-visit clinic or 24-hour BP variability. Thus, when BP is modestly elevated, inconsistency of BP control between visits plays a less important prognostic role than long-term average BP levels.

Topics: Adrenergic Antagonists; Aged; Antihypertensive Agents; Atenolol; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Carotid Artery Diseases; Carotid Intima-Media Thickness; Circadian Rhythm; Dihydropyridines; Double-Blind Method; Europe; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Office Visits; Prognosis; Prospective Studies; Treatment Outcome

Information on the features of long-term modifications of clinic and 24-h ambulatory blood pressure (ABP) by treatment is limited. The present study aimed to address this issue.. Ambulatory BP monitoring and clinic BP (CBP) measurements were performed at baseline and at yearly intervals over a 4-year follow-up period in 1523 hypertensives (56.1 +/- 7.6 years) randomized to treatment with lacidipine or atenolol in the European Lacidipine Study on Atherosclerosis (ELSA).. CBP was always greater than ABP, while reductions in all BP values (greater for CBP than for ABP) were on average maintained throughout 4 years, CBP changes showing limited relationship with ABP changes (r = 0.14-0.27). BP reductions by treatment during daytime and night-time were correlated (r = 0.63-0.73). BP normalization was achieved in a greater percentage of patients for CBP (41.7%) than for ABP (25.3%), with systolic BP control being always less common than diastolic BP control. BP normalization was more frequent at single yearly visits than throughout the 4 years. Twenty-four-hour BP variability was reduced by treatment over 4 years in absolute but not in normalized units.. The present study provides the best evidence available on long-term effect of antihypertensive treatment on both ABP and CBP. On average, ABP was sustainedly reduced by treatment throughout the follow-up period, but 24-h BP was more difficult to control than CBP. In several patients, ABP control was unstable between visits, the percentage of patients under control over 4 years being much less than that of those controlled at each year. Treatment induced a reduction in absolute but not in normalized BP variability estimates. This has clinical implications because of the prognostic importance of ABP mean values and variability.

Topics: Antihypertensive Agents; Atenolol; Atherosclerosis; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged

The European Lacidipine Study on Atherosclerosis (ELSA) randomized 2334 hypertensive patients to either the lipophilic calcium antagonist lacidipine or the beta-blocker atenolol for 4 years. About 35% of subjects in both groups received additional hydrochlorothiazide (12.5-25 mg/day). The patients were followed up for carotid intima-media thickness (IMT) changes for 3.7 years.. The present post-hoc analyses were aimed at: describing the prevalence of the metabolic syndrome (MS) at baseline; investigating the effect of long-term antihypertensive therapy (and separately of atenolol and lacidipine) on MS prevalence; exploring whether MS at baseline influenced changes in carotid IMT and incidence of cardiovascular events during treatment; and describing the relations between MS and new cases of diabetes developing during treatment.. At baseline 2034 patients had, in addition to blood pressure (BP), measurements of blood glucose, serum high-density lipoprotein (HDL)-cholesterol, triglycerides and body mass index (BMI > 28.8 for men and > 26.2 for women were taken to correspond to waist circumference > 102 and > 88 cm, respectively). These measurements were repeated after 4 years of treatment in 1444 patients. MS was defined according to Adults Treatment Panel III (ATP III).. A high proportion of ELSA patients (33.3%) had MS at baseline, with no difference between atenolol and lacidipine. Baseline IMT was slightly greater in MS patients, but only the difference in mean maximum IMT at common carotids and bifurcations (CBMmax) achieved significance (P = 0.0325). Progression of CBMmax was also slightly greater in MS patients (P = 0.0241), but significance was lost when adjusted for covariates. No significant difference was found in the incidence of new cardiovascular events between patients with and without MS. The incidence of new MS was 21.4%, and significantly greater in patients under atenolol (25.2%) than lacidipine (17.7%; P = 0.0045). New-onset diabetes occurred in 5.54% of ELSA patients, and was three times higher among patients with than those without MS (10.28 versus 3.43%, P > 0.0001).. Our analyses show a high prevalence of MS in ELSA hypertensives, a substantial incidence of new cases of MS and diabetes, the latter mostly among patients with MS. These analyses also show that in ELSA lacidipine was superior to atenolol, not only in showing a lower progression of carotid atherosclerosis, but also in causing a significantly lower incidence of new MS.

Topics: Aged; Antihypertensive Agents; Atenolol; Atherosclerosis; Calcium Channel Blockers; Carotid Arteries; Cohort Studies; Diabetes Complications; Dihydropyridines; Europe; Female; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged

It has been postulated that the loss of arterial compliance may precede cardiovascular diseases, and that arterial compliance is an important parameter to consider when evaluating arterial diseases such as essential hypertension (EH) and the effects of antihypertensive treatment. In all, 133 EH patients and 147 healthy subjects were enrolled in this study. Large arterial compliance (C1) and small arterial compliance (C2) were measured by the CVProfilor DO-2020 CardioVascular Profiling System. Thirty-five patients randomly received magnesium potassium supplementation (magnesium, 70.8 mg/d; potassium, 217.2 mg/d) for four weeks, and 32 patients received lacidipin (4 mg/d) as a control. Before and after the four weeks, blood pressure, C1, and C2 were measured. It was found that arterial compliance was significantly lower in EH patients compared with healthy subjects (C1: 12.53 +/- 0.33 vs. 15.63 +/- 0.30 ml/mmHg x 10, p < 0.01;C2: 3.79 +/- 0.17 vs. 5.69 +/- 0.25 ml/mmHg x 100, p < 0.01). On lacidipine, systolic and diastolic BP decreased 13.27 +/- 1.76 mm Hg and 6.33 +/- 1.55 mm Hg, and C1 and C2 compliance values increased 25.05% +/- 4.49% and 34.50% +/- 7.40%, respectively. On K+ and Mg2+ supplementation, systolic and diastolic BP decreased 7.83 +/- 1.87 mm Hg and 3.67 +/- 1.03 mm Hg, and C1 and C2 compliance values increased 12.44% +/- 4.43% and 45.25% +/- 6.67%, respectively. Decreases in systemic vascular resistance (mean arterial pressure divided by cardiac output) by 11.9% and 16.6 % (p < 0.01) were seen between the drug-induced changes, respectively. Both large arterial compliance and small arterial compliance were decreased in essential hypertension patients. In essential hypertension patients, magnesium and potassium supplementation could improve small arterial compliance, while lacidipine improved large arterial compliance significantly.

Topics: Adult; Aged; Antihypertensive Agents; Arteries; Biomarkers; Blood Pressure; Case-Control Studies; Dietary Supplements; Dihydropyridines; Female; Follow-Up Studies; Humans; Hypertension; Magnesium; Male; Middle Aged; Multivariate Analysis; Potassium, Dietary; Time Factors; Treatment Outcome; Vascular Resistance

The European Lacidipine Study on Atherosclerosis (ELSA) has been planned to investigate the effect of reduction in office and ambulatory blood pressure by lacidipine versus atenolol on carotid artery wall thickness in mild to moderate essential hypertensive patients with no metabolic abnormalities. One prespecified sub-study of ELSA focused on measurements of arterial distensibility in the carotid as well as in the radial artery to determine the relationship of functional arterial properties with office versus ambulatory blood pressure (BP) values as well as the correspondence between functional and structural arterial alterations.. The sub-study was conducted on 124 patients recruited in four centres (Monza-Milan, Paris, Grenoble and Glasgow). BP was measured both by a mercury sphygmomanometer and by 24-h ambulatory monitoring. Common carotid artery wall thickness was measured by certified sonographers as described in the main study. Common carotid and radial artery distensibility were obtained by echotracking techniques, which allowed to relate changes in arterial diameter with systo-diastolic BP changes.. Carotid artery wall distensibility showed (1) a negative correlation with office and more so 24-h average systolic BP (r = -0.45 and -0.58, P < 0.008 and 0.001) but not with office or 24-h diastolic BP) and (2) a negative correlation with the corresponding wall thickness (r = -0.47, P < 0.005). In contrast, at the radial artery level distensibility and thickness showed no correlation with each other and with BP. Carotid (but not radial) artery distensibility also correlated with ambulatory systolic BP variability but the correlation was lost after adjustment for age and mean BP values.. These data suggest that stiffening of large elastic artery is reflected more by ambulatory than office BP elevations, systolic BP being much more important than diastolic. Alterations of large elastic arteries function is related to structural wall changes. Functional and structural properties of middle-size muscle arteries are independent of BP.

Topics: Antihypertensive Agents; Arteriosclerosis; Atenolol; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Carotid Artery, Common; Circadian Rhythm; Dihydropyridines; Europe; Female; Humans; Hypertension; Male; Middle Aged; Radial Artery; Ultrasonography

To evaluate and correlate the effects of long-term antihypertensive treatment on left ventricular (LV) mass and carotid structural changes in a large group of essential hypertensive patients, participating in the European Lacidipine Study on Atherosclerosis (ELSA).. In four (Brescia, Glasgow, Naples and Pisa) of 23 centres participating in the ELSA study, an echocardiographic examination was performed at baseline and repeated, until the end of the 4-year study, in essential hypertensive patients, followed-up for carotid quantitative ultrasound examination of intima-media thickness (IMT), after random allocation to treatment with either lacidipine or atenolol (and added hydrochlorothiazide, as required for control of blood pressure).. M-mode, two-dimensional guided echocardiography was used to measure left ventricular (LV) wall thickness and dimensions, from which LV mass was calculated, using an anatomically validated formula (Penn Convention) and indexed to body surface area (left ventricular mass index, LVMI). The echocardiographic tracings were blindly evaluated in a single reading centre (Brescia). Bilateral IMT was measured at the site of common carotid and bifurcation far walls (CBMmax).. At baseline, cardiac and carotid ultrasound scans were available in 278 patients (mean age 54 +/- 7 years, 57% males, 22% obese). A significant correlation was observed between baseline LVMI and CBMmax (r = 0.22, P < 0.001), independent of age. In multivariate analysis, CBMmax and mean 24-h pulse pressure were most strongly associated with baseline LVMI. A significant reduction in LVMI was observed both during lacidipine (n = 96) (-12.5% reduction) and atenolol (n = 78) (-13.9% reduction) treatments (up to 4 years) (P < 0.001 for both, without significant differences between treatments). Changes in LVMI were not related to changes in carotid wall thickness. In multivariate analysis, baseline LV mass and mean 24-h systolic blood pressure changes were significantly associated with changes in LV mass.. In this large, long-term controlled study, antihypertensive treatment with atenolol or lacidipine was accompanied by a similar and significant decrease in LV mass. Treatment-induced changes in LV mass were related to baseline LV mass and changes in 24-h mean systolic blood pressure, without any correlation with changes in carotid structure. In the whole ELSA population, carotid IMT changes have been shown to be unrelated to blood pressure reduction, but significantly influenced by the type of antihypertensive treatment.

Topics: Adult; Aged; Atenolol; Dihydropyridines; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Multivariate Analysis; Systole; Ventricular Function, Left

In the European Lacidipine Study on Atherosclerosis (ELSA), against a similar antihypertensive effect, a significantly greater effect of lacidipine was found on carotid intima-media thickness (IMT) progression, indicating a specific anti-atherosclerotic effect of lacidipine. However, not only the extent but also the composition of an atherosclerotic plaque is a determinant of subsequent events.. Among the 2334 patients enrolled in ELSA, 420 with 4-year treatment were chosen, videodensitometric analysis of their ultrasound carotid scan was performed and the maximum wall lesion (Tmax) was classified as lipidic, fibrolipidic and fibrotic by means of software previously validated against histology. Of the 420 patients, 244 had scans suitable for videodensitometry.. Excellent reproducibility of videodensitometry analysis was found using the Bland-Altman and other methods. At baseline, ELSA hypertensive patients had predominantly fibrolipidic walls (70%), with an echoreflectivity indicating a mean collagen content of 25%. After 4 years of antihypertensive treatment, little change in the frequency distribution of carotid lesions (fibrolipidic 73%) was found, with no significant differences between patients randomized to lacidipine or atenolol.. Our study provides previously unavailable information that carotid wall composition changes to an extremely small extent during 4-year effective blood pressure lowering. With lacidipine, stable composition is associated with a lower IMT progression than with atenolol.

Topics: Adult; Aged; Antihypertensive Agents; Atenolol; Carotid Arteries; Carotid Artery Diseases; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged; Reproducibility of Results; Tunica Intima; Tunica Media; Ultrasonography

To estimate the influence of therapy with amlodipine (A) or lacidipine (L) on heart rate variability (HRV) time and frequency domain parameters in hypertensive patients with stable angina pectoris and isolated left ventricular diastolic dysfunction.. After a 1-week washout period, the patients were randomized to receive amlodipine 10 mg (30 patients) or lacidipine 6 mg (30 patients) once-daily for 4 weeks. HRV parameters were determined over a period of 24 h, echocardiography and exercise test were performed before and after treatment.. All HRV time domain parameters after applying amlodipine did not change significantly. A reliable decrease only of the root mean square of differences between adjacent normal-to-normal intervals (RMSSD)-32.9 +/- 13 vs. 27.5 +/- 9-was noticed after treatment with lacidipine. In the lacidipine group, the change of RMSSD negatively correlated with the extent of ST segment depression during exercise testing (R = -0.43; P < 0.05). Both drugs reduced total power (A, 2234 +/- 1270 vs. 1813 +/- 889; L, 2205 +/- 1151 vs. 1825 +/- 896; P < 0.01), very low (A, 1451 +/- 733 vs. 1143 +/- 534; L, 1413 +/- 759 vs. 1213 +/- 616; P < 0.05), and low frequency power (A, 610 +/- 459 vs. 447 +/- 321; L, 569 +/- 323 vs. 442 +/- 241; P < 0.01). After amlodipine, high frequency power remained unchanged, whereas low-high frequency ratio decreased (4.54 +/- 1.72 vs. 3.77+/-1.73; P < 0.05). After lacidipine, high frequency power decreased (178.8 +/- 153.2 vs. 132.1 +/- 79.3; P < 0.05), whereas the ratio of low frequency to high frequency did not change.. Amlodipine and lacidipine reduce the influence of humoral control and sympathetic autonomic nervous system activity. The autonomic balance becomes shifted toward the increased vagal activity only by amlodipine.

Topics: Adult; Aged; Amlodipine; Angina Pectoris; Blood Pressure; Calcium Channel Blockers; Circadian Rhythm; Dihydropyridines; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Heart Rate; Humans; Hypertension; Male; Middle Aged; Treatment Outcome; Ventricular Dysfunction, Left

Impaired left ventricular (LV) diastolic and long axis functions are common in arterial hypertension and stable angina pectoris patients despite normal LV ejection fraction. Data concerning the effect of calcium channel blockers (CCB) on the LV long axis function in this context are lacking.. Fifty-nine hypertensive patients with associated coronary artery disease (stable angina pectoris) and isolated diastolic dysfunction were randomized to receive amlodipine (30 patients) or lacidipine (29 patients) for 4 weeks. Clinical investigation, exercise testing, echocardiography were performed before and after the active treatment period. LV diastolic function was analysed from transmitral flow using Doppler echocardiography. Mitral annulus motion was investigated for LV long axis function analysis using 2-D guided M-mode echocardiography (amplitudes of motion) and pulsed wave tissue Doppler (velocities). Amlodipine and lacidipine affected LV diastolic and long axis functions differently: during treatment with amlodipine isovolumic relaxation time (IVRT) and deceleration time of LV early filling (DT) decreased (IVRT--from 93 +/- 19 ms to 79 +/- 15 ms, DT--from 206 +/- 36 ms to 188 +/- 27 ms; p < 0.05), early diastolic velocity of mitral annulus motion (E') increased (from 10.0 +/- 1.9 cm/s to 10.8 +/- 1.8 cm/s after treatment; p < 0.05). Lacidipine did not significantly change these parameters (IVRT-- 88 +/- 15 ms before, 87 +/- 13 ms after treatment, DT--214 +/- 34 ms and 218 +/- 42 ms, E'-- 10.4 +/- 1.5 cm/s and 10.6 +/- 1.5 cm/s, respectively). More favourable effects of CCB on LV long axis function was found in patients with post-systolic shortening.. Amlodipine can improve diastolic and long axis functions of the left ventricle in patients with arterial hypertension and stable angina pectoris.

Topics: Aged; Amlodipine; Angina Pectoris; Calcium Channel Blockers; Coronary Angiography; Coronary Disease; Diastole; Dihydropyridines; Exercise Test; Female; Humans; Hypertension; Male; Middle Aged; Mitral Valve; Ultrasonography, Doppler; Ventricular Function, Left

To study the changes in macrophage inducible nitric oxide synthase (iNOS) activity, plasma levels of nitrite, lipid peroxidation (LPO) and melatonin in human essential hypertension before and 6 months after 4 mg/day lacidipine treatment.. The study was carried out in a total of 25 subjects--11 healthy subjects and 14 hypertensive patients. Blood pressure and peripheral blood samples were taken before and after 6 months of lacidipine treatment (4 mg/day).. Systolic (SBP) and diastolic blood pressure (DBP), renal function, lipid and carbohydrate metabolism, renin, aldosterone and catecholamine levels were measured by routine methods. The activity of macrophage iNOS and plasma nitrite, LPO and melatonin levels were also measured.. Besides reducing blood pressure, lacidipine treatment significantly decreased plasma LPO and macrophage iNOS activity, without changes in NO. Melatonin significantly increases in hypertensive patients, returning to control after lacidipine. Thus, lacidipine reduced blood pressure and free radicals, avoiding the oxidative damage to endothelium. It is suggested that administration of lacidipine plus melatonin may enhance the beneficial effects of each drug in essential hypertension.

Topics: Adult; Blood Pressure; Calcium Channel Blockers; Cholesterol; Dihydropyridines; Female; Humans; Hypertension; Lipid Peroxidation; Male; Malondialdehyde; Melatonin; Middle Aged; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress

In ELSA, a randomized, double-blind trial in 2334 hypertensives, 4-year antihypertensive treatment with lacidipine slowed down progression of carotid atherosclerosis significantly more than atenolol treatment. To avoid bias, the primary outcome was measured blindly at study-end on a randomized sequence of scans, but measurements were limited to the four far walls of common carotids and bifurcations (CBMmax) and to one of each couple of duplicate scans recorded yearly.. Secondary outcomes included measurements made on all duplicate scans of both near and far walls, not only of common carotids and bifurcations, but also of internal carotids (12 walls). These measurements were made blindly during the 4-year study, shortly after recording. To avoid possible readers' drift or bias, 250 duplicate baseline scans were re-read at yearly intervals (longitudinal on-line quality control) and a correction factor calculated.. Measurements during the 4-year study showed a trend toward decreased values, with the lacidipine effect significantly greater than the atenolol one. A trend toward lower values was also observed in the longitudinal quality control of baseline scans. After applying a correction factor calculated from this longitudinal control, all measurements no longer decreased with time, but significantly increased, with progression being significantly smaller in lacidipine than in atenolol patients. Corrected values were quite similar to those calculated on measurements carried out at study-end.. The relative benefit of lacidipine over atenolol could be measured precisely by reading scans either during the study or at study-end. However, absolute treatment-related changes (progression versus regression) cannot safely be judged by readings made during a long-term study, unless a longitudinal quality control of readings is performed.

Topics: Aged; Antihypertensive Agents; Atenolol; Carotid Artery Diseases; Carotid Artery, Common; Carotid Artery, Internal; Dihydropyridines; Disease Progression; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Time Factors; Tunica Intima; Tunica Media; Ultrasonography

Our aim was to compare the effect of lacidipine and chlorthalidone on cardiovascular outcome as a primary parameter and blood pressure as a secondary in elderly patients with isolated systolic hypertension in a prospective study with an open design.. 1882 males and females outpatients > or = 60 years were randomly assigned to the administration of chlorthalidone 12.5 mg o.d. or lacidipine 4 mg o.d. Patients were recruited if sitting systolic blood pressure was > or = 160 mmHg with a diastolic blood pressure equal or lower than 95 mmHg. Primary endpoint was a composite of cardiovascular and cerebrovascular events.. At randomization mean systolic blood pressure was 178.1 mmHg in the lacidipine and 178.2 mmHg in the chlorthalidone group, the corresponding mean diastolic values being 86.9 and 86.8 mmHg. In both lacidipine and chlorthalidone groups treatment caused a significant (p < 0.001) and marked systolic blood pressure reduction which was maintained throughout the treatment period with a significant (p < 0.001) and steady although less marked reduction in diastolic blood pressure as well. At the end of treatment period (median 32 months), the reduction was 36.8/8.1 mmHg (systolic/diastolic) in the chlorthalidone and 38.4/7.9 mmHg in the lacidipine group, the final on treatment blood pressures being 142.0/79.2 and 143.2/79.5 mmHg, respectively. Treatments were similarly effective in males and females and in age groups between 60 and 69 years (n = 763), 70 and 79 years (n = 744) and > or = 80 years (n = 375). Similar reductions were obtained in a subgroup of patients (n = 209) followed in double-blind fashion for 1 year. The overall incidence of the primary endpoints was 9.3% with no significant between-group difference. Total mortality was also similar between groups.. In elderly patients with isolated systolic hypertension, administration of lacidipine or chlorthalidone markedly reduced systolic blood pressure with no difference in the incidence of cardiovascular events and total mortality.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Chlorthalidone; Dihydropyridines; Female; Humans; Hypertension; Italy; Male; Prospective Studies; Systole; Time Factors; Treatment Outcome

This randomised, double-blind, double-dummy, parallel group, multicentre study compared the efficacy and tolerability of lercanidipine with lacidipine. Elderly patients with isolated systolic hypertension (supine blood pressure >/=160/<95 mmHg) were enrolled and underwent a placebo run-in period of 14-27 days before random allocation to lercanidipine tablets 10 mg once daily (n=111) or lacidipine tablets 2 mg once daily (n=111) for the assessment period (112-160 days). Titration to lercanidipine 20 mg once daily (two 10 mg tablets) or lacidipine 4 mg once daily (two 2 mg tablets) was allowed after 8 weeks, if required. Both treatments decreased supine and standing systolic and diastolic blood pressure between the end of the run-in period and the end of the assessment period (P<0.0001). At the end of the assessment period, the estimated mean treatment difference (95% confidence intervals) in supine systolic blood pressure was -0.81 (-4.45, 2.84) mmHg. These confidence intervals were within the limits specified for equivalence, that is, (-5, 5) mmHg. Ambulatory blood pressure monitoring showed that the antihypertensive effects of both drugs lasted for the full 24-h dosing period and followed a circadian pattern. Both treatments were well tolerated with a low incidence of adverse drug reactions and a low withdrawal rate. Significantly fewer patients withdrew from treatment with lercanidipine (P=0.015). Neither treatment had any clinically significant effect on pulse rate or cardiac conduction. In conclusion, both treatments were equally effective in controlling supine systolic blood pressure in patients with isolated systolic hypertension.

Topics: Aged; Aged, 80 and over; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Supine Position; Treatment Outcome

The aim of this study was to evaluate the effects of chronic treatment with lacidipine on blood pressure, heart rate and double product during and immediately after physical effort in mild to moderate hypertensive patients. This was a single-center, randomized, double-blind, crossover, placebo-controlled clinical trial. Eighteen hypertensive patients (56% males, median age 53 years) were randomized to lacidipine 4 mg o.i.d. followed by placebo or to placebo followed by lacidipine 4 mg o.i.d. Lacidipine compared with placebo exerted a significant antihypertensive effect, lowering SBP and DBP both at baseline and either during or after exercise test. The average incremental changes of SBP and DBP between pre-exercise stage and maximal effort did not show any significant differences between treatments. HR during treatment with lacidipine was higher than during treatment with placebo both at rest and after exercise, but at maximal effort, HR was not different from placebo. The average values of DP at maximal effort, and during recovery, did not show any significant differences. Lacidipine 4 mg was effective in lowering blood pressure and in maintaining its antihypertensive effect throughout and after physical exercise, without enhancing double product value, which is an indirect index of myocardial oxygen consumption.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Cross-Over Studies; Dihydropyridines; Double-Blind Method; Exercise; Exercise Test; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Oxygen Consumption

Most cardiovascular events associated with hypertension are complications of atherosclerosis. Some antihypertensive agents influence experimental models of atherosclerosis through mechanisms independent of blood pressure lowering.. The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind trial in 2334 patients with hypertension that compared the effects of a 4-year treatment based on either lacidipine or atenolol on an index of carotid atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in far walls of common carotids and bifurcations (CBM(max)). This index has been shown by epidemiological studies to be predictive of cardiovascular events. A significant (P<0.0001) effect of lacidipine was found compared with atenolol, with a treatment difference in 4-year CBM(max) progression of -0.0227 mm (intention-to-treat population) and -0.0281 mm (completers). The yearly IMT progression rate was 0.0145 mm/y in atenolol-treated and 0.0087 mm/y in lacidipine-treated patients (completers, 40% reduction; P=0.0073). Patients with plaque progression were significantly less common, and patients with plaque regression were significantly more common in the lacidipine group. Clinic blood pressure reductions were identical with both treatments, but 24-hour ambulatory systolic/diastolic blood pressure changes were greater with atenolol (-10/-9 mm Hg) than with lacidipine (-7/-5 mm Hg). No significant difference between treatments was found in any cardiovascular events, although the relative risk for stroke, major cardiovascular events, and mortality showed a trend favoring lacidipine.. The greater efficacy of lacidipine on carotid IMT progression and number of plaques per patient, despite a smaller ambulatory blood pressure reduction, indicates an antiatherosclerotic action of lacidipine independent of its antihypertensive action.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Atenolol; Blood Pressure; Calcium Channel Blockers; Carotid Arteries; Carotid Artery Diseases; Dihydropyridines; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Time; Treatment Outcome; Tunica Intima; Tunica Media; Ultrasonography

Irrespective of their clinical relevance, side effects cannot be considered a negligible problem in antihypertensive therapy. The aim of this trial was to evaluate the tolerability profile of lercanidipine with that of two other calcium antagonists (amlodipine and lacidipine) in elderly hypertensives.. In a multicenter, double-blind, parallel study 828 elderly (aged > or =60 years) hypertensives were randomized to lercanidipine 10 mg/day (n = 420), amlodipine 5 mg/day (n = 200), or lacidipine 2 mg/day (n = 208) (ratio 2:1:1). If blood pressure (BP) control was unsatisfactory (systolic BP/diastolic BP > or =140/90 mm Hg), the dose of the double-blind medication was doubled and, as a further step, enalapril or atenolol (plus diuretic, if needed) was added. Patients were treated for an average of 12 months.. Amlodipine patients had significantly (P <.001) higher rates of edema (19%) and of early study discontinuations due to edema (8.5%) compared with lercanidipine (9% and 2.1%) and lacidipine patients (4% and 1.4%). Similarly, edema-related symptoms (lower limb swelling and heaviness) occurred significantly (P <.01) more often with amlodipine (50% and 45%, respectively) than with lercanidipine (35% and 33%) and lacidipine (34% and 31%). Most edema cases occurred in the first 6 months, a between-treatment difference being evident since beginning of treatment. Other drug-related adverse events did not differ between treatments. Blood pressure was equally and effectively reduced in the three groups.. The two lipophilic dihydropyridine calcium antagonists, lercanidipine and lacidipine, have an antihypertensive effect comparable to that of amlodipine, but a better tolerability profile.

Topics: Aged; Amlodipine; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Drug Therapy, Combination; Edema; Female; Humans; Hypertension; Male; Peripheral Vascular Diseases; Treatment Outcome

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia

Topics: Aged; Ambulatory Care; Calcium Channel Blockers; Dihydropyridines; Electrocardiography, Ambulatory; Female; Humans; Hypertension; Male; Middle Aged; Posture

This study was carried out to assess whether with a similar degree of blood pressure reduction, Lisinopril compares favorably or otherwise with lacidipine in respect of effects on urinary albumin excretion and renal function as assessed by creatinine clearance, plasma creatinine, urea and electrolytes. Thirty hypertensive diabetic nephropathy patients with moderate hypertension were studied. After a 2-week washout period, they were allocated into two groups matched at baseline for age, sex, weight, blood pressure, and urinary albumin excretion rate as well as creatinine clearance. There were 8 males and 7 females in each group. One group received lisinopril (with furosemide if needed to control BP) and the other group received lacidipine. Staged increases in doses of antihypertensives were used until BP was controlled or maximum dose of 40 mg/day lisinopril or 8 mg/day lacidipine was reached. Furosemide was added to lisinopril if BP was not controlled at 40 mg/day. These medications were given for 12 weeks at the end of which measurements done at baseline were repeated. Comparison of baseline and end of study values of these parameters within the groups and between the two groups were made. Lisinopril group and lacidipine group achieved similar and highly significant reduction in blood pressure levels P < 0.001. There was reduction in urinary albumin excretion rate in both groups but this only reached statistical significance in the lisinopril group [480] [269] mg/day vs. 315 [202] mg/day P < 0.05] while for the lacidipine group it was not significant [491] [257] mg/day vs. 335 [182] mg/day P > 0.05]. However, comparison of albumin excretion rate between both groups at baseline and at end of the study did not show any significant difference, P > 0.1. With both drugs there is a tendency for creatinine clearance to increase and plasma creatinine to drop while plasma potassium tended to rise more with lisinopril than lacidipine but differences within and between both groups, did not reach statistical significance P > 0.05. In conclusion, blood pressure reduction was comparable in both drugs; both drugs reduced albuminuria but lisinopril appeared superior. Treatment with both drugs tended to increase creatinine clearance but both had no significant effects on blood sugar.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Glucose; Blood Pressure; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dihydropyridines; Disease Progression; Female; Humans; Hypertension; Lisinopril; Male; Metabolic Clearance Rate; Middle Aged; Potassium; Prospective Studies; Treatment Outcome; Urea

Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown. Since calcium antagonists can improve endothelial function in hypertensive patients, we tested whether this beneficial effect could be related to restoration of NO availability by antioxidant activity.. In 10 healthy subjects and 20 essential hypertensive patients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (from 0.15-15 microg/100 ml per min), bradykinin (0.005-0.05 microg/100 ml per min), two endothelium-dependent vasodilators, and sodium nitroprusside (1-4 microg/100 ml forearm tissue per min), an endothelium independent vasodilator, in the absence and presence of NG-monomethyl-L-arginine (L-NMMA) (100 microg/100 ml forearm tissue per min), an NO synthase inhibitor.. In controls, vasodilation to acetylcholine and bradykinin was inhibited by L-NMMA. In hypertensive patients, vasodilation to acetylcholine and bradykinin, but not to sodium nitroprusside, was blunted and resistant to L-NMMA. Hypertensive patients were randomized to a 12-week treatment with lacidipine (4-6 mg/daily) or atenolol (50-100 mg/daily) (n = 10 each group). Lacidipine but not atenolol increased the vasodilation to acetylcholine and bradykinin and restored the inhibiting effect of L-NMMA on endothelium-dependent vasodilation, without affecting the response to sodium nitroprusside. Moreover, lacidipine reduced circulating markers of oxidative stress including plasma and low-density lipoprotein (LDL) hydroperoxides, the susceptibility of LDL to Cu2+-induced oxidation and the reactive oxygen species generated from human umbilical vein endothelial cells after incubation with LDL derived from plasma of the patients.. Lacidipine increases endothelium-dependent vasodilation by restoring NO availability, and this effect possibly is related to antioxidant activity.

Topics: Adrenergic beta-Antagonists; Adult; Antioxidants; Atenolol; Biological Availability; Biomarkers; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Vasodilation

Baseline data from the European Lacidipine Study on Atherosclerosis (ELSA) have shown that carotid intima-media thickness (IMT) is not related to diastolic blood pressure (BP), but that it is related to clinic systolic (S) or pulse pressure (PP) and more so to their 24 h average values. The aim of the present study was to determine whether IMT independently relates to additional information obtained through ambulatory BP, in particular to SBP or PP variability.. In 1663 hypertensive patients, after a wash-out period from antihypertensive treatment (mean age 56.2 +/- 7.65 years), IMT was assessed from 12 different carotid sites. Ambulatory BP measurements were performed every 15 min (day) and every 20 min (night). IMT values were positively related to 24 h, day and night average SBP and PP. There was some relationship of IMT with day-night or clinic-day SBP and PP differences. The most important finding, however, was that IMT values were related with 24 h SBP or PP standard deviation (P < 0.001), a measure of overall SBP or PP variability. The relationship was seen also by multiple regression analysis, the standard deviation for SBP or PP only following age and 24 h average SBP or PP in accounting for IMT values.. This is the first demonstration from a large database that not only average 24 h PP and SBP values, but also 24 h BP fluctuations, are associated with, and possibly determinants of, the alterations of large artery structure in hypertension.

Topics: Aged; Antihypertensive Agents; Arteriosclerosis; Blood Pressure; Carotid Arteries; Cross-Sectional Studies; Dihydropyridines; Humans; Hypertension; Middle Aged; Prospective Studies; Pulse; Tunica Intima; Tunica Media; Ultrasonography

Focal cerebral hypoperfusion is a common finding in uncomplicated hypertensives even in the absence of large vessel atherosclerosis, and neuropsychological deficits correlate with cerebral hypoperfusion in hypertensive patients with cerebral microangiopathy. We investigated the effects on cerebral perfusion of the dihydropiridine calcium antagonist lacidipine and of hydrochlorothiazide (HCTZ) in asymptomatic hypertensive patients with concomitant atherosclerosis of the carotid arteries. Fifteen essential hypertensives (including 13 males, aged 55-75 years) with at least one 30-60% stenosis of the internal carotid artery at echo-color Doppler examination were treated in a double-blind, randomized, parallel study with lacidipine (4-6 mg od) or HCTZ (25-50 mg od) for 3 months after a 4-week single-blind placebo period. Regional cerebral perfusion was assessed at baseline and at the end of the treatment period with HMPAO-SPECT. Relative perfusion of cortical and subcortical areas was calculated as the ratio between their tracer activity and that of the cerebellum. At baseline, mean relative perfusion (MRP) of the cortical and subcortical areas was similar in the stenotic and the contralateral side. Despite the fall in pressure, lacidipine increased MRP both in the cortical and in the subcortical areas, whereas HCTZ increased MRP only in the cortical areas. The mean change in local vascular resistance, adjusted for initial perfusion value, was -20 A.U. (arbitrary unit) with lacidipine and -12 A.U. with HCTZ (p < 0.001). These differential effects of antihypertensive drugs on subcortical perfusion may be of benefit in the long-term prevention of vascular dementia in hypertensive patients.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Carotid Stenosis; Cerebrovascular Circulation; Dihydropyridines; Diuretics; Double-Blind Method; Female; Humans; Hydrochlorothiazide; Hypertension; Intracranial Arteriosclerosis; Male; Middle Aged; Sodium Chloride Symporter Inhibitors; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Vascular Resistance

With the aim of evaluating the effects on blood pressure, platelet function and insulin sensitivity of the dihydropiridines lacidipine and nifedipine GITS, a parallel double-blind study was carried out in a group of 20 patients with mild to moderate essential hypertension. They received a placebo for 4 weeks; then were divided at random into two groups of 10 patients each. Nifedipine GITS, 30 mg and lacidipine, 4 mg, were given during 16 weeks of active treatment. Blood pressure and heart rate were measured at the clinic in supine, sitting and standing positions, 24 +/- 1 h after the last dose. After the placebo and active phases were carried out, a platelet aggregation test was performed to determine platelet malondialdehyde production and a tolerance to 100 g of glucose by measuring glucaemia and plasma insulin. Both drugs reduced systolic and diastolic blood pressure at the same level, however there were observable differences in the rate of reduction. The nifedipine GITS reduced supine systolic blood pressure by 25 mm Hg in the first week, while the lacidipine did so by 11 mm Hg. At the end of the study period nifedipine reduced supine systolic blood pressure by 28 mm Hg and lacidipine by 20 mm Hg. Heart rate was increased slightly but significantly in the nifedipine GITS group only in the standing position. Both drugs reduced platelet aggregation ex vivo only marginally but they modified the malondialdehyde production, indicating an action on the arachidonic acid metabolic pathway.

Topics: Arachidonic Acid; Biomarkers; Blood Platelets; Blood Pressure; Calcium Channels; Dihydropyridines; Female; Heart Rate; Humans; Hypertension; Male; Malondialdehyde; Middle Aged; Nifedipine; Platelet Aggregation; Posture; Single-Blind Method

Topics: Aged; Antihypertensive Agents; Calcium Channel Blockers; Cross-Over Studies; Dihydropyridines; Humans; Hypertension

The aim of our study was to assess the effects of lacidipine, a long-acting calcium antagonist, on 24-hour average blood pressure, blood pressure variability, and baroreflex sensitivity. In 10 mildly to moderately hypertensive patients with type II diabetes mellitus (aged 18 to 65 years), 24-hour ambulatory blood pressure was continuously monitored noninvasively (Portapres device) after a 3-week pretreatment with placebo and a subsequent 4-week once daily lacidipine (4 mg) or placebo treatment (double-blind crossover design). Systolic blood pressure, diastolic blood pressure, and heart rate means were computed each hour for 24 hours (day and night) at the end of each treatment period. Similar assessments were also made for blood pressure and heart rate variability (standard deviation and variation coefficient) and for 24-hour baroreflex sensitivity, which was quantified (1) in the time domain by the slope of the spontaneous sequences characterized by progressive increases or reductions of systolic blood pressure and RR interval and (2) in the frequency domain by the squared ratio of RR interval and systolic blood pressure spectral power approximately 0.1 and 0.3 Hz over the 24 hours. Compared with placebo, lacidipine reduced the 24-hour, daytime, and nighttime systolic and diastolic blood pressure (P<0.05) with no significant change in heart rate. It also reduced 24-hour, daytime, and nighttime standard deviation (-19.6%, -14.4%, and -24.0%, respectively; P<0.05) and their variation coefficient. The 24-hour average slope of all sequences (7.7+/-1.7 ms/mm Hg) seen during placebo was significantly increased by lacidipine (8.7+/-1.8 ms/mm Hg, P<0.01), with a significant increase being obtained also for the 24-hour average alpha coefficient at 0.1 Hz (from 5.7+/-1.5 to 6.4+/-1.3 ms/mm Hg, P<0.01). Thus, in diabetic hypertensive patients, lacidipine reduced not only 24-hour blood pressure means but also blood pressure variability. This reduction was accompanied by an improvement of baroreflex sensitivity. Computer analysis of beat-to-beat 24-hour noninvasive blood pressure monitoring may offer valuable information about the effects of antihypertensive drugs on hemodynamic and autonomic parameters in daily life.

Topics: Antihypertensive Agents; Baroreflex; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Circadian Rhythm; Cross-Over Studies; Diabetes Complications; Dihydropyridines; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Reproducibility of Results; Signal Processing, Computer-Assisted; Treatment Outcome

The aim of this study was to compare the chronic effects of four dihydropyridine calcium antagonists with different pharmacologic characteristics, amlodipine, felodipine, lacidipine and manidipine,on blood pressure (BP), heart rate (HR) and plasma norepinephrine (NE) levels in patients with mild to moderate essential hypertension.. After a 4-week placebo period, 60 patients of both sexes were randomly administered amlodipine 5-10 mg once daily (o.d.) (n = 15); felodipine 5-10 mg o.d. (n = 15); lacidipine 4-6 mg o.d. (n = 15); manidipine 10-20 mg o.d. (n = 15), for 24 weeks, according to a double blind, parallel group design. Initially, for the first 2 weeks, the lowest dose of each drug was used, then higher doses were administered if sitting diastolic blood pressure (DBP) was > 90 mmHg. BP, HR and plasma NE were evaluated at the end of the placebo and active treatment periods. NE was assessed at trough, at peak and after 12 h from drug ingestion.. Administration of all four drugs reduced clinic BP to the same level after 24 weeks, whereas HR increased only with felodipine (+ 3.1 bpm; P< 0.05). Significant increases in plasma NE levels were observed after chronic therapy with amlodipine and felodipine (+ 34.9 and + 39.4% respectively; P< 0.01 versus placebo) but not with lacidipine (+ 7.1%, NS) and manidipine (+ 2.9%, NS).. These findings suggest that sympathetic activation occurred during chronic treatment with amlodipine and felodipine, whereas manidipine and lacidipine did not increase plasma noradrenaline at the times measured. The reasons for this difference are unclear; they could be related to the different pharmacological characteristic of the two drugs, lacidipine and manidipine.

Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Felodipine; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Nitrobenzenes; Norepinephrine; Piperazines; Sympathetic Nervous System

This is an open trial investigating the efficacy and metabolic effects of 3 months' treatment with lacidipine in 25 Nigerian Africans with mild to moderate hypertension. There was a significant fall in sitting diastolic blood pressure, with treatment (p = 0.01). There were no significant weight changes. The heart rate initially rose significantly with the drug but this normalised with time. All biochemical and haematological indices remained essentially unchanged during therapy. Lacidipine therefore proved an efficacious and metabolically neutral antihypertensive in mild to moderate hypertension in Africa.

Topics: Antihypertensive Agents; Black People; Consumer Product Safety; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged; Nigeria

Previous studies have shown areas of cerebral hypoperfusion in the frontal and parietal lobes of asymptomatic hypertensives, in the absence of extracranial carotid artery stenosis. The aims of the present study were: (a) to correlate the presence of focal cortical hypoperfusion with the presence of white matter lesions (WML), lacunae and extracranial carotid artery stenosis; and (b) to compare the effects on cerebral perfusion of the dihydropyridine calcium entry blocker lacidipine and of hydrochlorothiazide (HCTZ) in hypertensive patients with carotid artery stenosis. Forty-one patients (30 males, aged 40-75) with mild to moderate essential hypertension and with negative history for cerebrovascular diseases were investigated. Twenty-four had normal extracranial carotid arteries at echo-colourDoppler examination, while 17 had at least one 50-70% stenosis of the internal carotid artery (ICA). At computed tomography (CT) scan, five patients had one or more lacunar infarctions, four WML, three lacunar infarctions and WML, and 26 a normal CT scan. Three, with old cortical infarctions, were excluded from further analysis. The prevalence of lesions was significantly higher among the patients with carotid artery stenosis (44% vs. 29%; p < 0.05). Distribution of mean relative cortical perfusion (MRCP) of regions of interest [hexamethyl-propileneamine oxime-single photon emission tomography (SPET)] was not normal, with a negative skewness in patients with lacunae. MRCP was slightly but significantly reduced in patients with lacunae in comparison with hypertensives with normal CT scan and with WML. The asymmetry index of tracer distribution was significantly greater in the patients with lacunar infarctions and WML than in the hypertensive patients with normal CT scan, irrespective of the presence of internal carotid artery stenosis. Fifteen hypertensives (13 males, aged 55-75 years) with at least one moderate stenosis of ICA at duplex scanning were treated in a double-blind, randomised, parallel study with lacidipine (4-6 mg o.d.) or HCTZ (25-50 mg o.d.) for 3 months after a 4-week single-blind placebo period. At baseline, perfusion of the cortical and basal areas was similar in the stenotic and the contralateral side. Despite the fall in pressure, both treatments increased MRCP in the stenotic side and in the contralateral side. The lower the baseline perfusion, the larger its increase with treatment. The decrease of local cerebral vascular resistance was signific

Topics: Adult; Aged; Antihypertensive Agents; Carotid Stenosis; Cerebrovascular Circulation; Dihydropyridines; Diuretics; Double-Blind Method; Echoencephalography; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Radiopharmaceuticals; Sodium Chloride Symporter Inhibitors; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

All studies suggesting a lower incidence of edema on lacidipine than on amlodipine are based on subjective scoring. Therefore, we have compared edema formation on two dihydropyridine calcium channel blockers, using an accurate method for quantitative assessment of foot volume. In a randomized study, we treated 62 patients with essential hypertension for 12 weeks starting with either lacidipine 4 mg o.d. (n = 30) or amlodipine 5 mg o.d. (n = 32). At 6 weeks, the doses were increased to that maximally allowed (lacidipine 6 mg, n = 18; amlodipine 10 mg, n = 12) if trough diastolic blood pressure response was insufficient (>90 mmHg and decrease < 10 mmHg). Edema, scored visually, occurred more frequently (p = 0.02) on amlodipine (15/32) than on lacidipine (6/30); this was confirmed by an increase of foot volume above the 95% upper limit of normal variation in 15 patients on amlodipine and in only five patients on lacidipine (p = 0.01). In the whole group of patients, both the increases of foot volume and the decreases of blood pressure just failed to be significantly different between amlodipine and ]acidipine (foot volume, +3.3+/-1.0% on amlodipine and +1.2+/-0.5% on lacidipine, p = 0.08; mean arterial pressure, -11+/-1% on amlodipine and -8+/-1% on lacidipine, p = 0.052). In patients requiring dose increase, the increase of foot volume on amlodipine was more pronounced (p < 0.05), and the antihypertensive effect was larger (p < 0.05) than on lacidipine. In conclusion, our data show a higher incidence of edema on amlodipine than on lacidipine, which has to be explained at least partly by a comparably higher dose c.q. a larger antihypertensive effect of amlodipine. Other mechanisms might have contributed to these differences and need to be explored.

Topics: Adolescent; Adult; Aged; Amlodipine; Ankle; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Edema; Female; Foot; Humans; Hypertension; Joint Diseases; Male; Middle Aged; Single-Blind Method

We compared antihypertensive efficacy and safety of a single administration of equipotent doses of lacidipine versus nifedipine in the hypertensive urgencies. Twenty-nine asymptomatic essential hypertensive patients (nine men, 20 women) with a mean age of 55.03+/-11.19 years and baseline diastolic blood pressure (DBP) of > or =120 mm Hg after resting 30 min, not taking antihypertensive drugs for the last 24 h, were randomized in a single-blind fashion to receive lacidipine, 4 mg (LCD, 15 patients) or short-acting nifedipine, 20 mg (NFD, 14 patients) in a single dose. Blood pressure (BP) and heart rate (HR) were taken every 30 min during the first 8 h and every 2 h until 24 h of follow-up. Baseline BP values were similar in the two groups (LCD, 222.5+/-32.8/124.6+/-8.4 mm Hg vs. NFD, 215.9+/-20.6/128+/-7.7 mm Hg; p = NS). Both drugs promoted a significant reduction of systolic blood pressure (SBP; 169.6+/-27.8 vs. 170.6+/-25.3 mm Hg) and diastolic blood pressure (DBP; 104.1+/-16 vs. 102.9+/-12.4 mm Hg) after 8 h. However, either SBP (165+/-27.3 vs. 190.6+/-18.2 mm Hg; p = 0.008) and DBP (99.9+/-12.3 vs. 117.2+/-11.4 mm Hg; p = 0.001) were significantly higher in the NFD group after 24-h dosing. Eleven patients in the LCD group had a decrease in BP >25% of the baseline value both 8 and 24 h after the dose. Although 10 patients showed the same response in the NFD group 8 h after the dose, only four patients maintained these values at 24 h. One patient treated with NFD had a transient cerebrovascular ischemic attack. No adverse effects were observed in the LCD group. We conclude that the long-acting calcium antagonist lacidipine was more effective than the short-acting nifedipine in both controlling BP and maintaining this BP reduction over 8 h in essential hypertensive patients with acute asymptomatic BP increase.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Diastole; Dihydropyridines; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Nifedipine; Reference Values; Single-Blind Method; Systole; Treatment Outcome

The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls.. The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment.. Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universität München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses.. Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure.. Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.

Topics: Adrenergic beta-Antagonists; Aged; Arteriosclerosis; Atenolol; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Carotid Arteries; Dihydropyridines; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Prospective Studies; Risk Factors; Ultrasonography

The study was designed to investigate whether a long-acting dihydropyridine calcium antagonist has additional antihypertensive effect when combined with currently used low-dose thiazide diuretic therapy. After 6 weeks with open chlorthalidone monotherapy at 25 mg daily, hypertensive patients with trough diastolic BP 90-115 mm Hg were randomly assigned to receive double-blind lacidipine, 4 mg daily or matching placebo for 4 weeks, while continuing to receive background chlorthalidone. Then patients crossed over to the alternative regimen for a second 4-week period. Clinic and 24-h ambulatory blood pressure (BP) were measured on the final day of chlorthalidone monotherapy and on the final day of each double-blind treatment. Seventeen patients completed the study [mean age, 51.0 +/- 6.9 (SD) years]. Clinic BP was lower with lacidipine versus placebo (systolic, p < 0.01; diastolic, p < 0.05). Daytime ambulatory BP was reduced with lacidipine (p < 0.05), whereas nighttime BP was unchanged. Mean 24-h ambulatory diastolic BP also was reduced on lacidipine (p < 0.05). Heart rate was increased on lacidipine during both daytime (p < 0.01) and nighttime (p < 0.05). In conclusion, when added to chlorthalidone, lacidipine produced a significant reduction in clinic and ambulatory BP during daytime but not nighttime. This was associated with increased heart rate. Modem long-acting dihydropyridines may produce small but clinically significant additive antihypertensive effects in patients uncontrolled on low-dose thiazide monotherapy.

Topics: Antihypertensive Agents; Benzothiadiazines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Chlorthalidone; Dihydropyridines; Diuretics; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Pulse; Sodium Chloride Symporter Inhibitors

Topics: Adult; Aged; Antihypertensive Agents; Dihydropyridines; Emergencies; Female; Humans; Hypertension; Male; Middle Aged

There are few studies on the use of dihydropyridine calcium antagonists in hypertensive patients with moderate renal insufficiency. We undertook an open study on the effects on renal function, albumin excretion and blood pressure of the slow-onset, long-acting dihydropyridine calcium antagonist, lacidipine, in 14 patients with stable, chronic renal insufficiency (mean assessed GFR 0.78 ml/s, range 0.50-1.17 ml/s) and moderate hypertension. Following a 2 week washout phase, lacidipine was administered for 24 weeks in a dose of 2 mg/day with the dose being titrated at 2 weekly intervals to a maximum of 6 mg/day in order to achieve adequate blood pressure control. Frusemide was introduced if blood pressure was not controlled on the maximum lacidipine dose. Blood pressure, creatinine clearance, 24 h urinary albumin excretion and plasma creatinine and albumin concentrations were measured at regular intervals throughout the study. Isotopic GFR was determined at the end of the washout period and at week 24. Lacidipine was not very effective in controlling blood pressure and had an adverse effect on renal function. In 3 patients with an incipient nephrotic syndrome this necessitated withdrawal from the study. Mean GFR of the 10 patients who completed the study decreased from 0.69 ml/s/1.73 m2 at baseline to 0.56 ml/s/1.73 m2 at week 24 (p = 0.006) with a decline in GFR being observed in 9 of these patients. The decrease in GFR was greatest in patients with poorly controlled blood pressure. An insignificant increase in mean urinary albumin excretion occurred during the study with this increase being observed only in patients with albuminuria > 1 g/24 h at baseline. These findings indicated that systemic hypertension altered glomerular hemodynamics and that the vasodilatation of pre-glomerular vessels which followed introduction of the calcium antagonist may have exacerbated this situation. The withdrawal of an angiotensin converting enzyme inhibitor during the washout period may have contributed to these changes. We suggest that renal function should be monitored closely in patients with renal insufficiency when a calcium antagonist is being used to control blood pressure, particularly in those with either marginal blood pressure control, significant albuminuria or an incipient nephrotic syndrome.

Topics: Adult; Aged; Albuminuria; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Female; Furosemide; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Male; Middle Aged; Renal Insufficiency; Serum Albumin

To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension.. Nineteen elderly subjects (five men and 14 women, median age 71 years, range 62-79 years) participated in the study, which had a randomized double-blind crossover design. For each subject there were four treatment phases, each of duration 4 weeks. The initial treatments in each phase were 2 mg lacidipine once a day and 25 mg hydrochlorothiazide once a day, separately and in combination, and placebo. Doses of each agent could be doubled after 2 weeks in each phase if the patient's goal systolic blood pressure had not been achieved. The numbers of subjects administered the higher dose of each treatment were 13 for placebo, 14 for lacidipine, 11 for hydrochlorothiazide and eight for lacidipine plus hydrochlorothiazide.. End-of-phase mean clinic blood pressures were 164/85 mmHg with placebo, 159/82 mmHg with lacidipine, 157/84 mmHg with hydrochlorothiazide and 152/82 mmHg with lacidipine plus hydrochlorothiazide. Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases. There was no difference between sitting and standing blood pressure for any phase. Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered. Ambulatory blood pressure monitoring confirmed the pattern of the responses of blood pressure and showed that administration of hydrochlorothiazide had a significantly greater effect on systolic blood pressure and a longer duration of action than did administration of lacidipine. There was no difference in the frequency of adverse effects among any of the phases.. In treating elderly systolic hypertensives the diuretic hydrochlorothiazide is a more effective antihypertensive agent with a longer duration of action than is the calcium channel antagonist lacidipine. In combination the effects of these two drugs on blood pressure are additive.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Aorta; Blood Pressure; Cross-Over Studies; Dihydropyridines; Double-Blind Method; Drug Combinations; Female; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Monitoring, Ambulatory; Systole

Excessive adrenergic responses have been reported in hypertensive patients treated with short-acting dihydropiridine calcium channel antagonists that might worsen cardiovascular risk. In this study we addressed whether lacidipine, a long-acting dihydropiridine, increases the sympathetic excitation produced by moderate dynamic exercise.. Because of the wide changes in autonomic drive during everyday life, the possible influence of antihypertensive regimens should be assessed not only at rest but also during spontaneous, behaviourally induced alterations of sympathovagal balance. This study was designed to test whether treatment with lacidipine might alter the autonomic response to supine moderate dynamic exercise.. We studied 16 moderate hypertensive patients (arterial pressure 151/102 mmHg) at rest and during 30% of nominal maximum recumbent bicycle exercise. The low frequency spectral component of RR interval and of systolic variability (Finapres) furnished markers of sympathetic modulation of the sinoatrial node and of the vasculature, respectively. Studies were performed during placebo and active treatment (lacidipine 4 mg per day).. Lacidipine treatment significantly reduces arterial pressure values at rest and during moderate dynamic exercise, without affecting RR interval and systolic arterial pressure variabilities, both at rest and during moderate exercise.. In conclusion, spectral analysis of RR interval and systolic arterial pressure variabilities indicate that antihypertensive treatment with lacidipine is not associated to an excessive sympathetic drive during moderate exercise.

Topics: Administration, Oral; Autonomic Nervous System; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Dose-Response Relationship, Drug; Electrocardiography; Exercise; Exercise Test; Female; Humans; Hypertension; Male; Middle Aged; Treatment Outcome

Calcium channel blockers are increasingly used in the treatment of hypertension. Newer calcium channel blockers of the dihydropyridine group have longer elimination half-lives (t1/2) that permit once-daily dosage and are generally better tolerated than their parent compound. In this study, the efficacy and safety of lacidipine and amlodipine were compared in 65 patients with mild-to-moderate hypertension attending the hypertension outpatient clinic of a teaching hospital in a randomized double-blind cross-over trial with dose titration. Lacidipine and amlodipine both significantly reduced systolic blood pressure (SBP: by 19.2 +/- 13.5 and 22.3 +/- 15.3 mm Hg, respectively) and diastolic BP (DBP: 13.3 +/- 4.2 and 12.3 +/- 5.3 mm Hg, respectively) 24 h postdose. There were no significant differences in their antihypertensive effects. The incidence of adverse events (AE) was 3% for lacidipine and 8% for amlodipine. The incidence of withdrawal from the study due to side effects was 0% for lacidipine and 3% for amlodipine. These results suggest that lacidipine is well-tolerated, and is as effective as amlodipine as a once-daily antihypertensive agent.

Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Dihydropyridines; Double-Blind Method; Female; Half-Life; Humans; Hypertension; Male; Middle Aged; Pulse

In the ELSA trial, the effects of lacidipine-based treatment and beta-blocker (atenolol)-based treatment on the development and progression of carotid wall alterations are assessed in hypertensive patients. The primary endpoint of this study is the rate of change in the intima-media thickness of the carotid artery wall, measured with B-mode ultrasound. About 2300 hypertensive patients have been recruited and randomized to either of the antihypertensive agents. Baseline data for 1965 patients are available, showing a high prevalence of carotid wall lesions: about 82% of the subjects have an intima-media thickness > or = 1.3 mm, defined as plaque in the ELSA protocol; 16% of the subjects have intima-media thickening (> or = 1.0 mm, < 1.3 mm) and only about 1% have normal carotid artery walls. Analysis of demographic data and risk factor prevalence in ELSA patients, and comparison of these preliminary observations with data from other intervention or observational studies indicate that high blood pressure is a very important risk factor for carotid atherosclerosis.

Topics: Antihypertensive Agents; Arteriosclerosis; Carotid Artery Diseases; Dihydropyridines; Europe; Female; Humans; Hypertension; Male; Middle Aged; Prevalence

Up to the present the relationship between arterial hypertension or its treatment and cardiovascular complications has been evaluated in terms of the incidence of events, such as fatal and nonfatal myocardial infarction or stroke and cardiac deaths. However, cardiovascular events are not the direct consequence of blood pressure elevation, which, on the contrary, is responsible for atherosclerotic disease. Quantitative ultrasonography is a sensitive, specific and reproducible technique which, in comparison to arteriography, is non invasive and less expensive. The availability of this technique has allowed us to do some studies, one just published, another in the elaboration phase and others ongoing, aimed at evaluating the effects of antihypertensive agents on carotid changes in hypertensive patients. The European Lacidipine Study on Atherosclerosis (ELSA) compares the effects of lacidipine, a calcium-antagonist and of atenolol, a beta-blocker, on blood pressure, on carotid vessel modifications, and on the incidence of cardiovascular events in patients with mild to moderate hypertension with a 4-year follow-up period. Preliminary results of the study, which were concerned with the demographic characteristics of the first 1000 randomized patients enrolled, indicate that 84% of the patients had a carotid plaque, 15% had thickening of the intima-media, and 1% had a normal vessel. These results are both surprising and significant in that they admonish the physician not to neglect patients with mild to moderate hypertension even when they have neither complications nor other risk factors.

Topics: Aged; Antihypertensive Agents; Arteriosclerosis; Atenolol; Calcium Channel Blockers; Carotid Artery Diseases; Delayed-Action Preparations; Dihydropyridines; Double-Blind Method; Europe; Humans; Hypertension; Middle Aged

To assess the benefits of the calcium antagonist lacidipine on the prevention of cardiovascular events and the prevention of organ damage in two long-term clinical trials. SYSTOLIC HYPERTENSION IN THE ELDERLY LONG-TERM LACIDIPINE (SHELL) TRIAL: In the SHELL trial, the efficacy of lacidipine-based treatment is to be compared with that of thiazide-like diuretic (chlorthalidone)-based treatment in elderly patients with isolated systolic hypertension. The incidence of cardiovascular mortality and cardiovascular morbidity over a 5-year period are endpoints.. In the ELSA trial, the effects of lacidipine-based treatment and beta-blocker (atenolol)-based treatment on the development and progression of carotid atherosclerosis are to be assessed in hypertensive patients. The primary endpoint of this study is the rate of change in the thickness of the carotid artery wall, measured with B-mode ultrasound.

Topics: Antihypertensive Agents; Arteriosclerosis; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension

The European Lacidipine Study on Atherosclerosis (ELSA) has been designed to compare the effects of two antihypertensive agents, the calcium antagonist lacidipine and the beta-blocker atenolol, on the development of atherosclerosis in hypertensive patients stratified according to the presence of carotid plaques, or the presence or absence of carotid artery intima-media thickening. ELSA is a multinational, multicenter, randomized, double-blind, parallel group study that is to be conducted over a 5-year period. Recruitment and treatment will take place at 23 referral centers in seven countries. A total cohort of 3,660 patients, aged between 45 and 75 years, with diastolic blood pressure 95-115 mm Hg and systolic blood pressure < or = 210 mm Hg at enrollment, will be stratified into three groups according to a B-mode ultrasound analysis of the carotid wall morphology. After a 1-month placebo run-in period, patients will be randomized to receive either lacidipine (4-6 mg once daily) or atenolol (50-100 mg once daily). Nonresponders will be treated with hydrochlorothiazide (12.5 mg, eventually titrated to 25 mg if required), on an open basis. During the course of the study, patients will be monitored by carotid ultrasound assessment and ambulatory blood pressure monitoring. The results of this study should further understanding of the pathobiology of atherosclerosis, and its development and prevention.

Topics: Adrenergic beta-Antagonists; Arteriosclerosis; Atenolol; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Carotid Arteries; Dihydropyridines; Double-Blind Method; Europe; Humans; Hypertension; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Ultrasonography

Ambulatory blood pressure monitoring (ABPM) is a particularly useful method for evaluating the effects of antihypertensive drugs. ABPM allows the therapeutic effect of an agent to be assessed continually by a large number of measurements, and the greater number of readings contributes to the higher degree of reproducibility associated with ABPM compared to other methods for measuring blood pressure. ABPM also enable measurements to be taken in "real-life" situations and removes the problem of observer bias. The number of patients required for clinical studies can be significantly reduced by using ABPM. It is still essential, however, to identify "white coat" subjects, placebo responders, and patients who do not respond to the treatment. ABPM studies have demonstrated that the novel dihydropyridine calcium antagonist, lacidipine, significantly reduces both systolic and diastolic blood pressures over a 24-h period, both during the day and at night. Furthermore, although the trough-to-peak ratios of many calcium antagonists have been shown to fall below the recommended level of 50%, lacidipine has a ratio above 60%. Other ABPM studies have also shown that lacidipine can correct the 'early morning increase' in blood pressure without effecting the 24-h nycthemeral profile.

Topics: Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Circadian Rhythm; Dihydropyridines; Humans; Hypertension; Placebo Effect

In an open, multicenter study, the calcium antagonist lacidipine was tested for efficacy and safety, particularly with respect to any influence on lipid and carbohydrate metabolism. The study was performed in 2,127 patients with essential hypertension. The patients were treated orally, with lacidipine in a dosage of 2-6 mg once daily for 48 weeks. Lacidipine significantly reduced both systolic and diastolic blood pressure by 20 +/- 17 mm Hg and 14 +/- 10 mm Hg, respectively, from baseline values (both p < 0.0001). Decreases in blood pressure were achieved without any adverse effects on lipid and carbohydrate metabolism, either in the total group or in subsets of diabetic or hyperlipidemic patients. It is concluded that lacidipine is a safe and effective drug in the long-term antihypertensive treatment of patients with essential hypertension and with concomitant metabolic disorders such as diabetes mellitus or dyslipidemia.

Topics: Calcium Channel Blockers; Cholesterol; Cholesterol, HDL; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged

In a large, open, multicenter study, 2,206 outpatients with mild-to-moderate essential hypertension were recruited by 755 cardiologists throughout France. Patients received treatment with lacidipine for 12 weeks at a dose of 2-6 mg once daily. In 1,637 evaluable patients, lacidipine was shown to reduce blood pressure from a mean of 173/101 mm Hg at baseline to 147/85 mm Hg after 12 weeks, with negligible effects on heart rate. Adverse events were experienced by 29% of patients, of which only 20% were definitely or probably related to lacidipine; these adverse events were generally mild and led to premature discontinuation of treatment in only 8.7% of cases. Overall assessment of efficacy and tolerability by practitioners was very satisfactory. Acceptability and ease of use were assessed highly by the large majority of patients. Subgroup analysis of patients > or = 65 years showed no significant difference when compared to younger patients in terms of efficacy and tolerability. The current study therefore confirms, in a large study population and in general practice, that lacidipine, in a once-daily dose of 2-6 mg, has a significant antihypertensive effect and is well tolerated.

Topics: Aged; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Female; France; Humans; Hypertension; Male; Middle Aged

Lacidipine is an orally administered calcium channel blocker of the dihydropyridine class, which shows selectivity for vascular smooth muscle over cardiac tissue and has a long duration of action. In studies using ambulatory blood pressure monitoring, lacidipine 2 to 8mg administered once daily in the morning reduced blood pressure over 24 hours, with the reductions being greater during the day than at night in some studies. 77 to 87% of patients with mild to moderate hypertension had their blood pressure controlled by treatment with lacidipine 2 to 8 mg/day for 1 to 4 months in dose-finding studies. When administered once daily, lacidipine 4 to 6 mg was equivalent in antihypertensive efficacy to hydrochlorothiazide 25 to 50 mg/day, atenolol 50 to 100 mg/day, and the prototype calcium channel blocker nifedipine 20 to 40 mg twice daily (sustained-release formulation). The adverse effects of lacidipine are those common to other dihydropyridine calcium channel blockers, and include headache, flushing, ankle oedema, dizziness and palpitations. The long term effects of lacidipine on cardiovascular morbidity and mortality, and possible additional clinical benefits in terms of its antiatherosclerotic effects, are under investigation; the outcome of these studies will be important in defining the future role of this agent in the treatment of hypertension. Thus, available evidence suggests lacidipine provides a further alternative to the dihydropyridine calcium channel blockers currently available for the treatment of essential hypertension.

Topics: Adult; Aging; Animals; Antihypertensive Agents; Calcium Channel Blockers; Cross-Over Studies; Dihydropyridines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Hemodynamics; Humans; Hypertension; Middle Aged; Tissue Distribution

The clinical safety of lacidipine, a new dihydropyridine calcium antagonist, has been assessed in a long-term, comparative study in hypertensive patients. Slow-release (SR) nifedipine was used for comparison. The type and incidence of adverse events seen with both drugs are characteristic of the dihydropyridine class of drugs and were mainly due to pharmacologically induced vasodilation, but lacidipine caused a significantly lower incidence of ankle edema than nifedipine SR. There were no unexpected adverse events during the treatment. The addition of atenolol 50 mg once daily did not increase the frequency of adverse events. Therefore, lacidipine can be considered a safe antihypertensive drug, which can be used as a suitable agent for first-line treatment of hypertension.

Topics: Adult; Aged; Antihypertensive Agents; Atenolol; Blood Pressure; Calcium Channel Blockers; Delayed-Action Preparations; Dihydropyridines; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Nifedipine; Single-Blind Method

Arterial hypertension is a chronic condition regarded as one of the main risk factors for development of coronary atherosclerosis. As dyslipidemia and reduced glucose tolerance are also risk factors for coronary disease, it is considered important to use antihypertensive drugs having no negative effects on lipid and glucose metabolism when diabetic patients are treated for hypertension. Lacidipine, a new dihydropyridine-like calcium antagonist, has been shown in in vivo and in vitro preclinical studies to possess potent, long-lasting antihypertensive activity. The present study compared the efficacy and safety of once-daily treatment with lacidipine versus nifedipine SR given twice-daily in non-insulin-dependent diabetic patients. Results have shown a similar efficacy of the two treatments: 6 months later, both drugs had reduced blood pressure values [lacidipine from 184.8/105.2 mm Hg to 144.4/87.1 mm Hg; nifedipine slow-release (SR) from 182.3/106.8 mm Hg to 143.6/89.4 mmHg]. However, lacidipine exhibited a lower incidence of adverse events (particularly ankle edema and tachycardia) than nifedipine SR. Finally, both treatments showed no negative effect on metabolic parameters (total cholesterol, high-density lipoprotein cholesterol, triglycerides, and blood glucose).

Topics: Antihypertensive Agents; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Cholesterol; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dihydropyridines; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Nifedipine; Triglycerides

The aim of this study was to evaluate the effect of lacidipine and nifedipine on lower limb veins. Forty hypertensive patients, aged 30-50 years, with no deep venous thrombosis, venous insufficiency, or hypothyroidism underwent double-blind treatment with placebo (1 week), lacidipine 4 mg once daily (1 week), and slow-release nifedipine 20 mg twice daily (1 week) in randomized sequence. Echo-color Doppler examination of superficial, deep, communicating, and perforating veins of the legs was performed. The results showed venous insufficiency and hypertension after 1-week administration of lacidipine (5 and 15%, respectively) and nifedipine (10 and 25%, respectively) and only two cases (5%) of venous hypertension during placebo administration. Lower limb edema was observed in two patients (5%) during treatment with nifedipine slow-release (SR). The hemodynamic effects of lacidipine and nifedipine were reversible but may contribute to the mechanism of lower limb edema.

Topics: Adult; Calcium Channel Blockers; Delayed-Action Preparations; Dihydropyridines; Double-Blind Method; Female; Hemodynamics; Humans; Hypertension; Leg; Male; Middle Aged; Nifedipine; Regional Blood Flow; Ultrasonography, Doppler, Color; Veins

Diabetes mellitus is often associated with hypertension and is an additional cardiovascular risk factor. It is therefore important that antihypertensive drugs should have no negative metabolic effects. We present here the results of two distinct studies investigating the clinical efficacy and the metabolic effects of lacidipine in hypertensive patients without concomitant diabetes. Patients in the first study (group A) were hypertensive with non-insulin-dependent diabetes mellitus (NIDDM) and stable blood glucose levels in the 3 months before entering the study. Patients in the second study (group B) were hypertensive without diabetes mellitus. Before the commencement of the study, antihypertensive treatment was discontinued in all patients for a 4-week washout period, followed by 4 weeks of run-in with placebo. Patients were then treated with lacidipine (4 mg o.d.) for 6 months. After 1-2 months, the dose was doubled in patients with uncontrolled blood pressure. Every 2 months, lipid and carbohydrate metabolism were investigated by blood chemistry analyses. The results demonstrate that lacidipine 4-8 mg o.d. is efficacious and well tolerated in hypertensive patients, even in the presence of diabetes mellitus.

Topics: Adult; Aged; Antihypertensive Agents; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Female; Humans; Hypertension; Lipids; Male; Middle Aged

In the present study, we examined the circadian profile of blood pressure (BP) in 10 patients with moderate essential hypertension before and after 6 months of lacidipine therapy. Ambulatory BP was measured at 30-min intervals using SpaceLabs 90207. To account for the unequal time intervals between successive readings, BP means and variances were weighted for the time span between successive readings, and weighted linear-regression analysis was applied. The 24-h BP values were carried out using Fourier analysis, comparing the values from the baseline with those after 24 weeks of lacidipine. After 24 weeks BP values showed a significant decreased compared with baseline values (all p < 0.01). The daily BP curves obtained from Fourier analysis with four harmonics showed that the significant circadian rhythm in nine patients was not altered by lacidipine treatment. The night/day differences were statistically significant at 24 weeks vs. 0 week (all p < 0.01). The overall amplitude and acrophase of the BP curve were statistically significant at 24 weeks (all p < 0.01). After 24 weeks of lacidipine therapy, according to the nocturnal BP fall, we found three intermediate dippers, six dippers, and one non-dipper. By use of the two-step Fourier analysis method, which provides a formal and statistical method to evaluate the presence of a significant diurnal BP rhythm and parametrization of the 24-h BP recordings, we showed that lacidipine long-term therapy is effective in lowering BP and preserving the diurnal BP rhythm.

Topics: Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Circadian Rhythm; Dihydropyridines; Female; Fourier Analysis; Humans; Hypertension; Male; Middle Aged

This study estimated the efficacy of sublingual nifedipine 10 mg vs. sublingual lacidipine 4 mg in the management of hypertensive crises. We studied 40 patients with diastolic blood pressure > or = 120 mm Hg, who were divided into two groups of 20. Blood pressure and heart rate were assessed in the recumbent position before treatment and after 30, 120, and 240 min. Comparison of the effectiveness of these drugs was analyzed by Student's t test. Both drugs tested revealed a statistically significant hypotensive effect on diastolic and systolic blood pressure, and few side effects. Compared with lacidipine, nifedipine had a greater hypotensive effect on diastolic and systolic blood pressure in the first 30 min and on the diastolic blood pressure after the first 120 min. However, the hypotensive effect of lacidipine is statistically significant. After 4 h, both drugs showed a similar efficacy without significant statistical variations. We concluded that in the management of hypertensive crises the use of each of these drugs can have a particular range: nifedipine can be used when a pronounced and rapid blood pressure decrement is necessary, whereas lacidipine can be used when a more gradual effect is preferable.

Topics: Administration, Sublingual; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Emergency Medical Services; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine

Isolated systolic hypertension (ISH) is a definite risk factor for cardiovascular complications (i.e., cardiac failure, coronary artery disease, and stroke) independent of diastolic elevation. The prevalence of ISH is estimated to be approximately 15-20% in the population above the age of 60 years, and increases with advancing age. The Systolic Hypertension in the Elderly (SHELL) study is planned to evaluate the efficacy and tolerability of lacidipine, matched with the diuretic chlorthalidone, in treatment of ISH in elderly hypertensive patients (EHP). One hundred fifteen Italian centers will participate in the study. Fifty centers are associated with the Società Italiana di Geriatria Ospedaliera and 65 centers are departments of internal medicine or outpatient clinics for management of hypertension. A total of 4,800 patients will be enrolled in the trial. Two subprojects will consist of periodical echocardiographic evaluation and 24-h ambulatory blood pressure monitoring. The primary end point of the SHELL study is the incidence of cardiovascular and cerebrovascular events in EHP with ISH, treated with either lacidipine or chlorthalidone. In particular, the SHELL trial is intended to determine whether lacidipine treatment will significantly reduce fatal myocardial events and total cardiovascular mortality.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Chlorthalidone; Dihydropyridines; Double-Blind Method; Echocardiography; Female; Humans; Hypertension; Italy; Male; Middle Aged

Topics: Aged; Antihypertensive Agents; Arteriosclerosis; Atenolol; Dihydropyridines; Double-Blind Method; Humans; Hypertension; Middle Aged

Hypertension is well recognized to be an important cardiovascular risk factor and antihypertensive therapy has been shown to decrease cardiovascular mortality and morbidity as blood pressure control is achieved. At present, management of hypertension is obtained with effective compounds that exhibit a satisfactory safety profile. Among the antihypertensive drugs, calcium antagonists have been proven to possess this property. In the present study, our objective was to compare the antihypertensive effect of two new long-acting dihydropyridines, lacidipine and amlodipine, as once-daily monotherapies in mild-to-moderate hypertensive patients. Eighty hypertensive patients were recruited and after a 3-week washout period were randomized to receive lacidipine 4 mg once daily or amlodipine 10 mg once daily. After 4 weeks, hydrochlorothiazide 12.5 mg was added in patients not adequately controlled, and patients were treated for a total of 8 weeks. At this time, supine mean diastolic blood pressure decrease was 16 mm Hg in the lacidipine group and 10 mm Hg in the amlodipine group (p < = 0.01). Adverse events were reported in 28% of patients treated with lacidipine and in 48% of patients receiving amlodipine. Results of our pilot clinical experience show that lacidipine is a well-tolerated and effective compound, compared with amlodipine, in mild-to-moderate hypertensive patients.

Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged

The carotid artery is one of the most important sites in the progression of atherosclerotic lesions. Atherosclerosis is known to be determined by a variety of factors, among which arterial hypertension is one of the most important. Blood pressure control by antihypertensive treatment is thus of great benefit in management of atherosclerosis, particularly in view of the direct action of some classes of antihypertensive agents on atheromatous lesions. Today, modern diagnostic technique allow a non-invasive examination of the artery wall (B-mode ultrasound and pulsed-Doppler), so that early detection of structural and functional alterations is possible. In order to evaluate the efficacy of the long term blood pressure reduction in the progression and/or in the regression of cardiovascular structural abnormalities, we studied intima-media thickness and arterial compliance during one-year antihypertensive treatment with a new calcium-antagonist, lacidipine, or a diuretic hydrochlorothiazide. In both groups we observed a comparable blood pressure reduction (lacidipine: from 166 +/- 5/100 +/- 1 to 142 +/- 4/88 +/- 2 mmHg; hydrochlorothiazide: from 154 +/- 5/102 +/- 2 to 140 +/- 4/88 +/- mmHg; both p < 0.01). On the contrary, only in patients treated with lacidipine did we obtain a significant improvement in carotid blood flow (383 +/- 16 vs 411 +/- 16 ml/min p <) and in arterial compliance (0.8 +/- 0.1 vs 1.2 +/- 0.2 cm/dyne p < 0.01). Indeed, we observed a different behaviour of the intima-media thickness in the two groups (lacidipine: 1.11 +/- 1.4 vs 1.13 +/- 1.5 mm n.s.; hydrochlorothiazide: 1.15 +/- 0.15 vs 1.21 +/- 0.17 mm p < 0.06). Our results demonstrate that an effective antihypertensive treatment with calcium antagonists may influence the progression of carotid vascular abnormalities.

Topics: Aged; Antihypertensive Agents; Blood Circulation; Blood Pressure; Calcium Channel Blockers; Carotid Arteries; Carotid Stenosis; Dihydropyridines; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Time Factors; Tunica Intima; Ultrasonography, Doppler; Vascular Resistance

Topics: Blood Pressure; C-Peptide; Dihydropyridines; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Insulin Resistance; Male; Middle Aged; Potassium

Topics: Adult; Antihypertensive Agents; Calcium Channel Blockers; Coronary Vessels; Dihydropyridines; Humans; Hypertension; Middle Aged; Single-Blind Method; Vasodilation

1. The aim of this randomised, double-blind four way crossover study was to assess the interaction between the new calcium antagonist, lacidipine and atenolol, in patients with mild to moderate hypertension. 2. Sitting blood pressure at 4 h post-dosing with lacidipine (4 mg) and atenolol (100 mg) alone was significantly lower compared with placebo (137/89 +/- 3/3 mmHg; 142/89 +/- 5/3 mmHg; and 154/98 +/- 5/3 mmHg respectively; P < 0.001). Co-administration of both drugs produced a significant additive effect compared with atenolol and lacidipine alone (124/80 +/- 4/2 mmHg; P < 0.002). 3. Heart rate on treatment with lacidipine alone was significantly greater at 4 h compared with placebo (86 +/- 1 beats min-1 and 74 +/- 2 beats min-1 respectively; P < 0.001). When both drugs were used in combination, there was a significant decrease in pulse rate compared with lacidipine alone (58 +/- 1 beats min-1 and 86 +/- 1 beats min-1 respectively; P < 0.001). 4. Home blood pressure recordings confirmed the statistically significant reduction in blood pressure on co-dosing (120/82 +/- 10/2 mmHg) compared with lacidipine (140/92 +/- 5/3 mmHg) and atenolol (146/90 +/- 6/3 mmHg) given alone (P < 0.05). 5. Lacidipine alone produced a significant exercise tachycardia compared with atenolol alone and the atenolol/lacidipine combination (97 +/- 8 beats min-1; 65 +/- 4 beats min-1 and 75 +/- 7 beats min-1 respectively; P < 0.001). Exercise tolerance was not adversely affected by the co-administration of both lacidipine and atenolol.

Topics: Adult; Antihypertensive Agents; Atenolol; Blood Pressure; Dihydropyridines; Double-Blind Method; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Exercise; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Pulse

Antihypertensive agents are routinely studied in terms of changes in the level of systolic, diastolic, and mean arterial pressure. Pulse pressure may be independently modified from these parameters as a consequence of specific changes in the mechanical properties of the large arteries and in the timing of incident and reflected pressure waves. The aim of this study was to evaluate the changes in pulse pressure produced by acute calcium blockade by the dihydropiridine derivative, lacidipine, in a double-blind design versus placebo in 18 subjects with mild to moderate hypertension. Carotid and femoral pressure waveforms were recorded noninvasively by applanation tonometry using a Millar micromanometer-tipped probe. Early (Pi) and mid-to-late (Ppk) systolic peaks of carotid pressure waveform were evaluated, enabling the effect of incident pressure wave to be quantified as the ratio of Pi to the total height of carotid pulse wave (PP) (Pi/PP) and the effect of wave reflections as the ratio (Ppk-Pi)/PP. Travel time of the reflected wave (delta tp) was timed from the foot of the pressure wave to the foot of the late systolic peak. Pulsatile changes in diameter were studied using noninvasive echo-tracking techniques. Whereas mean arterial pressure significantly decreased following lacidipine, pulse pressure measured at three different sites (brachial, carotid, and femoral arteries) was unchanged. Carotid-femoral pulse wave velocity, carotid and femoral arterial stiffness, and delta tp were not modified, whereas the (Ppk-Pi)/PP ratio and left ventricular ejection time was significantly reduced and the Pi/PP ratio was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arteries; Blood Pressure; Calcium Channel Blockers; Carotid Arteries; Diastole; Dihydropyridines; Double-Blind Method; Elasticity; Femoral Artery; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Systole

Topics: Adult; Aldosterone; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Renin; Verapamil

Importance of systolic over diastolic blood pressure measurements: Systolic pressure is known to be a more important independent cardiovascular risk factor than diastolic pressure in subjects over 50 years of age; after that age, a high incidence of two types of systolic hypertension is observed, sustained essential hypertension with a disproportionate increase in systolic pressure and isolated systolic hypertension. Effects of lacidipine on blood pressure in the elderly: The effects of vasodilators on blood pressure have been studied extensively. Recently, lacidipine, nitrendipine and enalapril were compared in a multicenter, randomly allocated, double-blind trial in elderly hypertensive patients with a disproportionate increase in systolic pressure treated for 8 weeks (n = 278). In these patients, supine systolic pressure decreased to a greater extent with lacidipine and enalapril than with nitrendipine, the difference between lacidipine and nitrendipine reaching statistical significance. In another trial, lisinopril produced a greater reduction in systolic pressure than atenolol. Finally, in a study in elderly patients with systolic hypertension, long-acting isosorbide dinitrate induced a selective sustained decrease in systolic pressure. Mechanisms of action of vasodilators: A fall in systolic blood pressure may be produced by vasodilators through a reduction in peripheral resistance with or without an active change in arterial compliance. Dihydralazine-like substances do not increase arterial compliance whereas angiotensin converting enzyme inhibitors, calcium entry blockers and nitrates tend to increase arterial compliance for the same decrease in mean arterial pressure.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Enalapril; Female; Heart Rate; Humans; Hypertension; Male; Nitrendipine; Time Factors; Vasodilator Agents

Renal vascular resistance is increased in essential hypertension, with a consequent reduction in renal plasma flow together with a normal or slightly reduced glomerular filtration rate. Non-specific vasodilators may exacerbate this effect while loop diuretics, beta-blockers, angiotensin converting enzyme inhibitors and calcium antagonists may increase these renal hemodynamic parameters. We studied the effect of lacidipine, a new long-lasting calcium antagonist, on renal hemodynamics in 11 essential hypertensives. Lacidipine (4 mg once a day) acutely increased renal plasma flow without affecting the glomerular filtration rate. A transient, but non-significant, diuresis and natriuresis occurred. After 4 weeks of lacidipine treatment, all the parameters of renal function returned to basal levels. These results suggest that the well known renal effects of calcium antagonists are, at least in part, related to the onset of the antihypertensive effect being more pronounced with compounds such as nifedipine which have a rapid-onset, blood pressure-lowering effect.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Diuretics; Drug Evaluation; Humans; Hypertension; Kidney; Renal Circulation; Vascular Resistance

The effects of calcium antagonists in reducing blood pressure at rest and during exercise were examined in patients with mild-to-moderate essential hypertension. The haemodynamic effects of calcium antagonists were evaluated at rest and during exercise. We also examined 10 patients with mild-to-moderate essential hypertension taking lacidipine, a new dihydropyridine calcium antagonist (4 mg once a day, at 0700 h). Compared with placebo, lacidipine induced significant mean reductions in 24-h blood pressure (P less than 0.001 for systolic blood pressure; P less than 0.002 for diastolic blood pressure). After 24 h, the blood pressure reductions were still significant (P less than 0.02 for systolic blood pressure; P less than 0.04 for diastolic blood pressure). The heart rate did not change. During dynamic exercise, blood pressure at maximal effort was reduced (P less than 0.01 for systolic and diastolic blood pressure) and the external workload reached at the anaerobic threshold was significantly increased (P less than 0.001), but not at maximum effort. Ventilation and tidal volume were similar at both the anaerobic threshold and peak exercise, while oxygen uptake and carbon dioxide production were increased at the anaerobic threshold (P less than 0.02 for carbon dioxide production) but were similar at peak exercise.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Anaerobic Threshold; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Dihydropyridines; Diuretics; Exercise; Exercise Test; Female; Hemodynamics; Humans; Hypertension; Male

Eleven centers in Tuscany, Italy, recruited 96 patients (aged 21-75 years) with mild-to-moderate essential hypertension [diastolic blood pressure (DBP) 95-115 mm Hg; systolic blood pressure (SBP) less than or equal to 200 mm Hg]. After a 4-week, single-blind, placebo run-in period, patients received lacidipine 4 mg once daily. If blood pressure was not controlled after 1 month (control = DBP less than or equal to 90 mm Hg, or less than or equal to 95 mm Hg if reduced by greater than or equal to 15 mm Hg from baseline), the dose was increased to lacidipine 8 mg once daily. Atenolol 50 mg once daily was added after 2 months' monotherapy, if required for blood pressure control. The study continued for 13 months. About 40% of patients were titrated to 8 mg lacidipine; only 7% required addition of atenolol. Lacidipine significantly reduced blood pressure, with 84% of patients showing control of pressure values 24 h after the previous dose on completion of 5 months' monotherapy (63% controlled with lacidipine 4 mg/day; 21% with lacidipine 8 mg/day). There was no clinically relevant difference in the first-dose effect between the two doses of lacidipine (4 mg and 8 mg); both smoothly reduced blood pressure, with maximum effect after 2 h. Lacidipine was well tolerated. Adverse events were those expected with dihydropyridines, were mainly mild and occurred early, disappearing without discontinuation of treatment. Results indicate that 4-8 mg of lacidipine, administered once daily, is effective and well tolerated in mildly to moderately hypertensive patients.

Topics: Adult; Aged; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged

Calcium plays an important role in endocrine reactions such as hormone biosynthesis, release, secretion, and action on target organs. The aim of this study was to evaluate the effects of a new long-lasting calcium-channel blocker, lacidipine, on basal and stimulated anterior pituitary hormone secretion. In a single-blind crossover study comparing lacidipine 4 mg p.o. once daily with placebo, variations in plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH) were evaluated in 10 hypertensive patients. Basal or stimulated anterior pituitary hormone secretion was similar after lacidipine and placebo. Lacidipine treatment significantly reduced blood pressure. It can thus be concluded that lacidipine is an effective calcium antagonist that has no effect on pituitary function.

Topics: Administration, Oral; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Female; Humans; Hypertension; Male; Pituitary Gland, Anterior; Pituitary Hormones, Anterior; Single-Blind Method

Selection of the appropriate dose of a new drug for initiation of treatment and then for maintenance is a complicated task. It requires the careful assessment and weighing of benefit vs. risk. A series of studies was carried out with lacidipine to determine the optimal initial dose in a general hypertensive population as well as in special populations in whom the pharmacokinetics may be different. The conclusions of these studies are that (a) in a general adult population, the initial dose should be 4 mg once daily; (b) in the elderly and in those with impaired liver function, the starting dose should be 2 mg once daily; and (c) renal dysfunction does not alter the usual starting dose of 4 mg once daily.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Drug Administration Schedule; Female; Humans; Hypertension; Male; Middle Aged

Thirty-one centers in the U.K. recruited 637 patients (aged 21 to 75 years) with mild-to-moderate essential hypertension [diastolic blood pressure (DBP) of 95 to 115 mm Hg, and systolic blood pressure (SBP) less than or equal to 200 mm Hg on three occasions]. After a 4-week placebo run-in period, 533 patients were randomized to receive double-blind 4 mg of lacidipine once daily (n = 268) or 50 mg of atenolol once daily (n = 265). If blood pressure was not controlled after 1 month (control = DBP less than or equal to 90 mm Hg, or less than or equal to 95 mm Hg if reduced by greater than or equal to 15 mm Hg from baseline), dosages were increased to 6 mg of lacidipine once daily or 100 mg of atenolol once daily. Hydrochlorothiazide (HCTZ, 25 mg once daily) was added after 2 months of active treatment if required for blood pressure control. Both lacidipine and atenolol reduced blood pressure to a similar degree over the 5 months of double-blind active treatment. The reduction achieved was maintained for the duration of the open phase of the study (to month 14). The incidence of adverse events was also similar for both drugs, and serious adverse events were rare and thought to be unrelated to the study drug therapy. The results indicate that lacidipine once daily for mild-to-moderate hypertension has an efficacy and safety similar to that of atenolol.

Topics: Adult; Aged; Atenolol; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Safety

The aim of this study was to compare the antihypertensive efficacy and tolerability of lacidipine, a new dihydropyridine calcium antagonist, and slow-release nifedipine (SR) in patients with mild-to-moderate essential hypertension. After a 1-month placebo run-in period, 435 patients were randomized into a double-blind, parallel-group study to receive either 4 mg of lacidipine once daily (n = 220) or 20 mg of nifedipine twice daily (n = 215). After 4 weeks, the doses for "nonresponders" were increased to 6 mg of lacidipine once daily (n = 82) and to 40 mg of nifedipine SR twice daily (n = 62). After 4 weeks, 50 mg of atenolol once daily was added to the regimens of patients still uncontrolled by lacidipine (n = 32) and nifedipine SR (n = 23) as monotherapy. Sitting blood pressure and heart rate were measured at 22-24 h after lacidipine and 10-12 h after nifedipine SR. Both calcium antagonists similarly and significantly reduced the blood pressure at rest (sitting) and on exercise, while the heart rate did not change significantly. The nature and incidence of side effects and withdrawals also did not differ between the two. In conclusion, lacidipine once daily is as effective and well tolerated as nifedipine SR twice daily in patients with mild-to-moderate essential hypertension.

Topics: Adult; Aged; Blood Pressure; Calcium Channel Blockers; Delayed-Action Preparations; Dihydropyridines; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension; Italy; Male; Middle Aged; Nifedipine

This multicenter study was designed to assess the clinical efficacy and safety of the new once-daily calcium antagonist lacidipine in the treatment of mild-to-moderate essential hypertension. Patients were randomly assigned to receive, double-blind, either lacidipine (n = 180) or hydrochlorothiazide (HCTZ, n = 182) following a 1-month placebo run-in period. Both drugs were titrated after 1 month if blood pressure was not controlled: lacidipine, from 4 to 6 mg once daily; HCTZ, from 25 to 50 mg once daily. Atenolol was added later if necessary to achieve blood pressure control. Lacidipine and HCTZ were equally effective in controlling the blood pressure levels in the majority of patients (approximately 90% after 4 months). Adverse events were those to be expected with these classes of drug and were reported in 48 (26.7%) of the patients receiving lacidipine treatment and in 34 (18.7%) of those receiving HCTZ. The diuretic produced a significantly higher incidence of hypokalemia.

Topics: Administration, Oral; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Safety

Elderly patients are becoming a greater proportion of the hypertensive population. In addition, they may respond differently to drugs, both pharmacodynamically and pharmacokinetically. Therefore, approximately 25% of the patients treated with lacidipine in early studies were over 65 years old. In three double-blind, parallel-group comparative trials, 118 elderly hypertensive patients were treated with lacidipine or comparators, either atenolol, nifedipine SR, or hydrochlorothiazide (HCTZ). Lacidipine was at least as effective in lowering blood pressure as the comparators, as well tolerated as nifedipine SR (but with a significantly lower incidence of edema) and HCTZ, and better tolerated than atenolol. In a double-blind, placebo-controlled, parallel-group, dose-response study of 131 elderly hypertensive patients randomized to receive either lacidipine or placebo, lacidipine significantly reduced the diastolic blood pressure compared with placebo. In the long-term evaluation, more patients required titration with 2 mg of lacidipine than with 4 mg. These results suggest that 4 mg once daily is an effective and well-tolerated antihypertensive treatment in the elderly and, as with the general adult population, represents the optimal long-term maintenance dose.

Topics: Aged; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypertension; Male; Safety

Ambulatory blood pressure monitoring gives a more representative blood pressure profile than office blood pressure measurements and is free of any placebo effect. It is therefore useful for studying the effect of antihypertensive agents. Although ambulatory blood pressure is less variable than office blood pressure, spontaneous fluctuations have been found in whole-day blood pressure when repeated measurements are taken. In the multicentre Triveneto Study, the mean difference between 24-h blood pressure recordings taken 3 months apart in 85 mild hypertensives was -0.1/-0.7 mmHg and the coefficient of repeatability (2 s.d.) was 17.3/12.6 mmHg. The corresponding values for office blood pressure were -8.7/-2.0 and 29.8/16.5 mmHg, respectively. This reduction in inter-measurement variability with ambulatory blood pressure monitoring makes it possible to reduce the sample size required to prove the effect of an antihypertensive agent in pharmacological trials. However, in the individual subject, the results of ambulatory blood pressure monitoring should be considered with caution, as 24-h blood pressure averages and profiles are subject to a degree of variability. This technique was used in 21 mild-to-moderate hypertensives to test the antihypertensive effect of lacidipine given once a day (4-6 mg) versus placebo. The drug proved effective throughout the day and night, showing a 24-h effect on blood pressure without reflex tachycardia or other intolerable side effects.

Topics: Adult; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitors; Circadian Rhythm; Dihydropyridines; Drug Administration Schedule; Humans; Hypertension; Middle Aged; Reproducibility of Results

Recent multicenter trials have demonstrated that, in hypertensive elderly people, blood pressure control can significantly decrease the rate of cardiovascular and cerebrovascular events. Twenty-four-hour ambulatory blood pressure monitoring has proved to be superior to isolated sphygmomanometer blood pressure readings in the diagnostic evaluation of hypertension and in assessing the blood pressure response to treatment. We used 24-h ambulatory monitoring in a small, double-blind, randomly-allocated, placebo-controlled, parallel-group study of antihypertensive treatment with lacidipine given once a day at 2 or 4 mg. In our elderly subjects, the lacidipine treatment provided adequate blood pressure control both by day and by night with no effect on the heart rate profile. Furthermore, after drug therapy, we found a significant reduction in systolic blood pressure variability (standard deviation). This study shows that lacidipine can provide adequate control of arterial hypertension in the elderly.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitors; Circadian Rhythm; Dihydropyridines; Double-Blind Method; Drug Administration Schedule; Humans; Hypertension

We evaluated the effects of lacidipine and hydrochlorothiazide on blood pressure and left ventricular mass in hypertensive patients of mild-to-moderate degree. Both antihypertensive agents significantly decreased systolic and diastolic blood pressure without relevant symptoms and signs of reflex activation of the sympathetic nervous system. Posterior wall and interventricular septal thickness and the left ventricular mass were significantly decreased by lacidipine and hydrochlorothiazide after 3 and 6 months of treatment without clinical symptoms of reduced cardiac function.

Topics: Blood Pressure; Calcium Channel Blockers; Cardiomegaly; Dihydropyridines; Double-Blind Method; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Time Factors

The efficacy of the new once-daily dihydropyridine calcium antagonist, lacidipine, in reducing ambulatory intraarterial blood pressure (BP) was examined in 12 untreated hypertensive patients. The intraarterial recording was commenced 24 hours before the first 4-mg dose and was continued for a further 24 hours thereafter. After dose titration and chronic therapy, a second 24-hour ambulatory BP recording was made. There was a steady onset of drug action, maximal at 2 hours, but with reflex tachycardia after the first dose. Chronic administration reduced BP throughout the 24-hour period, without tachycardia. Mean daytime reduction in BP was 20 mm Hg systolic (p less than 0.005) and 12 mm Hg diastolic (p less than 0.02). Mean nighttime reduction was 8-mm Hg systolic (p less than 0.05) and 6-mm Hg diastolic (difference not significant). There was no postural decrease in BP on 60 degrees head-up tilting and hypotensive action was maintained during isometric exercise (reduction at peak of 32/18 mm Hg, p less than 0.05) and throughout dynamic exercise (reduction at peak of 23/14 mm Hg, p less than 0.05). Lacidipine is an effective once-daily antihypertensive agent, with good control of stress response.

Topics: Blood Pressure; Blood Pressure Determination; Blood Pressure Monitors; Calcium Channel Blockers; Dihydropyridines; Drug Administration Schedule; Exercise Test; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged

We conducted a randomly allocated, double-blind study in 16 essential hypertensive patients, eight of whom were treated with nifedipine and eight with lacidipine. The antihypertensive efficacy was evaluated and any modifications to peripheral haemodynamic parameters were observed in the brachial artery by a mechanographic method and B-mode scanner with a 10-MHz probe. Statistically significant reductions in blood pressure from basal values were observed after 1 and 6 months' treatment. Enhanced compliance (P less than 0.005), reduced characteristic impedance (P less than 0.001) and lower peripheral resistances (P less than 0.01) were also noted. Variations in pulse wave velocity and mean blood pressure showed a statistically significant correlation as early as the first month of treatment (P less than 0.01). Our results suggest that therapy with nifedipine and lacidipine allows an improvement in peripheral haemodynamics in hypertensive patients. This response is maintained in chronic treatment, even just before the next dose administration at the end of the longest dose interval.

Topics: Adult; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Nifedipine; Randomized Controlled Trials as Topic; Time Factors

Topics: Dihydropyridines; Drug Carriers; Drug Liberation; Humans; Hypertension

Lacidipine is a potent dihydropyridine calcium channel blocker used for management of hypertension and atherosclerosis. The drug has low and fluctuating oral bioavailability owing to its extensive hepatic first-pass metabolism and reduced water solubility. Accordingly, this work aimed at overcoming the aforementioned challenges through the formulation of intranasal nano-sized lacidipine glycerosomes. Box-Behnken was successfully employed for the formulation and in vitro optimization of the glycerosomes. Statistical analysis revealed that cholesterol concentration exhibited a significant effect on the vesicle size, while Phospholipon® 90G and glycerol concentrations exhibited significant effects on both entrapment efficiency and deformability index. The optimized formulation showed spherical shape, good deformability, vesicular size of 220.25 nm, entrapment efficiency of 61.97%, and enhanced ex vivo permeation by 3.65 fold compared to lacidipine suspension. Confocal laser scattering microscope revealed higher penetration depth via nasal mucosa for rhodamine labelled glycerosomes (up to 60 µm) in comparison to rhoadamine dye solution (26 µm). In addition, the optimized lacidipine glycerosomes caused significant reduction in methylprednisolone acetate-induced hypertension in rats for up to 24 h in comparison to oral drug suspension. Histopathological assessment showed intact nasal mucosal epithelial lining with no signs of inflammation or necrosis confirming the safety and tolerability of the proposed glycerosomes. The declared results highlights the potential of utilizing the proposed glycerosomes as safe and effective platform for intranasal delivery of lacidipine.

Topics: Administration, Intranasal; Administration, Oral; Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cholesterol; Dihydropyridines; Disease Models, Animal; Drug Compounding; Drug Liberation; Glycerol; Hypertension; Liposomes; Male; Methylprednisolone Acetate; Nasal Absorption; Nasal Mucosa; Permeability; Phosphatidylcholines; Rats, Wistar; Solubility

Drug-induced nephrotic syndrome (NS) can be resolved by eliminating the causative agents. However, patients with metastatic cancer have not been previously reported to achieve complete recovery from anticancer drug-induced NS after discontinuation of treatment, because many patients die of cancer progression before NS is restored.. A 67-year-old man presented with edema of both lower extremities. He received pazopanib therapy for recurrent metastatic renal cell carcinoma (mRCC) for 17 months. Laboratory examinations revealed 7484.58 mg/day of 24-h urine protein, 434 mg/dL of serum cholesterol, and 2.9 g/dL of serum albumin. He was diagnosed with NS, and pazopanib treatment was discontinued. Four months later, he completely recovered from NS. He was then treated with temsirolimus and nivolumab sequentially for > 26 months. Pazopanib was re-introduced following disease progression, and demonstrated antitumor effects for 7 months without NS recurrence.. Pazopanib-induced NS can occur late in patients with mRCC, and its subsequent discontinuation can enable patients to completely recover from its adverse effects. Moreover, pazopanib treatment may be re-introduced without the recurrence of NS.

Topics: Aged; Amlodipine; Angiogenesis Inhibitors; Antihypertensive Agents; Antineoplastic Agents; Carcinoma, Renal Cell; Combined Modality Therapy; Diabetic Nephropathies; Dihydropyridines; Drug Substitution; Edema; Everolimus; Humans; Hypertension; Indazoles; Kidney Failure, Chronic; Lung Neoplasms; Male; Nephrotic Syndrome; Nivolumab; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pneumonectomy; Protein Kinase Inhibitors; Pyrimidines; Sirolimus; Sulfonamides; Sunitinib

This study was performed to evaluate the possible protective effect of two calcium channel blocker's "lacidipine (LAC) and amlodipine (AML)" on bone metabolism in an experimental ovariectomized and inflammation-induced osteoporosis rat model (OVXinf). For the purpose of this study, the rats were divided into eight groups, each containing eight rats: sham-operated control (group 1, SH), sham + inflammation (group 2, SHinf), ovariectomy (group 3, OVX), ovariectomy + inflammation (group 4, OVXinf), ovariectomy + LAC 4 mg/kg (group 5, OVX + LAC), ovariectomy + inflammation + LAC 4 mg/kg (group 6, OVXinf + LAC), ovariectomy + AML 5 mg/kg (group 7, OVX + AML), ovariectomy + inflammation + AML 5 mg/kg (group 8, OVXinf + AML). The levels of osteocalcin and osteopontin decreased in OVXinf + LAC and OVXinf + AML groups. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. Gene expression levels of the osteogenic factor runt-related transcription factor 2 (Runx2) and type I collagen 1A1 (Col1A1) significantly decreased in the OVXinf group, when compared with the control group. AML or LAC administrations increased the levels of Runx2 and Col1A1. These results suggest that amlodipine and lacidipine may be a novel therapeutic target for radical osteoporosis treatment in hypertensive patients.

Topics: Amlodipine; Animals; Bone Density; Calcium Channel Blockers; Collagen Type I; Collagen Type I, alpha 1 Chain; Core Binding Factor Alpha 1 Subunit; Dihydropyridines; Female; Humans; Hypertension; Inflammation; Interleukin-1beta; Interleukin-6; Osteocalcin; Osteopontin; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

In adults, lacidipine seems to have no CYP3A4-inhibiting action. This particular characteristic makes it advantageous when combined with drugs metabolized by CYP3A4, such as cyclosporine. Until now, no data on the efficacy or safety of this calcium antagonist have been available in children. Thirty-nine hypertensive children (age: 0.13-14 years) receiving lacidipine in oncohematology for a mean of 75 days were included in this retrospective study. The causes of high blood pressure were renal tumor (n=7), catecholamine-secreting tumor (n=4), corticoid treatment (n=5), and cyclosporine treatment (n=23). An initial dosage of 0.05 mg/kg/day was sufficient for 41% of the patients. The remaining patients needed to increase the dosage, by steps of 0.03 mg/kg/day, until reaching an average effective dosage of 0.1 mg/kg/day. Lacidipine significantly decreased blood pressure by 30 (±14) mmHg for systolic blood pressure and by 26 (±13) mmHg for diastolic blood pressure. A medication plan with twice-daily administration was not significantly more effective than a single administration per day. Lacidipine was well tolerated, and no toxicity-related withdrawal of treatment occurred. For 22 patients treated with both cyclosporine and lacidipine, renal function was not disturbed over time, suggesting its preservation by lacidipine. No significant increase in cyclosporine blood concentration was detected. Lacidipine seems to be an effective calcium antagonist in pediatric oncohematology, is well tolerated, has a kidney-protector effect and no drug interaction when combined with cyclosporine.

Topics: Adolescent; Antihypertensive Agents; Child; Child, Preschool; Cyclosporine; Dihydropyridines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glomerular Filtration Rate; Glucocorticoids; Humans; Hypertension; Immunosuppressive Agents; Infant; Male; Neoplasms; Retrospective Studies

Cyclosporine (CsA) is frequently responsible for hypertension in bone marrow transplant children. Calcium channel blockers (CCBs) are considered to be the best treatment for CsA-induced hypertension, but they may alter the exposure and the effect of CsA by inhibiting the CYP3A4 pathway of CsA metabolism or P-gp. However, the inhibitory effect on CYP3A4 may vary among CCBs.. This study aimed to quantify the pharmacokinetic drug-drug interaction between CsA and nicardipine, amlodipine, and lacidipine. In all, 51 children who received CsA and CCB concomitantly were included.. Dose-normalized CsA trough blood concentrations significantly increased in patients treated with nicardipine and amlodipine, whereas they remained stable in patients treated with lacidipine.. Because lacidipine appears to have no effect on CsA exposure, it may be the best option among CCBs for treating high blood pressure caused by CsA in children.

Topics: Adolescent; Amlodipine; Calcium Channel Blockers; Child; Child, Preschool; Cyclosporine; Dihydropyridines; Drug Interactions; Female; Hematopoietic Stem Cell Transplantation; Humans; Hypertension; Immunosuppressive Agents; Infant; Male; Nicardipine; Retrospective Studies

Endothelial progenitor cells (EPCs) play a critical role in maintaining the integrity of vascular endothelium following arterial injury. Lacidipine has a beneficial effect on endothelium of hypertensive patients, but limited data are available on EPCs-mediated endothelial protection. This study tests the hypothesis that lacidipine treatment can improve endothelial repair capacity of EPCs from hypertensive patients through increasing CXC chemokine receptor four (CXCR4) signaling.. In vivo reendothelialization capacity of EPCs from hypertensive patients with or without in vitro lacidipine treatment was examined in a nude mouse model of carotid artery injury. Expression of CXCR4 and alteration in migration and adhesion functions of EPCs were evaluated.. Basal CXCR4 expression was markedly reduced in EPCs from hypertensive patients compared with normal subjects. In parallel, the phosphorylation of Janus kinase-2 (JAK-2) of EPCs, a CXCR4 downstream signaling, was also significantly decreased. Lacidipine promoted CXCR4/JAK-2 signaling expression of in vitro EPCs. Transplantation of EPCs pretreated with lacidipine significantly accelerated in vivo reendothelialization. The enhanced in vitro function and in vivo reendothelialization capacity of EPCs were inhibited by shRNA-mediated knockdown of CXCR4 expression or pretreatment with JAK-2 inhibitor AG490, respectively. In hypertensive patients, lacidipine treatment for 4 weeks also resulted in an upregulation of CXCR4/JAK-2 signaling of EPCs, which was associated with augmented EPCs-mediated reendothelialization and improved endothelial function.. Deterioration of CXCR4 signaling may lead to impaired EPCs-mediated reendothelialization of hypertensive patients. Lacidipine-modified EPCs via a partially CXCR4 signaling contribute to enhanced endothelial repair capacity in hypertension.

Topics: Adult; Animals; Antihypertensive Agents; Cells, Cultured; Dihydropyridines; Endothelial Cells; Endothelium, Vascular; Essential Hypertension; Humans; Hypertension; Male; Mice; Mice, Nude; Middle Aged; Stem Cells

Calcium channel blockers are increasingly used for the treatment of hypertension. Hypertension is an important risk factor for liver damage and several other circulatory abnormalities. The aim of this study was to determine the effects of lacidipine in a irradiation-induced hepatocellular damage model in Deoxyc Orticosterone Acetate (DOCA)-salt-induced hypertensive model in rats. In this study, animals were divided into five groups as follows: control (Group 1), hypertensive (Group 2), irradiated (Group 3), irradiated and hypertensive (Group 4) and irradiated, hypertensive and lacidipine-treated (Group 5). At the end of the experiment, the livers were removed and its homogenates were biochemically examined. Significant differences were found between values of all groups (p < 0.05). Group 3 and particularly Group 4 showed significant increase in lipid peroxidation and Nitric Oxide (NO) and serum tumor necrosis factor-alpha (TNF-alpha) with a significant reduction in serum level of alanine amine transferase (ALT) enzyme and in superoxide dismutase in red blood cells lysates. Lacidipine-treated group (5) showed a significant reduction in elevated systolic blood pressure together with a great protection of ALT and SOD enzymes from the destructive effects of irradiation and hypertension. Additionally, this CCB reduces hepatic NO and serum TNF-alpha levels that were increased in groups (2,3,4). The present study suggests that lacidipine has some important protective effects on liver of hypertensive irradiated albino rats.

Topics: Alanine Transaminase; Animals; Blood Pressure; Desoxycorticosterone Acetate; Dihydropyridines; Disease Models, Animal; Hypertension; Lipid Peroxidation; Liver; Liver Diseases; Nitric Oxide; Random Allocation; Rats; Salts; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Antihypertensive treatment may reduce prolonged QT duration in hypertension. Generally, the reductions of blood pressure and/or of cardiac mass are believed to be the responsible factors. However, drugs are not equivalent in QT modulation despite similar antihypertensive and antihypertrophic action. We investigated the effect of a calcium channel blocker, lacidipine and an angiotensin-converting enzyme inhibitor, enalapril on QT duration in rats. Normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were treated with lacidipine (at the dose of 1.5 mg/kg per day for WKY and 3 mg/kg per day for SHR) or enalapril (5 mg/kg per day for WKY and 10 mg/kg per day for SHR) during 8 weeks. Tail-cuff systolic blood pressure (sBP), left ventricular weight (LVW), vascular function of isolated aorta and mesenteric artery and duration of QT (and QTc) interval on Frank electrocardiograms were evaluated. As expected, untreated SHR showed elevated sBP, impaired vascular reactivity, increased LVW and prolonged QT when compared with WKY (p < 0.05). After treatment, both agents markedly improved vascular reactivity and reduced sBP in SHR (p < 0.05). Additionally, enalapril reduced LVW in both hypertensive (by 17%; p < 0.05) and normotensive rats (by 13%; p < 0.05) and, consequently, corrected QT duration in SHR. Interestingly, lacidipine also reduced LVW in SHR (by 9%; p < 0.05), but without influence on prolonged QT. Moreover, lacidipine had no effect on LVW in WKYs but prolonged their QT interval (by 10%; p < 0.05). In conclusion, lacidipine did not reverse a progressive prolongation of QT in SHR, despite sBP lowering and LVW reduction. Thus, the lowering of blood pressure and/or reduction of LVW are not sufficient per se to normalize ventricular repolarization in hypertensive cardiac disease. More likely, modulation of QT prolongation by antihypertensive drugs is a function of their complex action on blood pressure, vascular function, cardiac mass and on reflex neurohumoral activation.

Topics: Acetylcholine; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Calcium Channels; Dihydropyridines; Disease Models, Animal; Enalapril; Heart Ventricles; Hypertension; Male; Mesenteric Arteries; Norepinephrine; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Topics: Blood Pressure; Cardiovascular Diseases; Carotid Artery Diseases; Circadian Rhythm; Dihydropyridines; Female; Humans; Hypertension; Male; Office Visits

Calcium channel blockers are increasingly used for the treatment of hypertension. Menopause and hypertension are both important risk factors for liver damage and several other circulatory abnormalities. The aim of this study was to determine the effects of amlodipine and lacidipine in an ovariectomy-induced postmenopausal period model and a deoxycorticosterone acetate-salt-induced hypertensive model in rats.. In this study, animals were divided into six groups as follows: control (Group 1), hypertension (Group 2), ovariectomy (Group 3), ovariectomy and hypertension (Group 4), ovariectomy, hypertension and amlodipine-treated (Group 5), and ovariectomy, hypertension and lacidipine-treated (Group 6). At the end of the experiment, the livers were removed and tissue samples were histologically and stereologically examined.. The numerical densities of the hepatocytes according to group were 0.000422, 0.00329, 0.000272, 0.00259, 0.00374 and 0.000346 μm3, respectively. Significant differences were found between values of all groups (p<0.01, Mann-Whitney U test). According to histopathological investigation, Group 3 and particularly Group 4 showed some microscopic abnormalities such as dilatation in sinusoids central veins and branches of portal vein, irregularities of the hepatocyte columns, significant mononuclear cell infiltrations, and unstained vacuoles in the cytoplasm of the hepatocytes. Histological structure was protected from the destructive effects of ovariectomy and hypertension in Groups 5 and 6.. Our experimental results show that both hypertension and the postmenopausal period have negative effects on the number of hepatocytes and histological structure of the liver. Both amlodipine and lacidipine appear to ameliorate the hypertension and/or postmenopausal period-related decrease in hepatocyte number. We thus suggest that lacidipine and particularly amlodipine have important protective and recovering effects on the liver.

Topics: Amlodipine; Animals; Calcium Channel Blockers; Cytoprotection; Dihydropyridines; Female; Hepatocytes; Hypertension; Liver; Ovariectomy; Postmenopause; Rats; Rats, Inbred Strains

Baseline carotid intima-media thickness (IMT) and plaques are considered predictors of cardiovascular events, but whether they maintain predictive value in treated hypertensive patients and whether time-related (or treatment-induced) IMT changes are additional predictors are unknown.. Analyses were performed of the data from the European Lacidipine Study on Atherosclerosis (ELSA), a large, randomized, intervention trial in which 2334 hypertensive patients from 7 European countries were followed up under effective antihypertensive treatment for 3.75 years. Kaplan-Meier curves indicated progressively lower survival free of any type of outcome except stroke, with increasing baseline IMT quartiles or increasing IMT values, even after adjustment for major baseline risk factors. Incidence of any outcome except stroke also was related to baseline number of carotid plaques. However, when both baseline and on-treatment IMT values were entered in Cox proportional-hazards models, differences in IMT compared with baseline did not predict cardiovascular outcomes. Although on-treatment rather than baseline IMT values significantly entered some of the proportional-hazards models, baseline and on-treatment IMTs were highly correlated, and therefore these results are inconclusive.. ELSA shows that carotid intima-media thickening and plaques are important added risks of cardiovascular outcomes in a treated hypertensive population independently of blood pressure and traditional risk factors. However, the analysis failed to show a predictive role of treatment-dependent IMT changes. These negative conclusions should be tempered by the limitations inherent in the smallness of these changes compared with the large individual differences in baseline IMTs.

Topics: Antihypertensive Agents; Cardiovascular Diseases; Carotid Arteries; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged; Randomized Controlled Trials as Topic; Tunica Intima; Tunica Media

Changes in myocardial expression of Na+/K+-ATPase alpha-subunit isoforms have been demonstrated in different models of cardiac hypertrophy and hypertension. Here we studied the expression of these isozymes in stroke-prone spontaneously hypertensive rats (SHRSP) and the influence of high salt diet and treatment with the dihydropyridine lacidipine. Adult SHRSP were offered either 1% NaCl or water as drinking solution for 6 weeks. Salt-loaded SHRSP were treated or not with 1 mg/kg/day lacidipine. Compared to Wistar Kyoto (WKY) rats, non-salt-loaded SHRSP presented significant hypertension and cardiac hypertrophy. Salt intake markedly enhanced cardiac hypertrophy, an effect blunted by lacidipine. [3H]Ouabain binding assays on total particulate fractions from heart ventricles revealed the existence of two high-affinity sites with Kd approximately 25 and approximately 200 nM, ascribed to the alpha3 and alpha2 isoforms, respectively. Bmax of alpha3 was unexpectedly high (40% of total high-affinity binding) in ventricles from WKY rats but very low in all groups of SHRSP. On the other hand, Bmax of alpha2 was similar in WKY and non-salt-loaded SHRSP; however, salt loading of SHRSP resulted in a Bmax reduction of 20% (P<0.05), an effect blocked by lacidipine. These effects were largely confirmed by immunoblotting analysis, which, in addition, demonstrated that the density of the ubiquitous alpha1 isoform was comparable among the experimental groups. In conclusion, WKY rats showed a high myocardial expression of the Na+/K+-ATPase alpha3 subunit, which was not found in SHRSP; the level of the alpha2 isoform was similar in untreated SHRSP and WKY; salt-loading of SHRSP promoted reduction of the alpha2 isoform, and this effect was completely hampered by lacidipine.

Topics: Animals; Calcium Channel Blockers; Cardiomegaly; Dihydropyridines; Heart Ventricles; Hypertension; Isoenzymes; Male; Ouabain; Protein Subunits; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium Chloride, Dietary; Sodium-Potassium-Exchanging ATPase; Stroke

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Atenolol; Blood Pressure; Dihydropyridines; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Metoprolol; Middle Aged; Treatment Outcome

Topics: Arteriosclerosis; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension; Randomized Controlled Trials as Topic; Tunica Intima; Tunica Media

Endothelium-dependent vasorelaxation is defective in hypertensive rats, especially in conduit arteries. In the stroke-prone spontaneously hypertensive rat, impaired endothelium-dependent vasorelaxation appears to contribute to the pathogenesis of stroke independent of blood pressure. Because treatment with lacidipine, a long-acting calcium channel blocker, protects against stroke and cardiovascular remodeling in this model, we investigated the effect of this treatment on endothelium-dependent vasorelaxation in the aorta. Stroke-prone rats were exposed to a salt-rich diet (1% NaCl in drinking water) with or without lacidipine (1 mg. kg(-1). d(-1)) for 6 weeks. A high-sodium diet (1) increased systolic blood pressure, aortic weight, and wall thickness and plasma renin activity (P<0.05); (2) markedly reduced nitric oxide (NO)-mediated, endothelium-dependent relaxation of aortic rings to acetylcholine and the sensitivity to the relaxing effect of S-nitroso-N-acetylpenicillamine, an NO donor (P<0.001); and (3) induced an elevation of preproendothelin-1 mRNA levels in aortic tissue (P<0.01) without affecting endothelial NO synthase mRNA levels. Lacidipine treatment prevented the salt-dependent functional and structural alterations of the aorta, including the overexpression of the preproendothelin-1 gene, and increased endothelial NO synthase mRNA levels in aortic tissue (P<0.01). In conclusion, lacidipine protects stroke-prone hypertensive rats against the impairment of endothelium-dependent vasorelaxation evoked by a salt-rich diet, and this effect may contribute to its beneficial effect against end-organ damage and stroke.

Topics: Animals; Antihypertensive Agents; Aorta; Calcium Channel Blockers; Dihydropyridines; Endothelin-1; Endothelium, Vascular; Gene Expression; Hypertension; Nitric Oxide Synthase; Rats; Rats, Inbred SHR; Sodium, Dietary; Vasodilation

Topics: Antihypertensive Agents; Antioxidants; Arteriosclerosis; Calcium Channel Blockers; Clinical Trials as Topic; Dihydropyridines; Humans; Hypertension

Topics: Adrenergic beta-Antagonists; Arteriosclerosis; Atenolol; Calcium Channel Blockers; Dihydropyridines; Disease Progression; Humans; Hypertension; Randomized Controlled Trials as Topic

The main objective of this study was to evaluate well-being and physical activity of 248 hypertensive patients, including 177 females, who had previously been included in the Latin-American Study on Lacidipine in Hypertension (LASTLHY).. This open study was carried out in 12 clinical centers in Argentina, Brazil, Colombia, Mexico and Venezuela, to compare, over a period of 16 weeks, the antihypertensive action of a fixed-dose, once daily of 4 mg lacidipine administered orally to 120 patients and 30 mg nifedipine GITS (Gastro-Intestinal Therapeutic System) administered to 128 patients, aged between 40 and 65 years. All patients had mild to moderate hypertension and treatment was begun at the end of a one-week placebo run-in period (end of week -1). Well-being and physical activity were assessed by means of single questionnaire, which reflected the physical and cultural diversities amongst the clinical centers and patients. The questionnaire included 13 multiple-choice and 8 contingent open questions. The score of each question was multiplied by a coefficient related to the importance of each question to the patient (semipersonalization); the coefficient was obtained from cultural and socioeconomic data collected at the time of enrollment. The semipersonalization was carried out by a blind psychological study with respect to the medication and had a high repeatability in the assignment of personalized coefficients to the score of each question. The scores of each question were added to obtain an overall well-being and activity scoring. The possible theoretical range for the overall scoring in this study was 10 - 124.. See Table 1.. The study revealed that the administration of calcium channel blockers such as lacidipine and nifedipine GITS, and lacidipine in particular, produced low incidence of side effects, and lacidipine in particular induced significant improvement in the quality of life.

Topics: Activities of Daily Living; Administration, Oral; Adult; Aged; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Exercise; Female; Health Surveys; Humans; Hypertension; Male; Middle Aged; Nifedipine; Psychometrics; Quality of Life

1. Calcium channel blockers (CCBs) are anti-hypertensive drugs that are usually considered to act mainly as vasodilators. We investigated the relation between the reduction of blood pressure evoked by two long-acting CCBs and their protective effect against cardiac and renal damage in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP were exposed to high dietary salt intake (1% NaCl in drinking solution) from 8 to 14 weeks of age, with or without amlodipine or lacidipine at three dosage regimens producing similar effects on blood pressure. 3. The lowest dosages of both drugs had non-significant effects on blood pressure but inhibited the paradoxical increases in plasma renin activity (PRA) and in renin mRNA in kidney that were found in salt-loaded SHRSP. The lowest dosage of lacidipine (but not of amlodipine) restored the physiological downregulation of renin production by high salt and reduced left ventricular hypertrophy and mRNA levels of atrial natriuretic factor and transforming growth factor-beta1. 4. The intermediate dosages reduced blood pressure and PRA in a comparable manner, but cardiac hypertrophy was more reduced by lacidipine than by amlodipine. 5. Although the highest doses exhibited a further action on blood pressure, they had no additional effect on cardiac hypertrophy, and they increased PRA and kidney levels of renin mRNA even more than in the absence of drug treatment. 6. We conclude that reduction of blood pressure is not the sole mechanism involved in the prevention of cardiac remodelling by CCBs, and that protection against kidney damage and excessive renin production by low and intermediate dosages of these drugs contributes to their beneficial cardiovascular effects.

Topics: Actins; Amlodipine; Animals; Atrial Natriuretic Factor; Blood Pressure; Calcium Channel Blockers; Collagen Type I; Dihydropyridines; Dose-Response Relationship, Drug; Fibrosis; Gene Expression Regulation; Heart Ventricles; Hypertension; Hypertrophy; Kidney; Male; Muscle, Skeletal; Rats; Rats, Inbred SHR; Renin; RNA, Messenger; Sodium Chloride, Dietary; Transforming Growth Factor beta; Transforming Growth Factor beta1

Topics: Aged; Antihypertensive Agents; Arteriosclerosis; Atenolol; Calcium Channel Blockers; Carotid Stenosis; Dihydropyridines; Double-Blind Method; Humans; Hypertension; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors; Ultrasonography, Doppler, Color

Normotensive rats fed a high-fructose diet (HFD) develop hypertriglyceridemia, hyperinsulinemia, and hypertension. The glomerular changes observed in the kidneys of these animals are similar to those observed in diabetic rats. The aim of this study was to evaluate whether lacidipine, a calcium antagonist, could have a protective effect with this animal model. Forty male Wistar-Kyoto (WKY) rats were divided into four groups treated with HFD + placebo; HFD + lacidipine, 0.3 mg/kg/day; HFD + lacidipine, 3 mg/kg/day; or standard diet + placebo for 4 weeks. Urinary excretion of the stable metabolic products of nitric oxide (NO) was determined, because this vasoactive agent has been found to cause hemodynamic changes in the diabetic kidney. Glomerular size was determined by means of morphometric analysis. The results of this study show that lacidipine prevents (a) the HFD-induced increase in blood pressure in a dose-dependent manner; (b) the HFD-induced increase in glomerular size and fibronectin synthesis; and (c) the increase of collagen III synthesis in the heart. The drug had no effect on the increased urinary excretion of the stable metabolic products of NO. These data suggest that lacidipine might be useful in preventing the renal and cardiac damage caused by hypertension and non-insulin-dependent diabetes mellitus.

Topics: Animals; Antihypertensive Agents; Blood Glucose; Blood Pressure; Body Weight; Collagen; Creatinine; Dietary Carbohydrates; Dihydropyridines; Dose-Response Relationship, Drug; Fibronectins; Fructose; Heart Diseases; Hypertension; Insulin; Kidney; Kidney Diseases; Kidney Glomerulus; Male; Myocardium; Nitric Oxide; Organ Size; Rats; Rats, Inbred WKY; Triglycerides

The stroke-prone spontaneously hypertensive rat (SHRSP) is a strain with high incidence of cerebrovascular accidents increased by salt-rich diet and decreased by calcium-antagonist treatment. In the SHRSP rat basilar artery the authors have previously shown reduced contractility and altered structure including regions of smooth muscle cell (SMC) disorganization. The aims of this study have been to analyze (1) the morphology of these abnormal regions, (2) the structural modifications responsible for the reduced function, and (3) the effect of salt and calcium-antagonist treatment on vascular structure and function. Wistar Kyoto and SHRSP rats, untreated or treated from week 8 through 14 with 1% NaCl or 1% NaCl + 1 mg x kg(-1) x d(-1) lacidipine, were used. Function was studied with wire myography. Structure was analyzed in fixed intact arteries with confocal microscopy. Basilar arteries from SHRSP rat showed (1) reduced contractility, (2) discrete foci of SMC disarray with altered proportion of adventitia to SMC, and (3) decreased SMC and increased adventitial cell number. Arteries from salt-loaded SHRSP rats showed a higher degree of SMC disarray and further reduction in contractility. Lacidipine treatment of salt-loaded rats significantly improved structure and function. These data suggest that vascular remodeling can provide an explanation for the observed reduction in vascular contractility of SHRSP rat basilar arteries and might show light on the effects of salt load and calcium-channel blockers in life span and the incidence of cerebrovascular accidents in SHRSP rats.

Topics: Animals; Antihypertensive Agents; Basilar Artery; Calcium Channel Blockers; Cerebrovascular Disorders; Dihydropyridines; Genetic Predisposition to Disease; Hypertension; Microscopy, Confocal; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium Chloride, Dietary

Normotensive rats fed a high fructose diet (HFD) develop hypertriglyceridemia, hyperinsulinemia and hypertension. The glomerular changes observed in the kidneys of these animals are similar to those observed in diabetic rats. The aim of this study was to evaluate whether lacidipine could be effective not only in preventing, but also in inducing the regression of hypertension, and renal and cardiac damage in rats fed HFD.. Thirty male Wistar-Kyoto (WKY) rats received HFD for 1 month; thereafter, five rats were sacrificed (Group 1) and the other 25 rats were divided into three groups: Group 2 (five rats) received HFD plus placebo, Group 3 (10 rats) HFD plus lacidipine 3 mg/kg per day, and Group 4 (10 rats) HFD plus hydralazine 10 mg/kg per day. At the end of the second month all animals were sacrificed. Kidneys and hearts were immediately removed. Renal deposits of collagen I, collagen IV, fibronectin and cardiac deposits of collagen III were assessed by means of immunohistochemistry.. In the rats receiving HFD plus placebo, blood pressure was increased after the first and the second month of diet. This increase was reversed by lacidipine and hydralazine but, although both drugs normalized blood pressure, only lacidipine was effective in reducing renal and cardiac damage.. These data suggest that lacidipine is effective in reversing hypertension and reducing target organ damage induced by HFD. Moreover, this protective effect on target organs appears to be not simply a consequence of blood pressure reduction, but seems to be connected to the type of hypotensive drug administered.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Collagen; Diet; Dihydropyridines; Fibronectins; Fructose; Hypertension; Kidney Glomerulus; Male; Myocardium; Rats; Rats, Inbred WKY

The aim of this study was to investigate the therapeutic effectiveness of lacidipine in stroke-prone spontaneously hypertensive rat (SHRSP) with cerebrovascular lesions in comparison with nicardipine. SHRSP were fed 1% saline as drinking water. After the onset of stroke, saline was replaced with water and each drug was administered orally once a day for 3 weeks. In the drug-untreated group, recurrence of stroke was repeated, deterioration and amelioration of neurological deficits (ND) were repeated, and histological examination and measurement of regional blood flow (rBF) using nonradioactive colored microspheres performed at the end of treatment revealed severe damages and significantly decreased rBF in brain and kidney, respectively. In kidney, not only lacidipine (1 mg/kg) but also nicardipine (30 mg/kg) decreased vascular lesions and ameliorated low-rBF significantly. Both drugs also inhibited the recurrence of stroke completely even at a low dose that did not ameliorate severe hypertension. Neuronal damages and ND in each lacidipine-treated group were ameliorated significantly, whereas those in each nicardipine-treated group were slightly improved. Lacidipine at 1 mg/kg alone ameliorated the cerebral low-rBF significantly even at 24 hr after administration. These results suggest that a long-lasting improvement of low-rBF after stroke may be useful in the treatment of SHRSP with cerebrovascular lesions.

Topics: Animals; Blood Pressure; Body Weight; Brain; Calcium Channel Blockers; Cerebellum; Cerebrovascular Disorders; Dihydropyridines; Hypertension; Kidney; Male; Nicardipine; Rats; Rats, Inbred SHR; Recurrence; Regional Blood Flow; Renal Artery; Systole

Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension

To analyze the effect of the long-acting calcium channel blocker lacidipine on cardiovascular remodeling induced by salt loading in a genetic model of hypertension.. We examined the influence of threshold doses of lacidipine, with little blood-pressure lowering effect, on cardiac weight and gene expression in stroke-prone spontaneously hypertensive rats (SHRSP).. SHRSPs (8-week-old) were randomly allocated to four groups: control, salt-loaded SHRSP and salt-loaded SHRSP treated with lacidipine at 0.3 and 1 mg/kg per day. Systolic blood pressure was measured by the tail-cuff method. At the end of 6 weeks of treatment, ventricles were collected and weighed. Ventricular messenger RNA was extracted and subjected to Northern blot analysis.. Lacidipine (0.3 mg/kg per day) not only prevented the salt-dependent cardiac hypertrophy and the slight increase in systolic blood pressure induced by salt, but also prevented, largely or completely, salt-dependent increases in ventricular levels of several gene products: skeletal and cardiac alpha-actin, beta-myosin heavy chain (beta-MHC), type I collagen, long-lasting (L)-type calcium channel and preproendothelin-1. At a higher dose of 1 mg/kg per day, lacidipine further decreased systolic blood pressure below the level of control SHRSP, completely prevented salt-dependent overexpression of the beta-MHC gene and markedly attenuated salt-dependent overexpression of the transforming growth factor-beta1 gene.. Lacidipine prevents the cardiac remodeling and enhanced gene expression induced by salt loading in SHRSP at doses that only minimally affect the high systolic blood pressure.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Cardiomegaly; Cerebrovascular Disorders; Dihydropyridines; Follow-Up Studies; Gene Expression; Hypertension; Male; Myosin Heavy Chains; Random Allocation; Rats; Rats, Inbred SHR; RNA, Messenger; Sodium Chloride; Ventricular Remodeling

To evaluate the modifications of the morphology of mesenteric small resistance vessels in spontaneously hypertensive rats (SHR) induced by lacidipine treatment.. Lacidipine was administered at three different dosages, 20, 10, and 0.3 mg/kg per day. Fifty rats were studied. Nine SHR and 11 Wistar-Kyoto (WKY) rats were not treated. Each lacidipine dose was administered to 10 SHR. The drug and the placebo were administered by gavage from age 4 to age 12 weeks. The blood pressure was measured noninvasively every week. The animals were killed when they were aged 13 weeks, and the relative left ventricular mass (left ventricular weight plus septum weight/body weight) was calculated. Small mesenteric resistance vessels were dissected and mounted on a micromyograph (Mulvany's technique), and morphological parameters of the vessels were studied (media thickness and media: lumen ratio).. The systolic blood pressure of SHR administered 20 and 10 mg/kg lacidipine per day was reduced significantly during the treatment period, whereas that of rats treated with 0.3 mg/kg lacidipine per day did not change. A significant reduction in media: lumen ratio was observed for all three groups of treated rats, including those to which 0.3 mg/kg lacidipine per day had been administered, and no reduction in systolic blood pressure could be detected. The relative left ventricular mass was reduced significantly only in rats to which 20 and 10 mg/kg lacidipine per day had been administered.. A significant reduction in magnitude of vascular structural alternations was observed even in SHR treated with a low, nonhypotensive dose of lacidipine.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Heart Ventricles; Hypertension; Mesenteric Arteries; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Cardiovascular hypertrophy is a common feature of hypertension, but it is not known if this is related only to increased blood pressure or also to non-hemodynamic factors. Indeed, drug treatment of hypertension with hydralazine does reduce blood pressure but not cardiovascular hypertrophy. We used Stroke-prone rats (SHRSP) who are sensitive to salt load in order to better characterize the action of an antihypertensive agent on salt-dependent vascular hypertrophy and change in reactivity of calcium channels. SHRSP were submitted to salt load from 8 to 14 weeks of age with or without lacidipine, a long acting dihydropyridine. We observed that the cardiovascular hypertrophy was attenuated by lacidipine 0.3 mgkg-1 day-1 which did not change high blood pressure. The action of 1 mgkg-1 day-1 was higher on hypertrophy but, in addition, it reduced blood pressure. The salt-related increase in vascular responsiveness to the calcium channel activator Bay K 8644 was blunted by lacidipine treatment in both basilar and mesenteric arteries. By contrast with basilar artery, in mesenteric artery, this increased responsiveness was insensitive to bosentan, an endothelin antagonist but could be related to smooth muscle cell depolarization inhibited by lacidipine treatment. The present results confirm that lacidipine has blood pressure-independent effect on tissue remodeling in hypertension. They show that vascular response to salt is heterogeneous among vessels but is equally sensitive to lacidipine.

Topics: Animals; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Hypertension; Rats; Rats, Inbred SHR; Sodium Chloride

Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to test whether antihypertensive treatment with the calcium antagonist lacidipine can improve endothelium-dependent vasodilation in essential hypertensive patients. In 12 normotensive subjects (mean age, 47.8+/-8.6 years; blood pressure, 118.6+/-4.2/76.7+/-3.9 mm Hg) and 19 hypertensive patients (mean age, 49.4+/-10.2 years; blood pressure; 153.5+/-13.3/101.3+/-6.4 mm Hg), we studied forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute) and bradykinin (5, 15, and 50 ng/100 mL per minute), two endothelium-dependent vasodilators that act through different receptors and signal transduction pathways, and sodium nitroprusside (1, 2, and 4 microg/100 mL per minute), an endothelium-independent vasodilator. In essential hypertensive patients, vascular reactivity was repeated during prolonged (8 weeks of oral treatment at 6 mg/d) lacidipine administration and 2 weeks after withdrawal of chronic (32-week) treatment. Hypertensive patients showed significantly (P<.01) blunted vasodilation in response to acetylcholine (vascular resistance, 31.5+/-4.9 to 7.6+/-2.4 SU) and bradykinin (vascular resistance, 32.3+/-5.8 to 8.5+/-3.0 SU) compared with control subjects (vascular resistance: acetylcholine, 24.3+/-3.9 to 3.7+/-1.2 SU; bradykinin, 24.7+/-0.4 to 4.1+/-1.3 SU), whereas the response to sodium nitroprusside was similar. After either 8 or 32 weeks of lacidipine treatment, the vasodilation in response to acetylcholine (30.6+/-7.7 to 5.7+/-1.5 and 34.3+/-6.6 to 5.9+/-1.9 SU, respectively) and bradykinin (31.3+/-7.2 to 6.4+/-1.6 and 33.7+/-5.4 to 6.1+/-1.5 SU, respectively), but not to sodium nitroprusside, proved to be significantly (P<.05) increased compared with baseline. In essential hypertensive patients, oral treatment with lacidipine increased forearm vasodilation in response to acetylcholine and bradykinin, suggesting that this drug can improve endothelial function in patients with essential hypertension.

Topics: Acetylcholine; Blood Pressure; Bradykinin; Calcium Channel Blockers; Dihydropyridines; Endothelium, Vascular; Female; Forearm; Humans; Hypertension; Male; Middle Aged; Nitroprusside; Reference Values; Regional Blood Flow; Vascular Resistance; Vasodilation

Thirty patients with mild to moderate essential hypertension had received four weeks treatment with Lacidipine and serum lipid peroxide (LPO), superoxide dismutase (SOD) and insulin levels were measured before and after treatment. The results showed: (1) there were decreased in SOD activity and increased Lpo content the patients group (P < 0.01); (2) after treated with Lacidipine, the SOD acitvity increased and Lpo content decreased (P < 0.01); (3) Lacidipine had obvious antihypertensive effect with no significant changes in heart rate; (4) Lacidipine had no significant effects on insulin, blood glucose and lipids. The results suggest that lacidipine is a safe and effective antihypertensive agent and can improve the metabolic balances in free radical system.

Topics: Aged; Antihypertensive Agents; Dihydropyridines; Female; Humans; Hypertension; Insulin; Lipid Peroxides; Male; Middle Aged; Superoxide Dismutase

The aim of this study was to compare the effects of angiotensin converting enzyme (ACE) inhibition, angiotensin II (AII) AT1-receptor blockade, and dihydropyridine calcium antagonism on hypertrophy and on vascular albumin permeability in kidney, heart, and mesenteric artery in a model combining genetic hypertension and diabetes mellitus. Diabetes mellitus was induced by streptozotocin in 8-week-old spontaneously hypertensive rats. The animals were randomized to receive no treatment, the angiotensin converting enzyme inhibitor ramipril, the AII AT1-receptor blocker valsartan, or the dihydropyridine calcium antagonist lacidipine for 3 weeks. Vascular albumin permeability was measured as the tissue content of intravenously injected Evans blue dye (EB) in kidney, heart, and mesenteric artery and the tissue/plasma EB ratio was calculated. Systolic blood pressure was reduced by all three antihypertensive regimens. Glycemic control was similar in all diabetic groups. Kidney hypertrophy was not affected by any of the antihypertensive drugs. Hypertrophy of the mesenteric artery was enhanced by lacidipine but was not affected by ramipril or valsartan. Relative heart weight was also increased by lacidipine. Vascular albumin permeability, expressed as EB content in micrograms/gram dry weight or as tissue/plasma EB ratio, was higher in the kidneys of lacidipine-treated rats than in any other group of diabetic rats. There was a positive correlation between kidney weight/body weight and kidney/plasma EB ratio in the diabetic rats. These findings indicate that the dihydropyridine calcium antagonist lacidipine is associated with an unfavorable effect on vascular hypertrophy and on vascular albumin permeability in the kidneys in rats with hypertension and diabetes mellitus. Furthermore, there seems to be a coupling in the diabetic kidney between hypertrophy and increased vascular albumin permeability.

Topics: Analysis of Variance; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Glucose; Blood Pressure; Capillary Permeability; Cardiomegaly; Coloring Agents; Coronary Vessels; Diabetes Mellitus, Experimental; Dihydropyridines; Evans Blue; Hypertension; Hypertrophy; Kidney; Male; Mesenteric Arteries; Ramipril; Rats; Rats, Inbred SHR; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin; Serum Albumin; Tetrazoles; Valine; Valsartan

We reviewed the clinical safety profile of lacidipine with the help of the rather comprehensive datafile of the manufacturer. Although a number of prospective, randomly allocated trials under way at present are investigating the effects of treatment with calcium antagonists on cardiovascular morbidity and mortality, these results are not yet available. Therefore, the present approach may be useful. A fuller account of this work has been published in Blood Pressure.. Since 1985,50 phase III-IV trials have been performed to investigate antihypertensive efficacy in patients with hypertension; 32 were controlled trials with comparison treatment and 18 were open studies of lacidipine treatment. Only data from trials completed before 1 January 1995 are presented here.. In all, 16590 patients were treated with lacidipine; 13419 in open studies and 3171 in double-blind comparative trials. A total of 1810 patients were given active comparative treatment and 451 were given placebo. Altogether, 5124 person-years of data were obtained.. Numbers of both fatal and non-fatal cardiovascular events were estimated. Efficacy (change in blood pressure and heart rate), adverse event rates and drop-out rates were compared for the different treatment regimens.. In all trials, 2-6 mg lacidipine was effective in lowering blood pressure. In the controlled trials, systolic/diastolic blood pressure fell from 166/102 to 144/85 mmHg and the heart rate fell from 75.6 to 74.1 beats/min. The estimated event rate for a possible myocardial infarction in all studies was 5.46/1000 person-years; the fatal (all-cause) event rate was 5.27/1000 person-years and the estimated fatal cardiovascular event rate was 2.93/1000 person-years. There were 21 malignant events during treatment with lacidipine, for all studies yielding a crude incidence of 4.10/1000 person-years. In patients treated with lacidipine, the age-standardized (according to the world population) incidences were 1.49 (men) and 0.79/1000 person-years (women) compared with 2.74 (men) and 2.09/1000 person-years (women) in the European Community in 1990. The overall incidence in the comparative studies of one or more adverse events included 30.3% for lacidipine, 43.8% for other calcium antagonists, 18.7% for diuretics, 48.7% for beta-receptor blockers, 10.4% for angiotensin converting enzyme inhibitors and 15.7% for placebo. The adverse effects of lacidipine were, as expected, headaches, flushing, pedal oedema and palpitations.. Lacidipine proved to be an effective and well tolerated drug in almost 19000 hypertensive patients. It displayed a reasonable adverse profile that was typical of a calcium antagonist of the dihydropyridine group. This analysis has two obvious limitations: (1) it is a retrospective analysis; and (2) the data were obtained from a large cohort of patients, but most were treated with lacidipine for a relatively short period of time. Although we found a lower fatal event rate than that reported by Collins et al., their meta-analysis included 10 times more person-years than our analysis, and therefore our event rate may be less accurate. Further prospective studies are under way at present to determine whether these drugs can produce reductions in atherosclerosis or in the incidence of cardiovascular disease.

Topics: Adolescent; Adult; Aged; Calcium Channel Blockers; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Dihydropyridines; Humans; Hypertension; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

To evaluate the relationship between the mechanical properties of the carotid artery wall and baroreflex function after acute reduction of blood pressure with lacidipine in essential hypertension.. After 15 days of placebo washout, the hypertensive patients underwent a single-blind haemodynamic study before and 90 min after administration of 4 mg lacidipine (a dihydropyridine calcium antagonist).. Brachial intra-arterial blood pressure was recorded in eight mild-to-moderate essential hypertensive patients aged 40-53 years (mean +/- SEM 46.8 +/- 4.7 years). The carotid pulse diameter was recorded simultaneously by an echo-tracking technique. The mechanical properties of the carotid artery wall were evaluated by calculating Peterson's incremental elastic modulus (Ep) both as an averaged value of 10 heart cycles with stable blood pressure and was the dynamic correlation, on a beat-to-beat basis, of Ep and the systolic blood pressure during a 20 mmHg increase in blood pressure following a bolus injection of phenylephrine. The elastic properties of the carotid artery were investigated further by determining the correlation between the systolic pressure and systolic diameter, beat by beat, during a ramped increase of blood pressure after phenylephrine administration. The baroreceptor reflex sensitivity was measured simultaneously by the Oxford method and by correlating Ep and the electrocardiographic R-R' interval on a beat-to-beat basis during phenylephrine injections.. After lacidipine administration Peterson's elastic modulus, measured under resting steady-state conditions, was reduced (18.7 +/- 7.4 versus 16.4 +/- 6 x 10(5) dyne/cm2), whereas the baroreflex sensitivity was unchanged (6.6 +/- 3.3 versus 6.3 +/- 0.2 ms/mmHg) and resetting of the baroreflex had occurred. At the same time, the correlations between the systolic blood pressure and Ep and between the systolic blood pressure and carotid systolic diameter over a 20 mmHg increase in blood pressure were unchanged. Moreover, the correlations between the systolic blood pressure and the R-R' interval and between Ep and R-R' interval during the phenylephrine-induced blood pressure increase did not differ statistically.. The results suggest that the resetting of the baroreflex after the acute reduction in blood pressure caused by lacidipine is dissociated from mechanical changes in the carotid artery wall.

Topics: Adult; Carotid Arteries; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged; Pressoreceptors; Reflex

The aim of this study was to compare the renal effects of angiotensin converting enzyme (ACE) inhibition with calcium channel blockade in a model combining genetic hypertension with diabetes. Streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). The animals were then randomized to receive no treatment, the ACE inhibitor, perindopril, or the dihydropyridine calcium antagonist lacidipine. Body weight, systolic blood pressure, glycemic control, renal function, and albumin excretion rate (AER) were assessed serially over the 32-week study period. At week 32 the animals were killed and glomerular volume was measured. Both antihypertensive regimens significantly reduced systolic blood pressure in diabetic SHR. There was no significant difference in glycemic control, serum creatinine, or glomerular filtration rate among the three groups at week 32. The ACE inhibitor perindopril significantly reduced AER and glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist lacidipine failed to reduce AER or glomerular hypertrophy. Thus, in contrast to the effects of ACE inhibition, calcium channel blockade with lacidipine, despite significantly reducing blood pressure, failed to reduce renal injury in this model. These results support the hypothesis that antihypertensive regimens may differ in their capacity to protect the diabetic kidney, despite similar effects on systemic blood pressure.

Topics: Albuminuria; Animals; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Dihydropyridines; Disease Models, Animal; Hypertension; Indoles; Kidney Diseases; Male; Perindopril; Random Allocation; Rats; Rats, Inbred SHR; Renin

Lacidipine is a second-generation 1,4-dihydropyridine calcium antagonist, whose potent and long-lasting antihypertensive properties prompted us to investigate whether its chronic administration to Dahl-S rats prevented salt-induced hypertension, vasculopathy, and accelerated mortality. These studies revealed that lacidipine proved vasoprotective when administered both prophylactically and therapeutically at doses of 0.1 and 0.3 mg/kg p.o. once a day, largely equivalent to the therapeutic doses. A generalized dose-related protection against necrotizing vasculopathy and brain damage was detected, although only the highest dose used (10 mg/kg) controlled the development of hypertension. These protective properties were further confirmed in stroke-prone spontaneously hypertensive rats, which develop accelerated mortality as a result of salt-induced cerebral apoplexy and renal lesions. All untreated controls died within 12 weeks of salt-rich diet, whereas all animals survived during the same period when treated prophylactically with lacidipine at 0.3 and 1 mg/kg p.o. once a day, although a slight reduction in systolic blood pressure was measured only with the highest dose. No cerebral lesions and a clear protection against renal damage were detected in lacidipine-treated animals. In conclusion, these findings reinforce the concept that the beneficial effects of calcium antagonists are not simply restricted to a reduction in blood pressure.

Topics: Animals; Calcium Channel Blockers; Desoxycorticosterone; Dihydropyridines; Hypertension; Kidney; Proteinuria; Rats; Rats, Inbred Strains

We investigated the effect on cardiac hypertrophy of a once-daily treatment with lacidipine, at doses that do not reduce systolic blood pressure. Spontaneously hypertensive stroke-prone rats (SHR-SP) were fed a 1% NaCl enriched diet and treated daily by gastric gavage with lacidipine at doses of 0.3, 1, or 3 mg/kg/die or vehicle. At 15 weeks of age the rats were sacrificed. The heart was removed, weighed and processed for transmission electron microscopy, scanning electron microscopy and ultrastructural morphometry. Though the treatment did not reduce systolic blood pressure, heart weight and heart weight/body weight ratio were lower in the lacidipine-treated rats than in those treated with vehicle alone. Medial and subendothelial lesions were visible in coronaries of vehicle-treated SHR-SP but not in animals treated with lacidipine. In the cardiocytes of the lacidipine-treated rats, the myofibrils had a more regular arrangement and the intercalated discs did not show the irregular course and infoldings seen in the vehicle-treated rats. Morphometry showed a significantly higher density of mitochondria in the cardiocytes of lacidipine-treated SHR-SP. Scanning electron microscopy identified a decrease in the width of cardiocytes and in the number and length of lateral branches following lacidipine-treatment. The cardio-protective action of this calcium-antagonist at doses that do not reduce systolic blood pressure is attributable both to its vascular activity and to improvement in cytoplasmic organization of cardiocytes.

Topics: Animals; Calcium Channel Blockers; Cardiomegaly; Cerebrovascular Disorders; Coronary Vessels; Dihydropyridines; Disease Models, Animal; Hypertension; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Myocardium; Rats; Rats, Inbred SHR

To evaluate the effects of antihypertensive therapy with lacidipine on the increase in radial artery compliance observed in mild essential hypertensive patients.. The study was performed in eight mild to moderate essential hypertensive patients in whom clinic blood pressure, radial artery diameter and radial artery compliance were evaluated before and after 3 months' administration of lacidipine, at a single daily dose of 4 mg. Radial artery diameter and compliance were evaluated by means of a high precision echo-tracking device able to assess arterial compliance over the blood pressure oscillations that characterize the cardiac cycle.. Lacidipine treatment caused a significant reduction in clinic systolic and diastolic blood pressure, while the heart rate was not modified by the drug. Radial artery diameter and compliance were both reduced by lacidipine over the entire systolodiastolic blood pressure range.. Chronic administration of lacidipine seems to reverse the increase in compliance observed in essential hypertension at the radial artery level. We suggest that lacidipine treatment can reverse an increase in the smooth muscle component in the arterial wall induced by hypertension.

Topics: Adult; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged; Radial Artery; Vascular Resistance

To examine the molecular basis for the unique pharmacokinetics of lacidipine by defining interactions between lacidipine and biological membranes, which may explain the long clinical half-life of this calcium channel antagonist.. Radiotracer analysis was used to determine the membrane partition coefficient and washout kinetics of lacidipine with membranes of different composition. Small-angle X-ray diffraction with angstrom resolution was used to determine the location of lacidipine in membranes.. Lacidipine had a high membrane partition coefficient, which decreased as cholesterol in the membrane increased, and a slow rate of membrane washout. The drug was found deep within the membrane's hydrocarbon core, which was consistent with the other membrane drug parameters.. Lacidipine's location and interaction within membranes may provide a longer duration of therapeutic action and can explain the unique pharmacokinetics of this drug.

Topics: Animals; Calcium Channel Blockers; Calcium Channels; Cattle; Cell Division; Cell Membrane; Cholesterol; Dihydropyridines; Half-Life; Humans; Hypertension; In Vitro Techniques; Lipid Bilayers; Membrane Lipids; Radioligand Assay; X-Ray Diffraction

Lacidipine is a long-lasting 1,4-dihydropyridine calcium antagonist that has been reported to protect salt-loaded Dahl-S rats from vascular damage and accelerated mortality when it is administered prophylactically at 0.1 and 0.3 mg/kg p.o. once a day (equivalent to the recommended dose in humans). The aim of this study was to investigate the vasoprotective properties of lacidipine in Dahl-S rats that had already developed sustained hypertension after 4 weeks of a salt-rich diet. Although none of the dosages of lacidipine (0.3, 1, and 3 mg/kg) reduced the elevated values of blood pressure, an almost complete protection from mortality was obtained. Moreover, lacidipine dose-dependently inhibited the development of macroscopic and microscopic alterations in the distal branches of mesenteric arteries and in the brain. A clear regression of vascular damage and cardiac hypertrophy was observed at the highest dose tested (3 mg/kg). These findings further support the assumption that the protective properties of lacidipine are not restricted to a reduction in blood pressure.

Topics: Animals; Blood Pressure; Body Weight; Calcium Channel Blockers; Dihydropyridines; Heart; Heart Rate; Hypertension; Male; Organ Size; Rats; Rats, Inbred Strains; Retinal Diseases; Vascular Diseases

Topics: Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension

The effects of nifedipine SR and lacidipine on blood pressure, left ventricular (LV) hypertrophy, and diastolic function were evaluated in 15 male patients (mean age of 45 +/- 8 years) with mild-to-moderate hypertension. Clinical evaluation and complete echocardiography were performed at baseline (after 15 days of washout). Seven patients received nifedipine SR (20-40 mg twice daily) and eight lacidipine (4-6 mg once daily). Clinical evaluation and complete echocardiography studies were repeated after 1 and 6 months of active treatment. In addition, full echocardiographic evaluations were carried out in 10 normotensive subjects (for comparison). Results were similar with either drug. After 1 month of therapy, systolic and diastolic blood pressures were significantly decreased (p less than 0.05); after 6 months of therapy, further changes were observed, confirming their significance. Analysis of our data suggests that (a) mild essential hypertension induces early modifications of LV geometry with consequent LV diastolic function characterized by a prolonged and incomplete diastolic filling; thus, LV wall thickness may be increased with a simultaneous reduction in LV end-diastolic short-axis diameter and volume; and (b) antihypertensive treatment with calcium antagonists such as nifedipine SR and lacidipine leads to early normalization of LV geometry and diastolic function without a significant change in total LV mass.

Topics: Adult; Blood Pressure; Calcium Channel Blockers; Delayed-Action Preparations; Dihydropyridines; Heart Rate; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Models, Cardiovascular; Nifedipine; Ultrasonography; Ventricular Function, Left

The effect of lacidipine, a dihydropyridine calcium antagonist on lipid metabolism, has been followed in 8 patients with uncomplicated mild to moderate essential hypertension treated for up to 14 months. There were significant reductions in the systolic and diastolic pressures, from 167/102 to 146/91 mm Hg at 2 months, and to 137/85 mm Hg at the end of the study. Blood lipid concentrations did not change during the observation period (cholesterol 5.1 vs 5.3 mmol.l-1, triglycerides 1.1 vs 1.0 mmol.l-1, HDL-cholesterol 1.1 vs 1.2 mmol.l-1). The results show that lacidipine did not affect lipid metabolism and suggest that calcium antagonists may be safely prescribed for a prolonged period to patients with combined hypertension and hyperlipidaemia.

Topics: Adult; Antihypertensive Agents; Calcium Channel Blockers; Delayed-Action Preparations; Dihydropyridines; Female; Follow-Up Studies; Humans; Hypertension; Lipids; Male; Middle Aged

To determine whether it is possible to assess baroreceptor sensitivity by measuring changes in blood velocity in the carotid artery and changes in the heart rate, we performed a series of 108 experiments in 19 hypertensives aged 20-57 years (mean 46.6 +/- 8.6). In each experiment, we took simultaneous measurements of carotid artery blood flow velocity (Doppler technique), the brachial intra-arterial blood pressure and the heart rate, during a rapid and transient increase in blood pressure induced by injections of phenylephrine. We then calculated the maximum slope of the regression lines correlating blood velocity with the heart period (Trieste method) and blood pressure with the heart period (Oxford method). We obtained good accuracy from the Trieste method compared with the Oxford method, as assessed by the mean of the sum of the squares (difference + 5%, NS). After the administration of 4 mg oral lacidipine to 13 essential hypertensives, aged 37-54 years (47.6 +/- 5.3), baroreflex sensitivity was not changed, as assessed by either method (Oxford method 10.1 +/- 5.5 versus 9.8 +/- 6.2 ms/mmHg; Trieste method - 0.57 +/- 0.32 versus - 0.49 +/- 0.31 ms/Hz). The coefficients of variation for the two methods, calculated for the measurements taken before and after the administration of lacidipine, were not statistically different (Oxford method 25.0 +/- 18.4 versus 36.2 +/- 16.0; Trieste method 36.7 +/- 19.2 versus 39.7 +/- 19.2). The new non-invasive Trieste method thus showed the same accuracy and precision as the invasive Oxford method in measuring baroreflex sensitivity and can be used in pharmacological studies.

Topics: Antihypertensive Agents; Blood Flow Velocity; Carotid Arteries; Dihydropyridines; Heart Rate; Humans; Hypertension; Middle Aged; Phenylephrine; Pressoreceptors; Reflex; Reproducibility of Results; Ultrasonography