enalapril and Cardiovascular-Diseases

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiovascular Diseases; Drug Combinations; Enalapril; Enzyme Inhibitors; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Neprilysin; Ramipril; Severity of Illness Index; Stroke Volume; Valsartan; Ventricular Dysfunction, Left

The Angiotensin Converting Enzyme (ACE) inhibitor class of drugs has been in clinical use since the 1970s for the management of all grades of heart failure, hypertension, diabetic nephropathy and prophylaxis of cardiovascular events. Because of the advantages associated with transdermal delivery compared with oral delivery many researchers have investigated the skin as a portal for administration of ACE inhibitors. This review summarises the various studies reported in the literature describing the development and evaluation of transdermal formulations of ACE inhibitors. Captopril, enalapril maleate, lisinopril dihydrate, perindopril erbumine and trandolapril are the most studied in connection with transdermal preparations. The methodologies reported are considered critically and the limitations of the various skin models used are also highlighted. Finally, opportunities for novel transdermal preparations of ACE inhibitor drugs are discussed with an emphasis on rational formulation design.

Topics: Administration, Cutaneous; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiovascular Diseases; Diabetic Nephropathies; Enalapril; Heart Failure; Humans; Hypertension; Indoles; Lisinopril; Perindopril; Skin

Blood pressure (BP) is monitored and managed to prevent cardiovascular complications of hypertension, but BP variability (BPV) has not been sufficiently studied. This analysis assessed whether patients receiving amlodipine vs other antihypertensive agents had lower BPV after ≥12 weeks of treatment. Studies were included if individual subject data were available, had ≥1 active comparator, and treatment duration was ≥12 weeks. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) of systolic BP across visits from 12 weeks. Individual trial and meta-analyses were performed for SD- and CV-based methodology. Five studies (47,558 BPV-evaluable patients) were included. Patient characteristics were largely consistent across the studies, but BP measurements varied from ∼4 months to ∼6 years. BPV with amlodipine was significantly (P < .0001) lower vs atenolol and lisinopril; significantly (P < .0001) lower than enalapril in one study and numerically, but not significantly lower in another; and similar to chlorthalidone and losartan. Meta-analysis revealed a treatment difference (standard error) for amlodipine vs all active comparators of -1.23 (0.46; P = .008) mm Hg using SD and -0.86 (0.31; P = .005) using CV. These findings suggest that amlodipine is effective for minimizing BPV. Future studies need to confirm a causal link between BPV and cerebrovascular/cardiovascular outcomes.

Topics: Amlodipine; Antihypertensive Agents; Atenolol; Blood Pressure; Cardiovascular Diseases; Chlorthalidone; Enalapril; Humans; Hypertension; Lisinopril; Losartan; Randomized Controlled Trials as Topic

Angiotensin II and other components of the renin-angiotensin-aldosterone system (RAAS) have a central role in the pathogenesis and progression of diabetic renal disease. A study in patients with type 1 diabetes and overt nephropathy found that RAAS inhibition with angiotensin-converting-enzyme (ACE) inhibitors was associated with a reduced risk of progression to end-stage renal disease and mortality compared with non-RAAS-inhibiting drugs. Blood-pressure control was similar between groups and proteinuria reduction was responsible for a large part of the renoprotective and cardioprotective effect. ACE inhibitors can also prevent microalbuminuria in patients with type 2 diabetes who are hypertensive and normoalbuminuric; in addition, ACE inhibitors are cardioprotective even in the early stages of diabetic renal disease. Angiotensin-II-receptor blockers (ARBs) are renoprotective (but not cardioprotective) in patients with type 2 diabetes and overt nephropathy or microalbuminuria. Studies have evaluated the renoprotective effect of other RAAS inhibitors, such as aldosterone antagonists and renin inhibitors, administered either alone or in combination with ACE inhibitors or ARBs. An important task for the future will be identifying which combination of agents achieves the best renoprotection (and cardioprotection) at the lowest cost. Such findings will have major implications, particularly in settings where money and facilities are limited and in settings where renal replacement therapy is not available and the prevention of kidney failure is life saving.

Topics: Albuminuria; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Nephropathies; Disease Progression; Enalapril; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Nisoldipine; Predictive Value of Tests; Renin-Angiotensin System

Eprosartan is an angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) used in the treatment of hypertension. In large, randomized trials, eprosartan (with or without hydrochlorothiazide [HCTZ]) demonstrated superior antihypertensive efficacy to that of placebo and, when administered at comparable dosage regimens, had similar blood pressure-lowering effects to enalapril. Eprosartan was generally well tolerated in clinical trials and had a lower incidence of persistent dry cough than enalapril. Eprosartan has a neutral effect on metabolic parameters, such as serum lipid levels and glucose homeostasis, and a low propensity for pharmacokinetic drug interactions. The use of eprosartan or other ARBs in combination with HCTZ tends to reverse the potassium loss associated with thiazide diuretics. Independent of its antihypertensive effects, eprosartan was associated with improved clinical outcomes (primary composite endpoint of all causes of mortality and all cardiovascular and cerebrovascular events, including all recurrent events) compared with nitrendipine in a randomized, secondary prevention trial in hypertensive patients with previous cerebrovascular events (MOSES trial). Eprosartan also reduced blood pressure and was associated with a modest improvement in cognitive function in a large observational study in patients > or =50 years of age with newly diagnosed hypertension (OSCAR study). In both of these trials, additional antihypertensive therapy, such as HCTZ, was permitted. Therefore, eprosartan is a useful treatment option in the management of a broad range of patients with hypertension, and its use with HCTZ provides a rational combination regimen.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Clinical Trials as Topic; Cough; Enalapril; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Incidence; Nitrendipine; Randomized Controlled Trials as Topic; Receptors, Angiotensin; Recurrence; Risk Factors; Sodium Chloride Symporter Inhibitors; Thiophenes; Treatment Outcome

Renal pathophysiology is elicited by activation of angiotensin II type 1 (AT(1)) receptors at all stages of renovascular disease. Angiotensin receptor blockers (ARBs) that specifically block the AT(1) receptor offer the potential to prevent or delay progression to end-stage renal disease independently of reductions in blood pressure. Proteinuria--an early and sensitive marker for progressive renal dysfunction--is reduced by ARB use in patients with type 2 diabetic nephropathy and microalbuminuria or macroalbuminuria. Retrospective analysis of data available from early trials has confirmed this finding and has shown that albuminuria reduction is associated with lessening of cardiovascular risk. The ARB telmisartan is equivalent to enalapril in preventing glomerular filtration rate decline, and equivalent to valsartan in reducing proteinuria. Telmisartan is more effective than conventional therapy in lowering the risk of transition to overt nephropathy in hypertensive and normotensive patients. An additive effect has been seen in smaller studies when telmisartan has been added to lisinopril therapy, and high-dose telmisartan reduces albuminuria better than low-dose telmisartan. Similar data were obtained with other ARBs such as candesartan, losartan, valsartan, or irbesartan. These data support the proposition that blockade of the renin-angiotensin system beyond that required for maximum blood pressure reduction provides optimum renal protection.

Topics: Albuminuria; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Biomarkers; Cardiovascular Diseases; Diabetic Nephropathies; Drug Therapy, Combination; Enalapril; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Telmisartan; Tetrazoles; Treatment Outcome; Valine; Valsartan

Clinical trials have shown that effective control of blood pressure reduces the risk of cardiovascular events in high-risk patients. For example, data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study show significant reductions in the incidence of cardiac events, stroke and all-cause mortality in patients in whom blood pressure control was achieved compared with those in whom blood pressure remained uncontrolled. Although the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) demonstrated no significant difference in cardiovascular mortality and morbidity between patients receiving diuretics, calcium channel blockers or angiotensin-converting enzyme (ACE) inhibitors, this finding might have been confounded by differences in the blood pressure reductions achieved with the three treatments. Other studies have consistently shown that newer antihypertensive agents, such as ACE inhibitors and calcium channel blockers, reduce cardiovascular events to a similar, or possibly greater, extent as older therapies, such as diuretics and beta-blockers. In particular, ACE inhibitors appear to offer additional benefits beyond blood pressure reduction in terms of reducing cardiovascular events and producing renoprotective effects. Angiotensin II receptor blockers (ARBs) have been less extensively studied, but there is evidence already that they have heart failure, stroke and renoprotective benefits. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) is currently comparing the effects of the ARB telmisartan 80 mg and the ACE inhibitor ramipril 10 mg, alone and in combination, on cardiovascular events in high-risk patients.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Enalapril; Humans; Hypertension; Randomized Controlled Trials as Topic; Telmisartan

Therapeutic activation of the vascular NO/cGMP pathway is induced by a variety of stimuli/mediators including physical activity, supplementation with the precursor L-arginine and organic nitrates which generate NO in the vasculature. The necessity of an enzymatic reduction for NO generation from these drugs as well as differences in the activity of the NO/cGMP pathway within the vascular tree determine the unique hemodynamic changes elicited by organic nitrates. These changes include preferential venodilation, vessel-size specific arterial dilation and improvement of the aortic distensibility and Windkessel-function. Some animal experiments and clinical investigations suggest that nitrates may also be endowed with cardioprotective and/or vasoprotective effects. "Early entry" therapy with nitrates do not significantly improve survival in myocardial infarction but increases the beneficial effects of the ACE-inhibitor enalapril by 50%. Furthermore, nitrates have been shown to improve survival in heart failure, but prognostic effects in stable angina pectoris are unknown. Short-term experimental and clinical investigations suggest that nitrate tolerance induced by nitroglycerin is associated with toxic effects in the vasculature, but this is not true for pentaerythrityl tetranitrate and isosorbide mononitrate. The observed endothelial dysfunction induced by a continuous treatment with nitroglycerin may be an additional risk for patients who receive continuous nitroglycerin to treat conditions such as unstable angina and acute heart failure. In general, nitrates are remarkably safe drugs and are well tolerated. Appropriate clinical trials are needed to answer the question whether nitrates can do more than symptomatic relief in cardiovascular disease.

Topics: Angina, Unstable; Animals; Cardiovascular Diseases; Cyclic GMP; Enalapril; Endothelium, Vascular; Hemodynamics; Humans; Myocardial Infarction; Nitrates; Nitric Oxide; Nitroglycerin; Platelet Aggregation

The beta-adrenergic receptor blockers play an important role in the management of cardiovascular disease, including hypertension and chronic heart failure. However, concerns regarding safety and tolerability with currently available agents can limit their use. The beta-blockers vary with regard to several pharmacologic properties, including beta1/beta2 selectivity, intrinsic sympathomimetic activity, and, with the newest beta-blockers, vasodilation. These pharmacologic differences may result in clinically important differences in tolerability and hemodynamic properties. Nebivolol is a novel beta-blocker with both a greater degree of selectivity for beta1-adrenergic receptors than other agents in this class and an ability to stimulate endothelial nitric oxide production, leading to vasodilation and other potential clinical effects. Published randomized, controlled, multicenter studies with nebivolol have shown that once-daily treatment significantly reduces systolic and diastolic blood pressure in patients with mild-to-moderate hypertension, compared with placebo, in a dose-dependent manner, and is well tolerated, with an adverse event profile similar to that of placebo. When compared with other beta-blockers as well as with other antihypertensive classes of agents in head-to-head trials, nebivolol demonstrated similar antihypertensive efficacy and a lower incidence of adverse events. Nebivolol has also been shown to significantly reduce morbidity and mortality in a large population of elderly patients with chronic heart failure, independent of left ventricular ejection fraction. Nebivolol is currently available in Europe for the management of hypertension and is expected to be available soon in the United States.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Antihypertensive Agents; Atenolol; Benzopyrans; Cardiovascular Diseases; Clinical Trials as Topic; Enalapril; Ethanolamines; Female; Heart Failure; Hemodynamics; Humans; Hypertension; Labetalol; Losartan; Male; Metoprolol; Middle Aged; Nebivolol; Nifedipine; Receptors, Adrenergic, beta-1; Receptors, Adrenergic, beta-2; Sympathomimetics

Angiotensin-converting enzyme (ACE) inhibitors are widely used for the treatment of cardiovascular disease since they improve blood pressure control in patients with hypertension and prolong survival in patients with acute myocardial infarction, asymptomatic left ventricular dysfunction and congestive heart failure. Most of the information about the therapeutic role of ACE-inhibitors has been achieved during the last 20 years since the publication of some pivotal trials mostly involving the use of ACE-inhibitors like captopril and enalapril. In particular the treatment with enalapril has considerably improved the clinical outcome of patients with either mild-to-moderate (SOLVD studies) or severe (CONSENSUS trial) congestive heart failure. The benefit of ACE-inhibitors in patients with congestive heart failure has also involved a remarkable reduction in the rate of hospitalization, thus contributing to improve the pharmaco-economic approach to the disease. Most of the beneficial effect of ACE-inhibitors in clinical practice is dependent on their capacity of inhibiting the renin-angiotensin system, although some recent trials have supported a primary role for such drugs (in particular enalapril) in the prevention of atrial fibrillation. After more than 25 years from their discovery, ACE-inhibitors must be again considered among the first-line treatment in many patients with cardiovascular disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Captopril; Cardiovascular Diseases; Enalapril; Heart Failure; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia; Renin-Angiotensin System; Ventricular Dysfunction

When first introduced in 1981, angiotensin-converting enzyme (ACE) inhibitors were indicated only for treatment of refractory hypertension. Since then, they have been shown to reduce morbidity or mortality in congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease. Pathologies underlying these conditions are, in part, attributable to the renin-angiotensin-aldosterone system. Angiotensin II contributes to endothelial dysfunction. altered renal hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate these effects. Clinical outcomes of ACE inhibition include decreases in myocardial infarction (fatal and nonfatal), reinfarction, angina, stroke, end-stage renal disease, and morbidity and mortality associated with heart failure. ACE inhibitors are generally well tolerated and have few contraindications. (Am Fam Physician 2002;66:473.)

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Captopril; Cardiovascular Diseases; Clinical Trials as Topic; Contraindications; Diabetic Nephropathies; Drug Costs; Enalapril; Fosinopril; Heart Failure; Humans; Hypertension; Indoles; Isoquinolines; Lisinopril; Meta-Analysis as Topic; Myocardial Infarction; Perindopril; Quinapril; Ramipril; Renin-Angiotensin System; Risk; Tetrahydroisoquinolines; United States

In the paper general remarks concerning ACE-inhibitors (especially enalapril) use in children have been described. Kidney artery stenosis, hypovolemia, and shock are only ones contraindications to this treatment in a childhood, even in the first period after birth. Anyhow, it was stressed on the basis of literature that at a beginning of extrauterine life the kinetics of these drugs is changed, thus they should be recommended carefully and in low doses. It was stressed, as well, that up to now appeared only a few papers concerning ACE-inhibitors use a childhood. It is suggested that enalapril can be used as an rather safety drug in pediatric patients suffering from circulatory insufficiency or arterial hypertension.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Child; Contraindications; Drug Administration Schedule; Enalapril; Humans; Infant; Infant, Newborn; Shock

Hypertension is a major health problem for patients over 65 years of age. Control of elevated blood pressure reduces cardiovascular morbidity and mortality rates among older hypertensive patients. Increased total peripheral vascular resistance is the primary hemodynamic abnormality in these patients. Initially, diuretics were used alone to lower total peripheral vascular resistance, and thus blood pressure, in older patients. The antihypertensive efficacy of angiotensin-converting enzyme inhibitors has been questioned in this age group, in which low-renin hypertension is common. The latter condition might be thought to favor blood pressure control with diuretics and impair the response to angiotensin-converting enzyme inhibitor therapy. However, recent studies with lisinopril, a new long-acting, nonsulfhydryl angiotensin-converting enzyme inhibitor, indicate that reductions in systolic and diastolic blood pressure in older hypertensive patients receiving either angiotensin-converting enzyme inhibitor or hydrochlorothiazide monotherapy were not significantly different. These data demonstrate that angiotensin-converting enzyme inhibitor monotherapy can effectively lower blood pressure in older hypertensive patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black or African American; Cardiovascular Diseases; Enalapril; Hemodynamics; Humans; Hypertension; Lisinopril; Renin-Angiotensin System; Time Factors; Vascular Resistance

Lisinopril is an orally active, nonsulfhydryl angiotensin-converting-enzyme (ACE) inhibitor that is not metabolized or bound to protein. Peak serum concentrations occur 6-8 h after oral dosing. Lisinopril bioavailability (approximately 25%) is not significantly affected by food, age, or coadministration of hydrochlorothiazide (HCTZ), propranolol, digoxin, and glibenclamide. Lisinopril is excreted unchanged in the urine. Steady state is achieved in 2-3 days with little accumulation. Significant accumulation occurs in patients with severe renal impairment (creatinine clearance less than or equal to 30 ml/min). Lisinopril inhibits ACE activity, thereby reducing plasma angiotensin II and aldosterone and increasing plasma renin activity. Lisinopril produces a smooth, gradual blood pressure (BP) reduction in hypertensive patients without affecting heart rate or cardiovascular reflexes. The antihypertensive effect begins within 2 h, peaks around 6 h, and lasts for at least 24 h. Lisinopril produces greater systolic and diastolic BP reductions than HCTZ. Lisinopril is similar to atenolol and metoprolol in reducing diastolic BP, but superior in systolic BP reduction. Lisinopril and nifedipine produce comparable reductions in systolic and diastolic BP. When lisinopril is given once daily as monotherapy, the range of BP reductions is 11-15% in systolic and 13-17% in diastolic. HCTZ addition enhances its antihypertensive effect. Lisinopril does not produce hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia. Lisinopril has natriuretic properties; renal blood flow remains stable or increases. Lisinopril increases cardiac output, and decreases pulmonary capillary wedge pressure and mean arterial pressure in patients with congestive heart failure refractory to conventional treatment with digitalis and diuretics. Human experience to date (2,800 patients/subjects) indicates that lisinopril is well tolerated and has a good safety profile.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Drug Interactions; Enalapril; Humans; Lisinopril

The development of angiotensin-converting enzyme (ACE) inhibitors is of landmark importance in the understanding and treatment of cardiovascular disorders, particularly hypertension and congestive heart failure. Enalapril has recently joined captopril as an approved, orally active ACE inhibitor. Like captopril, it has been effective in the treatment of hypertension and congestive heart failure, with minimal adverse reactions noted. Differences in pharmacology exist between enalapril and captopril which may prove to be of clinical significance.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Enalapril; Humans

A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease.. The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40-75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle-eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome-occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)-was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985.. Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study-3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5-92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55-0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49-0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51-1·12; p. Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs.. Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.

Topics: Adult; Aged; Anticholesteremic Agents; Antihypertensive Agents; Aspirin; Atorvastatin; Blood Pressure; Cardiovascular Agents; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus; Drug Combinations; Enalapril; Female; Humans; Hydrochlorothiazide; Male; Medication Adherence; Middle Aged; Platelet Aggregation Inhibitors; Secondary Prevention; Valsartan

The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial.. Etiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy.. We examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite of cardiovascular death or HF hospitalization, and components, and death from any cause. Outcomes were adjusted for known prognostic variables including N terminal pro-B type natriuretic peptide.. Among the 8,399 patients randomized, 5,036 patients (60.0%) had an ischemic etiology. Among the 3,363 patients (40.0%) with a nonischemic etiology, 1,595 (19.0% of all patients; 47% of nonischemic patients) had idiopathic dilated cardiomyopathy, 968 (11.5% of all patients; 28.8% of nonischemic patients) had a hypertensive cause, and 800 (9.5% of all patients, 23.8% of nonischemic patients) another cause (185 infective/viral, 158 alcoholic, 110 valvular, 66 diabetes, 30 drug-related, 14 peripartum-related, and 237 other). Whereas the unadjusted rates of all outcomes were highest in patients with an ischemic etiology, the adjusted hazard ratios (HRs) were not different from patients in the 2 major nonischemic etiology categories; for example, for the primary outcome, compared with ischemic (HR: 1.00), hypertensive 0.87 (95% confidence interval [CI]: 0.75 to 1.02), idiopathic 0.92 (95% CI: 0.82 to 1.04) and other 1.00 (95% CI: 0.85 to 1.17). The benefit of sacubitril/valsartan over enalapril was consistent across etiologic categories (interaction for primary outcome; p = 0.11).. Just under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies. Adjusted outcomes were similar across etiologic categories, as was the benefit of sacubitril/valsartan over enalapril. (Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure; NCT01035255).

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiomyopathy, Alcoholic; Cardiomyopathy, Dilated; Cardiotoxicity; Cardiovascular Diseases; Cause of Death; Dangerous Behavior; Diabetic Cardiomyopathies; Drug Combinations; Enalapril; Female; Heart Failure; Heart Valve Diseases; Hospitalization; Humans; Hypertension; Infections; Male; Middle Aged; Mortality; Myocardial Ischemia; Peripartum Period; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan; Virus Diseases

Plasminogen activator inhibitor-1 (PAI-1) is implicated in the pathophysiology of cardiovascular disease (CVD) and increased in individuals with type 2 diabetes mellitus (T2DM). Adipose tissue produces PAI-1, and pericardial fat is a CVD risk factor. We sought to determine the relationship between PAI-1 and pericardial fat in males and females with well-controlled T2DM.. The study population consisted of 32 males and 19 females, aged 35-70 years with T2DM, without clinical evidence of CVD or other active medical problems except for hypertension. Subjects were studied under good cardiometabolic control. Study procedures included fasting blood work and cardiovascular imaging. Cardiac magnetic resonance imaging of the heart was used to identify and quantify pericardial fat from the bifurcation of the pulmonary trunk to the last slice containing cardiac tissue.. PAI-1 was positively correlated with pericardial fat (β = 0.72, r = 0.72, P < 0.001) as well as with homeostatic model assessment of insulin resistance (r = 0.31, P = 0.03) and serum triglycerides (r = 0.27, P = 0.05). In a multivariable regression model, controlling for insulin sensitivity, triglycerides, and body mass index, pericardial fat was independently associated with PAI-1 (β = 0.80, P < 0.001).. PAI-1 is positively associated with pericardial fat in individuals with T2DM.

Topics: Adipose Tissue; Adiposity; Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Enalapril; Female; Humans; Male; Middle Aged; Pericardium; Plasminogen Activator Inhibitor 1; Risk Factors; Simvastatin

This study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability.. Despite the benefit of sacubitril/valsartan therapy shown in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, it has been suggested that switching from an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker should be delayed until occurrence of clinical decompensation.. Outcomes were compared among patients who had prior hospitalization within 3 months of screening (n = 1,611 [19%]), between 3 and 6 months (n = 1,009 [12%]), between 6 and 12 months (n = 886 [11%]), >12 months (n = 1,746 [21%]), or who had never been hospitalized (n = 3,125 [37%]).. Twenty percent of patients without prior HF hospitalization experienced a primary endpoint of cardiovascular death or heart failure (HF) hospitalization during the course of the trial. Despite the increased risk associated with more recent hospitalization, the efficacy of sacubitril/valsartan therapy did not differ from that of enalapril according to the occurrence of or time from hospitalization for HF before screening, with respect to the primary endpoint or with respect to cardiovascular or all-cause mortality.. Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiovascular Diseases; Case-Control Studies; Disease Progression; Double-Blind Method; Drug Combinations; Drug Substitution; Enalapril; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Neprilysin; Tetrazoles; Treatment Outcome; Valsartan

Cardiovascular autonomic neuropathy (CAN) and abnormal circadian blood pressure (BP) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN, non-dipping of nocturnal BP and coronary artery disease have been demonstrated. We aimed to test if bedtime dosing (BD) versus morning dosing (MD) of the ACE inhibitor enalapril would affect the 24-hour BP profile in patients with type 1 diabetes (T1D), CAN and non-dipping.. Secondary healthcare unit in Copenhagen, Denmark.. 24 normoalbuminuric patients with T1D with CAN and non-dipping were included, consisting of mixed gender and Caucasian origin. Mean±SD age, glycosylated haemoglobin and diabetes duration were 60±7 years, 7.9±0.7% (62±7 mmol/mol) and 36±11 years.. In this randomised, placebo-controlled, double-blind cross-over study, the patients were treated for 12 weeks with either MD (20 mg enalapril in the morning and placebo at bedtime) or BD (placebo in the morning and 20 mg enalapril at bedtime), followed by 12 weeks of switched treatment regimen.. Primary outcome was altered dipping of nocturnal BP. Secondary outcomes included a measurable effect on other cardiovascular risk factors than BP, including left ventricular function (LVF).. Systolic BP dipping increased 2.4% (0.03-4.9%; p=0.048) with BD compared to MD of enalapril. There was no increase in mean arterial pressure dipping (2.2% (-0.1% to 4.5%; p=0.07)). No difference was found on measures of LVF (p≥0.15). No adverse events were registered during the study.. We demonstrated that patients with T1D with CAN and non-dipping can be treated with an ACE inhibitor at night as BD as opposed to MD increased BP dipping, thereby diminishing the abnormal BP profile. The potentially beneficial effect on long-term cardiovascular risk remains to be determined.. EudraCT2012-002136-90; Post-results.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Autonomic Nervous System; Autonomic Nervous System Diseases; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Administration Schedule; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Risk Factors

The complexity of treatment regimens, costs and pill burden decrease the medication adherence and contribute to shortfall in cardiovascular preventive drug coverage. The polypill, a fixed dose combination pill of established drugs, is expected to increase adherence and reduce the costs whilst preventing major cardiovascular events (MCVE).. The PolyIran trial is a pragmatic cluster randomized trial nested within the Golestan Cohort Study (GCS). Subjects were randomized to either non-pharmacological preventive interventions alone (minimal care arm) or together with a polypill (polypill arm) comprising hydrochlorothiazide, aspirin, atorvastatin and either enalapril or valsartan. This study benefits from the infrastructure of the primary health care system in Iran and the interventions are delivered by the local auxiliary health workers (Behvarz) to the participants. The primary outcome of the study is the occurrence of first MCVE within five years defined as non-fatal and fatal myocardial infarction, unstable angina, sudden death, heart failure, coronary artery revascularization procedures, and non-fatal and fatal stroke.. From February 2011 to April 2013, 8410 individuals (236 clusters) attended the eligibility assessment. Of those, 3421 in the polypill arm and 3417 in the minimal care arm were eligible. The study is ongoing.. The infrastructure of GCS and the primary health care system in Iran enabled the conduct of this pragmatic large-scale trial. If the polypill strategy proves effective, it may be implemented to prevent cardiovascular disease in developing countries.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Aspirin; Atorvastatin; Cardiovascular Agents; Cardiovascular Diseases; Clinical Protocols; Drug Combinations; Enalapril; Female; Humans; Hydrochlorothiazide; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Iran; Male; Middle Aged; Polypharmacy; Primary Prevention; Research Design; Secondary Prevention; Sodium Chloride Symporter Inhibitors; Time Factors; Treatment Outcome; Valsartan

The PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) found a combination drug containing sacubitril (a neprilysin inhibitor) and valsartan (an angiotensin II receptor blocker) superior to enalapril (an angiotensin-converting enzyme inhibitor) in patients with systolic heart failure. Recently approved by the US Food and Drug Administration, sacubitril-valsartan is the first new drug in over a decade to decrease death rates in patients with systolic heart failure.

Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiovascular Diseases; Cough; Double-Blind Method; Drug Combinations; Enalapril; Female; Heart Failure, Systolic; Hospitalization; Humans; Hyperkalemia; Hypotension; Male; Middle Aged; Neprilysin; Renal Insufficiency; Tetrazoles; Valsartan

There is considerable interest in pharmacogenetic and molecular biomarkers. Our aim was to evaluate the effects of enalapril/lercanidipine combination on some emerging biomarkers for cardiovascular risk stratification of hypertensive patients, such as lipoprotein(a) [Lp(a)], soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L) and serum myeloperoxidase (MPO).. Three hundred and forty-five patients were enrolled in this randomized, double-blind, clinical trial: 120 hypertensive patients were randomized to enalapril 20 mg, 110 to lercanidipine 10 mg and 115 to enalapril/lercanidipine 20/10 mg fixed combination. We measures the following markers at baseline and after 6, 12, 18 and 24 months: blood pressure, fasting plasma glucose (FPG), lipid profile, Lp(a), sRAGE, sCD40L and MPO.. There was a decrease in blood pressure in all groups compared with baseline, even if, as expected, enalapril/lercanidipine combination was more effective in reducing blood pressure compared with the monotherapies. No variations in lipid profile or FPG were recorded in any of the groups. Lercanidipine, but not enalapril, improved Lp(a) levels compared with baseline. The combination enalapril/lercanidipine improved it more than the single therapies. All treatments increased sRAGE levels, and decreased sCD40L and MPO, with a better effect seen with the enalapril/lercanidipine combination compared with single monotherapies.. The combination enalapril/lercanidipine seems to be better than the single monotherapies in reducing not only blood pressure, but also the levels of some emerging biomarkers, potentially useful for cardiovascular risk stratification of hypertensive patients.

Topics: Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; CD40 Ligand; Dihydropyridines; Double-Blind Method; Drug Combinations; Enalapril; Female; Humans; Hypertension; Lipids; Male; Middle Aged; Peroxidase; Risk Factors

Some studies suggest that the sympathetic nervous system and the renin-angiotensin system are activated in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in negative cardiopulmonary and muscular effects. The aim of this pilot study was to evaluate the efficacy of an angiotensin converting enzyme (ACE) inhibitor on cardiopulmonary exercise performance in COPD patients. Primary outcome was the effect of treatment on the ventilatory response to exercise (VE/VCO(2) slope). Secondary outcomes were exercise variables evaluated by the cardiopulmonary exercise test, and pulmonary function according to ACE genotyping.. 4 weeks treatment with enalapril (10 mg od) or placebo was evaluated in 21 COPD patients (FEV(1) < 60%) and without cardiovascular disease in a double-blind, cross-over study.. 18 patients completed the study. Enalapril did not exert a significant effect on exercise VE/VCO(2) slope or on peak O(2) consumption. However enalapril significantly improved peak O(2) pulse and work rate compared to placebo. A mild but significant worsening of the diffusion capacity of the lung was observed. ACE genotype did not significantly affect patients' response to treatment, except for a trend toward a more evident effect of treatment in patients with II ACE genotype in terms of O(2) pulse and gas diffusion.. In this pilot study, ACE inhibition did not affect the ventilatory response to exercise in COPD patients. However, treatment resulted in improvement in work rate and O(2) pulse, suggesting that ACE inhibitor therapy warrants consideration and may provide beneficial effect on the cardiovascular response to exercise in COPD.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiovascular Diseases; Cross-Over Studies; Double-Blind Method; Enalapril; Exercise Test; Female; Genotype; Humans; Male; Middle Aged; Oxygen Consumption; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

Our objective was to investigate the effects and tolerability of fixed-dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels.. This was a double-blind randomised placebo-controlled trial in residents of Kalaleh, Golestan, Iran. Following an 8-week placebo run-in period, 475 participants, aged 50 to 79 years, without cardiovascular disease, hypertension or hyperlipidaemia were randomised to fixed-dose combination therapy with aspirin 81 mg, enalapril 2.5 mg, atorvastatin 20 mg and hydrochlorothiazide 12.5 mg (polypill) or placebo for a period of 12 months. The primary outcomes were changes in LDL-cholesterol, systolic and diastolic blood pressure and adverse reactions. Analysis was by intention-to-treat basis.. At baseline, there were differences in systolic blood pressure (6 mmHg). Taking account of baseline differences, at 12 months, polypill was associated with statistically significant reductions in blood pressure (4.5/1.6 mmHg) and LDL-cholesterol (0.46 mmol/l). The study drug was well tolerated, but resulted in the modest reductions in blood pressure and lipid levels.. The effects of the polypill on blood pressure and lipid levels were less than anticipated, raising questions about the reliability of the reported compliance. There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease.

Topics: Aged; Anticholesteremic Agents; Antihypertensive Agents; Aspirin; Atorvastatin; Blood Pressure; Cardiovascular Diseases; Cholesterol, LDL; Chronic Disease; Double-Blind Method; Drug Combinations; Enalapril; Female; Heptanoic Acids; Humans; Hydrochlorothiazide; Male; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Pyrroles; Risk Factors; Tablets

Although serum phosphorus, calcium, and calcium-phosphorus product levels have been associated with cardiovascular events and mortality in patients with normal kidney function, most studies have not examined the association of these minerals with outcomes when collected repeatedly over time.. We evaluated the association of serum phosphorus, calcium, and calcium-phosphorus product levels with cardiovascular events and mortality in 950 participants of the Appropriate Blood Pressure Control in Diabetes trial by both time-dependent Cox regression models using the cumulative average of minerals measured over time and fixed covariate Cox regression models with only baseline values of these minerals.. There were 42 deaths and 193 cardiovascular events among the participants, who were followed for an average of 4.8 years following randomization. A significant association was noted between baseline serum phosphorus >3.9 mg/dL and baseline calcium-phosphorus product >36.8 mg(2)/dL(2) compared with the lowest referent category with the adjusted risk of cardiovascular death (hazard ratio [HR] 5.00; 95% confidence interval [CI], 1.70-14.72) and (HR 10.01; 95% CI, 2.55-39.31), respectively. However, in time-dependent models using mineral values repeated during the course of the study, only the average of serum phosphorus remains significant (HR 4.25; 95% CI, 1.15 to 16.65).. In the Appropriate Blood Pressure Control in Diabetes cohort, serum phosphorus, but not serum calcium or calcium-phosphorus product, was associated with cardiovascular mortality in time-dependent Cox regression models. Thus, serum phosphorus levels may be more reliable in predicting cardiovascular mortality in patients with type 2 diabetes.

Topics: Antihypertensive Agents; Calcium; Cardiovascular Diseases; Cohort Studies; Comorbidity; Diabetes Mellitus, Type 2; Enalapril; Female; Humans; Male; Middle Aged; Nisoldipine; Phosphorus; Proportional Hazards Models

This prospective, randomized trial evaluated the effect of monotherapy and different combination therapies on cardiovascular target organ damage and metabolic profile in 520 hypertensive patients. Patients were allocated to a single agent: carvedilol 25 mg, amlodipine 10 mg, enalapril 20 mg, or losartan 50 mg (groups C, A, E, and L, respectively). After 2 months (level 2), nonresponders received a low-dose thiazide diuretic, and after 4 months (level 3), amlodipine (groups E, C, and L) and carvedilol (group A). Twenty-four-hour blood pressure was significantly lowered in all treatment groups. Blood pressure control was more pronounced in patients receiving two or three drugs. At the end of the study, the carotid intima-media thickness decreased in group L (P<.01), left ventricular mass index in groups E and L (P<.05 and P<.001, respectively), with a concomitant reduction in cholesterol in group L (P<.03). Diastolic function improved significantly in group L (P<.05). This study describes the need to control blood pressure with two or more drugs in most hypertensive patients and illustrates good clinical outcomes, independent of blood pressure lowering, using combination therapy with losartan, low-dose thiazide, and amlodipine.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Carbazoles; Cardiovascular Diseases; Carvedilol; Drug Therapy, Combination; Enalapril; Humans; Hypertension; Losartan; Male; Middle Aged; Propanolamines; Ultrasonography

The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease (CAD) and normal blood pressure remains uncertain.. To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD.. Double-blind, randomized, multicenter, 24-month trial (enrollment April 1999-April 2002) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD (>20% stenosis by coronary angiography) and diastolic blood pressure <100 mm Hg. A substudy of 274 patients measured atherosclerosis progression by intravascular ultrasound (IVUS).. Patients were randomized to receive amlodipine, 10 mg; enalapril, 20 mg; or placebo. IVUS was performed at baseline and study completion.. The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo. Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo. Events included cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke or transient ischemic attack, and new diagnosis of peripheral vascular disease. The IVUS end point was change in percent atheroma volume.. Baseline blood pressure averaged 129/78 mm Hg for all patients; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups, respectively (P<.001 for both vs placebo). Cardiovascular events occurred in 151 (23.1%) placebo-treated patients, in 110 (16.6%) amlodipine-treated patients (hazard ratio [HR], 0.69; 95% CI, 0.54-0.88 [P = .003]), and in 136 (20.2%) enalapril-treated patients (HR, 0.85; 95% CI, 0.67-1.07 [P = .16]. Primary end point comparison for enalapril vs amlodipine was not significant (HR, 0.81; 95% CI, 0.63-1.04 [P = .10]). The IVUS substudy showed a trend toward less progression of atherosclerosis in the amlodipine group vs placebo (P = .12), with significantly less progression in the subgroup with systolic blood pressures greater than the mean (P = .02). Compared with baseline, IVUS showed progression in the placebo group (P<.001), a trend toward progression in the enalapril group (P = .08), and no progression in the amlodipine group (P = .31). For the amlodipine group, correlation between blood pressure reduction and progression was r = 0.19, P = .07.. Administration of amlodipine to patients with CAD and normal blood pressure resulted in reduced adverse cardiovascular events. Directionally similar, but smaller and nonsignificant, treatment effects were observed with enalapril. For amlodipine, IVUS showed evidence of slowing of atherosclerosis progression.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Coronary Artery Disease; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Ultrasonography, Interventional

Peripheral arterial disease (PAD) and diabetes are both associated with a high risk of ischemic events, but the role of intensive blood pressure control in PAD has not been established.. The Appropriate Blood Pressure Control in Diabetes study followed 950 subjects with type 2 diabetes for 5 years; 480 of the subjects were normotensive (baseline diastolic blood pressure of 80 to 89 mm Hg). Patients randomized to placebo (moderate blood pressure control) had a mean blood pressure of 137+/-0.7/81+/-0.3 mm Hg over the last 4 years of treatment. In contrast, patients randomized to intensive treatment with enalapril or nisoldipine had a mean 4-year blood pressure of 128+/-0.8/75+/-0.3 mm Hg (P<0.0001 compared with moderate control). PAD, which is defined as an ankle-brachial index <0.90 at the baseline visit, was diagnosed in 53 patients. In patients with PAD, there were 3 cardiovascular events (13.6%) on intensive treatment compared with 12 events (38.7%) on moderate treatment (P=0.046). After adjustment for multiple cardiovascular risk factors, an inverse relationship between ankle-brachial index and cardiovascular events was observed with moderate treatment (P=0.009), but not with intensive treatment (P=0.91). Thus, with intensive blood pressure control, the risk of an event was not increased, even at the lowest ankle-brachial index values, and was the same as in a patient without PAD.. In PAD patients with diabetes, intensive blood pressure lowering to a mean of 128/75 mm Hg resulted in a marked reduction in cardiovascular events.

Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Nisoldipine; Odds Ratio; Peripheral Vascular Diseases; Risk Assessment; Stroke; Treatment Outcome

Although several important studies have been performed in hypertensive type 2 diabetic patients, it is not known whether lowering blood pressure in normotensive (BP <140/90 mm Hg) patients offers any beneficial results on vascular complications. The current study evaluated the effect of intensive versus moderate diastolic blood pressure (DBP) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients.. The current study was a prospective, randomized controlled trial in normotensive type 2 diabetic subjects. The subjects were randomized to intensive (10 mm Hg below the baseline DBP) versus moderate (80 to 89 mm Hg) DBP control. Patients in the moderate therapy group were given placebo, while the patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication. The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion, progression of retinopathy and neuropathy and the incidence of cardiovascular disease.. The mean follow-up was 5.3 years. Mean BP in the intensive group was 128 +/- 0.8/75 +/- 0.3 mm Hg versus 137 +/- 0.7/81 +/- 0.3 mm Hg in the moderate group, P < 0.0001. Although no difference was demonstrated in creatinine clearance (P = 0.43), a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria (P = 0.012) and microalbuminuria to overt albuminuria (P = 0.028). The intensive BP control group also demonstrated less progression of diabetic retinopathy (P = 0.019) and a lower incidence of strokes (P = 0.03). The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent.. Over a five-year follow-up period, intensive (approximately 128/75 mm Hg) BP control in normotensive type 2 diabetic patients: (1) slowed the progression to incipient and overt diabetic nephropathy; (2) decreased the progression of diabetic retinopathy; and (3) diminished the incidence of stroke.

Topics: Adult; Aged; Albuminuria; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Disease Progression; Enalapril; Female; Humans; Male; Middle Aged; Nisoldipine; Prospective Studies; Single-Blind Method; Stroke

The Japan Multicenter Investigation of Antihypertensive Treatment for Nephropathy in Diabetics (J-MIND) study was conducted to evaluate the effect of nifedipine retard or enalapril on nephropathy in hypertensive patients with type 2 diabetes. A total of 436 patients with normoalbuminuria [urinary albumin excretion rate (AER) <30 mg/day] or microalbuminuria [AER: 30-300 mg/day] were randomized to receive nifedipine retard or enalapril and were followed for 24 months. There were no differences in baseline characteristics between the two groups (the mean AER was 45 and 42 mg/day, respectively). Intent-to-treat analysis showed no significant difference in AER after 2 years, although the mean AER increased to 64 and 74 mg/day in the nifedipine retard and enalapril groups, respectively. The AER increased in patients with normoalbuminuria, whereas it did not change in those with microalbuminuria. There were no differences between the two groups with respect to progression from normoalbuminuria to microalbuminuria, progression from microalbuminuria to overt proteinuria, and regression from microalbuminuria to normoalbuminuria. The incidence of cardiovascular events was also similar in both groups. In conclusion, nifedipine retard and enalapril had a similar effect on nephropathy in hypertensive type 2 diabetic patients without overt proteinuria.

Topics: Albuminuria; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Enalapril; Female; Glycated Hemoglobin; Humans; Hypertension; Japan; Male; Middle Aged; Nifedipine; Prospective Studies; Statistics, Nonparametric

The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective randomized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications. The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy, retinopathy, and neuropathy.. The 470 hypertensive subjects, defined as having a baseline diastolic blood pressure of > or = 90 mmHg, were randomized to intensive blood pressure control (diastolic blood pressure goal of 75 mmHg) versus moderate blood pressure control (diastolic blood pressure goal of 80-89 mmHg).. The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group. During the 5-year follow-up period, no difference was observed between intensive versus moderate blood pressure control and those randomized to nisoldipine versus enalapril with regard to the change in creatinine clearance. After the first year of antihypertensive treatment, creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria. In contrast, patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5-6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy. There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria (25% intensive therapy vs. 18% moderate therapy, P = 0.20) or microalbuminuria to overt albuminuria (16% intensive therapy vs. 23% moderate therapy, P = 0.28). Intensive therapy demonstrated a lower overall incidence of deaths, 5.5 vs. 10.7%, P = 0.037. Over a 5-year follow-up period, there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy. In addition, the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy.. Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period. The more intensive blood pressure control decreased all-cause mortality.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Nisoldipine; Placebos

It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications. Because this issue remains controversial, we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were randomly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study.. The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective, randomized, blinded trial comparing the effects of moderate control of blood pressure (target diastolic pressure, 80 to 89 mm Hg) with those of intensive control of blood pressure (diastolic pressure, 75 mm Hg) on the incidence and progression of complications of diabetes. The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes. In the current study, we analyzed data on a secondary end point (the incidence of myocardial infarction) in the subgroup of patients in the ABCD Trial who had hypertension.. Analysis of the 470 patients in the trial who had hypertension (base-line diastolic blood pressure, > or = 90 mm Hg) showed similar control of blood pressure, blood glucose and lipid concentrations, and smoking behavior in the nisoldipine group (237 patients) and the enalapril group (233 patients) throughout five years of follow-up. Using a multiple logistic-regression model with adjustment for cardiac risk factors, we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infarctions (a total of 24) than enalapril (total, 4) (risk ratio, 9.5; 95 percent confidence interval, 2.7 to 33.8).. In this population of patients with diabetes and hypertension, we found a significantly higher incidence of fatal and nonfatal myocardial infarction among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril. Since our findings are based on a secondary end point, they will require confirmation.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Logistic Models; Male; Middle Aged; Myocardial Infarction; Nisoldipine; Prospective Studies; Treatment Outcome

In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P

Topics: Aged; Aged, 80 and over; Calcium Channel Blockers; Cardiovascular Diseases; Double-Blind Method; Drug Therapy, Combination; Enalapril; Europe; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Nitrendipine; Prognosis; Systole

Investigators from the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) previously reported that the isradipine group had a higher incidence of cardiovascular disease (CVD) events than the diuretic group. The ultimate objective of the analyses presented here was to assess how indices of glycemia (specifically, serum glucose, serum insulin, and HbA1c) might have influenced the effects of the two agents on blood pressure control and CVD events.. Inclusion criteria included men and women > or = 40 years of age with ultrasonographically confirmed carotid atherosclerosis and a diastolic blood pressure of > 90 mmHg. Although insulin-dependent diabetic patients were excluded, the three glycemia indices had wide enough ranges to include patients who may be classified as prediabetic. A total of 883 patients were randomized either to the dihydropyridine calcium antagonist (CA) isradipine (2.5-5 mg twice a day) or to the diuretic hydrochlorothiazide (12.5-25 mg twice a day) and followed in double-blind fashion for 3 years.. Both treatment groups had achieved comparable control of diastolic blood pressure, and there were no statistically significant differences in any of the glycemia indices, either at baseline or during follow-up. However, the excess isradipine events were noted to be clustered among those patients with elevated baseline levels of HbA1c who also experienced greater blood pressure reductions during follow-up.. The increased cardiovascular risk associated with dihydropyridine CAs in prediabetic patients may be an explanation for the overall CA debate.

Topics: Antihypertensive Agents; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Coronary Disease; Diabetic Angiopathies; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hydrochlorothiazide; Hypertension; Insulin; Isradipine; Male; Prediabetic State; Time Factors

The ABCD (Appropriate Blood Pressure Control in Diabetes) Trial is a large, prospective, randomized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus (NIDDM) designed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in NIDDM. The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and an angiotensin-converting-enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations aged 40-74 years, 470 hypertensive patients (diastolic blood pressure of > or = 90.0 mmHg at time of randomization) and 480 normotensive patients (diastolic blood pressure of 80.0 mmHg at time of randomization). The study duration is 5 years and is scheduled to end in May of 1998. Patients are randomized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy. Patients are also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control is necessary. The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance. Secondary outcome measures are urinary albumin excretion, left ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity and mortality will also be evaluated. Given the data showing the impact of hypertension on complications in NIDDM, the ABCD Trial is designed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM.

Topics: Adult; Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Enalapril; Exercise; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Nisoldipine; Prospective Studies; Sex Characteristics

The angiotensin converting enzyme inhibitors constitute a major treatment modality for cardiovascular diseases, including congestive heart failure and hypertension. In addition to their beneficial hemodynamic effects, they offer other advantages, such as a relative lack of adverse effects on other cardiovascular risk factors. When used judiciously, the angiotensin converting enzyme inhibitors may also contribute to improved renal function. These agents induce vasodilation of both efferent and afferent renal vessels, which may facilitate improved renal blood flow and glomerular filtration rate in individuals whose renal insufficiency results from hyperadrenergic activity. Improvements in renal function may also be observed when angiotensin converting enzyme inhibitors are employed in other clinical conditions, such as diabetic nephropathy or proteinuric renal disease. Although the renal protective effects of the angiotensin converting enzyme inhibitors are well recognized, their use in certain circumstances may actually contribute to renal dysfunction. The factors which may predispose an individual to angiotensin converting enzyme inhibitor-induced renal dysfunction must be recognized by the clinician and appropriate interventions taken to prevent this potentially deleterious effect. This article reviews those factors which increase risk for angiotensin converting enzyme inhibitor-induced renal dysfunction and provides recommendations for prevention.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiovascular Diseases; Creatinine; Drug Interactions; Enalapril; Guidelines as Topic; Humans; Kidney; Kidney Diseases; Prospective Studies

It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting--enzyme inhibitor, enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure.. Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months.. There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P less than 0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group; vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P less than 0.001).. The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril.

Topics: Blood Pressure; Cardiovascular Diseases; Double-Blind Method; Electrolytes; Enalapril; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Kidney; Male; Middle Aged; Stroke Volume

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiovascular Diseases; Enalapril; Follow-Up Studies; Heart Failure; Humans; Myocardial Infarction; Ventricular Function, Left

Diabetes Mellitus (DM) is a prominent health care issue worldwide. One of the most prevalent comorbidities of DM is cardiovascular disease (CVD). The objective of this study was to assess the utilization patterns of cardiovascular medications in patients with DM in Iran from 2013 to 2017.. This retrospective cross-sectional study was undertaken using prescription claims data from 2013 to 2017 in Iran. Epidemiological data elements used in this study were obtained from the Global Burden of Disease (GBD) 2019 study. In addition, data on total medication sales were obtained from the national regulatory authority database. The data on medication utilization were analyzed according to the Anatomical Therapeutic Chemical Classification (ATC) /Defined Daily Doses (DDD) international system.. Based on the findings, Acetylsalicylic acid was the mainstay of treatment with a utilization rate of 191.7 DDD/ patient/ year in 2017, followed by Atorvastatin with 170.0 and Losartan with 115.1. Although there was an increasing trend in the utilization rate of the medications, the rate of Atenolol and Enalapril was constantly declining during the 2013-17 period. On the other hand, Valsartan and Metoprolol were attracting attention. Almost all medication utilization rates increased from the 30-39 age group up to the 80 + age group. Females had a higher utilization rate in each age group during the whole study period.. The present study reflects that medication utilization patterns were rational, according to the standard treatment guidelines. Utilization patterns of medications that are recommended for both prevention and treatment of CVD in diabetes were observed to be the highest. Implementation of further policies is needed to minimize cardiovascular complications of diabetes.

Topics: Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus; Enalapril; Female; Humans; Retrospective Studies

Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a

Topics: Acute Kidney Injury; Animals; Animals, Genetically Modified; Cardio-Renal Syndrome; Cardiovascular Diseases; Digoxin; Disease Models, Animal; Drug Evaluation, Preclinical; Enalapril; Epithelial Cells; Humans; Kidney Tubules; Larva; Metronidazole; Regional Blood Flow; Thioctic Acid; Treatment Outcome; Zebrafish

Whether sex influences the association of obstructive sleep apnea (OSA) with markers of cardiovascular risk in patients with hypertension is unknown. In this study, 95 hypertensive participants underwent carotid-femoral pulse wave velocity, 24-hour ambulatory blood pressure monitoring, echocardiogram, and polysomnography after a 30-day standardized treatment with hydrochlorothiazide plus enalapril or losartan. OSA was present in 52 patients. Compared with non-OSA patients, pulse wave velocity values were higher in the OSA group (men: 11.1±2.2 vs 12.7±2.4 m/s, P=.04; women: 11.8±2.4 vs 13.2±2.2 m/s, P=.03). The proportion of diastolic dysfunction was significant in men and women with OSA. Compared with non-OSA patients, nondipping systolic blood pressure in OSA was higher in men (14.3% vs 46.4%) and in women (41.4% vs 65.2%). OSA was independently associated with pulse wave velocity (β=1.050; P=.025) and nondipping systolic blood pressure (odds ratio, 3.03; 95% confidence interval, 1.08-8.55; P=.035) in the regression analysis. In conclusion, OSA is independently associated with arterial stiffness and nondipping blood pressure in patients with hypertension regardless of sex.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Brazil; Cardiovascular Diseases; Diuretics; Echocardiography; Enalapril; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Polysomnography; Pulse Wave Analysis; Risk Factors; Sleep Apnea, Obstructive; Vascular Stiffness

We aimed to test the impact of achieved blood pressure (BP) on first stroke among patients with grade 1 hypertension and without cardiovascular diseases in the China Stroke Primary Prevention Trial.. A total of 3187 patients with uncomplicated grade 1 hypertension were included. The risk of outcomes was assessed according to: (1) the proportion of visits in which BP was reduced to <140/90 mm Hg, and (2) the time-averaged systolic BP (SBP) or diastolic BP levels during the study treatment period. The median antihypertensive treatment duration was 4.6 years. Only 1.5% of the participants discontinued the treatments because of adverse reaction. Overall, the risk of stroke decreased with the increase of the proportion of study visits with BP <140/90 mm Hg (for per 5% increase; hazard ratio, 0.92 [95% CI, 0.87-0.98]). Consistently, compared with patients with time-averaged SBP ≥140 or diastolic BP ≥90 mm Hg, the risk of stroke was lower in patients with time-averaged SBP of 120 to <140 mm Hg (1.1% versus 2.9%; hazard ratio, 0.39 [95% CI, 0.22-0.69]) or diastolic BP <90 mm Hg (1.5% versus 2.7%; hazard ratio, 0.41 [95% CI, 0.17-0.98]). The beneficial results were consistent across age (<60 versus ≥60 years), sex, baseline SBP (<150 versus 150 to <160 mm Hg), study treatment groups (enalapril or enalapril-folic acid), and hypertension subtypes (isolated systolic hypertension or systolic-diastolic hypertension). However, a time-averaged SBP <120 mm Hg (versus 120-140 mm Hg) was associated with an increased risk for stroke. Similar results were observed for composite cardiovascular events or all-cause death.. Achieved BP <140/90 mm Hg was significantly associated with a decreased risk of stroke or all-cause death in patients with uncomplicated grade 1 hypertension.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Cause of Death; China; Double-Blind Method; Enalapril; Female; Folic Acid; Humans; Hypertension; Male; Middle Aged; Mortality; Proportional Hazards Models; Randomized Controlled Trials as Topic; Severity of Illness Index; Stroke; Treatment Outcome; Vitamin B Complex

The objective of this study was to determine the cost-effectiveness and cost per quality-adjusted life year (QALY) gained of sacubitril-valsartan relative to enalapril for treatment of heart failure with reduced ejection fraction (HFrEF).. Compared with enalapril, combination angiotensin receptor-neprilysin inhibition (ARNI), as is found in sacubitril-valsartan, reduces cardiovascular death and heart failure hospitalization rates in patients with HFrEF.. Using a Markov model, costs, effects, and cost-effectiveness were estimated for sacubitril-valsartan and enalapril therapies for the treatment of HFrEF. Patients were 60 years of age at model entry and were modeled over a lifetime (40 years) from a third-party payer perspective. Clinical probabilities were derived predominantly from PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). All costs and effects were discounted at a 3% rate annually and are presented in 2015 U.S. dollars.. In the base case, sacubitril-valsartan, compared with enalapril, was more costly ($60,391 vs. $21,758) and more effective (6.49 vs. 5.74 QALYs) over a lifetime. The cost-effectiveness of sacubitril-valsartan was highly dependent on duration of treatment, ranging from $249,411 per QALY at 3 years to $50,959 per QALY gained over a lifetime.. Sacubitril-valsartan may be a cost-effective treatment option depending on the willingness-to-pay threshold. Future investigations should incorporate real-world evidence with sacubitril-valsartan to further inform decision making.

Topics: Aged; Aged, 80 and over; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiovascular Diseases; Cost-Benefit Analysis; Drug Combinations; Enalapril; Female; Heart Failure; Hospitalization; Humans; Male; Markov Chains; Middle Aged; Neprilysin; Quality-Adjusted Life Years; Stroke Volume; Tetrazoles; Valsartan

Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age.

Topics: Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Arterial Pressure; Birth Weight; Cardiovascular Diseases; Enalapril; Female; Fetal Growth Retardation; Hypertension; Male; Pregnancy; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Risk Factors; Testosterone

This post hoc analysis of CAMELOT and PREVENT analyzed the impact of blood pressure variability (BPV, assessed as within-subject standard deviation of SBP from 12 weeks onward) on the incidence of major adverse cardiovascular events (MACE, defined according to original studies). Patients (n = 1677 CAMELOT; n = 776 PREVENT) were stratified by BPV quartile. Regardless of study, BPV was significantly lower for amlodipine versus other treatments. In CAMELOT, a significant association between BPV quartile and MACE was observed with amlodipine treatment. Significant associations between BPV quartile and MACE were observed for both studies, when analyzed overall (adjusting for treatment). In CAMELOT, with amlodipine treatment, an increased risk for MACE was observed with high (BPV ≥ Q3) versus low BPV (< Q1; adjusting for characteristics and risk factors). In both studies, increased risk for MACE was observed for BPV ≥ Q3 versus BPV < Q1 (analyzed overall, adjusting for treatment and covariates). For both studies, BPV, but not mean SBP, was associated with cardiovascular events. BPV was associated with cardiovascular outcomes in patients with CAD and well-controlled BP.

Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Coronary Artery Disease; Enalapril; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors

Some angiotensin converting enzyme (ACE) inhibitors are efficiently removed from circulation by hemodialysis ('high dialyzability'), whereas others are not ('low dialyzability'). In patients receiving hemodialysis, this may influence the effectiveness of ACE inhibitors.. Using linked healthcare databases we identified older patients receiving chronic hemodialysis who filled new ACE inhibitor prescriptions. The low dialyzability group (n = 3,369) included fosinopril and ramipril. The high dialyzability group (n = 5,974) included enalapril, lisinopril, and perindopril. The primary outcome was all-cause mortality within 180 days of first ACE inhibitor prescription.. There were 361 deaths among 5,974 patients (6.0%) prescribed with low dialyzability ACE inhibitors and 179 deaths among 3,369 patients (5.3%) prescribed with high dialyzability ACE inhibitors (relative risk 1.1, 95% CI 0.9-1.3, p = 0.6).. In this study of older patients receiving hemodialysis, the dialyzability of ACE inhibitors was not associated with mortality or cardiovascular outcomes.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Diseases; Enalapril; Female; Fosinopril; Hemorheology; Humans; Kidney Failure, Chronic; Kidneys, Artificial; Lisinopril; Male; Middle Aged; Perindopril; Ramipril; Renal Dialysis; Retrospective Studies; Survival Analysis

This retrospective study aimed to compare systolic and diastolic blood pressures between patients with acute kidney injury (AKI) after initiation of angiotensin-converting enzyme (ACE) inhibitor therapy and those of patients who do not experience AKI after ACE inhibitor therapy. Of 332 patients who received an ACE inhibitor as inpatients at our institution from 1 January 2010 to 1 July 2012, 20 patients had a doubling of serum creatinine (SCr) within 72 h after initiation or dose uptitration of an ACE inhibitor (AKI group). These cases were matched one to four by age and gender to patients who received an ACE inhibitor but did not have a doubling of SCr (control group). The patients in the AKI group had a significantly greater decrease in systolic and diastolic blood pressures before their AKI than the control group. Pediatric patients who experience ACE inhibitor-associated AKI have a significantly greater decrease in blood pressure than patients who do not experience ACE inhibitor-associated AKI. The authors suggest that the risk and benefits of ACE inhibitor use be stringently evaluated before initiation of therapy.

Topics: Acute Kidney Injury; Adolescent; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Creatinine; Enalapril; Female; Humans; Hypotension; Infant; Male; Retrospective Studies

Endothelial dysfunction is now widely recognized as an early marker of cardiovascular disease, making its treatment, or complete avoidance, an emerging, interesting therapeutic target. This study investigated the ability of the highly intriguing amino acid L-arginine to influence endothelial function. Its therapeutic potential is also compared to that of known cardiovascular medications, namely nitroglycerin [a nitric oxide (NO) donor] and enalapril [an angiotensin-converting enzyme (ACE) inhibitor]. Fifty male New Zealand rabbits were included in the study, divided into 5 equal groups: control, hypercholesterolemia (untreated), hypercholesterolemia (+L-arginine), hypercholesterolemia (+enalapril), and hypercholesterolemia (+nitroglycerin). Biochemical investigations included measurement of circulating NOx, malondialdehyde (MDA), and lipid profile markers, as well as dimethylarginine dimethylaminohydrolase (DDAH) and ACE activities. Furthermore, aortic ACE activity and blood platelet aggregation were estimated. A histopathological examination and intimal thickness measurement were also conducted. Compared to the untreated hypercholesterolemic group, all agents were capable of positively influencing MDA levels, platelet aggregation and intimal thickness; however, only the L-arginine group was capable of beneficially and significantly altering both NOx levels and serum and aortic ACE activities. No agents were capable of modulating serum DDAH activity inhibited by hypercholesterolemia. Based on the results of this study, L-arginine appears to be a novel cardio-protective agent, illustrated by its ability to ameliorate the deleterious effects of hypercholesterolemia on endothelial function, in a manner comparable to, and sometimes more potent than, commonly used cardiovascular medications.

Topics: Amidohydrolases; Angiotensin-Converting Enzyme Inhibitors; Animals; Arginine; Cardiotonic Agents; Cardiovascular Diseases; Dietary Supplements; Disease Models, Animal; Enalapril; Endothelium, Vascular; Heart; Hypercholesterolemia; Male; Malondialdehyde; Nitric Oxide; Nitroglycerin; Oxidative Stress; Rabbits

Differences in clinical effectiveness between angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in the primary treatment of hypertension are unknown. The aim of this retrospective cohort study was to assess the prevention of type 2 diabetes and cardiovascular disease (CVD) in patients treated with ARBs or ACEis. Patients initiated on enalapril or candesartan treatment in 71 Swedish primary care centers between 1999 and 2007 were included. Medical records data were extracted and linked with nationwide hospital discharge and cause of death registers. The 11,725 patients initiated on enalapril and 4265 on candesartan had similar baseline characteristics. During a mean follow-up of 1.84 years, 36,482 patient-years, the risk of new diabetes onset was lower in the candesartan group (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.96, P=0.01) compared with the enalapril group. No difference between the groups was observed in CVD risk (HR 0.99, 95% CI 0.87-1.13, P=0.86). More patients discontinued treatment in the enalapril group (38.1%) vs the candesartan group (27.2%). In a clinical setting, patients initiated on candesartan treatment had a lower risk of new-onset type 2 diabetes and lower rates of drug discontinuation compared with patients initiated on enalapril. No differences in CVD risk were observed.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Enalapril; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Primary Health Care; Retrospective Studies; Risk Factors; Sweden; Tetrazoles; Time Factors; Treatment Outcome

The European Society of Cardiology (ESC) Annual Congress is the largest cardiology conference in the world and this year ran in Barcelona from August 30 to September 3. During the meeting, more than 30,000 cardiologists from over 100 countries met to share their knowledge in all cardiovascular fields, from basic science to management and prevention of cardiovascular diseases. Apart from more than 4,500 interesting abstracts presented in posters and oral sessions, five new ESC Clinical Practice Guidelines were presented among the latest clinical trial results, updates and registries.

Topics: Aminobutyrates; Benzaldehydes; Benzazepines; Biphenyl Compounds; Cardiology; Cardiovascular Diseases; Drug Combinations; Enalapril; Humans; Ivabradine; Oximes; Stents; Tetrazoles; Valsartan

To examine the impact of tissue selectivity of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients following acute myocardial infarction (AMI).. A retrospective cohort study using a Medicaid claims database was conducted. Patients hospitalized for an AMI and subsequently filling a prescription for an ACE inhibitor were followed longitudinally for the occurrence of cardiovascular-related hospitalizations and all-cause mortality. A subanalysis was also conducted to account for switching/discontinuation of ACE inhibitor therapy. Stepwise (forward conditional) Cox-proportional hazards models were used to analyze the effect of tissue selectivity on study outcomes.. The final study sample consisted of 689 AMI and the results indicated that tissue-selective ACE inhibitors had a protective effect against hospitalization due to stroke/transient ischemic attack (TIA) (hazard ratio [HR] = 0.265; 95% confidence interval [CI] = 0.101-0.698). A similar lower rate in hospitalizations due to heart failure was observed in the group using tissue-selective ACE inhibitors; however, the results were not statistically significant (HR = 0.681; 95% CI = 0.436-1.063). A protective effect was also observed on the combined outcome of hospitalization due to any cardiovascular condition (HR = 0.712; 95% CI = 0.536-0.945). Hospitalizations due to recurrent AMI, need for coronary revascularization procedures, and mortality were not significantly different between patients using tissue-selective and non-tissue-selective ACE inhibitors. The completer subanalysis provided similar findings regarding the impact of tissue selectivity on study outcomes.. Tissue-selective ACE inhibitors may have a protective effect against hospitalization due to stroke/TIA or heart failure when compared to non-tissue-selective ACE inhibitors for patients following AMI.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Comorbidity; Enalapril; Female; Heart Failure; Humans; Lisinopril; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Organ Specificity; Proportional Hazards Models; Ramipril; Retrospective Studies; Secondary Prevention; Stroke; Survival Analysis

The administration of most angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) at bedtime results in a greater reduction of nighttime blood pressure (BP) than dosing upon awakening. It has been proposed that this effect may be a consequence of a short half-life and duration of action. However, those findings were also documented for long-acting medications, such as the ARB telmisartan. Accordingly, we investigated the administration-time-dependent effects on ambulatory BP of spirapril, an ACEI with an elimination half-life of about 40 h. We studied 165 previously untreated hypertensive subjects, 42.5 +/- 13.9 yrs of age, treated with spirapril (6 mg/day) as monotherapy for 12 weeks either upon awakening or at bedtime. BP was measured by ambulatory monitoring for 48 h before and after treatment. The BP reduction during diurnal activity was similar for both treatment times. Bedtime spirapril administration, however, was significantly more efficient than morning administration in reducing asleep BP. The awake/asleep BP ratio was decreased with the upon-awakening spirapril treatment schedule but significantly increased toward a more dipping pattern with the bedtime treatment schedule. The proportion of patients with controlled ambulatory BP increased from 23 to 59% (p < 0.001) with bedtime treatment. Sleep-time BP regulation is significantly better achieved with bedtime spirapril administration. This might be clinically important, as the sleep-time BP mean has been shown to be a more relevant marker of cardiovascular risk than the awake mean values. These administration-time-dependent effects of spirapril seem to be a class-related feature, and may be associated with the nocturnal activation of the renin-angiotensin-aldosterone system.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Enalapril; Female; Half-Life; Humans; Hypertension; Hypotension; Male; Middle Aged; Receptors, Angiotensin; Renin-Angiotensin System; Risk; Telmisartan

To investigate the cost-utility of eprosartan versus enalapril (primary prevention) and versus nitrendipine (secondary prevention) on the basis of head-to-head evidence from randomized controlled trials.. The HEALTH model (Health Economic Assessment of Life with Teveten for Hypertension) is an object-oriented probabilistic Monte Carlo simulation model. It combines a Framingham-based risk calculation with a systolic blood pressure approach to estimate the relative risk reduction of cardiovascular and cerebrovascular events based on recent meta-analyses. In secondary prevention, an additional risk reduction is modeled for eprosartan according to the results of the MOSES study ("Morbidity and Mortality after Stroke--Eprosartan Compared to Nitrendipine for Secondary Prevention"). Costs and utilities were derived from published estimates considering European country-specific health-care payer perspectives.. Comparing eprosartan to enalapril in a primary prevention setting the mean costs per quality adjusted life year (QALY) gained were highest in Germany (Euro 24,036) followed by Belgium (Euro 17,863), the UK (Euro 16,364), Norway (Euro 13,834), Sweden (Euro 11,691) and Spain (Euro 7918). In a secondary prevention setting (eprosartan vs. nitrendipine) the highest costs per QALY gained have been observed in Germany (Euro 9136) followed by the UK (Euro 6008), Norway (Euro 1695), Sweden (Euro 907), Spain (Euro -2054) and Belgium (Euro -5767).. Considering a Euro 30,000 willingness-to-pay threshold per QALY gained, eprosartan is cost-effective as compared to enalapril in primary prevention (patients >or=50 years old and a systolic blood pressure >or=160 mm Hg) and cost-effective as compared to nitrendipine in secondary prevention (all investigated patients).

Topics: Acrylates; Antihypertensive Agents; Cardiovascular Diseases; Cost-Benefit Analysis; Enalapril; Europe; Geography; Humans; Hypertension; Imidazoles; Male; Meta-Analysis as Topic; Middle Aged; Monte Carlo Method; Nitrendipine; Primary Prevention; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke; Thiophenes

Our previous studies have shown vascular dysfunction in small coronary and mesenteric arteries in Zucker obese rats, a model of the metabolic syndrome, and Zucker Diabetic Fatty (ZDF) rats, a model of type 2 diabetes. Because of their lipid lowering action and antioxidant activity, we predicted that treatment with Rosuvastatin, an HMG-CoA reductase inhibitor (statin) or Enalapril, an angiotensin converting enzyme (ACE) inhibitor would improve vascular dysfunction associated with the metabolic syndrome and type 2 diabetes.. 20-week-old Zucker obese and 16-week-old ZDF rats were treated with Rosuvastatin (25 mg/kg/day) or Enalapril (20 mg/kg/day) for 12 weeks. We examined metabolic parameters, indices of oxidative stress and vascular dysfunction in ventricular and mesenteric small arteries (75-175 microm intraluminal diameter) from lean, Zucker obese and ZDF rats (untreated and treated).. Endothelial dependent responses were attenuated in coronary vessels from Zucker obese and ZDF rats compared to responses from lean rats. Both drugs improved metabolic parameters, oxidative stress, and vascular dysfunction in Zucker obese rats, however, only partial improvement was observed in ZDF rats, suggesting more aggressive treatment is needed when hyperglycemia is involved.. Vascular dysfunction is improved when Zucker obese and, to a lesser degree, when ZDF rats were treated with Rosuvastatin or Enalapril.

Topics: Age Factors; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Cholesterol; Coronary Vessels; Diabetes Mellitus, Type 2; Enalapril; Endothelium, Vascular; Fatty Acids; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mesenteric Arteries; Metabolic Syndrome; Oxidative Stress; Pyrimidines; Rats; Rats, Zucker; Rosuvastatin Calcium; Sulfonamides; Triglycerides

Progression of renal disease and cardiovascular complications in type II diabetes mellitus have been shown to correlate with control of blood glucose, lipids, blood pressure, and smoking. These factors, however, do not appear to totally explain these diabetic complications. Renal disease and cardiovascular complications in type II diabetes are associated with vascular abnormalities and fibrosis, both of which may occur with impaired fibrinolysis. A cross-sectional study was therefore performed in 107 type II diabetic patients recruited from the Denver Metropolitan Area to examine the effect of impaired fibrinolysis, as assessed by the ratio of plasminogen activator inhibitor (PAI-1) to tissue-type plasminogen activator (t-PA). With urinary albumin excretion (UAE) as a risk factor for both renal disease progression and cardiovascular complications, the patients were analyzed with respect to UAE less than and greater than 1 gm/day. The age, blood glucose, hemoglobin A1C, duration of diabetes, lipids, body mass index, and smoking were no different between the groups. As expected, the group with greater UAE had worse renal function, the serum creatinine (1.98 +/- 0.24 vs 1.21 +/- 0.05 mg/dl, P < 0.001) and creatinine clearance (55.5 +/- 6.0 vs 76.8 +/- 2.7 ml/min, P < 0.001) were significantly different. The type II diabetic patients with greater UAE exhibited significantly higher PAI-1/t-PA (2.43 +/- 0.26 vs 1.85 +/- 0.07, P < 0.03). The past history of cardiac complications was also higher (87.5 vs 72.3%, P < 0.07) in the diabetic patients with more impaired fibrinolysis and greater UAE. Thus a prospective, randomized clinical trial in type II diabetes with PAI-1 inhibitors is needed.

Topics: Aged; Albuminuria; Antihypertensive Agents; Atenolol; Cardiovascular Diseases; Cohort Studies; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Enalapril; Fibrinolysis; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Plasminogen Activator Inhibitor 1; Risk Factors; Time Factors; Tissue Plasminogen Activator

Increasing evidence suggests that angiotensin converting enzyme (ACE) inhibitors exert antithrombotic effects. Based on the assumption of differential effects of various ACE inhibitors on coagulation, the aim of the present study was to evaluate the coagulative activities of cardiovascular (CV) patients treated with either ramipril, captopril, and enalapril, and to compare these with patients treated with established antithrombotics such as aspirin (ASA) and clopidogrel or none of these medication.. Blood samples of 320 CV patients with coronary artery disease and/or arterial hypertension were analyzed by wholeblood aggregometry. Platelet aggregation was determined by measuring the increase in impedance across paired electrodes in response to the aggregatory agents collagen and adenosine diphosphate (ADP), respectively. These data were correlated with medical treatment.. Platelet aggregation was attenuated ex vivo by ramipril and captopril as well as by ASA and clopidogrel. While collagen-induced platelet aggregation was significantly reduced by ramipril (35%; P <0.01) and captopril (27%; P = 0.01), no change was seen with enalapril. After induction with ADP, platelet aggregation was reduced in the presence of captopril therapy by 46% (P <0.05). There was a trend of inhibition with ramipril (32%, P = n.s.), whereas no antithrombotic effect was seen with enalapril.. Our findings demonstrate that ACE inhibitors decrease platelet aggregation ex vivo. The differential antiaggregatory profile may explain at least in part different effects of ACE inhibitors on cardiovascular endpoints as observed in large clinical trials.

Topics: Adenosine Diphosphate; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Captopril; Cardiovascular Diseases; Clopidogrel; Collagen; Coronary Artery Disease; Electric Impedance; Enalapril; Female; Fibrinolytic Agents; Germany; Humans; Hypertension; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Prospective Studies; Ramipril; Ticlopidine; Treatment Outcome

The implication of various cytokines in a subclinical inflammatory process has been documented in heart failure (HF). The role of temporal changes of more conventional markers of inflammation, such as the white blood cell (WBC) count, on clinical outcomes remains largely unknown.. We performed a retrospective analysis of patients included in the Studies Of Left Ventricular Dysfunction that had documented eligibility at the baseline visit, a documented WBC count at baseline and at least 1 measurement during follow-up. We evaluated the association between variations in WBC count, WBC subfractions and mortality and non-fatal events. An increase in WBC count during follow-up compared with baseline was associated with a significantly higher risk of all-cause and cardiovascular (CV) mortality, HF mortality and arrhythmic death (all P < .05). A relative increase in the neutrophil count was associated with higher risk of all-cause and CV mortality, HF mortality and cardiac ischemic events (all P < .05). No significant interaction was present in regards to the etiology of HF.. Temporal increases in WBC and neutrophil counts are associated with increased risks of death and CV events. This relationship appears to be independent of HF etiology.

Topics: Aged; Blood Cell Count; Cardiovascular Diseases; Enalapril; Female; Follow-Up Studies; Humans; Inflammation; Leukocyte Count; Lymphocyte Count; Male; Middle Aged; Neutrophils; Prognosis; Retrospective Studies; Risk Assessment; Time Factors; Ventricular Dysfunction, Left

Hypertension is prevalent in over 25% of populations in developed countries, and poses an increasing economic burden on health resources. Therefore it is predicted that future medical treatment of hypertension will be increasingly affected by cost considerations. Several classes of antihypertensive drugs are used as first-line agents for the treatment of hypertension, but the economic impact of using these agents in different countries remains to be addressed. In this study, we compared health costs associated with treatment of hypertension using the calcium channel blocker amlodipine and the angiotensin-converting enzyme inhibitor enalapril in the US and Japan. Pharmaceutical costs and hospitalization costs were analyzed from established databases. The data for the prevalence of myocardial infarction and stroke were derived from the Framingham study and the Hisayama study. Analysis of the economic impacts using relative risk differences between the calcium channel blocker and angiotensin-converting enzyme inhibitor together with regional hospitalization costs resulted in an apparent 11.2 billion yen health cost reduction in favor of the calcium channel blocker in the case of Japan, in contrast to an apparent 5.7 billion yen reduction in favor of the angiotensin-converting enzyme inhibitor in the case of the US. The trends in Japan for 2000 and 2004 were similar. These results suggest that there are regional differences in the health costs associated with different classes of hypertensive agents, which could affect national policies on the choice of antihypertensive drugs. It is predicted that future treatment of hypertension will be increasingly tailored to the epidemiologic profiles and medical costs of individual communities.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Diseases; Cost-Benefit Analysis; Drug Costs; Enalapril; Female; Health Care Costs; Hospitalization; Humans; Hypertension; Japan; Male; Prevalence; United States

Topics: Amlodipine; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Coronary Artery Disease; Coronary Vasospasm; Enalapril; Humans

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Coronary Artery Disease; Disease Progression; Enalapril; Humans

Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Enalapril; Humans; Hypertension; Risk Factors

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Clinical Trials as Topic; Enalapril; Humans; Perindopril; Protease Inhibitors; Pyridines; Stroke; Thiazepines; Ventricular Dysfunction, Left

The French experts present at the Eutherapy Symposium held in Prague confirmed the importance of left ventricular hypertrophy (LVH) and microalbuminuria as major independent risk factors for cardiovascular disease. Factors that must be considered for the treatment of hypertension in patients, particularly with type 2 diabetes. Professor J.M. Mallion stressed the contribution of thiazide and thiazide-like diruetics as indapamid, especially the 1.5 mg SR formulation. Professor F. Forette and Doctor O. Hanon recalled that the HYVET study is expected to confirm the beneficial effect of this same treatment on morbidity and mortality in very elderly patients. Professor O. Dubourg recalled the beneficial effect of indapamid SR on LVH demonstrated in the LIVE study. Likewise, Professor M. Marre emphasized its important impact on microalbuminuria as shown in the NESTOR study.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzothiadiazines; Cardiovascular Diseases; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diuretics; Double-Blind Method; Echocardiography; Electrocardiography; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Sodium Chloride Symporter Inhibitors; Time Factors

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Cardiovascular Diseases; Clinical Trials as Topic; Enalapril; Heart Failure; Humans; Indoles; Isoquinolines; Myocardial Infarction; Perindopril; Prodrugs; Quinapril; Ramipril; Stroke; Stroke Volume; Tetrahydroisoquinolines; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Enalapril; Follow-Up Studies; Heart Failure; Humans; Hypertension; Myocardial Infarction; Nisoldipine

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Enalapril; Humans; Hypertension; Myocardial Infarction; Nisoldipine

To determine the effect of preoperative therapy with angiotensin-converting enzyme (ACE) inhibitors on clinical outcome after cardiovascular surgery.. Inception cohort.. A tertiary care 54-bed cardiothoracic ICU.. All admissions to an ICU over a 42-month period after cardiovascular surgery.. Extraction of preoperative, operative, and ICU data from a database.. Incidence of acute organ dysfunction, length of mechanical ventilation, ICU stay, and death after cardiovascular surgery.. The study cohort consisted of four groups: normal or moderately impaired left ventricular function control (group A, n=6,400); normal or moderately impaired left ventricular function treated with ACE inhibitors (group B, n=1,375); severe left ventricular dysfunction control (group C, n=1,905); and severe left ventricular dysfunction treated with ACE inhibitors (group D, n=1,650). The incidence of three or more organ dysfunction was similar on comparison of group A vs group B (5% vs 6%) or group C vs group D (15% vs 13%). There were no differences in the total duration of mechanical ventilation or length of stay in the ICU in group A vs group B or group C vs group D. Death occurred in 2% of groups A and B, and at 6% in groups C and D. Preoperative severe left ventricular dysfunction in both groups C and D was associated with an increased incidence of three or more organ dysfunction, duration of mechanical ventilation, length of stay in ICU, and death after surgery. Multivariate analysis indicated that therapy with ACE inhibitors did not affect the clinical outcome after cardiovascular surgery.. Preoperative therapy with ACE inhibitors did not influence the clinical outcome after cardiac surgery. It is unlikely that therapy with ACE inhibitors can alter the clinical sequelae of cardiopulmonary bypass and cardiac surgical procedures performed in high-risk patients because of underlying severe left ventricular dysfunction.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiopulmonary Bypass; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Case-Control Studies; Electrocardiography; Enalapril; Female; Follow-Up Studies; Hospital Mortality; Humans; Incidence; Intra-Aortic Balloon Pumping; Lisinopril; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Preoperative Care; Retrospective Studies; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Aged; Animals; Cardiovascular Diseases; Enalapril; Humans

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiovascular Diseases; Enalapril; Humans; Lisinopril

Topics: Adolescent; Captopril; Cardiovascular Diseases; Child; Child, Preschool; Enalapril; Endocrine System Diseases; Humans; Hypertension, Renal; Infant; Infant, Newborn; Renin-Angiotensin System