trandolapril and Coronary-Disease

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction.. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years.. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced.. Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Coronary Disease; Female; Hospitalization; Humans; Indoles; Male; Middle Aged; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome

The results of the major clinical outcome trials related to the potential antiatherosclerotic effects of the angiotensin convertase (ACE) inhibitors are reviewed after the recently published EUROPA trial results. In the postinfarction clinical situation mortality reduction was revealed in the ISIS-4 (captopril), GISSI-3 (lisinopril), AIRE (ramipril), TRACE (trandolapril), CONSENSUS (enalapril), SAVE (captopril) and in the SOLVD (enalapril) trials. In the HOPE trial performed in a high risk population the preventive antiatherosclerotic, endothel-preserving effects of ramipril resulted in a significant mortality and morbidity reduction. In the EUROPA trial a lower risk population--symptomfree coronary patients--were treated by perindopril, and it was proven also in this cohort, that the long term ACE inhibitor treatment decreased the combined endpoint of cardiovascular mortality, myocardial infarction and resuscitated sudden death. Based on the above data it can be advised, that all coronary patients regardless of left ventricular function and symptoms should receive long term ACE inhibitor treatment besides the other established preventive medications (platelet aggregation inhibitors + statins + beta receptor blockers).

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Clinical Trials as Topic; Coronary Disease; Death, Sudden, Cardiac; Enalapril; Humans; Indoles; Lisinopril; Myocardial Infarction; Perindopril; Ramipril; Treatment Outcome

Asymptomatic left ventricular dysfunction should be treated as an early stage on the continuum that is chronic heart failure. The author presents the clinical trial data on which current management with angiotensin-converting enzyme inhibitors and beta-blockers is based. Issues surrounding screening are also discussed.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Coronary Disease; Drug Therapy, Combination; Echocardiography; Enalapril; Female; Heart Failure; Humans; Hypertension; Indoles; Male; Middle Aged; Myocardial Infarction; Norepinephrine; Ramipril; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

Preclinical studies were designed to investigate whether the combination of verapamil and trandolapril was more potent than either drug alone for the treatment of hypertension and concomitant cardiovascular or metabolic diseases.. In spontaneously hypertensive rats (SHR) oral treatment with the combination of verapamil plus trandolapril not only significantly reduced elevated blood pressure for 24 h but, after terminating treatment, the antihypertensive effect lasted longer than 48 h, indicating potentiation of each compound's effect. In stroke-prone SHR, life-long oral treatment with low doses of verapamil, trandolapril or their combination significantly prolonged life in each case, but results obtained with the combination were additive compared with monotherapy.. In an animal model of non-insulin-dependent diabetes, the obese Zucker rat, 2 weeks oral treatment with verapamil, trandolapril or both combined significantly improved leukocyte rheology, but only the combination treatment normalized the microcirculation. In insulin-dependent diabetes (streptozotocin-induced) in SHR, oral treatment with the combination for 12 weeks additively reduced blood pressure and totally normalized proteinuria and albuminuria. Verapamil was least effective. Trandolapril showed intermediate protection against insulin-dependent diabetes-related renal failure.. In SHR, almost in parallel with the progression of hypertension, progressive renal failure develops, as indicated by increasing proteinuria and albuminuria. With lifelong treatment in these rats, verapamil + trandolapril combined inhibited the progression towards end-stage renal failure more effectively than either compound used as monotherapy and also significantly prolonged survival. In a second study, in older rats with hypertension and proteinuria, chronic treatment with the combination reduced renal insufficiency in parallel with a reduction in glomerulosclerosis independently of a blood pressure reduction and significantly more potently than each drug alone.. In pigs subjected to consecutive left anterior descending artery occlusions, intravenous verapamil dose-dependently reduced ischaemic myocardial K+ loss. Trandolapril alone was ineffective. Combining two ineffective doses (0.02 mg/kg verapamil plus 0.1 mg/kg trandolapril) led to a significant, additive reduction in extracellular K+ concentrations during ischaemia. Combined intracoronary application of 0.5 mg/kg trandolapril and 0.1 mg/kg verapamil before occlusion in dogs improved myocardial contractility 3 h after reperfusion to a greater extent than monotherapy and reduced the incidence of reperfusion arrhythmias. In dogs exposed to hypoxaemia after ischaemic reperfusion injury, paradoxical coronary constriction was observed. Treatment with trandolapril (0.05 mg/kg) plus verapamil (0.1 mg/kg) inhibited this vasoconstriction in response to repeated hypoxia. In anaesthetized dogs, cyclic coronary flow reductions were induced. Trandolapril reduced these by 70-80% from a dose of 0.1 mg/kg onwards. Verapamil (0.2 mg/kg) had no effect. Combining ineffective doses of trandolapril (0.05 mg/kg) and verapamil (0.1 mg/kg) led to a 70% fall in the flow reductions. Further experiments using either the bradykinin B2 antagonist HOE 140 or the angiotensin II AT1-receptor antagonist Exp 3174 showed that this effect was not mediated by increases in bradykinin levels but by a decrease in angiotensin II.. Two weeks after occlusion of the left anterior descending artery, surviving rats were randomly allocated to no treatment or to verapamil at 20 or 40 mg/kg per day or to trandolapril at 0.3 or 0.7 mg/kg per day or to combinations of both drugs, orally for 24 weeks. (ABSTRACT TRUNCATED)

Topics: Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Coronary Disease; Diabetes Mellitus, Experimental; Dogs; Drug Therapy, Combination; Hypertension; Indoles; Rats; Rats, Inbred SHR; Rats, Zucker; Swine; Verapamil

Circulating biomarkers can offer insight into subclinical cardiovascular stress and thus have the potential to aid in risk stratification and tailoring of therapy.. We measured plasma levels of 4 cardiovascular biomarkers, midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and copeptin, in 3717 patients with stable coronary artery disease and preserved left ventricular ejection fraction who were randomized to trandolapril or placebo as part of the Prevention of Events With Angiotensin Converting Enzyme (PEACE) trial. After adjustment for clinical cardiovascular risk predictors and left ventricular ejection fraction, elevated levels of MR-proANP, MR-proADM, and CT-proET-1 were independently associated with the risk of cardiovascular death or heart failure (hazard ratios per 1-SD increase in log-transformed biomarker levels of 1.97, 1.48, and 1.47, respectively; P≤0.002 for each biomarker). These 3 biomarkers also significantly improved metrics of discrimination when added to a clinical model. Trandolapril significantly reduced the risk of cardiovascular death or heart failure in patients who had elevated levels of ≥2 biomarkers (hazard ratio, 0.53; 95% confidence interval, 0.36-0.80), whereas there was no benefit in patients with elevated levels of 0 or 1 biomarker (hazard ratio, 1.09; 95% confidence interval, 0.74-1.59; P(interaction)=0.012).. In patients with stable coronary artery disease and preserved left ventricular ejection fraction, our results suggest that elevated levels of novel biomarkers of cardiovascular stress may help identify patients who are at higher risk of cardiovascular death and heart failure and may be useful to select patients who derive significant benefit from angiotensin-converting enzyme inhibitor therapy.

Topics: Adrenomedullin; Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Coronary Disease; Death; Endothelin-1; Female; Glycopeptides; Heart Failure; Humans; Indoles; Male; Middle Aged; Peptide Fragments; Prognosis; Protein Precursors; Risk; Stress, Physiological; Stroke Volume

Secretory phospholipase A(2) (sPLA(2)) may contribute to atherogenesis. To date, few prospective studies have examined the utility of sPLA(2) for risk stratification in coronary artery disease (CAD).. We measured plasma sPLA(2) activity at baseline in 3708 subjects in the PEACE randomized trial of trandolapril vs placebo in stable CAD. Median follow-up was 4.8 years. We used Cox regression to adjust for demographics, clinical risk factors, apolipoprotein B, apolipoprotein A1, and medications.. After multivariable adjustment, sPLA(2) was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio Q4:Q1 1.55, 95% CI 1.13-2.14) and cardiovascular death or heart failure (1.91, 1.20-3.03). In further multivariable assessment, increased activity levels of sPLA(2) were associated with the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio 1.47, 95% CI 1.06-2.04), independent of lipoprotein-associated phospholipase A(2) mass and C-reactive protein, and modestly improved the area under the curve (AUC) beyond established clinical risk factors (AUC 0.668-0.675, P = 0.01). sPLA(2), N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T all were independently associated with cardiovascular death or heart failure, and each improved risk discrimination (P = 0.02, P < 0.001, P < 0.001, respectively).. sPLA(2) activity provides independent prognostic information beyond established risk markers in patients with stable CAD. These data are encouraging for studies designed to evaluate the role of sPLA(2) as a therapeutic target.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiovascular Diseases; Clinical Enzyme Tests; Coronary Disease; Double-Blind Method; Female; Heart Failure; Humans; Indoles; Inflammation; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Necrosis; Phospholipases A2, Secretory; Predictive Value of Tests; Prognosis; Risk Assessment; Stroke

Data supporting the prognostic significance of high-sensitivity C-reactive protein (hs-CRP) are derived largely from individuals with no overt coronary artery disease or from patients with acute coronary syndromes. In contrast, the ability of hs-CRP to predict outcomes in patients with stable coronary artery disease and the prognostic significance of the Centers for Disease Control/American Heart Association hs-CRP cut points in such a population remain relatively unexplored.. We measured hs-CRP in 3771 patients with stable coronary artery disease from the Prevention of Events With Angiotensin-Converting Enzyme Inhibition (PEACE) trial, a randomized placebo-controlled trial of the angiotensin-converting enzyme inhibitor trandolapril. Patients were followed up for a median of 4.8 years for cardiovascular death, myocardial infarction, or stroke, as well as new heart failure and diabetes. After adjustment for baseline characteristics and treatments, higher hs-CRP levels, even >1 mg/L, were associated with a significantly greater risk of cardiovascular death, myocardial infarction, or stroke (hs-CRP 1 to 3 mg/L: adjusted hazard ratio, 1.39; 95% CI, 1.06 to 1.81; P=0.016; hs-CRP >3 mg/L: adjusted hazard ratio, 1.52; 95% CI, 1.15 to 2.02; P=0.003). Similarly, elevated hs-CRP levels were an independent predictor of new heart failure (adjusted P<0.001 for trend) and new diabetes (adjusted P<0.001 for trend). There were no significant interactions between hs-CRP levels and the effects of trandolapril on any of the above outcomes.. In stable coronary artery disease, an elevated hs-CRP level, even >1 mg/L, is a significant predictor of adverse cardiovascular events independently of baseline characteristics and treatments. An elevated hs-CRP does not appear to identify patients with stable coronary artery disease and preserved ejection fraction who derive particular benefit from angiotensin-converting enzyme inhibition.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Coronary Artery Bypass; Coronary Disease; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Indoles; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Reference Standards; Stroke; Survival Analysis

Topics: Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Indoles; Middle Aged; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Angiotensin-converting-enzyme (ACE) inhibitors are effective in reducing the risk of heart failure, myocardial infarction, and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure. ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure.. In the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial, we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy. The trial was a double-blind, placebo-controlled study in which 8290 patients were randomly assigned to receive either trandolapril at a target dose of 4 mg per day (4158 patients) or matching placebo (4132 patients).. The mean (+/-SD) age of the patients was 64+/-8 years, the mean blood pressure 133+/-17/78+/-10 mm Hg, and the mean left ventricular ejection fraction 58+/-9 percent. The patients received intensive treatment, with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs. The incidence of the primary end point--death from cardiovascular causes, myocardial infarction, or coronary revascularization--was 21.9 percent in the trandolapril group, as compared with 22.5 percent in the placebo group (hazard ratio in the trandolapril group, 0.96; 95 percent confidence interval, 0.88 to 1.06; P=0.43) over a median follow-up period of 4.8 years.. In patients with stable coronary heart disease and preserved left ventricular function who are receiving "current standard" therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease, there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes, myocardial infarction, or coronary revascularization.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiovascular Diseases; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Indoles; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Renin-Angiotensin System; Ventricular Function, Left

The primary objective of the International Verapamil SR/Trandolapril Study (INVEST) is to compare the risk for adverse outcomes (all-cause mortality, nonfatal myocardial infarction [MI] or nonfatal stroke) in hypertensive patients with coronary artery disease (CAD) treated with either a calcium antagonist-based or a noncalcium antagonist-based strategy.. Treatment recommendations for hypertension include initial therapy with a diuretic or beta-adrenergic blocking agent, for which reductions in morbidity and mortality are documented from randomized trials but are less than expected from epidemiologic data. For this reason, recent attention has focused on calcium antagonists or angiotensin-converting enzyme inhibitors. While these agents reduce blood pressure, outcome data from large randomized trials are lacking, but some case-control data, dominated by short-acting dihydropyridines, suggest an increased risk of cardiovascular events. These studies had methodologic limitations and did not differentiate among calcium antagonist types and formulations. Several studies differentiating among calcium antagonist types and an overview of published randomized trials show no increased risk with verapamil and suggestion for benefit in CAD patients.. A total of 27,000 CAD patients with hypertension will be randomized at 1,500 primary care sites to receive either a calcium antagonist-based (verapamil) or beta-blocker/diuretic-based (atenolol/hydrochlorothiazide) antihypertensive care strategy. The study uses a novel, electronic "paper-less" system for direct on-screen data entry, randomization and drug distribution from a mail pharmacy linked to the coordination center via the Internet.. Contract negotiations with the United States and international sites are ongoing. Patients being enrolled are predominantly elderly (72% aged 60 years or older) men (54%), with either an abnormal coronary angiogram or prior MI (71%). In addition to hypertension, CAD and elderly age, most patients (89%) have one or more associated conditions (diabetes, dyslipidemia, smoking, cerebral or peripheral vascular disease, etc.) contributing to increased risk for adverse outcome. While 26% have diabetes, most of these are noninsulin dependent. Using the protocol strategies, target blood pressures (according to JNC VI) have been reached in 58% at the fourth visit, and as expected most (89%) are requiring multiple antihypertensive drugs.. The design and baseline characteristics of the initial patients recruited for a prospective, randomized, international, multicenter study comparing two therapeutic strategies to control hypertension in CAD patients are described.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Coronary Angiography; Coronary Disease; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypertension; Indoles; Male; Middle Aged; Prospective Studies; Research Design; Treatment Outcome; Verapamil

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. Phase separation has been exploited to fabricate intricate microstructures in many fields including cell biology, tissue engineering, optics, and electronics. The aim of this study was to use phase separation to tailor the spatial location of drugs and thereby generate release profiles of drug payload over periods ranging from 1 week to months by exploiting different mechanisms: polymer degradation, polymer diluent dissolution, and control of microstructure. To achieve this, we used drop-on-demand inkjet three-dimensional (3D) printing. We predicted the microstructure resulting from phase separation using high-throughput screening combined with a model based on the Flory-Huggins interaction parameter and were able to show that drug release from 3D-printed objects can be predicted from observations based on single drops of mixtures. We demonstrated for the first time that inkjet 3D printing yields controllable phase separation using picoliter droplets of blended photoreactive oligomers/monomers. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be "dialled up" without manipulation of device geometry. We exemplify this approach by fabricating a biodegradable, long-term, multiactive drug delivery subdermal implant ("polyimplant") for combination therapy and personalized treatment of coronary heart disease. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be easily exploited, which brings a hitherto unseen level of understanding to emergent material properties of 3D printing.

Topics: Antihypertensive Agents; Coronary Disease; Dioxanes; Drug Carriers; Drug Compounding; Drug Liberation; Excipients; Humans; Indoles; Methacrylates; Phase Transition; Polyesters; Polymers; Printing, Three-Dimensional; Pyrrolidinones; Structure-Activity Relationship

Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality. We assessed the association between albuminuria and the risks for death and cardiovascular events among patients with stable coronary disease.. We studied patients enrolled in the Prevention of Events with an ACE inhibitor (PEACE) trial, in which patients with chronic stable coronary disease and preserved systolic function were randomized to trandolapril or placebo and followed up for a median of 4.8 years. The urinary albumin to creatinine ratio (ACR) assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months) was related to estimated glomerular filtration rate and outcomes. The majority of patients (73%) had a baseline ACR within the normal range (<17 mug/mg for men and <25 mug/mg for women). Independent of the estimated glomerular filtration rate and other baseline covariates, a higher ACR, even within the normal range, was associated with increased risks for all-cause mortality (P<0.001) and cardiovascular death (P=0.01). The effect of trandolapril therapy on outcomes was not modified significantly by the level of albuminuria. Nevertheless, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 versus 14.6 mug/mg, P=0.0002), after adjustment for baseline ACR, time between collections, and other covariates. An increase in ACR over time was associated with increased risk of cardiovascular death (hazard ratio per log ACR 1.74, 95% CI 1.08 to 2.82).. Albuminuria, even in low levels within the normal range, is an independent predictor of cardiovascular and all-cause mortality.

Topics: Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Coronary Disease; Creatinine; Death; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Indoles; Kidney Diseases; Male; Middle Aged; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Factors; Survival Rate

Results from the HOPE and EUROPA trials showed that ACE inhibitors lower cardiovascular mortality of patients with atherosclerosis and preserved left ventricular function. However, despite apparently adequate study design, the recently conducted PEACE trial detected no benefit of an additional ACE inhibitor treatment in patients with coronary artery disease and no heart failure with respect to cardiovascular risk reduction. One of the main reasons for this discrepancy might be the lower cardiovascular baseline risk of the PEACE study population, which was more intensively treated with lipid lowering drugs and myocardial revascularization prior to enrollment than patients in HOPE or EUROPA. Another reason for the negative results of PEACE might be substance-specific differences between individual ACE inhibitors (trandolapril in PEACE, ramipril in HOPE, and perindopril in EUROPA) in their clinical efficacy to reduce cardiovascular end-points. The PEACE trial did not achieve the originally projected sample size and the addition of a soft end-point of revascularization has not been helpful. While the results from the PEACE trial suggest that low-risk patients with coronary artery disease and with preserved left ventricular function who receive intensive standard therapy including lipid lowering and coronary revascularization may not benefit from additional ACE inhibition therapy, this conclusion should be made with caution. A number of reasons, other than drug treatment efficacy, may explain the neutral results in the PEACE trial. Further studies are needed to try to resolve this issue. In the meantime, the overwhelming data still support the use of ACE inhibitors in patients with coronary artery disease with preserved left ventricular function.

Topics: Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Coronary Artery Bypass; Coronary Disease; Dose-Response Relationship, Drug; Humans; Indoles; Randomized Controlled Trials as Topic; Ventricular Function, Left

People of Hispanic origin are the fastest growing ethnic minority in the United States and often have hypertension and other comorbidities which increase the risk associated with coronary artery disease (CAD).. An analysis of the 8045 Hispanic patients enrolled in INVEST was conducted, and comparisons were made to the 14,531 non-Hispanic patients. INVEST was a prospective, randomized, open, blinded end point study in CAD patients with hypertension. After 61,835 patient-years of follow-up, treatment with either a verapamil sustained release (SR) or atenolol antihypertensive strategy resulted in greater blood pressure control in Hispanic patients, and Hispanic patients were at significantly lower risk of experiencing a nonfatal myocardial infarction, nonfatal stroke, or death (hazard ratio [HR] 0.87, 95% CI 0.78-0.97). Hispanic ethnicity was associated with an increase (HR 1.19, 95% CI 1.04-1.36), and randomization to the verapamil SR strategy was associated with a decrease (HR 0.85, 95% CI 0.76-0.95), in the risk of new-onset diabetes. Use of trandolapril in the verapamil SR strategy was associated with reduced risk of new-onset diabetes, whereas increasing doses of atenolol and hydrochlorothiazide in the atenolol strategy were associated with increased risk of new-onset diabetes.. The Hispanic cohort of INVEST had better blood pressure control and lower risk of adverse cardiovascular outcomes compared with the non-Hispanic cohort. A verapamil SR strategy is an alternative to an atenolol strategy for the treatment of Hispanic patients with hypertension and CAD and can reduce the risk of new-onset diabetes.

Topics: Aged; Antihypertensive Agents; Atenolol; Blood Pressure; Case-Control Studies; Cohort Studies; Coronary Disease; Delayed-Action Preparations; Female; Hispanic or Latino; Humans; Hypertension; Indoles; Male; Middle Aged; Randomized Controlled Trials as Topic; Systole; Treatment Outcome; Verapamil

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Coronary Disease; Humans; Indoles

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Coronary Disease; Humans; Indoles

Topics: Adrenergic beta-Antagonists; Adult; Aspirin; Blood Glucose; Calcium Channel Blockers; Clinical Trials as Topic; Coronary Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Diuretics; Female; Glycated Hemoglobin; Heart Failure; Humans; Hypertension; Hypolipidemic Agents; Indoles; Male; Platelet Aggregation Inhibitors; Prognosis; Risk Factors; Sex Factors; Verapamil

Topics: Angiotensin-Converting Enzyme Inhibitors; Cholesterol; Coronary Disease; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Humans; Indoles; Middle Aged; Randomized Controlled Trials as Topic; Severity of Illness Index; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiovascular Diseases; Chemotherapy, Adjuvant; Comorbidity; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Indoles; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Treatment Outcome; United States

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Clinical Trials as Topic; Coronary Angiography; Coronary Disease; Decision Making; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Indoles; Male; Middle Aged; Treatment Outcome

To understand the effects of single- and multiple-drug combinations for hypertension on the risk of adverse clinical outcomes, the authors analyzed data from the International Verapamil SR/Trandolapril Study (INVEST). This trial randomized 22,576 hypertensive patients with coronary artery disease to sustained-release verapamil or to atenolol as initial agents, followed by trandolapril or hydrochlorothiazide. Electronically collected prescription data from INVEST during 61,835 patient-years were analyzed using a Cox proportional hazards model with nine covariates (randomization strategy, four average daily dose terms, two ratios measuring the proportion of time the first two drugs in the treatment arm were coprescribed, and two interaction terms). Increasing doses of atenolol and sustained-release verapamil were associated with decreasing risk of the composite primary outcome (death, myocardial infarction, or stroke). Combination therapy with two drugs (verapamil/trandolapril or atenolol/hydrochlorothiazide) reduced the risk of primary outcome compared with monotherapy (verapamil or atenolol), and triple therapy (verapamil/trandolapril/hydrochlorothiazide or atenolol/hydrochlorothiazide/trandolapril) further reduced the risk.

Topics: Antihypertensive Agents; Atenolol; Calcium Channel Blockers; Chi-Square Distribution; Coronary Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Indoles; Male; Predictive Value of Tests; Proportional Hazards Models; Randomized Controlled Trials as Topic; Treatment Outcome; Verapamil

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Disease; Homocysteine; Humans; Hypertension; Indoles; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Stroke; Verapamil; Vitamins

Topics: Antihypertensive Agents; Coronary Disease; Drug Therapy, Combination; Europe; Humans; Hypertension; Indoles; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Research Design; Verapamil

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Coronary Disease; Heart Failure; Indoles; Treatment Failure; Ventricular Function, Left

Topics: Antihypertensive Agents; Coronary Disease; Diabetes Mellitus, Type 2; Drug Combinations; Humans; Hypertension, Renal; Indoles; Verapamil

Verapamil is effective as antianginal medication but contraindicated in patients with congestive heart failure. Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure but have limited effect on patients with angina pectoris. No studies have been published on the combined treatment with verapamil and ACE inhibitors in patients with stable angina pectoris and left ventricular dysfunction. We performed an open study in 14 patients with angina pectoris and ejection fraction < 40%. The patients received verapamil 180 mg and trandolapril 2 mg twice daily for 3 months. We found a significant increase in ejection fraction from 28 +/- 6 to 35 +/- 11 (p < 0.03), wall motion index from 1.0 +/- 0.3 to 1.2 +/- 0.3 (p < 0.03), exercise duration from 6.9 +/- 2.5 to 7.7 +/- 2.9 minutes (p < 0.01), and ratio of exercise to rest rate-pressure product from 2.2 +/- 0.4 to 2.5 +/- 0.6 (p < 0.02). Use of nitroglycerin and number of angina pectoris attacks were both significantly reduced after 3 months of treatment. These findings support the hypothesis that the combination of verapamil and trandolapril is useful in patients with attenuated left ventricular function and angina pectoris.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Coronary Disease; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Indoles; Male; Middle Aged; Ventricular Dysfunction, Left; Ventricular Function, Left; Verapamil

To assess the effectiveness of angiotensin converting enzyme inhibition in a proliferative porcine coronary restenosis model, 35 animals received orally administered trandolapril (10 mg) or captopril (200 mg) or no drug (control group) for 6 days before and 28 days after injury by oversized metallic coils in one or more coronary arteries. Twenty arterial lesions in the trandolapril group, 17 in the captopril group, and 18 in the control group were evaluated. There was no significant difference in neointimal thickness or percentage luminal area stenosis for the groups as a whole. However, in quantitative comparisons in which vessel injury score was used as a covariate, the fractional increase in mean neointimal thickness per unit of injury was significantly less for the trandolapril group (p = 0.019) but not for the captopril group when compared with control animals. In this model, neointimal proliferation from arterial injury was inhibited by angiotensin converting enzyme inhibition with trandolapril but only modestly. Such an effect may not be clinically significant.

Topics: Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Constriction, Pathologic; Coronary Disease; Coronary Vessels; Indoles; Peptidyl-Dipeptidase A; Recurrence; Swine; Tunica Intima