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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Issues raised recently concerning the safety of calcium channel blockers (CCBs) prompted an analysis of the occurrence of cardiovascular events and death in the Pfizer Inc. hypertension clinical trial databases for amlodipine (Norvasc) and nifedipine in the gastrointestinal therapeutic system (GITS) formulation (Procardia XL). Prospectively defined analyses of data from comparative and noncomparative trials of amlodipine and nifedipine GITS were conducted. Outcome measures included cardiovascular and noncardiovascular deaths, and adverse cardiovascular events including new/worsened angina, myocardial infarction (MI), serious arrhythmia, stroke, congestive heart failure, and bleeding. Among all amlodipine-treated patients (n = 32,920), the incidence rates for all-cause death, MI, and new/worsened angina were 3.0, 3.3, and 1.6/1,000 patient-years of exposure, respectively. Among those in comparative trials alone (n = 4,126), the all-cause death rate was 4.1/1,000 patient-years, which was comparable to that of other non-CCB agents and significantly less than that of other CCBs (23.8/1,000 patient-years, p = 0.015), although the difference in rates represents only 2 deaths. Among all nifedipine-GITS-treated patients (n = 2,645), the rate of all-cause death was 4.1/1,000 patient-years, of MI 6.5/1,000 patient-years, and of new/ worsened angina 5.7/1,000 patient-years. The incidence rates for MI and other cardiac events were low in these hypertension trials, and did not differ among treatment groups in either the amlodipine or nifedipine GITS comparative analyses. In the clinical trial databases analyzed, there is no signal suggesting excessive risk of death or cardiovascular events for hypertensive patients treated with amlodipine or nifedipine GITS.
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PMID:Safety of long-acting dihydropyridine calcium channel blockers in hypertensive patients. 959 99

Calcium antagonists, particularly the newer, longer-acting agents, are clearly effective in reducing elevated blood pressure with minimal to modest adverse effect profiles, and are therefore used extensively. The goal of antihypertensive therapy, however, is not simply to reduce blood pressure, but also to reduce vascular injury due to hypertension. Prospective controlled clinical trials evaluating cardiovascular morbidity and mortality are needed to test calcium antagonists in patients with hypertension. This review summarises the design and, in some cases, the results of 7 trials (5 of them still ongoing) that have provided insight into the effects of moderate- to long-acting calcium antagonists on mortality and target-organ damage in patients with hypertension. The Systolic Hypertension in Europe (Syst-Eur) trial studied 4695 elderly patients with isolated systolic hypertension, and demonstrated significant reductions in stroke and all fatal and nonfatal cardiac end-points in patients randomised to nitrendipine versus placebo. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compares the effects of standard diuretic treatment with 3 alternatives (amlodipine, lisinopril, and doxazosin) on the incidence of fatal coronary artery disease and nonfatal myocardial infarction in more than 42,000 hypertensive patients with additional cardiovascular risk factors. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) compares the effects of amlodipine +/- perindopril with atenolol +/- bendrofluazide on fatal coronary artery disease and nonfatal myocardial infarction in 18,000 high risk patients. The Controlled ONset Verapamil INvestigation of Cardiovascular End-points (CONVINCE) study is assessing the incidence of fatal or nonfatal myocardial infarction and stroke, and cardiovascular disease-related death in patients on controlled-onset extended-release verapamil compared with a standard regimen of hydrochlorothiazide or atenolol. The Nordic Diltiazem Study (NORDIL) also compares a calcium antagonist (diltiazem) with conventional antihypertensive drug treatment (diuretics or beta-blockers) with add-on therapy as needed, in preventing cardiovascular mortality or morbidity. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) tests a similar hypothesis, examining the effects of amlodipine on atherosclerotic lesions. The African-American Study of Kidney Disease (AASK) trial is evaluating the effects of amlodipine in hypertensive patients with renal disease. These important clinical trials of different classes of antihypertensive agents are critical for optimising the treatment of hypertensive patients in order to prevent coronary artery disease and other vascular diseases in this new millennium. Importantly, these randomised trials are free of the major problems of observational studies, i.e., confounding by indication, and should fully address the concerns raised by observational studies and small, under-powered, randomised trials that calcium antagonists may have adverse effects on myocardial infarction, bleeding and cancer. To date, these trials in progress have provided no evidence to support these concerns.
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PMID:[Calcium antagonists in cardiovascular disease. Clinical evidence from morbidity and mortality trials]. 1100 56

Myocardial infarction, stroke, heart failure and end-stage renal disease have all been linked to inadequate control of blood pressure. Despite overwhelming evidence that uncontrolled hypertension is responsible for a sizeable number of adverse health-related outcomes, control of the disease remains considerably suboptimal. Available data demonstrate that in order to achieve adequate blood pressure control, a large number of patients require therapy with more than one medication. Fixed dose combination antihypertensive therapy has many advantages over other treatment options. Positive effects on blood pressure control, rates of adherence, adverse effects and cost have been identified. Amlodipine/benazepril (Lotrel), Novartis) is a fixed dose combination product indicated for the treatment of hypertension. Although not currently recommended as first-line therapy, studies confirm that this combination of a long-acting calcium antagonist and an angiotensin-converting enzyme (ACE) inhibitor possesses substantial blood pressure lowering capabilities. Whereas adverse events tend to become more frequent with increasing doses of antihypertensive monotherapy, the rate of adverse events attributed to amlodipine/benazepril in clinical trials often correlates with rates ascribed to placebo. Amlodipine/benazepril is capable of sustaining blood pressure control over a 24 h period and appears to be minimally affected by an occasional dose omission. Unlike the older calcium antagonists, amlodipine is unlikely to cause alterations in myocardial contractility. Additionally, the amlodipine/benazepril combination product costs less than the same therapy administered as the individual components. It is, therefore, reasonable to consider therapy with amlodipine/benazepril in appropriate patients after an adequate trial of antihypertensive monotherapy.
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PMID:Amlodipine/benazepril: fixed dose combination therapy for hypertension. 1133 77