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Long-Acting Calcium Channel Blockers in Hypertension



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Am Fam Physician. 1998 Jul 1;58(1):244.

Published reports have suggested that the use of calcium channel blockers is associated with an increased risk of myocardial infarction compared with diuretic and beta-blocker therapy. These reports were retrospective studies of patients using short-acting formulations. The newer, longer-acting calcium channel blockers differ markedly from the earlier preparations in terms of pharmacokinetics, pharmacodynamics and tolerability profiles. Kloner and associates reviewed the hypertension clinical trial databases compiled by Pfizer Inc. to evaluate the incidence of adverse cardiovascular events and rates of mortality in patients taking amlodipine or nifedipine in the gastrointestinal therapeutic system (GITS) formulation.

Data from all worldwide Pfizer-sponsored studies for the treatment of hypertension were included. Adverse cardiovascular events that were recorded included new or worsened angina, myocardial infarction, serious arrhythmia, stroke, congestive heart failure and bleeding. Deaths were categorized as cardiovascular or noncardiovascular.

In the amlodipine hypertension trials, most patients were exposed to treatment for five to 16 weeks, with 2,576 patients (8 percent of the total) using amlodipine for 17 weeks to more than two years. The incidence of adverse events in this group was equal to or lower than that in the aggregate comparative trial and placebo groups. In the nifedipine GITS hypertension trials, in which large numbers of patients (30 percent) took the drug for over six months, the incidence of adverse events also was not significantly different from that of the comparative trial groups and placebo groups. Although exposure to the trial drug may have been short in many of the study patients, the mechanisms hypothesized by some investigators to cause an increase in cardiac events with calcium channel blockers, such as proarrhythmia, negative inotropic effects, worsening ischemia and bleeding, do not necessarily require long-term exposure for an event to occur. The adverse events that were described with use of short-acting calcium channel blockers after acute myocardial infarction were most common within the first few weeks of drug therapy.

The authors conclude that patients taking amlodipine or nifedipine GITS do not have an increased risk of death or cardiovascular adverse events.

Kloner RA, et al. Safety of long-acting dihydropyridine calcium channel blockers in hypertensive patients. Am J Cardiol. January 15, 1998;81:163–9.


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