Calcium channel antagonists are widely used
antihypertensive agents. Their popularity among primary care physicians is not only due to their blood pressure-lowering effects, but also because they appear to be effective regardless of the age or ethnic background of the patients. The first available
calcium channel antagonists utilized immediate-release formulations which, although effective in patients with
angina pectoris, were not approved by the US FDA for use in
hypertension. When long-acting once-daily formulations were approved in this indication, the short-acting preparations--which had by then become generic and inexpensive--retained some residual unapproved use for
hypertension. An observational case-controlled trial, based on such usage, noted that these agents were associated with a greater risk of
myocardial infarctions than conventional agents such as
diuretics and
beta-adrenoceptor antagonists. Further case-controlled trials showed, in fact, that the dangers of
calcium channel antagonists were confined to the short-acting agents and that approved long-acting agents were at least as well tolerated and effective as other
antihypertensive drugs. Cardiovascular outcomes during treatment with
calcium channel antagonists have been examined in randomized, controlled trials. Compared with placebo, the
calcium channel antagonists clearly prevented
strokes and other cardiovascular events and reduced mortality. The effects of these agents on survival and clinical outcomes were similar to those with other
antihypertensive drugs. There is a slight tendency for the
calcium channel antagonists to be more effective than other
drug types in preventing
stroke, but slightly less effective in preventing coronary events. These observations extend to high-risk patients with
hypertension including those with
diabetes mellitus. Even so, patients with evidence of nephropathy should not receive monotherapy with
calcium channel antagonists. Such patients are optimally treated with
angiotensin receptor antagonists or
ACE inhibitors, although addition of other drugs, including
calcium channel antagonists, is often required to achieve the tight blood pressure control necessary to provide adequate renal protection.
Calcium channel antagonists have a highly acceptable tolerability profile and careful reviews of available data have shown that their use is not associated with increased
bleeding or promotion of
tumor formation. It is now recognized that reduction of blood pressure in patients with
hypertension to levels often <130/85 mm Hg should be undertaken in presence of other cardiovascular risk factors or evidence of end organ damage. Because of this important concept,
calcium channel antagonists, like the other
antihypertensive drug classes, are progressively being prescribed less often as monotherapy, but more typically as part of combination regimens.