Recently, controversies have arisen concerning the proper use of calcium channel blockers. The medical literature has focused particular attention on the possibility that some of these agents may increase the risk of cardiovascular morbidity or mortality. This debate provides an impetus for us to review the pharmacologic and clinical characteristics of this heterogeneous group of agents.
In this monograph, Robert W. Piepho, PhD, points out that the phenylalkylamines (eg, verapamil), benzothiazepines (eg, diltiazem), and dihydropyridines (eg, nifedipine) have distinct chemical identities. The pharmacologic profiles of verapamil and diltiazem, however, are much more similar to one another than either is to that of the dihydropyridines. Each of the three agents has a specific binding site, tissue selectivity, hemodynamic effects, and adverse event profile.
In light of these characteristics, some observers have recommended that the nomenclature for this class of agents be changed such that verapamil and diltiazem are considered one subgroup and the dihydropyridines as another subgroup. One possibility would be to designate verapamil and diltiazem as "modulating" calcium channel blockers (because of their cardiac effects) and dihydropyridines as "vasodilating" calcium channel blockers. A less attractive suggestion is that all three be referred to as calcium antagonists, but that only verapamil and diltiazem be termed calcium channel blockers.
The Safety Controversy
Dr. Boden then reviews a metaanalysis in which Furberg et al found that short-acting nifedipine significantly increased the risk of total mortality among patients with coronary heart disease. He notes that several commentators cited methodologic problems and inconsistencies that may have influenced the analysis. These commentators have also stressed that, even if the findings were correct, it is not appropriate to extrapolate the conclusions to other short-acting calcium channel blockers or to the newer, longer-acting formulations.
Dr. Boden concludes that the current evidence provides no justification for discontinuing antihypertensive therapy with long-acting calcium channel blockers-particularly those that lower heart rate. His timely review should help physicians respond to patients questions and allay fears regarding the safety of these medications.
Treating Elderly Hypertensive Patients At the same time, the physician must take into account the high likelihood of comorbid conditions in the elderly. Diuretics tend to produce abnormalities in lipid and glucose metabolism, which can be an important consideration in view of the prevalence of significant atherosclerosis and noninsulin-dependent diabetes mellitus in the elderly. Beta blockers tend to increase peripheral vascular resistance, which already tends to be high in this population. Older patients are also apt to have low serum renin levels, a setting in which beta blockers are less effective. The angiotensin converting enzyme inhibitors offer an alternative, but may be less effective than other antihypertensive agents in some elderly patients.
Dr. Applegate suggests that the calcium channel blockers may be an advantageous group of drugs in older hypertensives, although the different hemodynamic profiles of the individual agents bear consideration. He proposes that the heart rate-lowering nondihydropyridines (verapamil and diltiazem) may provide optimal antihypertensive effects while avoiding the possible proischemic effects of the dihydropyridines.
It is hoped that the information presented here will contribute to a better understanding of the current roles of the various calcium channel blockers in the therapeutic armamentarium.
[Pharmacology | Cardiovascular Risk | Elderly Hypertensives
In the final article, William B. Applegate, MD, addresses issues involved in selecting optimal antihypertensive therapy for older patients. He notes that the treatment of hypertension, including isolated systolic hypertension, yields marked benefits in this population, including significant reductions in the risk of stroke, cardiovascular morbidity and mortality, and total mortality. Studies with low-dose diuretics have shown particular benefit.
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