Calcium Channel Blockers: Some Safe: Two 1995 studies linked high doses of short-acting nifedipine with an increased risk of heart attack and death. A more recent European study of 6,300 people ages 55 to 80 with blood pressures higher than 150/95 mm Hg or systolic BPs over 160 with at least one additional cardiovascular risk factor were randomized to either 30 mg/day of long-acting nifedipine or a diuretic combination (25 mg hydrochlorothiazide plus 2.5 mg amiloride). After about three years, both groups had the same average BP (138/82 mm Hg), and a similar proportion of each group (6%) had died from cardiovascular disease, had a heart attack, suffered a stroke, or developed heart failure. Nearly 40% of nifedipine users withdrew because of such side effects as swollen legs and skin flushing, compared with 33% of diuretic users. But more diuretic users suffered severe adverse effects, such as impaired kidney function. In another study, nearly 11,000 people aged 50 to 74 with diastolic BPs of 100 mm Hg or higher were assigned to diltiazen 180 to 360 mg or diuretics, beta-blockers, or both. Diltiazem users had slightly fewer strokes than those taking diuretics, beta-blockers, or both. Lancet. 2000;356:352-3, 359-65. 

Calcium Channel Blockers Inferior: A meta-analysis of larger long-term studies of hypertension found nine eligible trials included 27,743 participants. Calcium antagonists and other drugs achieved similar control of both systolic and diastolic blood pressure. Compared with patients assigned diuretics, beta-blockers, angiotensin-converting-enzyme inhibitors, or clonidine (n=15,044), those assigned calcium antagonists (n=12,699) had a significantly higher risk of acute myocardial infarction (odds ratio 1.26, p=0.0003), congestive heart failure (1.25, p=0.005), and major cardiovascular events (1.10, p=0.018). The treatment differences were within the play of chance for the outcomes of stroke (0.90 [0.80-1.02], p=0.10) and all-cause mortality (1.03, p=0.54). The longer-acting calcium antagonists cannot be recommended as first-line therapy for hypertension. Health outcomes associated with calcium antagonists compared with other first-line antihypertensive therapies: a meta-analysis of randomised controlled trials. Pahor M, Psaty BM, et al. Wake Forest University. Lancet. 2000 Dec 9;356(9246):1949-54

Nifedipine No Decrease in Death: In the DB PC ACTION study of 7665 patients, 52% were hypertensive. Some 80% were on a beta blocker; hypertensives were more often treated with other blood pressure-lowering drugs. Mean baseline blood pressure was 122/74 mmHg among normotensives and 151/85 mmHg among hypertensives. Follow-up blood pressures were reduced by nifedipine (P < 0.001) on the average by 3.9/2.4 and 6.6/3.5 mmHg among normotensives and hypertensives, respectively. Authors emphasize that nifedipine GITS (P < 0.05) reduced the combined incidence of all-cause mortality, myocardial infarction, refractory angina, heart failure, stroke and peripheral revascularization by 13% in hypertensives only. However, nifedipine did not affect all-cause death, cardiovascular death and myocardial infarction in either normo- or hypertensives, but increased the need for peripheral revascularization. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with symptomatic stable angina and hypertension: the ACTION trial. Lubsen J, Wagener G, et al. Erasmus Medical and Bayer Healthcare AG, Wuppertal, Germany. J Hypertens. 2005 Mar;23(3):641-8

Thomas E. Radecki, M.D., J.D.

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