A personal view of the controversy regarding the use of calcium channel blockers in hypertension

Abstract

Aim The purpose of this review is to add perspective to the current controversy surrounding the role of calcium channel blockers in the treatment of hypertension. Calcium blocker safety Well-conducted retrospective studies have raised concern about various aspects of the long-term safety of calcium blockers. These include: (1) a case cohort study by Psaty et al. in hypertensive patients indicating that calcium blockers were associated with an increased risk of myocardial infarction (> 50% increase) compared to diuretics or β-blockers; (2) a meta-analysis by Furberg et al. of 16 studies suggesting that nifedipine increases mortality in acute coronary syndromes; (3) a trial in which isradipine was associated with more cardiovascular events in hypertensive patients than in those taking hydrochlorothiazide; (4) a report by Pahor and colleagues of an increased risk of gastrointestinal bleeding in elderly patients taking isradipine; and (5) a further report by Pahor et al. that the incidence of most common cancers appeared to be higher in patients taking calcium blockers than other cardiac medications (relative risk = 1.72; 95% confidence interval 1.2–2.34, P = 0.0005). The majority of these observations were made with short-acting calcium blockers, which are not indicated for the treatment of hypertension. In contrast, other well-controlled clinical trials are consistent with long-term calcium blocker safety. Some reports support a difference in the safety of calcium blockers that increase heart rate and those that decrease heart rate. There is also an indication that longer acting formulations of dihydropyridines and verapamil and diltiazem may have a better long-term safety profile in hypertension than the short-acting calcium blockers (which were the primary focus of many of the adverse reports). Secondary prevention trials of diltiazem [Multicenter Diltiazem Postinfarction Trial (MDPIT), Diltiazem Reinfarction Study (DRS)] and secondary prevention trials of verapamil (Danish Study on Verapamil in Myocardial Infarction; DAVIT I, II) are generally supportive of long-term calcium blocker safety except in patients with heart failure. A retrospective study of > 11000 patients with coronary artery disease did not support an association between the use of calcium blockers and increased mortality. A case–control trial of general practice experience in the United Kingdom found no increased risk of myocardial infarction using calcium blockers compared to β-blockers for the treatment of hypertension. Conclusion I support the current recommendations of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure that thiazides and β-blockers be considered first as initial therapy. The studies questioning the safety of calcium blockers are certainly concerning but not sufficient to justify condemning their use in hypertension. Calcium blockers remain a reasonable alternative therapy in hypertension.