Heart rate-lowering and -regulating effects of once-daily sustained-release diltiazem

Background: Epidemiologic evidence suggests that an elevated heart rate (HR) is an adverse and independent prognostic factor in arterial hypertension and other cardiovascular diseases. Although diltiazem is characterized as an HR-lowering calcium antagonist, no studies have quantified the magnitude of HR changes in patients with angina or hypertension. Hypothesis: The study was undertaken to explore the magnitude of proportional HR reduction at varying levels of resting HR with the sustained-release formulation of diltiazem (SR diltiazem) at the usual clinical doses of 200 or 300 mg once daily. Methods: This meta-analysis was conducted on six comparative double-blind studies including 771 patients with angina or hypertension in which SR diltiazem 200-300 mg once daily was compared either with placebo or with other agents known not to influence HR (angiotensin-converting enzyme inhibitors, diuretics). Sustained-release diltiazem decreases elevated baseline HR, with an increasing effect at higher initial rates. Results: Multiple comparisons by baseline HR category showed a significant difference between both groups for baseline HR of 74-84 beats/min and greater than or equal to 85 beats/min (p = 0.001). Sustained-release diltiazem had no significant HR-decreasing effect on baseline HR less than or equal to 74 beats/min but appears to have a genuine regulating effect on HR: it reduces tachycardia without inducing excessive bradycardia. These findings are in contrast to those with dihydropyridine calcium antagonists, which tend to increase HR and have been associated with an adverse outcome in acute cardiovascular conditions. At the same time, there is evidence to suggest that HR-lowering calcium-channel blockers decrease cardiovascular event rates following myocardial infarction. Conclusion: When calcium antagonists are indicated for use in patients with angina or hypertension, an HR-lowering agent, that is, diltiazem rather than dihydropyridine, should be recommended.