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Heart rate-lowering and -regulating effects of once-daily sustained-release diltiazem
W E Boden1, M Vray, E Eschwege
1State University of New York Health Science Center and the Syracuse VA Medical Centre, Syracuse, New York, USA.
Insights
Sustained-release diltiazem effectively lowers elevated heart rate (HR) in patients with angina or hypertension, particularly at higher baseline HRs. This HR-lowering effect contrasts with dihydropyridine calcium antagonists, suggesting diltiazem as a preferred choice.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Elevated heart rate (HR) is an independent prognostic factor in arterial hypertension and cardiovascular diseases.
- Diltiazem is a calcium antagonist known to lower HR, but its effect magnitude in angina or hypertension lacked quantification.
Purpose of the Study:
- To quantify the proportional HR reduction with sustained-release diltiazem (SR diltiazem) at usual clinical doses (200-300 mg daily).
- To explore HR changes at varying levels of resting HR.
Main Methods:
- Meta-analysis of six double-blind studies involving 771 patients with angina or hypertension.
- Comparison of SR diltiazem (200-300 mg daily) against placebo or HR-neutral agents (ACE inhibitors, diuretics).
Main Results:
- SR diltiazem significantly decreased elevated baseline HR, with a greater effect at higher initial rates (74-84 bpm and ≥85 bpm).
- No significant HR reduction was observed at baseline HR ≤74 bpm.
- Diltiazem demonstrated a regulating effect, reducing tachycardia without causing excessive bradycardia, unlike dihydropyridines which can increase HR.
Conclusions:
- Diltiazem, an HR-lowering calcium antagonist, should be recommended over dihydropyridines for patients with angina or hypertension.
- HR-lowering calcium-channel blockers may decrease cardiovascular event rates post-myocardial infarction.
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 > or = 85 beats/min (p = 0.001). Sustained-release diltiazem had no significant HR-decreasing effect on baseline HR < or =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.