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

Abstract

SummaryBrrckgmui7d: 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.Morlzods: This meta-analysis was conducted on six comparative double-blind studies including 77 1 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 2 85 beatdmin (p = 0.001 ). Sustained-release diltiazem had no significant HR-decreasing effect on baseline HR 1 7 4 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 cardiovascularconditions. At the same time, there is evidence to suggest that HR-lowering calcium-channel blockers decrease cardiovascularevent 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.

Pharmacokinetics of a Novel Diltiazem HCl Extended‐Release Tablet Formulation for Evening Administration

“…It has been used widely in the treatment of angina, hypertension, and cardiac arrhythmias 2 . Sustained‐release diltiazem has been reported to reduce tachycardia without inducing excessive bradycardia and does not significantly reduce baseline heart rate below 74 beats/min 3 . Following oral administration, diltiazem is readily absorbed from the gastrointestinal tract and undergoes substantial first‐pass metabolism.…”

“…2 Sustainedrelease diltiazem has been reported to reduce tachycardia without inducing excessive bradycardia and does not significantly reduce baseline heart rate below 74 beats/min. 3 Following oral administration, diltiazem is readily absorbed from the gastrointestinal tract and undergoes substantial first-pass metabolism. The systemic bioavailability of the immediate-release preparation is approximately 40% to 50%, with an elimination half-life of 3.5 to 7 hours.…”

Diltiazem Hcl: Evaluation of Its Presence in Bangladesh

“…Many clinical data are available to prove these claims. It was found according to a study conducted by Boden et al in 2001, after the administration of diltiazem, 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 (at the usual clinical doses of 200 or 300 mg once daily) had no significant HR-decreasing effect on baseline HR 74 beats/min or less but appears to have a genuine regulating effect on HR: it reduces tachycardia without inducing excessive bradycardia 16 .…”

“…Diltiazem has also been found to be associated with a very low rate of hypotension and to be effective in decreasing HR adequately in a prehospital setting 12 . Pharmacokinetic features of Diltazem HCL make it a potential candidate for extended release once-a-day dosage form (Gal and Nussinovitch, 2007; Gondaliya and Pundarikakshudu, 2003) 13 . Diltiazem also prevents the tubular necrosis of kidneys through its calcium channel blocker action and maintains normal level of EPO which stimulates CFU cells in bone marrow for the production of hematopoietic cells.…”

Diltiazem como alternativa ao betabloqueador na angiotomografia de artérias coronárias

“…One alternative to beta-blockers for HR reduction in CTACor and that does not have contraindications in patients with bronchoconstriction pulmonary disease are nondihydropyridine calcium-channel blockers, such as verapamil (fenyl-alquilamines) and diltiazem (benzothiazepines) 19 . However, although mentioned in many texts as an alternative to beta-blockers, the efficacy of calcium-channel blockers used in the decrease of HR prior to the CTACor has not been clearly defined and comparative data are still unavailable.…”