title: Long-acting diltiazem HCl for the chronotherapeutic treatment of hypertension and chronic stable angina pectoris.
abstract: Hypertension is associated with increased cardio- and cerebrovascular morbidity and mortality; antihypertensive drugs have been shown to reduce the risk of adverse cardio- and cerebrovascular events. These events tend to be more common during the morning hours, a time when both normo- and hypertensives show a circadian peak in blood pressure (BP). Although clinicians have a number of safe and well-tolerated antihypertensive agents in various classes and formulations at their disposal, few are designed to specifically attenuate the morning BP surge while maintaining 24-h efficacy. A novel, once-daily, long-acting formulation of diltiazem HCl (DTZ-LA) has been developed with chronodynamics in harmony with diurnal BP variation. DTZ-LA effectively reduces BP in a dose-dependent fashion over a 24-h dosing interval in patients with moderate-to-severe essential hypertension. When compared with a morning dose, the evening dose is associated with significant and clinically meaningful greater reductions in BP during the morning hours, when adverse cardiovascular events tend to cluster. Evening-dosed DTZ-LA was more effective than morning-dosed amlodipine in reducing morning diastolic BP in African-Americans. Evening-dosed DTZ-LA was also more effective than evening-dosed ramipril in reducing morning BP. Evening dosing of DTZ-LA significantly increased exercise tolerance in patients with angina pectoris over the 24-h interval. DTZ-LA is associated with adverse effects consistent with other diltiazem formulations, and overall is safe and well tolerated, even when titrated to doses of 540 mg/day.
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota, 1300 South Second Street, Suite 300, Minneapolis, MN 55454-1015, USA. claas@epi.umn.edu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Claas
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Glasser
mesh_terms: D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy*; D002908:Chronic Disease; D019454:Chronotherapy / Q000379:methods*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004110:Diltiazem / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*
chemical_list: D003692:Delayed-Action Preparations; D004110:Diltiazem