title: Safety of long-acting dihydropyridine calcium channel blockers in hypertensive patients.
abstract: Issues raised recently concerning the safety of calcium channel blockers (CCBs) prompted an analysis of the occurrence of cardiovascular events and death in the Pfizer Inc. hypertension clinical trial databases for amlodipine (Norvasc) and nifedipine in the gastrointestinal therapeutic system (GITS) formulation (Procardia XL). Prospectively defined analyses of data from comparative and noncomparative trials of amlodipine and nifedipine GITS were conducted. Outcome measures included cardiovascular and noncardiovascular deaths, and adverse cardiovascular events including new/worsened angina, myocardial infarction (MI), serious arrhythmia, stroke, congestive heart failure, and bleeding. Among all amlodipine-treated patients (n = 32,920), the incidence rates for all-cause death, MI, and new/worsened angina were 3.0, 3.3, and 1.6/1,000 patient-years of exposure, respectively. Among those in comparative trials alone (n = 4,126), the all-cause death rate was 4.1/1,000 patient-years, which was comparable to that of other non-CCB agents and significantly less than that of other CCBs (23.8/1,000 patient-years, p = 0.015), although the difference in rates represents only 2 deaths. Among all nifedipine-GITS-treated patients (n = 2,645), the rate of all-cause death was 4.1/1,000 patient-years, of MI 6.5/1,000 patient-years, and of new/ worsened angina 5.7/1,000 patient-years. The incidence rates for MI and other cardiac events were low in these hypertension trials, and did not differ among treatment groups in either the amlodipine or nifedipine GITS comparative analyses. In the clinical trial databases analyzed, there is no signal suggesting excessive risk of death or cardiovascular events for hypertensive patients treated with amlodipine or nifedipine GITS.
authors.affiliation: Heart Institute, Good Samaritan Hospital and the University of Southern California, Los Angeles 90017, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Kloner
authors.forename: G W
authors.initials: GW
authors.lastname: Vetrovec
authors.forename: B J
authors.initials: BJ
authors.lastname: Materson
authors.forename: M
authors.initials: M
authors.lastname: Levenstein
mesh_terms: D017311:Amlodipine / Q000009:adverse effects* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000009:adverse effects* / Q000627:therapeutic use; D002423:Cause of Death; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000453:epidemiology; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced / Q000453:epidemiology; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology; D009543:Nifedipine / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D017311:Amlodipine; D009543:Nifedipine