Calcium antagonists and atherosclerosis protection in hypertension.
Calcium antagonists are effective in hypertensive patients of all ethnic groups, irrespective of age, dietary salt intake, salt-sensitivity status or plasma renin activity profile. Some prospective studies show that the calcium antagonists, nifedipine GITS and nitrendipine, reduce cardiovascular morbidity and mortality at least to the same extent as the diuretics. Other prospective studies are in progress to evaluate the effect of calcium antagonists on cardiovascular morbidity and mortality, and the progression of atherosclerosis in hypertensive patients. Calcium antagonists, especially the highly lipophilic amlodipine, lacidipine and nisoldipine, are shown to possess antioxidant properties. These drugs reduce the oxidation of LDL and its influx into the arterial wall, and reduce atherosclerotic lesions in animals. Platelet production of malondialdehyde, a marker of oxygen free radical formation, is suppressed by amlodipine, lacidipine or nifedipine in hypertensive patients. New evidence from long-term clinical trials of calcium antagonists indicates that these drugs can reduce the rate of progression of atherosclerosis in hypertensive and coronary heart disease patients. In the Regression Growth Evaluation Statin Study (REGRESS), co-administration of calcium antagonist, amlodipine or nifedipine with pravasatin caused a significant reduction in the appearance of new angiographic lesions. In the Verapamil in Hypertension and Atherosclerosis Study (VHAS), verapamil was more effective than chlorthalidone in promoting regression of thicker carotid lesions in parallel with a reduction in the incidence of cardiovascular events. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), amlodipine slowed the progression of early coronary atherosclerosis in patients with coronary artery disease. In a subprotocol of the Intervention as a Goal in the Hypertension Treatment (INSIGHT) study, nifedipine GITS significantly decreased intima-media thickness as compared to co-amilozide (hydrochlorothiazide + amiloride). Preliminary results of the European Lacidipine Study on Atherosclerosis (ELSA) show that lacidipine reduced the intima-media thickness progression rate as compared to atenolol. Thus, selective calcium antagonists are potential antiatherosclerotic agents.
Hernández
Rafael Hernández
RH
Clinical Pharmacology Unit, School of Medicine, Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Venezuela. rhernan@cantv.net
Armas-Hernández
María José
MJ
Velasco
Manuel
M
Israili
Zafar H
ZH
Armas-Padilla
María Cristina
MC
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D012307:Risk Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D008077:Lipoproteins, LDL; D014665:Vasodilator Agents