Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): Additional perspectives on tolerability of long-term treatment with lovastatin

This study presents the long-term safety data from AFCAPS/TexCAPS, the firs t primary prevention trial to demonstrate that men and women with average l evels of low-density lipoprotein cholesterol (LDL-C) and below average leve ls of high-density lipoprotein cholesterol (HDL-C) can significantly benefi t from long-term treatment to lower LDL-C; lovastatin 20 to 40 mg/day reduc ed the risk of a first acute major coronary event (fatal or nonfatal myocar dial infarction, unstable angina, or sudden death) by 37% (p = 0.00008). Th is double-blind randomized, placebo-controlled trial, in 6,605 generally he althy middle-aged and older men and women, had prespecified end point and c ancer analyses. All analyses were intention-to-treat. Safety monitoring inc luded history, physical examination, and laboratory studies (including hepa tic transaminases and creatine phosphokinase [CPK]). All participants, even those who discontinued treatment, were contacted annually for vital status , cardiovascular events, and cancer history. After an average of 5.2 years of follow-up, there were 157 deaths (80 receiving lovastatin and 77 receivi ng placebo; relative risk [RR] 1.04; 95% confidence interval [CI] 0.76 to 1 .42; p = 0.82); of which 115 were non-cardiovascular (RR 1.21;CI 0.84 to 1. 74; p = 0.31), and of these, 82 were due to cancer (RR 1.41; CI 0.91 to 2.1 9; p = 0.13). There were no significant differences between treatment group s in overall cancer rates, discontinuations for noncardiovascular adverse e xperiences, or clinically important elevations of hepatic transaminases or CPK, Among those who used cytochrome P450 isoform (CYP3A4) inhibitors, ther e were no treatment group differences in the frequency of clinically import ant muscle-related adverse events. Treatment with lovastatin 20 to 40 mg da ily for primary prevention of coronary heart disease was well tolerated and reduced the risk of first acute coronary events without increasing the ris k of either noncardiovascular mortality or cancer. (C) 2001 by Excerpta Med ica, Inc.