Showing papers by "Michael Clearfield published in 2001"

Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.

Abstract: Background Elevated levels of C-reactive protein, even in the absence of hyperlipidemia, are associated with an increased risk of coronary events. Statin therapy reduces the level of C-reactive protein independently of its effect on lipid levels. We hypothesized that statins might prevent coronary events in persons with elevated C-reactive protein levels who did not have overt hyperlipidemia. Methods The level of C-reactive protein was measured at base line and after one year in 5742 participants in a five-year randomized trial of lovastatin for the primary prevention of acute coronary events. Results The rates of coronary events increased significantly with increases in the base-line levels of C-reactive protein. Lovastatin therapy reduced the C-reactive protein level by 14.8 percent (P<0.001), an effect not explained by lovastatin-induced changes in the lipid profile. As expected, lovastatin was effective in preventing coronary events in participants whose base-line ratio of total cholesterol to high-de...

Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events☆

Abstract: BACKGROUND Elevated levels of C-reactive protein, even in the absence of hyperlipidemia, are associated with an increased risk of coronary events. Statin therapy reduces the level of C-reactive protein independently of its effect on lipid levels. We hypothesized that statins might prevent coronary events in persons with elevated C-reactive protein levels who did not have overt hyperlipidemia. METHODS The level of C-reactive protein was measured at base line and after one year in 5742 participants in a five-year randomized trial of lovastatin for the primary prevention of acute coronary events. RESULTS The rates of coronary events increased significantly with increases in the base-line levels of C-reactive protein. Lovastatin therapy reduced the C-reactive protein level by 14.8 percent (P<0.001), an effect not explained by lovastatin-induced changes in the lipid profile. As expected, lovastatin was effective in preventing coronary events in participants whose base-line ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol was higher than the median ratio, regardless of the level of C-reactive protein (number needed to treat for five years to prevent 1 event, 47; P=0.005). However, lovastatin was also effective among those with a ratio of total to HDL cholesterol that was lower than the median and a C-reactive protein level higher than the median (number needed to treat, 43; P=0.02). In contrast, lovastatin was ineffective among participants with a ratio of total to HDL cholesterol and a C-reactive protein level that were both lower than the median (number needed to treat, 983; P=0.80). CONCLUSIONS Statin therapy may be effective in the primary prevention of coronary events among subjects with relatively low lipid levels but with elevated levels of C-reactive protein.

Air force/texas coronary atherosclerosis prevention study (afcaps/texcaps): Additional perspectives on tolerability of long-term treatment with lovastatin

Abstract: This study presents the long-term safety data from AFCAPS/TexCAPS, the first primary prevention trial to demonstrate that men and women with average levels of low-density lipoprotein cholesterol (LDL-C) and below average levels of high-density lipoprotein cholesterol (HDL-C) can significantly benefit from long-term treatment to lower LDL-C; lovastatin 20 to 40 mg/day reduced the risk of a first acute major coronary event (fatal or nonfatal myocardial infarction, unstable angina, or sudden death) by 37% (p = 0.00008). This double-blind randomized, placebo-controlled trial, in 6,605 generally healthy middle-aged and older men and women, had prespecified end point and cancer analyses. All analyses were intention-to-treat. Safety monitoring included history, physical examination, and laboratory studies (including hepatic 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 receiving placebo; relative risk [RR] 1.04; 95% confidence interval [CI] 0.76 to 1.42; p = 0.82); of which 115 were noncardiovascular (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 2.19; p = 0.13). There were no significant differences between treatment groups in overall cancer rates, discontinuations for noncardiovascular adverse experiences, or clinically important elevations of hepatic transaminases or CPK. Among those who used cytochrome P450 isoform (CYP3A4) inhibitors, there were no treatment group differences in the frequency of clinically important muscle-related adverse events. Treatment with lovastatin 20 to 40 mg daily for primary prevention of coronary heart disease was well tolerated and reduced the risk of first acute coronary events without increasing the risk of either noncardiovascular mortality or cancer.

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): efficacy and tolerability of long-term treatment with lovastatin in women.

Abstract: The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is the first coronary heart disease (CHD) primary prevention trial of the cholesterol-reducing agents called "statins" to include women. For 5608 men and 997 postmenopausal women without clinical evidence of cardiovascular disease (CVD) who had average low-density lipoprotein cholesterol (LDL-C) and below average high-density lipoprotein cholesterol (HDL-C), 20-40 mg/day lovastatin reduced first acute major coronary events (AMCEs) 37% (for those receiving placebo and lovastatin, respectively, 183 and 116 first AMCEs defined as fatal or nonfatal myocardial infarction [MI], unstable angina, or sudden cardiac death; relative risk [RR] 0.63; 95% confidence interval [95% CI] 0.50, 0.79; p < 0.001). Statistically significant reductions in prespecified secondary end points (coronary revascularizations, unstable angina, MI, cardiovascular end point events, and coronary end point events) were also associated with lovastatin treatment in the overall cohort. This paper provides results in women, a prespecified subgroup. Among women, 20-40 mg/day lovastatin reduced LDL-C 25% and increased HDLC 9% (p < 0.001). A prespecified analysis revealed consistency with the overall results regardless of gender (i.e., there were no statistical differences between men and women in risk reduction for first AMCEs with lovastatin). However, the number of women who had an AMCE was small, and there was insufficient power to detect a treatment group difference among women (7 of 499 vs. 13 of 498 first AMCEs in those receiving lovastatin and placebo, respectively; RR 0.54; 95% CI 0.22, 1.35; p = 0.183). Numerical reductions in all prespecified secondary end points were observed for women treated with lovastatin, but again, the numbers of events were small and the differences were not statistically significant. Chronic long-term treatment with lovastatin was well tolerated, with no treatment group differences in the frequency of cancer, muscle symptoms, and clinically important liver enzyme elevations. In AFCAPS/TexCAPS, a consistent pattern of numerical reductions in all prespecified primary and secondary cardiovascular end points was observed in women treated with lovastatin for primary prevention of CHD. However, because of the small number of events, there was insufficient power to detect significant treatment group differences. Lovastatin treatment was associated with statistically significant decreases in LDL-C and increases in HDL-C, and chronic long-term treatment with 20-40 mg/day lovastatin was well tolerated in women.