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

John R. Downs, Michael Clearfield, H. Alfred Tyroler, Edwin J. Whitney, William Kruyer, Alexandra Langendorfer, Vladimir Zagrebelsky, Stephen Weis, Deborah R. Shapiro, Polly A. Beere, Antonio M. Gotto

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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.

Original languageEnglish
Pages (from-to)1074-1079
Number of pages6
JournalAmerican Journal of Cardiology
Volume87
Issue number9
DOIs
StatePublished - 1 May 2001

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Lovastatin
Coronary Artery Disease
Air
Confidence Intervals
Primary Prevention
Neoplasms
Creatine Kinase
Transaminases
LDL Cholesterol
Therapeutics
Placebos
Safety
Intention to Treat Analysis
Liver
Unstable Angina
Sudden Death
Cytochrome P-450 Enzyme System
HDL Cholesterol
Physical Examination
Coronary Disease

Cite this

Downs, John R. ; Clearfield, Michael ; Tyroler, H. Alfred ; Whitney, Edwin J. ; Kruyer, William ; Langendorfer, Alexandra ; Zagrebelsky, Vladimir ; Weis, Stephen ; Shapiro, Deborah R. ; Beere, Polly A. ; Gotto, Antonio M. / Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) : Additional perspectives on tolerability of long-term treatment with lovastatin. In: American Journal of Cardiology. 2001 ; Vol. 87, No. 9. pp. 1074-1079.
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title = "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.",
author = "Downs, {John R.} and Michael Clearfield and Tyroler, {H. Alfred} and Whitney, {Edwin J.} and William Kruyer and Alexandra Langendorfer and Vladimir Zagrebelsky and Stephen Weis and Shapiro, {Deborah R.} and Beere, {Polly A.} and Gotto, {Antonio M.}",
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Downs, JR, Clearfield, M, Tyroler, HA, Whitney, EJ, Kruyer, W, Langendorfer, A, Zagrebelsky, V, Weis, S, Shapiro, DR, Beere, PA & Gotto, AM 2001, 'Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): Additional perspectives on tolerability of long-term treatment with lovastatin', American Journal of Cardiology, vol. 87, no. 9, pp. 1074-1079. https://doi.org/10.1016/S0002-9149(01)01464-3

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) : Additional perspectives on tolerability of long-term treatment with lovastatin. / Downs, John R.; Clearfield, Michael; Tyroler, H. Alfred; Whitney, Edwin J.; Kruyer, William; Langendorfer, Alexandra; Zagrebelsky, Vladimir; Weis, Stephen; Shapiro, Deborah R.; Beere, Polly A.; Gotto, Antonio M.

In: American Journal of Cardiology, Vol. 87, No. 9, 01.05.2001, p. 1074-1079.

Research output: Contribution to journalArticle

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T2 - Additional perspectives on tolerability of long-term treatment with lovastatin

AU - Downs, John R.

AU - Clearfield, Michael

AU - Tyroler, H. Alfred

AU - Whitney, Edwin J.

AU - Kruyer, William

AU - Langendorfer, Alexandra

AU - Zagrebelsky, Vladimir

AU - Weis, Stephen

AU - Shapiro, Deborah R.

AU - Beere, Polly A.

AU - Gotto, Antonio M.

PY - 2001/5/1

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N2 - 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.

AB - 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.

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