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Original Contributions
Primary Prevention of Acute CoronaryEvents With Lovastatin in Men andWomen With Average Cholesterol Levels John R. Downs, MD; Michael Clearfield, DO; Stephen Weis, DO; Edwin Whitney, MD; Deborah R. Shapiro, DrPH; Polly A. Beere, MD, PhD; Alexandra Langendorfer, MS; Evan A. Stein, MD; William Kruyer, MD; Antonio M. Gotto, Jr, MD, DPhil; for the AFCAPS/TexCAPS Research Group Context.—Although cholesterol-reducing treatment has been shown to reduce
fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein choles- positive, continuous, independent, graded terol (LDL-C) in patients without CHD extends to individuals with average serum relation between plasma total choles-terol (TC) and the incidence of coronary cholesterol levels, women, and older persons.
Objective.—To compare lovastatin with placebo for prevention of the first acute
major coronary event in men and women without clinically evident atherosclerotic trations, including those considered nor- cardiovascular disease with average total cholesterol (TC) and LDL-C levels and mal or mildly elevated.1-3 In the Multiple below-average high-density lipoprotein cholesterol (HDL-C) levels.
Design.—A randomized, double-blind, placebo-controlled trial.
Setting.—Outpatient clinics in Texas.
in the first 6 years of follow-up occurred Participants.—A total of 5608 men and 997 women with average TC and LDL-C
and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and first 16 years of the Framingham HeartStudy, 40% of participants who devel- Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) oped a myocardial infarction had a TC level mmol/L (221 [21] mg/dL) (51st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women(25th and 16th percentiles, respectively), and median (SD) triglyceride levels were See also pp 1643 and 1659.
1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile).
Intervention.—Lovastatin (20-40 mg daily) or placebo in addition to a low–
saturated fat, low-cholesterol diet.
Main Outcome Measures.—First acute major coronary event defined as fatal
or nonfatal myocardial infarction, unstable angina, or sudden cardiac death.
lesterol-lowering treatment can sub-stantially reduce myocardial infarction Results.—After an average follow-up of 5.2 years, lovastatin reduced the inci-
dence of first acute major coronary events (183 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; PϽ.001), myocardial infarction (95 vs57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P = .002), unstable angina(87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P = .02), coro- From the Wilford Hall Medical Center, Lackland Air nary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52- Force Base, San Antonio, Tex (Dr Downs); University ofNorth Texas Health Science Center, Fort Worth (Drs 0.85; P = .001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, Clearfield and Weis); the Heart and Vascular Institute of 0.61-0.92; P = .006), and cardiovascular events (255 vs 194 cardiovascular events; Texas, San Antonio (Dr Whitney); Merck & Co Inc, WestPoint, Pa (Drs Shapiro and Beere and Ms Langendor- RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C fer); Metabolic and Atherosclerosis Research Center, by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L Cincinnati, Ohio (Dr Stein); Brooks Air Force Base, SanAntonio (Dr Kruyer); and Cornell University Medical (39 mg/dL). There were no clinically relevant differences in safety parameters be- Funding was provided by Merck & Co Inc. Drs Sha- piro and Beere and Ms Langendorfer are employees of Conclusions.—Lovastatin reduces the risk for the first acute major coronary
Merck & Co Inc. Dr Stein is a consultant, speaker, and event in men and women with average TC and LDL-C levels and below-average funded researcher for Merck & Co Inc. Dr Gotto is aconsultant and speaker for Merck & Co Inc.
HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assess- The opinions stated in the article are those of the au- ment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need thors and do not represent those of the Department ofDefense or the US Air Force.
for reassessment of the National Cholesterol Education Program guidelines regard- Reprints: Antonio M. Gotto, Jr, MD, DPhil, Cornell Uni- versity Medical College, 1300 York Ave, Room F105, New York, NY 10021 (e-mail:
Prevention of Coronary Events With Lovastatin—Downs et al 1998 American Medical Association. All rights reserved.
tract research organization with staff at of the clinical investigator. All personnel involved in participant care were blinded mortality across the spectrum of clinical to treatment assignment and lipid levels.
ondary end points were (1) fatal or nonfatal (2) unstable angina, (3) fatal or nonfatal with either lovastatin, 20 mg/d, or match- myocardial infarction, (4) fatal or nonfa- tal cardiovascular events, (5) fatal or non- fatal coronary events, (6) cardiovascular visit. The blind was maintained by titrat- tigate safety, that is, whether long-term placebo, would result in similar rates of tality (with subset analyses for uninten- levels. The primary end point analysis was nary events, defined as fatal or nonfatal cluding basal cell and squamous cell skin and at each subsequent year-end visit.
myocardial infarction, unstable angina, or Clinical visits were every 6 weeks for the sudden cardiac death. The inclusion of un- tion because of adverse drug effects.
stable angina was a unique feature of this study, and its inclusion as a primary end Participant Recruitment
point reflects the increasing frequency of and Follow-up
for follow-up by questionnaire, which in- the lipid entrance criteria and had no prior history, signs, or symptoms of definite myo- cardial infarction, angina, claudication, ce- rebrovascular accident, or transient ische- mic attack were eligible for participation in the study. Lipid entry criteria (TC, 4.65- 6.82 mmol/L [180-264 mg/dL]; LDL-C, 3.36- were to be met at both 4 and 2 weeks prior to randomization, with less than 15% dif- ference in LDL-C values. In addition, par- ment (day 1) and at the 1-year visit (post- rate of first acute major coronary events years of follow-up in a cohort without clini- tory also analyzed lipids for the National cal evidence of atherosclerotic cardiovas- ary hyperlipidemia, or type 1 or type 2 dia- et al11 (also P. S. Bachorik, PhD, unpub- with insulin or associated with a glycohe- moglobin level of at least 10% (20% above exertional angina, accelerated or rest an- gina, or both, and at least 1 of the follow- unteers were excluded if, according to the ing: (1) electrocardiographic findings of at versible defect on stress perfusion study, greater than the desirable limit for height.
(2) angiographic findings of at least 90% epicardial vessel stenosis or at least 50% stenosis in the left main coronary artery Statistical Analysis
(without exercise testing), or (3) at least and the institutional review boards of the 2 participating centers approved the con- sent form and protocol. The study was con- of at least 50% stenosis in a major epicar- ing committee. Administrative, clinical, and Prevention of Coronary Events With Lovastatin—Downs et al 1998 American Medical Association. All rights reserved.
tion-to-treat basis and all P values were ticipant within 3 months of the decision to 2-sided. A log-rank test, with study cen- ter and sex as stratification factors, was Baseline Characteristics
the rate of primary end point events.
center and sex as stratification factors.
average baseline lipid levels.14 Baseline lipid levels were similar in both treatment treatment-by-sex interaction effects. All dL) for men and 1.03 (0.14) mmol/L (40 [5] tiles, respectively); and median (SD) tri- spect to baseline demographics, risk fac- ment groups using the Fisher exact test.
detailed description of the baseline char- acteristics of the study cohort in compari- til a total of 320 participants had expe- or for a minimum of 5 years after the lastparticipant was randomized, whichever Adherence and Dropouts
analysis, 2 interim analyses of the trial was 5.2 (0.9) years (range, 0.2-7.2 years) for those treated with lovastatin and 5.2 and 240 participants, respectively, expe- (0.9) years (range, 0.1-7.2 years) in the not clinically important (Figure 2).
critical values for finding statistical sig- ure 1). Participants treated with placebo Early Termination for Efficacy
terim analysis (data from 267 participants stopped early for efficacy. The voting mem- Lipid Parameters
unanimously on July 3, 1997, to accept the Efficacy End Points
recommendation for early termination.
1 year (PϽ.001). Low-density lipopro- perienced a 37% lower incidence of the first participants and personnel continue to be blinded throughout the final visit of the point defined as fatal or nonfatal myocar- dial infarction, unstable angina, or sud- all additional end point and safety infor- den cardiac death) than did those treated mation in the final analysis. End point sta- tus was determined for all but 1 active par- Prevention of Coronary Events With Lovastatin—Downs et al 1998 American Medical Association. All rights reserved.
Table 1.—Baseline Characteristics and Medications for Study Cohort by Treatment Group* lative incidence and the number of par-ticipants at risk. By treatment year, the Lovastatin
Baseline Characteristic
(N = 3301)
(N = 3304)
with lovastatin was 43% in the first year statistically different from each other.
rate for subjects receiving lovastatin av- years observed for the placebo group.
during the study period (PϽ.001).
with lovastatin resulted in significant, con- sistent benefit compared with placebo, in- tions (P=.001), 32% reduction in unstable angina (P=.02), and 40% reduction in the incidence of fatal or nonfatal myocardial infarction (P=.002). For coronary and car- diovascular events (total fatal or nonfa-tal), treatment with lovastatin resulted in significant (P=.006 and P=.003, respec- events included all atherosclerotic cardio- Non–insulin-treated diabetes or fasting dents, transient ischemic attacks, and pe- ripheral arterial vascular disorders. For the secondary end points fatal cardiovas- treatment on the rate of the first primary sex, age (older defined as above the me- sion, active cigarette smoking, family his- line HDL-C. Treatment group, as well aseach of these factors, demonstrated a sig- *NCEP indicates National Cholesterol Education Program; CHD, coronary heart disease; HDL-C, high-density nificant association with risk (eg, smok- lipoprotein cholesterol; and ACE, angiotensin-converting enzyme.
†All Air Force/Texas Coronary Atherosclerosis Prevention Study participants met National Cholesterol Education Panel criteria for age-related risk (age Ն45 years for men and Ն55 years for women).
‡Hypertension includes those reporting history of hypertension and/or those treated with antihypertensive agents triglyceride level (P = .98) and history of diabetes (P = .34, 155 participants withdiabetes) were not significant predictors analysis (eg, the secondary end point, un- stable angina, is also a component of the rized in Table 3. Participants are counted who did not have the CHD risk factor (eg, similar to placebo-treated nonsmokers).
included in more than 1 analysis in Table on the rate of first acute major coronary Prevention of Coronary Events With Lovastatin—Downs et al 1998 American Medical Association. All rights reserved.
Table 2.—Treatment Effects on Plasma Lipid Levels at 1 Year* Placebo,
Mean or Median (SD)
Mean or Median (SD)
*Data are for paired samples. Sample sizes are 2387-2495 for men and 420-439 for women. TC indicates total cholesterol; LDL-C, low-density lipoprotein cholesterol; and HDL-C, high-density lipoprotein cholesterol.
Figure 2.—Comparison of percent change in lipid parameters from baseline to 1 year by treatment Tolerability and Safety
group. All differences between treatment groups were significant (PϽ.001). TC indicates total cho-lesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; and of the subgroups differed significantly in tiary end points to assess safety) did not was not different for participants with hy- nent disability, resulting in or prolonging hospitalization, or diagnosis of any can- subgroup interactions were significant).
cer), 1131 (34.2%) and 1126 (34.1%) in the (P = .99) or HDL-C (P = .16) when evalu- ter discontinuation of the study drug and treated patient, who discontinued therapy cebo group and 1 in the lovastatin group.
ticipants treated with lovastatin and pla- cancers, was 15.1 and 15.6 per 1000 patient- 12 per 1000 patient-years, respectively.
times the upper limit of normal in either cularizations (8 and 11 per 1000 patient- summarized in Table 4. The number of par- ticipants reporting nonmelanoma skin can- cers, predominantly diagnoses of basal cell participants and 11 [0.3%] of 3248 receiv- and squamous cell cancers, was 250 (7.6%) ing lovastatin and placebo, respectively).
in the lovastatin group and 243 (7.4%) in by final dose for those who were titrated verse experience that led to discontinua- also revealed no significant trends. Con- tion was 449 (13.6%) in the group treated tions and 7 presentations of unstable an- with lovastatin and 445 (13.8%) in the pla- Prevention of Coronary Events With Lovastatin—Downs et al 1998 American Medical Association. All rights reserved.
related elevations was significantly(P = .003) higher in the group treated Lovastatin
(N = 3301)
(N = 3304)
with lovastatin (110 [3.3%] and 70 [2.1%] Relative Risk
for lovastatin and placebo, respectively).
End Points
(95% CI)†
P Value‡
events defined as fatal or nonfatalmyocardial infarction, unstable angina, 1586, 10 [0.6%] of 1657, and 21 [0.6%] of 3248 receiving lovastatin, 20 mg/d, lova- having postrandomization tests; unlike theother comparisons of randomized treat- *CI indicates confidence interval; CHD, coronary heart disease; and ellipses, too few for survival analysis.
†To calculate risk reduction, subtract relative risk from 1. Relative risk and confidence interval calculated with Cox ‡P value calculated with log-rank test and adjusted for the interim analysis for the primary end point only. P values for secondary end points are unadjusted.
symptoms accompanied with CK eleva-tions Ͼ10 times the upper limit of nor-mal). There were 3 cases of rhabdomy- treated participants, and 1 case occurred in a participant treated with lovastatin fol- Ͻ.001) in the risk for first acute major coronary events, defined as fatal or non- fatal myocardial infarction, unstable an- was originally powered to detect a 30% dif- ter the second interim analysis (with 267 of such magnitude that the predefined con- ditions for stopping the study were met.
groups appeared as early as 1 year (40 par- ticipants with events in the placebo group nents: lovastatin therapy significantly re-duced the risk for fatal or nonfatal myo- vascular events was further confirmedby a 33% risk reduction in the need forrevascularizations (P = .001) and 25% Figure 3.—Cumulative incidence of primary end points (composite of fatal and nonfatal myocardial infarc-tion, sudden death, and unstable angina) and secondary end points (fatal and nonfatal myocardial infarc- tion, unstable angina, and coronary revascularizations) by treatment group.
cular and total coronary events (PՅ.006).
The number of deaths in AFCAPS/ of 1657 receiving lovastatin, 20 mg/d, and the upper limit of normal was similar be- tect treatment differences in the low fre- vastatin and placebo, respectively); how- Prevention of Coronary Events With Lovastatin—Downs et al 1998 American Medical Association. All rights reserved.
Table 4.—Treatment Group Comparison of Parti-cipants With Cancer No. of Events
Lovastatin Placebo
(N = 3301) (N = 3304) Value*
*P values are for between-treatment-group differ- tively. In the Helsinki Heart Study,18 the 47.3 years), and the mean baseline lipidvalues for TC, LDL-C, and HDL-C were (mean age, 55.2 years) and the mean base- mmol/L (44 mg/dL), respectively. All ofthese trials reported statistically signifi- cant reductions in the primary end pointof the combined incidence of nonfatal Figure 4.—Comparison of primary end point event rates (per 1000 patient-years at risk) and 95% confidence intervals by treatment within demographic and risk factor subgroups at baseline. CAD indicates coronary artery disease; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; as-terisks, bottom tertile; and daggers, top tertile.
LRC-CPPT,17 34% in the Helsinki HeartStudy,18 and 31% in WOSCOPS.8 Ex- trapolation of the results of these 3 trials levels, to women, and to older individuals cohorts8,17,18; however, treatment with lo- in secondary prevention trials,6,7 female the benefit to a lower-risk segment of the general population. In contrast with ear- better than, male participants. Lovastatin 2 or more risk factors) and 32% would not appeared to attenuate (Figure 4) the risk age, 58.2 years; upper limit, 73 years; 21% edge, the first primary prevention trial to modification in generally healthy men and centrations.8,17,18 In the Lipid Research mary end point analysis resulted from the 3.89 mmol/L [150 mg/dL], respectively) are observations that hospital admissions for similar to the average levels for age- and diagnostic and surgical intervention fol- Prevention of Coronary Events With Lovastatin—Downs et al 1998 American Medical Association. All rights reserved.
while myocardial infarction, as the cause for initial presentation, was decreasing.9 initially present with unstable angina and is particularly important in primary pre- lovastatin. These results support the in- hospitalization, and the cost of diagnos- was comparable to that seen in other pri- mary prevention trials,8,18 and frequency was similar in the treatment groups.
like to acknowledge the efforts of the members of reduction as the primary goal of therapy, the Data Safety Monitoring Board and the Steering, End Point, and Laboratory Committees, as well as William Russell, MD. We appreciate the help of the SPECTRUM Pharmaceutical Research Corpora-tion, San Antonio, Tex, in conducting the trial, and we thank specifically William D. Gibbons; Page Armstrong; Kamal S. Shah, MD; Wendy McPher- son; Robin D. Hartman; Michael Fellows; and George A. Reaves, Sr. In addition, we would like tothank the following individuals from the TexCAPS clinic at the University of North Texas Health Sci- ence Center, Fort Worth: Mel Johnson, DO; Jack Gramer, DO; George Esselman, DO; Keith Vese- nius, DO; Alvin J. Mathe, DO; John M. Willis, DO;Paul Garcia, DO; Raymond M. Pertusi, DO; Eck Prudhomme, MD; Kenneth Wiggins, MD; and Tho- centrations (Ͼ3 times the upper limit of mas Risley, MD. Finally, we would like to thank the that lovastatin, 20 to 40 mg/d, can reduce following employees of Merck & Co Inc, West Point, Pa, who were helpful in designing the trial andmanaging the data: Geraldine Mantell, MD; Barbara Conroy; Edward Schiff; Tommie Friday, Lyman References
Kannel WB. Range of serum cholesterol values in
8. Shepherd J, Cobbe SM, Ford I, et al, for the West
[CD-ROM]. Hyattsville, Md: Centers for Disease the population developing coronary artery disease.
of Scotland Coronary Prevention Study Group. Pre- Control and Prevention; 1996. DHHS public use data Am J Cardiol. 1995;76:69C-77C.
vention of coronary heart disease with pravastatin 2. Levine GN, Keaney JF Jr, Vita JA. Cholesterol
in men with hypercholesterolemia. N Engl J Med.
15. Clearfield M, Whitney E, Weis S, et al. Air
reduction in cardiovascular disease: clinical benefits Force/Texas Coronary Atherosclerosis Prevention and possible mechanisms. N Engl J Med. 1995;332: 9. Whitney EJ, Shear CL, Mantell G, et al. The case
Study (AFCAPS/TexCAPS): baseline characteris- for unstable angina pectoris as a primary endpoint 3. Chen ZM, Peto R, Collins R, MacMahon S, Lu JR,
in primary prevention studies. Am J Cardiol. 1992; 16. National Cholesterol Education Program Ex-
Li WX. Serum cholesterol concentration and coro- pert Panel. Summary of the second report of the nary heart disease in population with low choles- 10. Downs JR, Beere PA, Whitney E, et al. Air
National Cholesterol Education Program (NCEP) terol concentrations. BMJ. 1991;303:276-282.
Force/Texas Coronary Atherosclerosis Prevention Expert Panel on Detection, Evaluation, and Treat- 4. Stamler J, Wentworth D, Neaton JD, for the
Study (AFCAPS/TexCAPS): design and rationale.
ment of High Blood Cholesterol in Adults (Adult MRFIT Research Group. Is relationship between Am J Cardiol. 1997;80:287-293.
Treatment Panel II). JAMA. 1993;269:3015-3023.
serum cholesterol and risk of premature death from 11. Sempos CT, Cleeman JI, Carroll MD, et al.
17. Lipid Research Clinics Program. The Lipid Re-
coronary heart disease continuous and graded?: Prevalence of high blood cholesterol among US search Clinics Coronary Primary Prevention Trial findings in 356,222 primary screenees of the Mul- adults. JAMA. 1993;269:3009-3014.
results, I: reduction in incidence of coronary heart tiple Risk Factor Intervention Study (MRFIT).
12. Myers GL, Cooper GR, Winn CL, Smith SJ. The
disease. JAMA. 1984;251:351-364.
Centers for Disease Control–National Heart, Lung, 18. Frick MH, Elo O, Haapa K, et al. Helsinki Heart
5. Castelli WP. Cardiovascular disease in women.
and Blood Institute Lipid Standardization Program: Study: primary-prevention trial with gemfibrozil in Am J Obstet Gynecol. 1988;158:1553-1560.
an approach to accurate and precise lipid measure- middle-aged men with dyslipidemia. N Engl J Med.
6. Scandinavian Simvastatin Survival Study Group.
ments. Clin Lab Med. 1989;9:105-135.
Randomized trial of cholesterol lowering in 4444 par- 13. Friedewald WT, Levy RI, Fredrickson DS.
19. LaRosa JC, Hunninghake D, Bush D, et al. The
ticipants with coronary heart disease: the Scandi- Estimation of the concentration of low-density li- cholesterol facts. Circulation. 1990;81:1721-1733.
navian Simvastatin Survival Study (4S). Lancet. poprotein cholesterol in plasma, without use of 20. Bradford RH, Shear CL, Chremos AN, et al.
preparative ultracentrifuge. Clin Chem. 1972;18: Expanded Clinical Evaluation of Lovastatin 7. Sacks FM, Pfeffer MA, Moye LA, et al. The ef-
(EXCEL) study results, I: efficacy in modifying fect of pravastatin on coronary events after myo- 14. National Center for Health Statistics. Third Na-
plasma lipoproteins and adverse event profile in cardial infarction in patients with average choles- tional Health and Nutrition Examination Survey, 8245 patients with moderate hypercholesterolemia.
terol levels. N Engl J Med. 1996;335:1001-1009.
1988-94, US NHANES III Examination Data File Arch Intern Med. 1991;151:43-49.
Prevention of Coronary Events With Lovastatin—Downs et al 1998 American Medical Association. All rights reserved.


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