Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Lovastatin reduced coronary events in healthy persons with low HDL cholesterol levels

ACP J Club. 1998 Nov-Dec;129:58. doi:10.7326/ACPJC-1998-129-3-058


Source Citation

Downs JR, Clearfield M, Weis S, et al., for the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998 May 27;279:1615-22.


Abstract

Question

In generally healthy persons with average total and low-density lipoprotein (LDL) cholesterol levels and below-average high-density lipoprotein (HDL) cholesterol levels, does long-term lipid lowering with lovastatin prevent first acute major coronary events?

Design

Randomized, double-blind, placebo-controlled trial with a mean follow-up of 5.2 years.

Setting

An air force base and a health sciences center in Texas, United States.

Participants

6605 adults were included who were 45 to 73 years of age (mean age 58 y, 85% men) and had total cholesterol levels ranging from 4.65 to 6.82 mmol/L (180 to 264 mg/dL); LDL cholesterol levels ranging from 3.36 to 4.91 mmol/L (130 to 190 mg/dL); HDL cholesterol levels ≤ 1.16 mmol/L (45 mg/dL) for men or ≤ 1.22 mmol/L (47 mg/dL) for women; triglyceridelevels ≤ 4.52 mmol/L (400 mg/dL); and no evidence of clinical atherosclerotic cardiovascular disease. Persons with LDL cholesterol levels ranging from 3.23 to 3.34 mmol/L (125 to 129mg/dL) were included if the ratio of total cholesterol to HDL cholesterol was > 6. Exclusion criteria were uncontrolled hypertension, secondary hyperlipidemia, insulin-treated or poorly controlled diabetes mellitus, or body weight > 50% above the desirable limit. Follow-up was > 99%.

Intervention

After 12 weeks of an American Heart Association step 1 diet and 2 weeks of a placebo baseline run-in period, 3304 participants were allocated to lovastatin, 20 mg/d, and 3301 were allocated to a matching placebo. Participants with LDL cholesterol levels > 2.84 mmol/L (110 mg/dL) at 3 months in the lovastatin group had their dosages titrated to 40 mg/d.

Main outcome measures

First acute major coronary events (myocardial infarction, unstable angina, or sudden cardiac death) and adverse events.

Main results

Fewer persons allocated to lovastatin than to placebo had a first acute major coronary event (P < 0.001) (Table). Serious adverse events did not differ between groups (34% in each group).

Conclusion

In generally healthy persons with average total and low-density lipoprotein cholesterol levels and below-average high-density lipoprotein cholesterol levels, lovastatin reduced first acute major coronary events without increasing adverse events.

Source of funding: Merck & Co., Inc.

For correspondence: Dr. A.M. Gotto Jr., Cornell University Medical College, 1300 York Avenue, Room F105, New York, NY 10021, USA. FAX 212-821-0576.


Table. Lovastatin vs placebo in generally healthy persons with below-average high-density lipoprotein cholesterol levels at a mean of 5.2-years follow-up*

Outcome Lovastatin Placebo RRR (95% CI) NNT (CI)
Acute major coronary event† 4% 6% 37% (21 to 50) 50 (33 to 97)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
†Fatal or nonfatal MI, unstable angina, or sudden cardiac death.


Commentary

This methodologically valid study by Downs and colleagues extends the evidence of benefit from cholesterol-lowering drugs to healthy persons with low HDL cholesterol levels and average total cholesterol levels.

No effects among women and elderly persons were shown. The study had inadequate power to determine the effect of treatment with lovastatin among women, and only a trend toward benefit existed. With entry restricted to persons < 74 years of age, no conclusions could be drawn about elderly persons. Further, the study had inadequate power to show an effect on mortality.

Clinicians must decide for whom the benefit of treatment exceeds the risk. Because this lovastatin study investigated a lower-risk cohort than had previously been studied, the magnitude of the benefit was smaller. In addition, benefit was shown only for those with the lowest HDL levels.

What about risk? Previous studies raised questions about the safety of cholesterol lowering with respect to both noncardiovascular mortality (1) and breast cancer risk (2). This trial had inadequate power to address either question definitively.

In summary, this trial showed benefit of lovastatin in the primary prevention of nonfatal coronary events in persons with low HDL cholesterol levels and average total cholesterol levels. It did not address some questions that clinicians must consider in deciding whether to prescribe drugs to persons similar to those in this trial. Specifically, it reports little useful information about the benefits and risks of primary preventionfor women and no information about the treatment of elderly persons or persons who do not have low HDL levels.

William C. Taylor, MD
Beth Israel Deaconess Medical Center
Anna Berkenblit, MD
Harvard Pilgrim Health Care-Brigham and Women's Hospital Boston, Massachusetts, USA


References

1. Jacobs D, Blackburn H, Higgins M, et al. Report of the Conference on Low Blood Cholesterol: Mortality Associations. Circulation. 1992;86:1046-60.

2. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001-9.