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


Therapeutics

Pravastatin reduced cardiovascular events in older patients with myocardial infarction and average cholesterol levels

ACP J Club. 1999 Mar-April;130:32. doi:10.7326/ACPJC-1999-130-2-032


Source Citation

Lewis SJ, Moye LA, Sacks FM, et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) Trial. Ann Intern Med. 1998 Nov 1;129:681-9.


Abstract

Question

Among older adults with myocardial infarction (MI) and average cholesterol levels, does pravastatin reduce cardiovascular events?

Design

Subgroup analysis of a randomized, double-blind, placebo-controlled trial (Cholesterol and Recurrent Events [CARE] Trial) with median follow-up of 5 years.

Setting

80 hospitals in North America.

Patients

1283 patients aged 65 to 75 years (mean age 69 y, 82% men) who had had an acute MI within the previous 3 to 20 months and had plasma total cholesterol levels < 6.2 mmol/L, low-density lipoprotein cholesterol levels of 3.0 to 4.5 mmol/L, and fasting triglyceride levels < 4.0 mmol/L. All patients included in the final analysis.

Intervention

640 patients were allocated to pravastatin, 40 mg/d, and 643 patients were allocated to placebo. All patients received dietary counseling according to the National Cholesterol Education Program Step 1 guidelines.

Main outcome measures

Major coronary events (death from coronary artery disease [CAD], non-fatal MI, percutaneous transluminal coronary angioplasty [PTCA], or coronary artery bypass grafting [CABG]) and stroke.

Main results

Analysis was by intention to treat. Patients who received pravastatin had lower rates of major coronary events, stroke, death from CAD, and CABG than did patients who received placebo (Table), but they did not have lower rates of nonfatal MI (P = 0.09) or PTCA (P > 0.2).

Conclusion

Among older patients with myocardial infarction and average cholesterol levels, pravastatin reduced the risk for major coronary events and stroke.

Source of funding: Bristol-Myers Squibb.

For correspondence: Dr. S.J. Lewis, Legacy Health System, Portland Cardiovascular Institute, 2222 NW Lovejoy Street, Portland, OR 97210, USA. FAX 503-229-7287.


Table. Pravastatin vs placebo for cardiovascular events at median 5-year follow-up*

Outcomes Pravastatin Placebo RRR (95% CI) NNT (CI)
Major coronary events† 19.7% 28.1% 32% (15 to 46) 11 (8 to 24)
Stroke 4.5% 7.3% 40% (4 to 62) 34 (22 to 333)
Death from CAD 5.8% 10.3% 45% (18 to 63) 22 (15 to 53)
CABG 6.6% 11.0% 43% (16 to 61) 21 (15 to 56)

*CABG = coronary artery bypass grafting; CAD = coronary artery disease. Other abbreviations defined in Glossary.
†Major coronary events = death from CAD, nonfatal MI, percutaneous transluminal coronary angioplasty, or CABG.


Commentary

The CARE trial was reported in full 2 years ago (1). Analyses of data from two subgroups—the elderly and women (2)—were recently published. Neither of the subgroup reports contains data on additional patients or follow-up time, although the age cut-point is slightly different in these reports than in the main report (65 vs 60 y). The messages from the trial are unchanged.

Most patients with acute MI are older than 65 years of age. Compared with younger patients, they have a substantially higher risk for death; tend to be excluded from therapeutic trials; and are less likely to receive treatments of proven efficacy, such as thrombolysis (3).The CARE Trial nicely illustrates the general principle that an effective intervention that produces the same relative reduction in mortality or morbidity across age strata will achieve a greater absolute reduction in elderly persons because of their higher baseline risk. Consequently, the numbers needed to treat to prevent one event will be smaller in the elderly than in the young, and the cost-effectiveness of treatment may actually be greater in the elderly despite their shorter life expectancy. Clinical trials of cholesterol-lowering drugs that include sufficient numbers of elderly patients (CARE and the Scandinavian Simvastatin Survival Study [4]) confirm that relative treatment effects are not appreciably modified by age, although they may be altered by the multiple comorbid conditions and frailty often present in older patients. It is difficult to justify the use of age as a selection factor for cholesterol-lowering treatment unless life expectancy approaches the 2 years it took for treatment benefit to manifest in the CARE Trial.

Kent L. Woods, MD
University of LeicesterLeicester, England, UK


References

1. 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.

2. Lewis SJ, Sacks FM, Mitchell JS, et al. Effect of pravastatin on cardiovascular events in women after myocardial infarction: the Cholesterol and Recurrent Events (CARE) trial. J Am Coll Cardiol. 1998;32:140-6.

3. Translation of clinical trials into practice: a European population-based study of the use of thrombolysis for acute myocardial infarction. European Secondary Prevention Study Group. Lancet. 1996;347:1203-7.

4. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease. Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-9.