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


Therapeutics

Low-dose aspirin reduced the need for peripheral arterial surgery in apparently healthy men

ACP J Club. 1992 Nov-Dec;117:78. doi:10.7326/ACPJC-1992-117-3-078


Source Citation

Goldhaber SZ, Manson JE, Stampfer MJ, et al. Low-dose aspirin and subsequent peripheral arterial surgery in the Physicians' Health Study. Lancet. 1992 Jul 18;340:143-5.


Abstract

Objective

To compare the need for peripheral arterial surgery in apparently healthy U.S. male physicians who took low-dose aspirin with those who did not receive aspirin.

Design

5-year randomized, double-blind, placebo-controlled trial.

Setting

United States.

Participants

22 071 male physicians, aged 40 to 84 years at entry, who had no history of myocardial infarction, stroke, or transient cerebral ischemia. Patients with previous peripheral arterial surgery were excluded from the final analysis. Mean follow-up was 60 months (range 46 to 77 mo), and 99.7% were followed.

Intervention

Randomization was to 1 of 4 groups: aspirin, 325 mg every other day; β-carotene {50 mg every other day}(from report in Am J Prev Med 1990;6:290-4); both active medications; or both placebos. 11 037 physicians were assigned to aspirin and 11 034 to placebo.

Main outcome measures

At baseline participants completed questionnaires about past medical history, physical characteristics, cigarette smoking, alcohol consumption, and frequency of exercise. Questionnaires were completed at 6 and 12 months and yearly thereafter. Data were collected on new medical diagnoses and procedures and included peripheral arterial surgery and intermittent claudication.

Main results

At the end of follow-up, reported use of aspirin and other platelet-active drugs was 86% in the aspirin group and 14% in the placebo group. 56 physicians (20 [0.18%] taking aspirin, 36 [0.32%] taking placebo, P = 0.03) had peripheral arterial surgery during follow-up. {This absolute risk reduction of 0.14% means that 689 patients would need to be treated with low-dose aspirin for 5 years (compared with no aspirin) to prevent 1 additional patient from having peripheral arterial surgery, 95% CI 349 to 7842; the relative risk reduction was 44%, CI 5% to 68%.}* Adjusting for age, cigarette smoking, blood pressure, diabetes mellitus, or other coronary risk factors did not modify the effects of aspirin on peripheral arterial surgery. Risk factors for having peripheral arterial surgery were a history of diabetes mellitus (relative risk [RR] 3.6, CI 1.5 to 8.8, P < 0.005), elevated cholesterol levels (RR 2.3, CI 1.05 to 4.9, P = 0.04), and current cigarette smoking (RR 10.3, CI 4.1 to 25.4, P < 0.001). The groups did not differ for new cases of claudication (112 cases in patients taking aspirin vs 109 for placebo). 9 cases (1 aspirin, 8 placebo) of new-onset claudication required peripheral arterial surgery.

Conclusions

Regular use of low-dose aspirin by apparently healthy men reduced the need for peripheral arterial surgery. Aspirin use did not affect the reported incidence of intermittent claudication.

Source of funding: National Institutes of Health.

For article reprint: Dr. S.Z. Goldhaber, Brigham and Women's Hospital, 75 Francis Street, Room A-313, Boston, MA 02115, USA.

*Numbers calculated from data in article.


Commentary

For many years, peripheral arterial occlusive disease and its major symptom, intermittent claudication, were considered to be of only moderate clinical significance. This attitude was supported by the fact that relatively few of these patients developed gangrene or required amputation. Recent studies have shown that the presence of peripheral vascular arterial disease has wider importance than the progression of ischemic changes in the legs. Criqui and colleagues (1) have shown that the relative risk for dying from all causes was 3 times greater in those with large-vessel peripheral arterial disease as compared with controls and that the risk for death from cardiovascular disease was 6 times greater.

With this background, the findings in the report from Goldhaber and colleagues on the Physicians' Health Study showing that aspirin therapy reduced the need for peripheral arterial surgery are of special interest. Chronic low-dose aspirin therapy has been shown to inhibit platelet aggregation and thrombus formation but may not have any direct benefit in preventing atherosclerosis. Low-dose aspirin may, therefore, be most beneficial in advanced arterial disease when thrombosis within an already narrowed vessel can be critical. This is consistent with the findings that low-dose aspirin does not prevent development of angina pectoris but does reduce the risk for myocardial infarction. Similarly, intermittent claudication is not prevented by aspirin therapy, but the need for peripheral arterial surgery clearly seems to be reduced.

The use of aspirin as an antiplatelet medication, therefore, has clinical value, but the critical advance awaits the discovery of the cause and treatment of atherosclerosis.

Arthur W. Feinberg, MD
Cornell University Medical CenterManhasset, New York, USA

Arthur W. Feinberg, MD
Cornell University Medical Center
Manhasset, New York, USA


Reference

1. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of ten years in patients with peripheral arterial disease. N Engl J Med. 1992;326:281-6.