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


Therapeutics

Review: Statins prevent stroke, especially in patients with coronary heart disease

ACP J Club. 1998 Jan-Feb;128:1. doi:10.7326/ACPJC-1998-128-1-001


Source Citation

Crouse JR 3d, Byington RP, Hoen HM, Furberg CD. Reductase inhibitor monotherapy and stroke prevention. Arch Intern Med. 1997 Jun 23;157:1305-10. [PubMed ID: 9201004]


Abstract

Objective

To determine, using meta-analysis, the effectiveness of reducing levels of low-density lipoprotein (LDL) cholesterol by using reductase inhibitor monotherapy (statins) to prevent stroke in patients at risk for or who have coronary heart disease.

Data sources

Studies were identified by searching MEDLINE and by scanning bibliographies of relevant clinical trials.

Study selection

Randomized controlled trials of statins were selected if they evaluated change in atherosclerosis, clinical events, or both. Primary and secondary prevention studies were included.

Data extraction

Data were extracted on study drugs, number of patients, age, sex, levels of LDL cholesterol at baseline and after reduction, and duration of follow-up. The incidence of stroke was obtained from study investigators.

Main results

12 trials met the selection criteria (4 primary prevention trials that had 7808 patients and 8 secondary prevention trials that had 11 710 patients with coronary heart disease). 8 trials used pravastatin monotherapy, 3 used lovastatin, and 1 used simvastatin. All studies showed reduced LDL cholesterol levels (range 22% to 38%). 182 strokes occurred in the statin group and 248 in the placebo group (P = 0.001). Statins reduced stroke when the analysis used data from all trials or secondary prevention trials alone (P = 0.001 for both), but no difference between statins and placebo was found when data from primary prevention trials alone were used (P = 0.48) (Table).

Conclusion

Lowering LDL cholesterol levels by using statin monotherapy reduces stroke in patients with coronary heart disease.

Source of funding: Not stated.

For article reprint: Dr. J.R. Crouse 3d, Department of Medicine, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1047, USA. FAX 910-716-5895.


Table. Stroke reduction with statins vs placebo*

Trials Statin weighted EER Placebo weighted CER RRR (95% CI) Weighted ARR NNT (CI)
Combined 2.1% 2.5% 27% (11 to 40) 0.5% 221 (130 to 733)
Primary 1.2% 1.4% 15% (-27 to 42) 0.2% (CI -0.7 to 0.3) Not significant
Secondary 2.7% 3.3% 31% (13 to 45) 0.7% 154 (93 to 450)

*Abbreviations defined in Glossary; ARR, NNT, and CI calculated from data in article.


Commentary

Stroke is often devastating to patients and is a major public health burden. Some effective preventive measures, such as warfarin in atrial fibrillation (2-year number needed to treat [NNT] 19) and carotid endarterectomy in transient ischemic attack or minor stroke with high-grade carotid stenosis (NNT 6), are applicable to some patients. Aspirin (NNT 200) and antihypertensive therapy (NNT 100) do not prevent most strokes. No randomized controlled trial has shown that lipid lowering reduces stroke as a primary end point, and no clear statistical association of stroke incidence with serum cholesterol levels has been shown. Nevertheless, the meta-analysis by Crouse and colleagues reveals a reduction in stroke incidence, although the result may be limited to patients with coronary heart disease. Epidemiologic and pathophysiologic issues are thoroughly discussed in the original article and the accompanying editorial (1).

Should statin therapy be considered for stroke prevention, and would such therapy alter the evidence-based use of these drugs for more clearly defined indications? The 5-year NNT in patients with coronary heart disease to prevent myocardial infarction in patients with elevated cholesterol levels is 10; in persons with normal cholesterol levels, the NNT is 33. In these groups, prevention of coronary heart disease drives the use of statin drugs; stroke prevention is a welcome addition. In primary prevention (patients at risk), the NNT to prevent myocardial infarction is 39 compared with the nonsignificant NNT of 476 for stroke. Intervention is again justifiable without invoking stroke reduction. For patients with known carotid stenosis in whom surgical interventions are probably ineffective (symptomatic patients with moderate or low-grade carotid stenosis) or for controversial patients (asymptomatic patients with carotid stenosis), the potential benefit of stro! ke reduction may tip the scale toward treatment with statins. For patients with modestly elevated cholesterol levels and no other risks, the benefits for prevention of coronary heart disease and possibly stroke are more modest, although a patient-centered decision to use these drugs could be driven more by the fear of stroke than by fear of myocardial infarction.

Craig Redfern, DO
Providence Ambulatory Care and Education CenterPortland, Oregon, USA

Craig Redfern, DO
Providence Ambulatory Care and Education Center
Portland, Oregon, USA


Reference

1. Gotto AM. Stain therapy and reduced incidence of stroke. Implications of cholesterol-lowering therapy for cerebrovascular disease. Arch Intern Med. 1997;157: 1283-4. [PubMed ID: 9201001]