Reduction of Stroke Incidence After Myocardial Infarction With Pravastatin: The Cholesterol and Recurrent Events (CARE) Study
Abstract
Background —The role of lipid modification in stroke prevention is controversial, although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease. Methods and Results —To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infarction, we followed 4159 subjects with average total and LDL serum cholesterol levels (mean, 209 and 139 mg/dL, respectively) who had sustained an infarction an average of 10 months before study entry and who were randomized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events (CARE) trial. Using prospectively defined criteria, we assessed the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period. Patients were well matched for stroke risk factors and the use of antiplatelet agents (85% of subjects in each group). Compared with placebo, pravastatin lowered total serum cholesterol by 20%, LDL cholesterol by 32%, and triglycerides by 14% and raised HDL cholesterol by 5% over the course of the trial. A total of 128 strokes (52 on pravastatin, 76 on placebo) and 216 strokes or TIAs (92 on pravastatin, 124 on placebo) were observed, representing a 32% reduction (95% CI, 4% to 52%, P =0.03) in all-cause stroke and 27% reduction in stroke or TIA (95% CI, 4% to 44%, P =0.02). All categories of strokes were reduced, and treatment effect was similar when adjusted for age, sex, history of hypertension, cigarette smoking, diabetes, left ventricular ejection fraction, and baseline total, HDL, and LDL cholesterol and triglyceride levels. There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo (2 versus 6, respectively). Conclusions —Pravastatin significantly reduced stroke and stroke or TIA incidence after myocardial infarction in patients with average serum cholesterol levels despite the high concurrent use of antiplatelet therapy.
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LDL-C-lowering therapy using statins suppresses the risk for recurrence of both cerebrovascular and cardiovascular events in patients with coronary artery disease who have a cerebrovascular disease history.
“However, it has been reported that LDL-C-lowering therapy using statins suppresses the risk for recurrence of both cerebrovascular and cardiovascular events758–760).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [758]
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- Authors
- Plehn, J. F., Davis, B. R., Sacks, F. M., Rouleau, J. L., Pfeffer, M. A., Bernstein, V., Cuddy, T. E., Moyé, L. A., Piller, L. B., Rutherford, J., Simpson, L. M., & Braunwald, E.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Section of Cardiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (J.F.P.); School of Public Health, University of Texas Health Science Center at Houston (B.R.D., L.A.M., L.B.P., L.M.S.); Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (F.M.S., M.A.P., E.B.); Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.); Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada (V.B....
- Venue
- Circulation
- Published
- 1999-01-19
- Volume
- 99
- Issue
- 2
- Pages
- 216-223
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2165044111
- Cited by
- 429
- References
- 46
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 6 · 2016: 10 · 2015: 7 · 2014: 9 · 2013: 6 · 2012: 10
- FWCI
- 48.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- pravastatin, stroke prevention, myocardial infarction, statins, lipid-lowering therapy, LDL cholesterol, transient ischemic attack, hemorrhagic stroke, antiplatelet therapy, CARE trial, secondary prevention
- MeSH terms
- Aged, Animals, Anticholesteremic Agents, Cats, Ischemic Attack, Transient, Cerebrovascular Disorders, Cholesterol, Female, Follow-Up Studies, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Myocardial Infarction, Risk Factors, Triglycerides, Treatment Outcome, Pravastatin
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