Reduction of stroke incidence after myocardial infarction with pravastatin: The Cholesterol and Recurrent Events (CARE) study

Jonathan F. Plehn, Barry R. Davis, Frank M. Sacks, Jean L. Rouleau, Marc A. Pfeffer, Victoria Bernstein, T. Edward Cuddy, Lemuel A. Moyé, Linda B. Piller, John Rutherford, Lara M. Simpson, Eugene Braunwald

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)216-223
Number of pages8
JournalCirculation
Volume99
Issue number2
StatePublished - Jan 19 1999

Fingerprint

Pravastatin
Stroke
Myocardial Infarction
Cholesterol
Incidence
Placebos
Transient Ischemic Attack
LDL Cholesterol
HDL Cholesterol
Serum
Hydroxymethylglutaryl CoA Reductases
Platelet Aggregation Inhibitors
Hypercholesterolemia
Stroke Volume
Infarction
Coronary Artery Disease

Keywords

  • Arteriosclerosis
  • Cholesterol
  • Lipids
  • Myocardial infarction
  • Stroke

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Plehn, J. F., Davis, B. R., Sacks, F. M., Rouleau, J. L., Pfeffer, M. A., Bernstein, V., ... Braunwald, E. (1999). Reduction of stroke incidence after myocardial infarction with pravastatin: The Cholesterol and Recurrent Events (CARE) study. Circulation, 99(2), 216-223.

Reduction of stroke incidence after myocardial infarction with pravastatin : The Cholesterol and Recurrent Events (CARE) study. / Plehn, Jonathan F.; Davis, Barry R.; Sacks, Frank M.; Rouleau, Jean L.; Pfeffer, Marc A.; Bernstein, Victoria; Cuddy, T. Edward; Moyé, Lemuel A.; Piller, Linda B.; Rutherford, John; Simpson, Lara M.; Braunwald, Eugene.

In: Circulation, Vol. 99, No. 2, 19.01.1999, p. 216-223.

Research output: Contribution to journalArticle

Plehn, JF, Davis, BR, Sacks, FM, Rouleau, JL, Pfeffer, MA, Bernstein, V, Cuddy, TE, Moyé, LA, Piller, LB, Rutherford, J, Simpson, LM & Braunwald, E 1999, 'Reduction of stroke incidence after myocardial infarction with pravastatin: The Cholesterol and Recurrent Events (CARE) study', Circulation, vol. 99, no. 2, pp. 216-223.
Plehn JF, Davis BR, Sacks FM, Rouleau JL, Pfeffer MA, Bernstein V et al. Reduction of stroke incidence after myocardial infarction with pravastatin: The Cholesterol and Recurrent Events (CARE) study. Circulation. 1999 Jan 19;99(2):216-223.
Plehn, Jonathan F. ; Davis, Barry R. ; Sacks, Frank M. ; Rouleau, Jean L. ; Pfeffer, Marc A. ; Bernstein, Victoria ; Cuddy, T. Edward ; Moyé, Lemuel A. ; Piller, Linda B. ; Rutherford, John ; Simpson, Lara M. ; Braunwald, Eugene. / Reduction of stroke incidence after myocardial infarction with pravastatin : The Cholesterol and Recurrent Events (CARE) study. In: Circulation. 1999 ; Vol. 99, No. 2. pp. 216-223.
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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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AU - Davis, Barry R.

AU - Sacks, Frank M.

AU - Rouleau, Jean L.

AU - Pfeffer, Marc A.

AU - Bernstein, Victoria

AU - Cuddy, T. Edward

AU - Moyé, Lemuel A.

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AU - Braunwald, Eugene

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AB - 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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KW - Cholesterol

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