Journal article
Prevention of Stroke with the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).
- Bohula EA TIMI Study Group, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., S.D.W., R.P.G., J.-G.P., S.A.M., C.P.C., E.B.) ebohula@partners.org.
- Wiviott SD TIMI Study Group, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., S.D.W., R.P.G., J.-G.P., S.A.M., C.P.C., E.B.).
- Giugliano RP TIMI Study Group, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., S.D.W., R.P.G., J.-G.P., S.A.M., C.P.C., E.B.).
- Blazing MA Duke Clinical Research Institute, Durham, NC (M.A.B., J.A.W.).
- Park JG TIMI Study Group, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., S.D.W., R.P.G., J.-G.P., S.A.M., C.P.C., E.B.).
- Murphy SA TIMI Study Group, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., S.D.W., R.P.G., J.-G.P., S.A.M., C.P.C., E.B.).
- White JA Duke Clinical Research Institute, Durham, NC (M.A.B., J.A.W.).
- Mach F Cardiology Dvision, Geneva University Hospital, Switzerland (F.M.).
- Van de Werf F Departments of Cardiovascular Medicine and Cardiovascular Sciences, University of Leuven, Belgium (F.V.d.F.).
- Dalby AJ Milpark Hospital, Johannesburg, South Africa (A.J.D.).
- White HD Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand (H.D.W.).
- Tershakovec AM Merck & Co., Inc, Kenilworth, NJ (A.M.T.).
- Cannon CP TIMI Study Group, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., S.D.W., R.P.G., J.-G.P., S.A.M., C.P.C., E.B.).
- Braunwald E TIMI Study Group, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., S.D.W., R.P.G., J.-G.P., S.A.M., C.P.C., E.B.).
- 2017-10-04
Published in:
- Circulation. - 2017
acute coronary syndrome
ezetimibe
low-density lipoprotein cholesterol
risk stratification
secondary prevention
simvastatin
stroke
Acute Coronary Syndrome
Aged
Anticholesteremic Agents
Atrial Fibrillation
Cholesterol, LDL
Double-Blind Method
Ezetimibe
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Male
Middle Aged
Myocardial Infarction
Placebo Effect
Proportional Hazards Models
Recurrence
Risk Factors
Simvastatin
Stroke
Treatment Outcome
English
BACKGROUND
Patients who experience an acute coronary syndrome are at heightened risk of recurrent ischemic events, including stroke. Ezetimibe improved cardiovascular outcomes when added to statin therapy in patients stabilized after acute coronary syndrome. We investigated the efficacy of the addition of ezetimibe to simvastatin for the prevention of stroke and other adverse cardiovascular events in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), with a focus on patients with a stroke before randomization.
METHODS
Patients who experienced acute coronary syndrome were randomized to a placebo/simvastatin or ezetimibe/simvastatin regimen and followed for a median of 6 years. Treatment efficacy was assessed for the entire population and by subgroups for the first and total (first and subsequent) events for the end points of stroke of any etiology, stroke subtypes, and the primary trial end point at 7 years.
RESULTS
Of 18 144 patients, 641 (3.5%) experienced at least 1 stroke; most were ischemic (527, 82%). Independent predictors of stroke included prior stroke, older age, atrial fibrillation, congestive heart failure, diabetes mellitus, myocardial infarction, and renal dysfunction. There was a nonsignificant reduction in the first event of stroke of any etiology (4.2% versus 4.8%; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.73-1.00; P=0.052) with ezetimibe/simvastatin versus placebo/simvastatin, driven by a significant 21% reduction in ischemic stroke (3.4% versus 4.1%; HR, 0.79; 95% CI, 0.67-0.94; P=0.008) and a nonsignificant increase in hemorrhagic stroke (0.8% versus 0.6%; HR, 1.38; 95% CI, 0.93-2.04; P=0.11). Evaluating total events, including the first and all recurrent strokes, ezetimibe/simvastatin reduced stroke of any etiology (HR, 0.83; 95% CI, 0.70-0.98; P=0.029) and ischemic stroke (HR, 0.76; 95% CI, 0.63-0.91; P=0.003). Patients who had experienced a stroke prior to randomization were at a higher risk of recurrence and demonstrated an absolute risk reduction of 8.6% for stroke of any etiology (10.2% versus 18.8%; number needed to treat=12; HR, 0.60; 95% CI, 0.38-0.95; P=0.030) and 7.6% for ischemic stroke (8.7% versus 16.3%; number needed to treat=13; HR, 0.52; 95% CI, 0.31-0.86; P=0.011) with ezetimibe added to simvastatin therapy.
CONCLUSIONS
The addition of ezetimibe to simvastatin in patients stabilized after acute coronary syndrome reduces the frequency of ischemic stroke, with a particularly large effect seen in patients with a prior stroke.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00202878.
Patients who experience an acute coronary syndrome are at heightened risk of recurrent ischemic events, including stroke. Ezetimibe improved cardiovascular outcomes when added to statin therapy in patients stabilized after acute coronary syndrome. We investigated the efficacy of the addition of ezetimibe to simvastatin for the prevention of stroke and other adverse cardiovascular events in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), with a focus on patients with a stroke before randomization.
METHODS
Patients who experienced acute coronary syndrome were randomized to a placebo/simvastatin or ezetimibe/simvastatin regimen and followed for a median of 6 years. Treatment efficacy was assessed for the entire population and by subgroups for the first and total (first and subsequent) events for the end points of stroke of any etiology, stroke subtypes, and the primary trial end point at 7 years.
RESULTS
Of 18 144 patients, 641 (3.5%) experienced at least 1 stroke; most were ischemic (527, 82%). Independent predictors of stroke included prior stroke, older age, atrial fibrillation, congestive heart failure, diabetes mellitus, myocardial infarction, and renal dysfunction. There was a nonsignificant reduction in the first event of stroke of any etiology (4.2% versus 4.8%; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.73-1.00; P=0.052) with ezetimibe/simvastatin versus placebo/simvastatin, driven by a significant 21% reduction in ischemic stroke (3.4% versus 4.1%; HR, 0.79; 95% CI, 0.67-0.94; P=0.008) and a nonsignificant increase in hemorrhagic stroke (0.8% versus 0.6%; HR, 1.38; 95% CI, 0.93-2.04; P=0.11). Evaluating total events, including the first and all recurrent strokes, ezetimibe/simvastatin reduced stroke of any etiology (HR, 0.83; 95% CI, 0.70-0.98; P=0.029) and ischemic stroke (HR, 0.76; 95% CI, 0.63-0.91; P=0.003). Patients who had experienced a stroke prior to randomization were at a higher risk of recurrence and demonstrated an absolute risk reduction of 8.6% for stroke of any etiology (10.2% versus 18.8%; number needed to treat=12; HR, 0.60; 95% CI, 0.38-0.95; P=0.030) and 7.6% for ischemic stroke (8.7% versus 16.3%; number needed to treat=13; HR, 0.52; 95% CI, 0.31-0.86; P=0.011) with ezetimibe added to simvastatin therapy.
CONCLUSIONS
The addition of ezetimibe to simvastatin in patients stabilized after acute coronary syndrome reduces the frequency of ischemic stroke, with a particularly large effect seen in patients with a prior stroke.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00202878.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1161/CIRCULATIONAHA.117.029095
- PMID 28972004
- Persistent URL
- https://sonar.ch/global/documents/170200
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