Abstract | BACKGROUND: 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: CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00202878.
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Authors | Erin A Bohula, Stephen D Wiviott, Robert P Giugliano, Michael A Blazing, Jeong-Gun Park, Sabina A Murphy, Jennifer A White, Francois Mach, Frans Van de Werf, Anthony J Dalby, Harvey D White, Andrew M Tershakovec, Christopher P Cannon, Eugene Braunwald |
Journal | Circulation
(Circulation)
Vol. 136
Issue 25
Pg. 2440-2450
(Dec 19 2017)
ISSN: 1524-4539 [Electronic] United States |
PMID | 28972004
(Publication Type: Journal Article, Randomized Controlled Trial)
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Copyright | © 2017 American Heart Association, Inc. |
Chemical References |
- Anticholesteremic Agents
- Cholesterol, LDL
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Simvastatin
- Ezetimibe
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Topics |
- Acute Coronary Syndrome
(drug therapy, mortality, pathology)
- Aged
- Anticholesteremic Agents
(therapeutic use)
- Atrial Fibrillation
(complications)
- Cholesterol, LDL
(blood)
- Double-Blind Method
- Ezetimibe
(therapeutic use)
- Female
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(therapeutic use)
- Male
- Middle Aged
- Myocardial Infarction
(complications)
- Placebo Effect
- Proportional Hazards Models
- Recurrence
- Risk Factors
- Simvastatin
(therapeutic use)
- Stroke
(prevention & control)
- Treatment Outcome
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