Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial.
JAMA
; 292(11): 1307-16, 2004 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-15337732
ABSTRACT
CONTEXT Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome (ACS) event affect clinical outcome. OBJECTIVE:
To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS. DESIGN, SETTING, ANDPARTICIPANTS:
International, randomized, double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter (n = 2265) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin (n = 2232), who were enrolled in phase Z of the A to Z trial between December 29, 1999, and January 6, 2003. MAIN OUTCOMEMEASURE:
The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, readmission for ACS, and stroke. Follow-up was for at least 6 months and up to 24 months.RESULTS:
Among the patients in the placebo plus simvastatin group, the median low-density lipoprotein (LDL) cholesterol level achieved while taking placebo was 122 mg/dL (3.16 mmol/L) at 1 month and was 77 mg/dL (1.99 mmol/L) at 8 months while taking 20 mg/d of simvastatin. Among the patients in the simvastatin only group, the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL (1.76 mmol/L) and was 63 mg/dL (1.63 mmol/L) at 8 months while taking 80 mg/d of simvastatin. A total of 343 patients (16.7%) in the placebo plus simvastatin group experienced the primary end point compared with 309 (14.4%) in the simvastatin only group (40 mg/80 mg) (hazard ratio [HR], 0.89; 95% confidence interval [CI] 0.76-1.04; P =.14). Cardiovascular death occurred in 109 (5.4%) and 83 (4.1%) patients in the 2 groups (HR, 0.75; 95% CI, 0.57-1.00; P =.05) but no differences were observed in other individual components of the primary end point. No difference was evident during the first 4 months between the groups for the primary end point (HR, 1.01; 95% CI, 0.83-1.25; P =.89), but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin only group (HR, 0.75; 95% CI, 0.60-0.95; P =.02). Myopathy (creatine kinase >10 times the upper limit of normal associated with muscle symptoms) occurred in 9 patients (0.4%) receiving simvastatin 80 mg/d, in no patients receiving lower doses of simvastatin, and in 1 patient receiving placebo (P =.02).CONCLUSIONS:
The trial did not achieve the prespecified end point. However, among patients with ACS, the early initiation of an aggressive simvastatin regimen resulted in a favorable trend toward reduction of major cardiovascular events.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Hidroximetilglutaril-CoA Reductasas
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Simvastatina
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Angina de Pecho
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Hipolipemiantes
Tipo de estudio:
Clinical_trials
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
JAMA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos