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Odkazy a zdroje - Studie - A to Z (phase Z)



A to Z (phase Z)

Phase Z of the Aggrastat to Zocor Trial

Author(s)
(a) de Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KA, White HD, Rouleau JL, Pedersen TR, Gardner LH, Mukherjee R, Ramsey KE, Palmisano J, Bilheimer DW, Pfeffer MA, Califf RM, Braunwald E; A to Z Investigators.

Title(s)
(a) Early Intensive vs Delayed Conservative Simvastatin Strategy in Patients With Acute Coronary Syndromes. Phase Z of the A to Z Trial

Reference(s)
(a) JAMA 2004;292:1307-13016

Disease
Acute coronary syndrome (ACS)

Purpose
To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS.

Study design
Randomised, double-blind

Follow-up
721 days

Patients
4497 male and female patients with acute coronary syndrome and total cholesterol <250mg|/dl (<6.48 mmol/l), who were enrolled in phase Z of the A to Z trial between December 29, 1999, and January 6, 2003.

Treatment regimen
40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter compared with placebo for 4 months followed by 20 mg/d of simvastatin

Concomitant therapy
-

Results
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. Among the patients in the placebo plus simvastatin group, the median lowdensity 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 dinase>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.