(a) Blazing MA, de Lemos JA, White HD, Fox KAA, Verheugt FWA, Ardissino D, DiBattiste PM, Palmisano J, Bilheimer DW, Snapinn SM, Ramsey KE, Gardner LH, Hasselblad V, Pfeffer MA, Lewis EF, Braunwald E, Califf RM
(b) de Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KAA, White HD, Rouleau J-L, Pedersen TR, Gardner LH, Mukherjee R, Ramsey KE, Palmisano J, Bilheimer DW, Pfeffer MA, Califf RM, Braunwald E

(a) Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin
(b) Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes

(a) JAMA 2004;292:55–64
(b) JAMA 2004;292:1307–16

Acute coronary syndromes

Phase A: to assess the efficacy and safety of the combination of enoxaparin and tirofiban compared to unfractionated heparin and tirofiban in patients with non-ST-elevation acute coronary syndromes Phase Z: to compare early initiation of an intensive statin regimen with delayed initiation of a less intensive statin regimen in patients with acute coronary syndromes

Phase A: randomised, open Phase Z: randomised, double-blind

Phase A: 7 days Phase Z: mean 721 days

Phase A: 3987 patients (2026 enoxaparin, 1961 unfractionated heparin), median age 61 years, with ischaemic pain ≥ 10 min and ≤ 24 h, and either ST-segment depression ≥ 5 mm, transient ST elevation ≥ 1 mm, or elevated cardiac markers Phase Z: 4497 patients (2265 intensive simvastatin, 2232 less intensive simvastatin), median age 61 years, with either a non-ST-segment elevation acute coronary syndrome or ST-segment elevation MI, and total cholesterol ≤ 250 mg/dl

Phase A: enoxaparin, 1 mg/kg every 12 h, or unfractionated heparin, to target activated partial thromboplastin time 50–70 s Phase Z: simvastatin, 40 mg/day for 30 days, then 80 mg/day, or placebo for 4 months, then simvastatin, 20 mg/day

Phase A: tirofiban and ASA Phase Z: American Heart Association step 1 diet

Phase A: 3970 patients (2018 enoxaparin, 1952 unfractionated heparin) were included in the intention-to-treat efficacy analysis. The primary composite endpoint of all-cause mortality, new MI or refractory ischaemia occurred in 8.4% of patients receiving enoxaparin and in 9.4% of those receiving unfractionated heparin (hazard ratio 0.88, 95% CI 0.71–1.08). 3905 patients (1940 enoxaparin, 1965 unfractionated heparin) were included in the as-treated safety analysis. The incidence of TIMI major or minor bleeding was 3.0% in the enoxaparin group and 2.2% in the unfractionated heparin group (p = 0.13) Phase Z: The primary composite endpoint of cardiovascular death, nonfatal MI, readmission for an acute coronary syndrome, or stroke occurred in 14.4% of patients receiving intensive treatment with simvastatin and in 16.7% of those receiving less intensive treatment with simvastatin (hazard ratio 0.89, 95% CI 0.76–1.04; p 0.14)