The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Trial: Effects of Intensive Atorvastatin Treatment on Early Recurrent Events After an Acute Coronary Syndrome

Background: In the treatment of patients with unstable angina and non-ST segment elevation myocardial infarction (UA/NSTEMI), debate exists as to whether an early invasive vs. a conservative strategy is optimal therapy.Methods: In the international TACTICS-TIMI 18 trial, 2220 patients with UA/NSTEMI who had either electrocardiographic changes, elevated cardiac markers or a history of prior coronary artery disease, were immediately treated with aspirin, heparin and the glycoprotein (GP) IIb/IIIa inhibitor tirofiban.They were randomized to an early invasive strategy with routine catheterization and revascularization as appropriate within 4 -48 hours, or to a conservative, or "selective invasive" strategy, with catheterization performed only if the patient had objective evidence of recurrent ischemia or a positive stress test.The primary endpoint was a composite of death, myocardial infarction or rehospitalization for acute coronary syndromes at 6 months.Results: The rate of the primary endpoint was significantly reduced with the invasive strategy compared to the conservative strategy, 15.9% vs. 19.4%,odds ratio (OR) 0.78, pϭ0.025.The rate of death or MI at 6 months was also significantly reduced (9.5% vs. 7.3%, respectively, OR 0.74, pϽ0.05).Conclusion: In patients with UA/NSTEMI treated with the GP IIb/IIIa inhibitor tirofiban, an early invasive strategy resulted in a significant reduction in major cardiac events.These data suggest a need to update the ACC/AHA Unstable angina Guidelines, and to modify the clinical approach to managing unstable angina with broader use of an early invasive strategy with upstream GP IIb/IIIa inhibition. Effect of the Angiotensin Receptor Blocker Valsartan on Morbidity and Mortality in Heart Failure: the Valsartan Heart Failure Trial (Val-HeFT)Jay N. Cohn and Gianni Tognoni for the Val-HeFT Investigators, Minneapolis, Minnesota and Milan, Italy In order to assess the efficacy of the angiotensin receptor blocker valsartan in the treatment of heart failure (HF), 5010 patients were studied in 16 countries on 4 continents.Patients with chronic HF [NYHA II (62%), III (36%) and IV (2%)], ejection fraction (EF) Ͻ40% and left ventricular diastolic transverse diameter (LVIDD) Ͼ2.9 cm/m2 were randomly assigned to receive placebo (P) or valsartan (V) (titrated to 160 mg BID) in addition to all other appropriate therapy including ACE inhibitors (93%), beta blockers (36%), diuretics (86%) and digoxin (67%).Primary end-points were all-cause mortality (M) and mortality plus morbidity (MϩM), which included hospitalization for heart failure (adjudicated), cardiac arrest with resuscitation, or need for intravenous support for worsening heart failure.Time to death was similar in the two groups but time to first MϩM event was significantly reduced by 13.3% by V (32.1% in P, 28.8% in V; Pϭ0.009).HF hospitalization was significantly reduced by 27.5% by V (18.5% in P, 13.9% in V; (PϽ0.001).The benefit of V on MϩM was particularly prominent in patients not taking a beta blocker (37.0% to 30.8%, PϽ0.001) and in those not taking an ACE inhibitor (42.5% to 24.9%, PϽ0.001).The benefit on MϩM was accompanied by significant improvements in NYHA class, quality of life, and EF.These data demonstrate clinical efficacy of valsartan in heart failure in patients already receiving standard HF therapy.