MIRACL

Myocardial Ischemia Reduction with Aggressive Cholesterole Lowering (MIRACL)

Design: Randomized double-blinded RCT (2001)

P N = 3086
Adults > 18 yo with unstable angina or Q-wave acute MI
– CP of at least 15 mins duration that occurred at rest or with minimal ertion within the 24 hour period preceding hospitalization and represented a change from their usual anginal pattern
Excluded:
– total cholesterol > 7 mmol/L
– coronary revascularation was planned or anticipated at time of screening 
– PCI within preceding 6 months
– LBBB or paced ventricular rhythm
– NYHA IV CHF
– concurrent tx with other lipid regulating agents except niacin at doses of 500mg/d
– insulin-dependent diabetes
– hepatic dysfunction (ALT > 2x ULN)
– pregnancy/lactation
I Atorvastatin 80mg daily x 16 weeks
between 24-96 hours after hospital admission/presentation of the above
– Compliance 86%
C Matching placebo x 16 weeks
between 24-90 hours after hospital admission/presentation of the above
– 
Compliance 88%
O Primary end point: death, nonfatal acute MI, cardiac arrest with resuscitation or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization

Secondary end points:
individual occurrence of primary end point, nonfatal stroke, new/worsening CHF requiring hospitalization, worsening angina requiring rehospitalization but without new objective evidence of ischemia, coronary revascularization by surgical or percutaneous means, time to first occurrence of any primary or secondary end point and % of blood lipid levels from baseline to end of study

Patients:

  • 65 yo
  • 85% white
  • 46% unstable angina pectoris, 53% non-Q-wave MI
  • Placebo: 1.4% on lipid-lowering agents vs. Atorvastatin: 0.5% PTA
    – Placebo: 3%, Atorvastatin: 2% after hospitalization
    – ?Difference in baseline risk
  • Baseline mean LDL: 3.2 mmol/L, TG 2.0 mmol/L, HDl 1.2mmol/L

Outcomes:

  • Primary endpoint: RR 0.84 (0.7-1.00; P = 0.048)
    • NNT = 39
    • NSS for death, non-fatal acute MI or cardiac arrest with resuscitation
    • ?Primary endpoint made SS by making it composite
    • Risk of recurrent symptomatic myocardial ischemia with objective evidence requiring emergency rehospitalization: RR: 0.74 (0.57-0.95, P = 0.02)
  • Risk of incidence of non-fatal stroke: RR: 0.41 (0.20-0.87)
  • Risk of incidence of fatal/non-fatal stroke: RR: 0.50 (0.26-0.99)
    • NNT = 22
    • ?SS of fatal stroke alone
  • Surrogate markers
    • LDL increased in placebo by 12%, and decreased in ator by 40%
    • TG increased in placebo by 9%, and decreased in ator by 16%
    • Minor changes in HDL
  • Safety:
    • Increased abnormal liver transaminases
    • NNT = 54

Take-away points:

  •  In acute post-MI (no revascularization), atorvastatin 80mg daily reduced the risk of
    • recurrent symptomatic myocardial ischemia with objective evidence requiring emergency rehospitalization
    • non-fatal stroke
  • BUT…increased risk of abnormal liver transaminases (>3 times ULN)
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