MIRACL Study



MIRACL Study

Effects of Atorvastatin on Early Recurrent Ischemic Events in Acute Coronary Syndromes: The MIRACL Study

Jama 2001; Vol. 285, 1711-1718

History

-Statins are known to reduce death and CV events over long-term in pts with CAD

-Prior trials excluded pts with recent UA/MI

-This is the period pts experience highest rate of death and recurrent events

-Statins may improve endothelial fn, decrease PLT aggregability, reduce vasc inflamm.

Goal

-Show that treatment c atorvastatin soon p UA/NQWMI reduces early events/death

Methods

-122 centers in 4 different continents

-Inclusion: adults with CP/discomfort 15mins at rest/min exertion w/in 24h before hospitalization

-One of: new/dynamic ST-TW changes at least 2 contiguous leads

-new WMA by Echo

-reversible perfusion defect by radionuclide scan

-elevated cardiac enzymes

-Exclusion criteria: total cholesterol > 270, planned cor revascularization, QWMI w/in 4 wks

-CABG w/in 3 months, PCI w/in 6 months, LBBB/paced, class III/IV HF

-concurrent lipid lowering agent use. Renal failure, transaminases > 2x ULN

-insulin-dependent DM, pregnancy/lactation

-Design: atorvastatin 80mg/d vs. placebo start w/in 24-96 hrs, continue 16weeks

-Primary combined end point: death, nonfatal acute MI, cardiac arrest, recurrent ischemia-16wks

Results

-1538 assigned to atorvastatin vs. 1548 placebo; avg 65yo, mostly white, ¼ prior MI

-Equal number (about 200) pts dropped out of each arm – adverse eff/lost to follow up

-Similar use of ASA, IIb/IIIa, heparin, nitrates, B-blockers

-Mean time to start of study drug 63 hours

-Lipid levels at start identical in both groups: mean LDL 124, TG 184, HDL 46

-At 16weeks, LDL increased 12% placebo vs. decrease 40% in atorvastatin

-Primary end point event in 17.4% placebo vs. 14.8% in atorvastatin; (RRR .84 CI .70-1.00)

-No difference in death/nonfatal MI or cardiac arrest; major diff was risk recurrent ischemia

-Effects were independent of baseline LDL

-Abnormal liver transaminases (> 3x ULN) occurred 2.5% statin group vs. 0.6% placebo

Conclusions

-Early treatment with high dose statin reduced ischemic events over 16-week period

-Study not powered to show reduction in mortality

-Excluded STEMI/revasc pts in order to avoid confounding of short-term events; efficacy statin acutely not known but likely beneficial

-High dose statin chosen to produce maximum effect, however optimal dose not known – high dose statin likely a/w greater degree transaminitis and myositis, therefore use much lower doses (10-40mg).

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