Abstract 2259: Risk of Death and Beneficial Effects of Statins in Acute Coronary Syndromes Related to Inflammatory Markers in the MIRACL Study
Objective: To assess the relationships of inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL6) to prognosis after an acute coronary syndrome (ACS) and their modification by statin therapy.
Methods: Inflammatory markers were measured in 2925 of 3086 (95%) subjects within 24 to 96 hours after admission in the MIRACL study -a 16-week trial of atorvastatin 80mg/d or placebo in subjects presenting with unstable angina or non-Q-wave myocardial infarction (MI). Prognosis over the ensuing 16 weeks was assessed by survival analysis and hazard ratios (HR) per unit increase in log(marker), and by tertiles of each marker by treatment allocation (reference group was the lowest tertile in the placebo group). HR’s were adjusted by index event, age and gender. In addition to the primary composite endpoint (death, recurrent MI, resuscitated cardiac arrest, and hospital admission for unstable angina over 16 weeks), death as the sole endpoint was also considered.
Results: The primary composite endpoint occurred in 475 subjects and death in 127 subjects. Baseline CRP was not associated with the primary endpoint (HR=1.08, p=0.13), but was associated with death (HR=1.33, p=0.003). Similarly, baseline SAA (HR=1.26, p=0.01) and IL6 (HR=1.27, p=0.008) were only related to death. The risk of death was greatest with the highest tertile of CRP in the placebo group (HR=2.09, p=0.023), but was lower with the highest tertile of CRP in the atorvastatin group (HR=1.73, p=0.09). Atorvastatin also attenuated the elevated risk for the primary endpoint in the highest tertile of IL6 (HR: Placebo=1.51, p=0.014, Atorvastatin=1.15, p=0.4) and for death (HR: Placebo=2.63, p<0.01, Atorvastatin=1.94, p=0.07).
Conclusions: Inflammatory markers measured shortly after ACS are more strongly related to the 16 week risk of death than to the risk of composite outcomes including non-fatal events. Atorvastatin attenuates the risk of death from high levels of baseline markers, providing evidence for anti-inflammatory actions of statins in subjects with ACS.