Effect of Intensive Lipid-Lowering Therapy on Mortality After Acute Coronary Syndrome (a Patient-Level Analysis of the Aggrastat to Zocor and Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22 Trials)

Abstract

Compared with moderate lipid lowering with standard-dose statin therapy, intensive lipid lowering with high-dose statin therapy after acute coronary syndromes (ACS) significantly reduces cardiovascular events. However, the 2 trials of high-dose versus standard-dose statin therapy in patients with ACS, Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE-IT-TIMI 22), were not individually powered to evaluate the impact on mortality alone. In this study, a pooled, patient-level analysis of these trials of 8,658 post-ACS patients was performed to provide a more robust estimate of the impact of intensive statin therapy on mortality. By 8 months, achieved low-density lipoprotein levels were lower in the group with intensive statin therapy (median 64 mg/dl, interquartile range 51 to 81) than in the group with moderate statin therapy (median 87 mg/dl, interquartile range 71 to 107) (p <0.001). All-cause mortality was significantly reduced in the group with intensive statin therapy compared with the group with moderate statin therapy (3.6% vs 4.9%, hazard ratio 0.77, 95% confidence interval 0.63 to 0.95, p = 0.015), without significant interaction by trial (interaction p = 0.63). The reduction in all-cause mortality with intensive statin therapy was consistent across key subgroups. In conclusion, in this analysis of >8,600 patients, intensive lipid lowering with high-dose statin therapy after ACS was associated with reduced mortality compared with moderate lipid lowering with standard-dose statin therapy. On the basis of these findings, 1 death was prevented for every 95 patients treated with high-dose statin therapy for 2 years. The results of this pooled analysis provide further evidence for early intensive statin therapy after ACS.