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)

Sabina A. Murphy, Christopher P. Cannon, Stephen D. Wiviott, James A de Lemos, Michael A. Blazing, Carolyn H. McCabe, Robert M. Califf, Eugene Braunwald

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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.

Original languageEnglish (US)
Pages (from-to)1047-1051
Number of pages5
JournalAmerican Journal of Cardiology
Volume100
Issue number7
DOIs
StatePublished - Oct 1 2007

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tirofiban
Pravastatin
Simvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Acute Coronary Syndrome
Myocardial Infarction
Lipids
Mortality
Infection
Therapeutics
Atorvastatin Calcium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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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). / Murphy, Sabina A.; Cannon, Christopher P.; Wiviott, Stephen D.; de Lemos, James A; Blazing, Michael A.; McCabe, Carolyn H.; Califf, Robert M.; Braunwald, Eugene.

In: American Journal of Cardiology, Vol. 100, No. 7, 01.10.2007, p. 1047-1051.

Research output: Contribution to journalArticle

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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.",
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