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FOCUS ISSUE: PROVE IT-TIMI 22: STATE-OF-THE-ART PAPER

The Potential Relevance of the Multiple Lipid-Independent (Pleiotropic) Effects of Statins in the Management of Acute Coronary Syndromes

Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts

Manuscript received March 18, 2005; revised manuscript received May 12, 2005, accepted May 16, 2005.

^_* Reprint requests and correspondence: Dr. Kausik K. Ray, The TIMI Study Group, 350 Longwood Avenue, 1st Floor, Boston Massachusetts 02115 (Email: kkray{at}partners.org).

Emerging data suggest that acute presentations of coronary artery disease may involve a complex interplay between the vessel wall, inflammatory cells, and the coagulation cascade. Although a culprit thrombotic lesion may be treated effectively by antithrombotic therapy and revascularization, this will have little effect on the global processes that determine recurrent events at non-culprit sites. Thus, additional systemic treatment is required to modulate the adverse biological features that are the hallmark of acute coronary syndromes (ACS). Statins possess multiple beneficial effects that are independent of low-density-lipoprotein cholesterol (LDL-C) lowering and that have favorable effects on inflammation, the endothelium, and the coagulation cascade. In the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, differences were seen based on achieved LDL-C that could be further discriminated by the achieved C-reactive protein level. Studies of non-vascular disease such as multiple sclerosis have shown that statins reduce inflammation, supporting the presence of lipid-independent effects of statins. This review focuses on the potential importance of these effects in the management of ACS.

Abbreviations and Acronyms   ACS = acute coronary syndromes   CAD = coronary artery disease   CRP = C-reactive protein   HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)   ICAM = intercellular adhesion molecule   IL = interleukin   LDL-C = low-density lipoprotein cholesterol   NO = nitric oxide   PAI-1 = plasminogen activator inhibitor   PROVE IT-TIMI 22 = Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22   TF = tissue factor   TM = thrombomodulin   tPA = tissue plasminogen activator   vWF = von Willebrand factor

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