Research has shown that when compared with moderate-dose statins, intensive statin therapy can reduce major adverse cardiac events among patients with acute coronary syndrome (ACS). However, the results of intensive-versus-moderate lipid-lowering therapy after PCI for ACS are not well established. Furthermore, no studies have compared the effect of different statin dosages on target vessel revascularization (TVR) and non-TVR. In this patient subgroup, clinicians often focus on treating the stent rather than the whole patient. Stenting only treats one focal spot, not the whole bed of the coronary tree. Clopidogrel and aspirin are often used to keep the stent open, but the role of intensive lipid-lowering therapy in PCI is frequently undervalued.
Support for Intensive Lipid Lowering
In the December 8, 2009 Journal of the American College of Cardiology, my colleagues and I conducted a study in which we compared outcomes in 2,868 patients who underwent PCI for ACS just prior to enrollment in the PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) trial. The PROVE IT–TIMI 22 randomized ACS patients to either 80 mg atorvastatin or 40 mg pravastatin daily. Of the original cohort, 69% had undergone PCI just prior to randomization. The incidence of the primary composite end point of all-cause mortality, myocardial infarction, unstable angina leading to hospitalization, and revascularization after 30 days and stroke was evaluated. We also assessed the incidence of TVR and non-TVR during follow-up.
Treatment with 80 mg atorvastatin reduced the incidence of the composite end point (21.5% vs 26.5%) and lowered the incidence of TVR (11.4% vs 15.4%) and non-TVR (8.0% vs 10.5%) when compared with 40 mg pravastatin. Rates of recurrent ischemia, rehospitalization for unstable angina, revascularization 30 or more days after randomization, and the composite of death and myocardial infarction were also lower with higher-dose therapy. We observed no difference between the groups in the incidence of stroke. After adjusting for 30-day on-treatment serum LDL cholesterol and C-reactive protein concentrations, the odds of TVR with high-dose statin therapy remained significant while the odds of non-TVR did not. Our data strongly support the idea that patients who undergo PCI should be treated with intensive statin therapy, as indicated by the most recent PCI guidelines.
Part of the reduction in TVR may be mediated by a pleiotropic mechanism of high-dose treatment that was not accounted for by reductions in LDL-cholesterol or markers of systemic inflammation. These pleiotropic effects may include decreased inflammation, increased plaque stability, and improved endothelial function. Conversely, treatment intensity was not associated with any significant difference in end points among patients managed medically rather than by PCI.
Needs for the Future
The strict enrollment criteria for our study may have excluded some patients normally seen in clinical practice, so our findings probably can’t be generalized to all patients. However, our study does heighten awareness on taking the extra steps to ensure that aggressive, intensive lipid-lowering therapy be administered to patients receiving PCI to further enhance outcomes. More education is necessary for interventional cardiologists; simply put, stenting alone isn’t enough to treat ACS. In the future, clinicians need to gain a better understanding of the pleiotropic mechanisms of the benefits of statins and explore other agents or processes that might achieve the same goals.
Readings & Resources (click to view)
Gibson CM, Pride YB, Hochberg CP, Sloan S, Sabatine MS, Cannon CP; TIMI Study Group. Effect of intensive statin therapy on clinical outcomes among patients undergoing percutaneous coronary intervention for acute coronary syndrome PCI-PROVE IT: a PROVE IT-TIMI 22 (pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22) substudy. J Am Coll Cardiol. 2009;54:2290-2295. Abstract available at: http://content.onlinejacc.org/cgi/content/abstract/54/24/2290.
Jia XW, Fu XH, Zhang J, et al. Intensive cholesterol lowering with statin improves the outcomes of percutaneous coronary intervention in patients with acute coronary syndrome. Chin Med J (Engl). 2009;122:659-664.
Johnson C, Waters DD, DeMicco DA, et al. Comparison of effectiveness of atorvastatin 10 mg versus 80 mg in reducing major cardiovascular events and repeat revascularization in patients with previous percutaneous coronary intervention (post hoc analysis of the Treating to New Targets [TNT] Study). Am J Cardiol. 2008;102:1312-1317.
Leone AM, Rutella S, Giannico MB, et al. Effect of intensive vs standard statin therapy on endothelial progenitor cells and left ventricular function in patients with acute myocardial infarction: Statins for regeneration after acute myocardial infarction and PCI (STRAP) trial. Int J Cardiol. 2008;130:457-462.
Kumar A, Cannon CP. Importance of intensive lipid lowering in acute coronary syndrome and percutaneous coronary intervention. J Interv Cardiol. 2007;20:447-457.
Kinoshita M, Matsumura S, Sueyoshi K, Ogawa S, Fukuda K. Randomized trial of statin administration for myocardial injury: is intensive lipid-lowering more beneficial than moderate lipid-lowering before percutaneous coronary intervention? Circ J. 2007;71:1225-1228.