NEW YORK (Reuters Health) – Intensive statin therapy is more effective than standard doses in reducing the risk of major adverse events after angioplasty for acute coronary syndromes (ACS), investigators in Boston report.

“These data…strongly suggest that patients who undergo percutaneous coronary intervention (PCI) should be treated with intensive statin therapy,” as indicated by the most recent PCI guidelines, lead author Dr. C. Michael Gibson, of Beth Israel Deaconess Medical Center, and colleagues advise in the Journal of the American College of Cardiology for December 8.

The results of intensive versus moderate lipid-lowering therapy after PCI for ACS are not well established, the research team points out. Furthermore, they say, no one has compared the effect of different statin dosages on target-vessel and non-target vessel revascularization.

The investigators addressed these issues in a post hoc subgroup analysis of data from the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis in Myocardial Infarction 22) study. Subjects in this study had been randomly assigned to receive 40 mg/d of pravastatin or 80 mg/d of atorvastatin. Of the original cohort of 4162 patients, 69% had undergone PCI just prior to randomization (1442 in the atorvastatin group and 1425 in the pravastatin group).

In this subset, after a mean follow-up of 2 years, treatment with 80 mg atorvastatin was more effective than 40 mg pravastatin in reducing the incidence of the primary composite end point (mortality, myocardial infarction, hospitalization for unstable angina, stroke, and revascularization at least 30 days after randomization). Rates of the composite outcome were 21.5% with 80 mg of atorvastatin vs 26.5% with 40 mg of pravastatin (hazard ratio 0.78, p = 0.001).

Atorvastatin was also associated with greater reductions in the secondary composite endpoint (cardiovascular death, nonfatal myocardial infarction, recurrent ischemia, and rehospitalization for unstable angina): 15.4% vs 20.1%, respectively (HR 0.73, p = 0.001).

Rates of several individual components of the composite endpoints were also lower with higher-dose therapy, including recurrent ischemia, rehospitalization for unstable angina, revascularization 30 or more days after randomization, and the composite of death and myocardial infarction. There was no significant difference between the two groups in the incidence of stroke.

After adjusting for 30-day on-treatment serum levels of LDL-cholesterol and C reactive protein, intensive statin treatment was associated with a greater reduction in the rate of target vessel revascularization (adjusted odds ratio 0.74, p = 0.015). After adjustment, treatment assignment had no significant effect on reduction of non-target vessel revascularization.

Dr. Gibson’s team suggests that part of the reduction in target vessel revascularization may be mediated by a pleiotropic mechanism of high-dose treatment not accounted for by reductions in LDL-cholesterol or markers of systemic inflammation. Such pleiotropic effects may include decreased inflammation, increased plaque stability, and improved endothelial function.

By contrast, among patients managed medically rather than by PCI, treatment intensity was not associated with any significant difference in primary or secondary end points.

According to the authors, the strict enrollment criteria for the study likely excluded some patients normally seen in clinical practice, and therefore their findings probably cannot be generalized to all patients. Furthermore, because only bare metal stents were used during PCI in this cohort, the applicability of their findings to patients treated with drug-eluting stents remains unknown.

Reference:
J Am Coll Cardiol 2009;54:2290-2295.