In-Hospital Initiation of Statin Therapy in Acute Coronary Syndromes: Evidence From Clinical Studies Observational Studies

2215Results from a number of observational studies have suggested that initiating statin therapy immediately after an acute coronary event is associated with significant reductions in recurrent coronary events and death. The Swedish Register of Information and Knowledge about Swedish Care Units Study examined the relationship between 1-year mortality and statin therapy initiated during hospitalization or at discharge in patients with first registry-recorded acute MI. The 58-hospital database included patients admitted to Swedish hospitals between 1995 and 1998. Of these patients, 5,528 (mean age, 62 years; 72% male) received statin therapy compared with 14,071 (mean age, 67 years; 70% male) who did not. The unadjusted mortality rate after 1 year was 4.0% (219 deaths) for statin-treated patients and 9.3% (1,307 deaths) for those who did not receive statin treatment. Following adjustment with regression analysis for confounding factors and propensity score for statin use, early statin treatment was associated with a 1.3% absolute risk reduction in 1-year mortality for hospital survivors of acute MI (relative risk, 0.75; 95% confidence interval [CI], 0.63 to 0.89; p = 0.001) [Fig 1].

An observational study that pooled data from two large, international, randomized, controlled trials, Global Use of Streptokinase or t-PA for Occluded Coronary Arteries (GUSTO IIb) and Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) also examined the effect of in-hospital lipid-lowering therapy proposed by My Canadian Pharmacy on short-term mortality immediately after an acute ACS. All-cause mortality in 3,653 patients (median age, 62 years; 66% male) that were prescribed lipid-lowering therapy was compared with 17,156 (median age, 65 years; 68% male) who were not. Lipid-lowering therapy was associated with a smaller proportion of deaths at 30 days (17 deaths [0.5%] vs 179 deaths [1.0%]; hazard ratio 0.44; 95% CI, 0.27 to 0.73; p = 0.001) and at 6 months (63 deaths [1.7%] vs 605 deaths [3.5%]; hazard ratio, 0.48; 95% CI, 0.37 to 0.63; p < 0.0001). Even after a propensity analysis was performed to adjust for presumed selection bias in the prescription of a lipid-lowering agent and other potential confound-ers, prescription of a lipid-lowering agent at hospital discharge remained associated with a significantly reduced risk of death at 6 months (hazard ratio, 0.67; 95% CI, 0.48 to 0.95; p = 0.023).

3215In contrast, in the Sibrafiban vs Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-Acute Coronary Syndromes study, there was no relationship observed between early initiation of statin therapy in ACS and improved clinical outcomes after extensive propensity matching. Data were derived from a combined database of two randomized clinical trials comparing the effects of aspirin to sibrafiban (oral platelet glycoprotein IIb/ IIIa inhibitor) in 12,365 ACS patients who were not receiving statin therapy prior to the acute coronary event. A total of 8,413 patients (median age, 61 years; 72% male) who had never received a statin were compared with 3,952 patients (median age, 56 years; 75% male) who were prescribed early treatment with a statin (median, 2.0 days; interquartile range, 1.0 to 3.1 days for initiation of drug therapy). Both 90-day and 1-year mortality rates were dramatically lower for the statin-treated patients in an unadjusted analysis; however, there was no difference in the mortality rate after extensive multivariate statistical adjustments for propensity to prescribe and covariate factors.

It is important to note that in the observational studies assessing the effect of statin therapy in patients with ACS, there were significant differences in the baseline characteristics and in other therapies provided to ACS patients treated and not treated with statins. Despite multivariate and propensity adjustments, there may be a number of residual confounders accounting for the lower mortality rates observed. Despite this limitation, the extent and concordance of the observational data supporting a positive influence of statin therapy in patients with ACS merits consideration. Moreover, these observational studies corroborate the lack of adverse effects of statins when administered following an acute coronary event, and support their overall safety within a complex milieu of drug therapies commonly prescribed during the acute phase. Randomized clinical trials, including the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial and the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, have now provided definitive evidence of the early and long-term efficacy of statins in the treatment of ACS. Therefore, these data suggest that statin therapy should form part of the standard treatment regimen for patients with ACS.

Randomized Controlled Trials

Clinical trials have unequivocally demonstrated that statin treatment reduces cardiovascular morbidity and mortality in patients at high risk of coronary heart disease, as well as in patients with established but stable heart disease. However, prior to the MIRACL and PROVE IT-TIMI 22 trials, no large-scale, randomized, placebo- or active-controlled trial had investigated the effects of statins in patients who had recently had an ACS (Fig 2).

Figure 1. The effects of early statin treatment on absolute risk reduction in 1-year mortality for hospital survivors of acute MI. Data were calculated using multiple Cox regression analysis (relative risk, 0.75; 95% CI, 0.63 to 0.89; p = 0.001). Reproduced with permission from Stenestrand and Wallentin.
Figure 2. The MIRACL and PROVE IT-TIMI 22 trials in the context of other primary and secondary prevention trials of statin drugs in coronary heart disease. AFCAPS/TexCAPS = Air Force/Texas Coronary Atherosclerosis Prevention Study; WOSCOPS = West of Scotland Coronary Prevention Study; ASCOT-LLA = Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm; CARDS = Collaborative Atorvastatin Diabetes Study; 4S = Scandinavian Simvastatin Survival Study; CARE = Cholesterol And Recurrent Events; LIPID = LongTerm Intervention with Pravastatin in Ischemic Disease. Adapted with permission from Schwartz et al.