Expert Review: Lipid / Metabolic

A randomized, controlled trial of simvastatin versus rosuvastatin in patients with acute myocardial infarction: the Secondary Prevention of Acute Coronary Events–Reduction of Cholesterol to Key European Targets Trial.

The debate over the cholesterol hypothesis and statins has raged for decades. The early period following the onset of acute coronary syndrome represents a critical stage of coronary heart disease, with a high risk of recurrent events and deaths. The long-term effects of early treatment with statins on patient-relevant outcomes in patients suffering from acute coronary syndrome have led to recommend these drugs as first line treatment in secondary prevention of coronary heart disease. However, differences between statins are unclear. The SPACE ROCKET (Secondary Prevention of Acute Coronary Events–Reduction Of Cholesterol to Key European Targets) study was an independent, prospective, open-label, blinded-endpoint, multicenter, randomized, controlled, parallel-group trial to evaluate the effect of rosuvastatin and simvastatin on hyperlipidemia in patients after acute myocardial infarction (MI).
Patients who had an MI within 2 weeks of study entry and those who, in the opinion of the attending physician, required secondary prevention with a statin were included in the study. MI within 2 weeks was defined as either having a primary percutaneous coronary intervention (PCI) or an increase in biochemical markers of myocardial necrosis with 1 or more of the following: ischemic symptoms, Q waves on an electrocardiogram (ECG), or ECG changes indicative of ischemia (ST-segment elevation or depression).
The primary endpoint was achievement of ESC-03 lipid targets (total cholesterol [total-C] A total of 1263 patients were randomized to receive simvastatin 40 mg or rosuvastatin 10 mg for 3 months. Baseline patient characteristics were similar across both treatment groups. The mean age of patients was 62 years and the majority of patients were Caucasian (98.1% in simvastatin group, 96.8% in rosuvastatin group).
Overall, 79.9% (506/633) of rosuvastatin-treated patients and 77.6% (489/630) of simvastatin-treated patients achieved ≥1 of the ESC-03 lipid targets. There was no evidence of a difference between the 2 treatment groups per the adjusted analysis (odds ratio [OR], 1.162; 95% CI, 0.882-1.531). In a post hoc analysis, more patients achieved the ESC/American Heart Association (AHA)/American College of Cardiology (ACC) optimal LDL-C target of less than 70 mg/dL with rosuvastatin (45.0%) than with simvastatin (37.8%) (OR, 1.37; 95% CI, 1.09-1.72; p=0.007).
There was no difference between groups in the number of CV events reported and confirmed at the 3-month follow-up visit. Additionally, there was no difference in death from all causes at 3 months or after at least 1 year from randomization.

Conclusion
It can be concluded that the study did not find superiority of either treatment for the ESC-03 lipid targets. However, Rosuvastatin 10 mg lowered mean cholesterol more effectively than simvastatin and achieved better results for the latest, more stringent, ESC lipid targets.These results should be confirmed in further research that, in addition, must prove if the differences found translate in a reduction of CV events (death, MI, unstable angina or stroke) in the follow-up, as well as side effect profile.

Corresponding author from original paper
Hall AS
Department of Medicine, Leeds Institute for Genetics Health and Therapeutics, Leeds, UK

Citation: Hall AS, Jackson BM, Farrin AJ, Efthymiou M, Barth JH, Copeland J, Bailey KM, Romaine SP, Balmforth AJ, McCormack T, Whitehead A, Flather MD, Nixon J;SPACE ROCKET Trial Group. A randomized, controlled trial of simvastatin versus rosuvastatin in patients with acute myocardial infarction: the Secondary Prevention of Acute Coronary Events- Reduction of Cholesterol to Key European Targets Trial. Eur J Cardiovasc Prev Rehabil. 2009;16(6):712-21

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