Two RCTs were included in the review: one RCT (PROVE IT-TIMI 22 trial) looked at atorvastatin (80mg/day) versus pravastatin (40mg/day) (n=4,162); the other RCT (Colivicchi trial) looked at atorvastatin (80mg/day) versus standard care (n=81). Both trials reported appropriate randomisation procedures and methods of analysis. It was unclear whether outcome assessors were blinded in one trial. In the second trial, neither patients nor care providers were blinded, but outcome assessors were blinded.
Both trials found significantly lower LDL-C levels among patients receiving high-dose atorvastatin.
Event rates for the composite primary end point (death from any cause, myocardial infarction (MI), documented unstable angina requiring hospitalisation, revascularisation occurring at least 30 days after randomisation and stroke) in the PROVE IT-TIMI 22 trial at two years were 22.4% in the high dose group and 26.3% in the standard dose group. This represented a 16% (95% CI: 5% to 26%, p=0.005) reduction in risk in favour of the atorvastatin group (number needed to treat was 26). Statistically significant reductions in favour of high dose atorvastatin were also found for need for revascularisation (hazard ratio was 0.86, 95% 0.74 to 0.99, risk reduction was 14%, p=0.04), recurrent unstable angina requiring hospitalisation (hazard ratio was 0.71, 95% CI: 0.53 to 0.95; risk reduction 29%, p=0.02). A non-statistically significant reduction in favour of atorvastatin was found for rates of death from any cause (hazard ratio was 0.72, 95% CI: 0.50 to 1.03, risk reduction was 28%, p=0.07) and death or MI (hazard ratio was 0.82, 95% CI: 0.67 to 1.0, risk reduction was 18%, p=0.06). Event rates for the composite end point (cardiac death, non-fatal MI or recurrent symptomatic MI requiring emergency hospitalisation) in the Colivicchi trial found a reaction in favour of atorvastatin (odds ratio was 0.33, 95% CI 0.12 to 0.88), representing a number needed to treat of five.
Similar adverse events were reported in both trials: no cases of rhabdomyolysis were reported; and discontinuation of treatment following reports of myalgia, muscle ache or elevation in creatine kinase were similar in the two treatment arms in the larger trial. Only one patient withdrew (due to persistent muscle pain) in the other study. Elevations in aminotransferase levels were more than three times higher in the atorvastatin group in the PROVE IT-TIMI 22 trial.