High-intensity versus very-high-intensity statin, both on top of ezetimibe, in acute myocardial infarction: A pragmatic randomized study

Background: Early lipid-lowering therapy with "high-intensity" statins is recommended post-acute myocardial infarction (AMI), yet the optimal dose within such regimens remains uncertain. We compared efficacy and safety of very high-intensity versus high-intensity statin regimens, both combined with ezetimibe, initiated during AMI hospitalization. Methods: In a stepped-wedge cluster randomized controlled single-center trial, patients with ST- or non-ST-elevation AMI were assigned in sequential 6-month blocks to either very high-intensity statin (Group A: atorvastatin 80 mg or rosuvastatin 40 mg) or high-intensity statin (Group B: atorvastatin 40 mg or rosuvastatin 20 mg), both combined with ezetimibe 10 mg, daily. The primary endpoint was achieving both LDL-C < 55 mg/dL and ≥ 50% LDL-C reduction at 30 days post-discharge. Secondary endpoints included each primary endpoint component, mean LDL-C levels, safety, and need for dose reduction. Results: Two-hundred-and-twenty patients (mean age 67 years, 63% men) were enrolled. Groups were balanced at baseline for demographic, clinical, and laboratory characteristics. At 30 days, the primary (efficacy) endpoint occurred in 63% of patients in Group A and 52% of patients in Group B (p = 0.13). LDL-C < 55 mg/dL was achieved in 86% of Group A and 73% of Group B (p = 0.02). No significant difference was seen in ≥50% LDL-C reduction. Group A had lower mean LDL-C (43 ± 16 mg/dL vs 48 ± 14 mg/dL; p = 0.046). Statin dose reduction due to intolerance occurred, however, more often in Group A (8% vs 2%, p = 0.03). No differences in liver enzymes were observed. Conclusions: Very high-intensity and high-intensity statin regimens differed minimally in achieving LDL-C targets, but very high-intensity regimens had higher rates of intolerance-related dose reduction.