A Meta-Analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Hydrophilic Versus Lipophilic Statins in Acute Coronary Syndrome Patients

Statins differ in their solubility. Some previous studies suggested a difference in clinical efficacy and adverse events between hydrophilic and lipophilic statins. The purpose of this study is to compare the efficacy and safety of hydrophilic and lipophilic statins in patients with acute coronary syndrome. The databases of MEDLINE/PubMed, Cochrane Library, the Web of Science, and Scopus were systemically searched for articles published from inception until the 18th of July 2024. The primary outcome included major adverse cardiac events (MACE), while the secondary outcomes included myocardial infarction (MI), unstable angina (UA), revascularization, stroke, all-cause mortality, cardiovascular deaths, and adverse events. The results were pooled as risk ratio (RR) along with their 95% confidence intervals (CI). Nine studies were included. Hydrophilic statins showed a significantly higher risk of MACE and UA compared to lipophilic statins (RR 1.11 [95% CI 1.02, 1.21] and 1.30 [95% CI 1.04, 1.62]), but subgroup analysis showed a lack of significant difference between statins of similar intensity (1.01 [95% CI 0.86, 1.18] and 0.98 [0.67, 1.45], respectively). Both statins showed comparable results regarding the occurrence of MI (1.18 [95% CI 0.98, 1.40]), revascularization (1.09 [95% CI 0.99, 1.20]), stroke (1.16 [95% CI 0.80, 1.66]), all-cause mortality (1.13 [95% CI 0.92, 1.38]), cardiovascular deaths (1.14 [95% CI 0.76, 1.72]), adverse events leading to discontinuation (1.03 [95% CI 0.56, 1.90]), increased alanine aminotransferase (0.61 [95% CI 0.32, 1.16]), increased creatine kinase (0.90 [95% CI 0.30, 2.72]), and increased serum creatinine (1.03 [95% CI 0.49, 2.19]). The efficacy and safety of hydrophilic and lipophilic statins are comparable when the cholesterol-lowering intensity of statins is similar. This suggests that intensity, rather than the lipophilicity of the statin, plays a more important role in the secondary prevention of MACE and individual adverse events.