High-Dose Statin Preloading Before Percutaneous Coronary Intervention in Acute Coronary Syndrome

Introduction: Acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) remain at high risk for peri-procedural myocardial injury and major adverse cardiovascular events (MACE). Current guidelines recommend early high-intensity statin therapy because of its lipid-lowering and rapid pleiotropic effects. However, evidence regarding its efficacy and safety remains inconsistent. We performed a GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of statin preloading in ACS patients undergoing PCI. Methods: This systematic review and meta-analysis of RCTs was conducted in accordance with the PRISMA 2020. Electronic databases were searched upto April 2026 to identify eligible studies comparing statin preloading with controls. Primary outcome was MACE, while secondary outcomes included mortality, reinfarction, revascularization, and stroke. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Data were pooled using a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I 2 statistic. Prespecified subgroup analyses (dose, statin type, follow-up duration) and meta-regression (year, age, hypertension, LDL levels) were performed. Leave-one-out sensitivity analysis and trial sequential analysis were performed to assess robustness and control random error. Publication bias was evaluated using funnel plots (≥10 studies) and Egger’s regression test. Certainty of evidence was appraised using the GRADE approach. Results: A total of 13 studies (n=2982) were included. Statin preloading significantly reduced MACE (RR 0.55, 95% CI 0.46-0.67; I 2 =0%) as shown in figure 1, mortality (RR 0.43, 95% CI 0.24-0.78; I 2 =0%), reinfarction (RR 0.51, 95% CI 0.38-0.69; I 2 =0%), revascularization (RR 0.54, 95% CI 0.37-0.79; I 2 =0%), and stroke (RR 0.59, 95% CI 0.37-0.94; I 2 =0%). Subgroup analyses showed no differences by dose or follow-up, while statin type influenced MACE (p=0.028). Meta-regression demonstrated no significant effect modification by year, age, hypertension, or LDL levels. No publication bias was observed except for possible bias for stroke. Leave-one-out sensitivity analyses and Trial Sequential Analysis (TSA) confirmed robustness. Certainty of evidence was moderate for MACE, low for mortality, reinfarction, and revascularization, and very low for stroke. Conclusion: Single high-dose statin preloading prior to PCI in ACS patients significantly reduces MACE and key ischemic outcomes. While mortality and other secondary outcomes also favor statin preloading, the certainty of evidence remains variable. These findings support its use as an adjunct to guideline-directed therapy, though further high-quality trials are warranted to strengthen the evidence for less certain outcomes .