Comparative Safety and Efficacy of Coronary Calcified Lesion Preparation Strategies

Background: Coronary artery calcification complicates percutaneous coronary intervention (PCI) by promoting stent underexpansion and increasing rates of stent thrombosis, restenosis, and major adverse cardiovascular events (MACE). Four principal lesion preparation strategies are available: conventional balloon angioplasty, modified balloons (cutting/scoring), atherectomy (rotational/orbital), and intravascular lithotripsy (IVL). Prior evidence derives largely from pairwise trials; no study has simultaneously compared all four modalities. Methods: A systematic review and frequentist random-effects network meta-analysis (NMA) was conducted per Cochrane and PRISMA guidelines. Eight studies were included: ROTAXUS, ECLIPSE, BALI, PREPARE-CALC, ROTA-SHOCK, ROLLING STONE, COPS, and ROLLER COASTER-EPIC22. Treatment nodes comprised plain balloon angioplasty, modified balloon (cutting/scoring), atherectomy, and IVL. Procedural, angiographic, and follow-up clinical outcomes were analyzed using odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals. Treatment hierarchy was estimated via P-scores/SUCRA. Prespecified sensitivity and node-splitting analyses assessed robustness and consistency. Results: Across 8 studies and 4 lesion preparation strategies, IVL ranked highest for procedural success (P-score 47.9%) and procedure-related MACE (31.5%), while modified balloon ranked best for minimizing periprocedural MI (P-score 46.2%). Atherectomy was the only strategy associated with a statistically significant increase in coronary perforation risk compared to plain balloon angioplasty (OR 2.02; 95% CI 1.08–3.77; p=0.028), with plain balloon ranking most favorably for dissection risk. Procedure-related mortality was comparable across all strategies, with no statistically significant pairwise differences. At follow-up, IVL demonstrated the most favorable profile for all-cause mortality (P-score 89.4%), MI (50.6%), and target lesion revascularization (57.7%), while modified balloon ranked highest for follow-up MACE (58.4%). Sensitivity and node-splitting analyses confirmed robustness and consistency of findings across all endpoints. Conclusion: In this NMA simultaneously comparing all four calcified lesion preparation strategies, IVL and modified balloon techniques demonstrated consistently favorable profiles across procedural efficacy and follow-up ischemic outcomes, while atherectomy was associated with a significantly higher perforation risk. These findings, to be interpreted in the context of moderate certainty evidence and largely non-significant pairwise comparisons, provide a comprehensive comparative framework to guide operator decision-making for heavily calcified coronary lesions.