Am J Ther. 2026 Jun 25. doi: 10.1097/MJT.0000000000002156. Online ahead of print.
ABSTRACT
BACKGROUND: Cardiovascular disease remains the leading cause of global mortality (19.8 million deaths in 2022; 32% of all deaths worldwide). Drug repurposing-extending approved agents beyond their original indications-has emerged as a high-impact strategy in cardiovascular prevention, offering reduced development timelines, established safety profiles, and faster implementation than de novo molecular development.
STUDY QUESTION: Which repurposed cardiovascular agents demonstrate the most favorable pharmacoeconomic profiles, and how does the convergence of clinical benefit, patient risk stratification, and economic sustainability define the optimal hierarchy for cardiovascular prevention?
STUDY DESIGN: Narrative review synthesizing evidence from 19 pivotal cardiovascular outcomes trials and European and American guidelines. No formal meta-analysis was applied.
MEASURES AND OUTCOMES: For 13 agents across 8 therapeutic classes, efficacy was quantified as relative and absolute risk reductions, and as the number needed to treat or to harm. Pharmacoeconomic value was assessed via incremental cost-effectiveness ratio in US dollars per quality-adjusted life year, integrating mortality in years of life lost and morbidity in years lived with disability. Primary outcomes included all-cause mortality, cardiovascular mortality, major adverse cardiovascular events, and heart failure hospitalizations.
RESULTS: Three Incremental Cost-Effectiveness Ratio (ICER) tiers were identified: Low-cost (< $20,000/ Quality-Adjusted Life Year (QALY)): ramipril (Number Needed to Treat (NNT) 28), carvedilol (NNT 29), metformin ( NNT 9-15, highest Relative Risk Reduction (RRR) 38-42%), and generic statins - robust mortality benefits at negligible cost; Moderate-cost ($3,000-$50,000/QALY): empagliflozin (↓38% cardiovascular mortality, NNT 61), dapagliflozin (NNT 20 in Heart Failure with Reduced Ejection Fraction), liraglutide (NNT 51), semaglutide (NNT 43), colchicine (NNT 36, morbidity benefit only), and branded statins; High-cost ($80,000-$300,000/QALY): Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors (evolocumab NNT 63; alirocumab NNT 64) - proven benefit compromised by unaffordable biologic pricing.
CONCLUSIONS: Pharmacoeconomic stratification of repurposed cardiovascular agents identifies 3 distinct tiers. Generic agents-ramipril, carvedilol, metformin, and statins-demonstrate the most favorable cost-effectiveness profiles and should form the basis of any prevention protocol. SGLT2 inhibitors and GLP-1 receptor agonists offer clinically meaningful benefits in secondary prevention when applied to populations meeting pivotal trial eligibility criteria. PCSK9 inhibitors remain cost-effective only in patients with very high cardiovascular risk and inadequate LDL control on maximally tolerated statin therapy.
PMID:42340212 | DOI:10.1097/MJT.0000000000002156