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-ha...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.
BACKGROUND: Right-sided accessory pathways can cause ventricular dyssynchrony through early right ventricular preexcitation, mimicking left bundle branch block and leading to reversible cardiomyopathy even without sustai...BACKGROUND: Right-sided accessory pathways can cause ventricular dyssynchrony through early right ventricular preexcitation, mimicking left bundle branch block and leading to reversible cardiomyopathy even without sustained tachycardia. Although catheter ablation is standard, pharmacologic reversal in adults has not been reported. DATA SOURCES: Single-patient case from a US community hospital. Literature review (PubMed/Embase) confirmed no previous adult cases of complete pharmacologic reversal. MAIN FINDINGS: A 44-year-old man with known Wolff-Parkinson-White presented with palpitations, dyspnea, chest pain, and syncope. Electrocardiogram showed right-sided preexcitation with left bundle branch block morphology. Echocardiography demonstrated left ventricular systolic function with ejection fraction (LVEF) 10%-15% with LV dilation. Coronary arteries were normal and no other cardiomyopathy etiologies were identified. The patient declined ablation. Amiodarone was initiated. Within 2 months, preexcitation resolved (loss of delta wave) and LVEF improved to 30%-35%. By 4 months, LVEF normalized to 60% with resolution of dilation. Amiodarone was discontinued and switched to flecainide. LIMITATIONS: No cardiac MRI performed (patient preference and rapid improvement); no extended ambulatory rhythm monitoring; and no formal electrophysiology study. CONCLUSIONS: Amiodarone-induced suppression of antegrade right-sided accessory pathway conduction can lead to complete reversal of severe dyssynchrony-mediated cardiomyopathy in adults when ablation is declined.
BACKGROUND: Propofol is widely used for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP) due to its rapid onset and favorable recovery profile; however, it is associated with dose-dependent card...BACKGROUND: Propofol is widely used for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP) due to its rapid onset and favorable recovery profile; however, it is associated with dose-dependent cardiopulmonary adverse effects, particularly hypoxia and hypotension. AREAS OF UNCERTAINTY: Significant heterogeneity persists in the definition, severity classification, and reporting of these adverse events, limiting comparability across studies and hindering reliable risk stratification. Therefore, the aim of this systematic review was to evaluate the incidence and clinical characteristics of propofol-associated hypoxia and hypotension in adult patients undergoing ERCP, and to assess variability in reporting practices across studies. DATA SOURCES: A systematic review was conducted and reported in accordance with PRISMA guidelines. PubMed was searched for English-language studies published between 1995 and 2025 involving adult patients undergoing ERCP under propofol-based sedation. RESULTS: Across studies reporting extractable data, oxygen desaturation occurred in 16.9% of aggregated cases (1194/7049), whereas hypotension occurred in 13.0% (187/1440). These values represent descriptive estimates and should not be interpreted as meta-analytic pooled incidences. Both events were predominantly mild and transient, responding to standard supportive measures, whereas severe complications, including cardiopulmonary arrest, were exceptionally rare. Considerable variability in definitions, outcome reporting, and study design was observed across studies. CONCLUSIONS: Propofol sedation during ERCP is associated with frequent but generally manageable hypoxia and hypotension. Continuous respiratory and hemodynamic monitoring facilitates early recognition and prompt intervention. Standardization of outcome definitions and reporting, along with the development of structured risk stratification tools, may improve patient selection and enhance procedural safety.
BACKGROUND: Mescaline (3,4,5-trimethoxyphenethylamine) is a classic serotonergic psychedelic with a history of indigenous ceremonial use. There is renewed scientific interest in mescaline because of the potential psychia...BACKGROUND: Mescaline (3,4,5-trimethoxyphenethylamine) is a classic serotonergic psychedelic with a history of indigenous ceremonial use. There is renewed scientific interest in mescaline because of the potential psychiatric benefits of psychedelic-assisted therapy. Mescaline primarily exerts its psychoactive effects through serotonin-2A (5-HT 2A ) receptor agonism. AREAS OF UNCERTAINTY: There is a lack of controlled clinical trials evaluating mescaline in patient populations, and most modern safety data are derived from healthy volunteers. Consequently, its safety in individuals with cardiovascular, metabolic, or psychiatric comorbidities remains unclear. Additional uncertainty exists regarding its psychological risks, long duration of action, and long-term safety in therapeutic settings. THERAPEUTIC ADVANCES: Randomized, placebo-controlled studies in healthy participants demonstrate that mescaline produces dose-dependent subjective effects with moderate, transient autonomic stimulation and no serious medical complications under controlled conditions. Adverse effects are generally self-limited, and pooled safety analyses and observational data support an overall favorable safety profile in screened human populations. CONCLUSION: Mescaline shows preliminary safety in healthy humans but remains understudied in clinical populations. Controlled clinical trials are needed to establish its safety and therapeutic potential.