A New Era of Disease‐Modifying Pharmacotherapy in Cardiovascular Medicine

Background/Objectives: Cardiovascular disease (CVD) remains the leading cause of global morbidity and mortality. Although substantial therapeutic advances have been made over the past decades, the years 2024–2025 mark a turning point characterized by the emergence of mechanistically innovative, disease-modifying therapies that go beyond conventional risk-factor control. This narrative review aims to synthesize transformative pharmacological and regulatory milestones reshaping contemporary cardiovascular practice and establishing a roadmap for precision medicine implementation. Methods: We conducted a comprehensive narrative review of pivotal clinical trials, regulatory approvals and mechanistic frameworks for emerging cardiovascular therapeutics approved or under investigation during 2024–2025. The analysis encompasses novel agents across multiple disease domains including transthyretin amyloid cardiomyopathy (ATTR-CM), resistant hypertension, dyslipidemia, pulmonary arterial hypertension, hypertrophic cardiomyopathy, and cardiometabolic disease, with emphasis on their molecular targets, clinical efficacy, and practice-changing implications. Results: Key therapeutic advances include acoramidis and vutrisiran for ATTR-CM demonstrating significant reductions in cardiovascular mortality and hospitalization; aprocitentan for resistant hypertension alongside investigational angiotensinogen silencers and aldosterone synthase inhibitors; RNA-based dyslipidemia therapies (inclisiran, lepodisiran, pelacarsen, olezarsen) enabling durable lipid control; sotatercept introducing disease modification in pulmonary arterial hypertension; cardiac myosin inhibitors (mavacamten, aficamten) transforming hypertrophic cardiomyopathy management; and GLP-1 receptor agonist semaglutide receiving FDA approval for cardiovascular risk reduction in obesity. These agents collectively demonstrate mechanistic targeting, genetic precision, and disease modification beyond traditional risk-factor management. Conclusions: Cardiovascular medicine is transitioning from symptomatic palliation toward an era defined by molecular pathway targeting, individualized therapy, and durable disease control, establishing a new paradigm for precision cardiovascular care.