ischemic heart disease
Cardiovascular disease trials address coronary artery disease, heart failure, atrial fibrillation, and acute coronary syndromes β€” collectively the leading cause of mortality globally. After decades of incremental improvement in lipid-lowering and antithrombotic therapy, the field is now exploring RNA-based therapies, gene editing, and cardiac regeneration approaches.
Active research includes PCSK9 inhibitors and inclisiran for LDL reduction, SGLT2 inhibitors in heart failure with preserved ejection fraction (HFpEF), mavacamten for hypertrophic cardiomyopathy, cardiac stem cell therapies, and AI-guided device therapies. Wearables and remote monitoring are also being validated as clinical endpoints.
Enrollment eligibility typically depends on left ventricular ejection fraction (LVEF), NT-proBNP levels, and prior cardiovascular events.
Disease Burden & Epidemiology
Cardiovascular disease (CVD) is the leading cause of death globally, responsible for an estimated 18.6 million deaths annually β€” approximately one-third of all deaths worldwide. Coronary artery disease and stroke together account for the majority of CVD mortality. In the United States, the CDC reports that one person dies from cardiovascular disease every 33 seconds, with approximately 805,000 Americans experiencing a heart attack each year, of whom 200,000 have had a prior heart attack. Heart failure β€” a syndrome of pump dysfunction affecting the heart's ability to meet the body's demands β€” affects approximately 6.7 million Americans and 64 million people globally, with a five-year mortality rate exceeding 50%, comparable to many cancers. The global prevalence of heart failure is rising, driven by population aging, improved survival from acute myocardial infarction (creating a larger pool of patients with damaged myocardium), and increasing rates of hypertension, diabetes, and obesity β€” all independent risk factors. Despite dramatic improvements from statins, ACE inhibitors, beta-blockers, and implantable devices validated through decades of trials, residual cardiovascular risk remains high in optimally medicated populations, representing the primary driver of current clinical research activity.
Key Research Trends & Landmark Studies
The PARADIGM-HF trial established sacubitril/valsartan (Entresto) as superior to enalapril in reducing cardiovascular death and heart failure hospitalization in HFrEF, representing the first new heart failure treatment mechanism in over 20 years. The EMPEROR-Reduced and DAPA-HF trials confirmed that SGLT2 inhibitors (empagliflozin and dapagliflozin) reduce heart failure hospitalization and cardiovascular death in HFrEF, leading to guideline-directed medical therapy updates. The EMPEROR-Preserved trial subsequently demonstrated benefit of empagliflozin in HFpEF β€” the first pharmacological therapy to do so β€” reshaping treatment of a condition that had previously resisted all therapeutic approaches. The VICTORIA trial established vericiguat (a soluble guanylate cyclase stimulator) for high-risk HFrEF. Currently active landmark trials include HEART-FID testing IV ferric carboxymaltose for iron deficiency in heart failure, RESHAPE-HF2 evaluating transcatheter mitral valve repair in HFrEF with significant mitral regurgitation, and ARISE-HF testing aficamten for non-obstructive hypertrophic cardiomyopathy.
Patient Guide: How to Find & Join a Trial
Patients with established heart disease — including those with prior heart attack, heart failure, atrial fibrillation, or coronary artery disease — should ask their cardiologist about clinical trial eligibility at each follow-up visit, particularly if symptoms are not well-controlled on current therapy. For heart failure trials, your most recent echocardiogram result (specifically the ejection fraction percentage) is the single most important eligibility determinant — trials are strictly separated between HFrEF (EF <40%), HFmrEF (EF 40–49%), and HFpEF (EF ≥50%). Know your NT-proBNP or BNP value (a blood biomarker of heart failure severity), your NYHA functional class (I–IV), and your complete medication list including doses. Major academic heart failure programs — Cleveland Clinic, Mayo Clinic, MGH, Duke Heart Center — offer the broadest trial portfolios; however, community-based cardiology practices increasingly participate in multi-site trials and can offer local access to the same studies.