Heart Failure, Arrhythmia & Cardiometabolic
A comprehensive analysis of the cardiovascular clinical trial landscape — from cardiac imaging and biomarker-guided stratification to remote monitoring integration and pipeline dynamics across heart failure therapies, antiarrhythmics, and novel lipid-lowering agents.
The Cardiovascular Trial Landscape in 2026
Cardiovascular disease remains the leading cause of mortality worldwide, and the clinical trial landscape reflects the enormous scope of unmet need across heart failure, arrhythmia, atherosclerotic disease, and cardiometabolic conditions. Within the Clinitiative network, cardiovascular represents our second-largest therapeutic portfolio with 28 active studies spanning heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), atrial fibrillation, hypertension, lipid-lowering therapies, peripheral artery disease (PAD), and acute coronary syndromes (ACS). Globally, cardiovascular trails only oncology in total active interventional studies, accounting for approximately 18% of the registered clinical trial portfolio.
The distribution of studies within our network mirrors broader pipeline dynamics. Heart failure leads with 11 active protocols, driven by the remarkable crossover of SGLT2 inhibitors from diabetes into HFpEF and HFrEF indications, as well as emerging cardiac myosin activators and soluble guanylate cyclase stimulators. Lipid-lowering studies account for 7 active protocols, reflecting the surge in next-generation approaches including siRNA-based therapies, antisense oligonucleotides (ASOs), oral PCSK9 inhibitors, and ANGPTL3 inhibitors targeting residual cardiovascular risk beyond LDL-cholesterol reduction. Arrhythmia studies comprise 5 protocols focused on atrial fibrillation rhythm control and novel antiarrhythmic agents, while the remaining 5 studies span hypertension, PAD, and ACS indications.
A transformative trend in cardiovascular research is the growing interest in inflammation-targeted therapies. Building on the foundational CANTOS trial results, multiple programs now investigate IL-1 and IL-6 pathway inhibitors, colchicine derivatives, and other anti-inflammatory agents for residual cardiovascular risk reduction. This convergence of immunology and cardiology is creating novel trial designs that require both cardiovascular and inflammatory biomarker expertise — a capability increasingly demanded by sponsors evaluating site readiness.
Key Performance Metrics
Network-wide benchmarks from our cardiovascular portfolio provide critical reference points for study planning and site performance evaluation.
Across all cardiovascular indications, our network sites achieve a median enrollment rate of 2.4 patients per site per month, notably higher than the oncology benchmark of 1.8 due to larger addressable patient populations in chronic cardiovascular conditions. Heart failure studies average 2.8 patients per site per month, while lipid-lowering studies lead the portfolio at 3.1 patients per site per month owing to the prevalence of hyperlipidemia and established primary care referral pathways.
Screen failure rates across the cardiovascular portfolio average 24%, substantially lower than oncology. The primary gating factor varies by indication: echocardiographic criteria account for approximately 30% of screen failures in HFpEF studies, where precise LVEF thresholds and diastolic function parameters must be confirmed. Lipid panel and HbA1c thresholds drive the majority of screen failures in cardiometabolic studies, though pre-screening with routine laboratory values helps reduce unnecessary full screening visits.
From contract execution to first patient enrolled, cardiovascular sites within the network achieve a median startup time of 11.8 weeks, faster than the oncology benchmark of 14.2 weeks. This advantage reflects less complex laboratory requirements, more established regulatory pathways for cardiovascular protocols, and the availability of standardized cardiac imaging procedures that do not require the specialty laboratory partnerships often needed in biomarker-driven oncology studies.
The overall patient retention rate across cardiovascular studies is 88%, reflecting the high motivation of chronic disease populations who benefit from regular monitoring and specialist access during trial participation. Retention is highest in lipid-lowering and hypertension studies (92%), where treatment burden is low and visit schedules are manageable. Heart failure studies show slightly lower retention at 82%, driven by hospitalizations, disease progression, and the physical burden of frequent clinic visits for patients with advanced disease.
Network Capabilities
Executing cardiovascular trials at the complexity and scale required by modern outcome-driven protocols demands specialized imaging infrastructure, electrophysiology expertise, and integrated heart failure clinic workflows. Our network has been strategically developed to ensure deep cardiovascular-specific capabilities across every participating site.
Cardiac Imaging Infrastructure
Cardiovascular trials increasingly rely on advanced imaging as both eligibility criteria and efficacy endpoints. Echocardiography remains the foundational modality, with protocol-specified measurements of left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diastolic function parameters (E/e' ratio, tricuspid regurgitation velocity), and left atrial volume index driving screening and outcome assessments. All network sites maintain research-dedicated echocardiography capabilities with sonographers trained in protocol-specific acquisition sequences and core laboratory upload procedures.
For studies requiring cardiac MRI — including myocardial fibrosis assessment, T1/T2 mapping, and late gadolinium enhancement — 68% of our cardiovascular sites have on-site or rapid-access cardiac MRI with dedicated cardiac radiologists. Nuclear perfusion imaging, including SPECT and PET myocardial perfusion, is available at 72% of sites for ischemia-focused protocols.
Electrophysiology & Rhythm Monitoring
Arrhythmia studies and cardiovascular safety monitoring demand comprehensive rhythm assessment capabilities. Our network sites maintain 12-lead ECG infrastructure with digital transmission to central reading facilities, 24-hour and 48-hour Holter monitoring with rapid turnaround analysis, and extended-duration event monitors for intermittent arrhythmia detection. For atrial fibrillation burden quantification, sites support continuous monitoring patches and implantable loop recorder (ILR) data extraction, enabling precise AF burden measurement as a primary or secondary endpoint.
QTc monitoring capabilities are essential across the cardiovascular portfolio, as many investigational agents require thorough QT assessment. Sites maintain triplicate ECG acquisition protocols, standardized lead placement documentation, and established relationships with central ECG laboratories for interval analysis.
Heart Failure Clinic Integration
Heart failure trials benefit enormously from integration with dedicated HF clinics, where patient populations are already under active management and titration of guideline-directed medical therapy. Our network sites with embedded research coordinators in heart failure clinics achieve 35-40% higher pre-screening referral volumes compared to sites where clinical research operates independently. These coordinators participate in weekly HF clinic workflows, review patient lists for potential study candidates, and facilitate real-time eligibility discussions with treating cardiologists.
For acute heart failure studies, network sites with emergency department integration enable rapid identification and consent of patients presenting with acute decompensated heart failure (ADHF), meeting the narrow enrollment windows that characterize these time-sensitive protocols.
Cardiac Biomarker & Central Lab Capabilities
Biomarker-guided stratification has become central to modern cardiovascular trial design. NT-proBNP and BNP measurements serve as both eligibility criteria and efficacy endpoints in heart failure studies, requiring standardized assay platforms and established reference ranges. High-sensitivity troponin (hs-cTnI, hs-cTnT) is routinely monitored for myocardial injury detection and cardiovascular safety assessment across multiple indications. Lipid panels with advanced lipoprotein profiling — including Lp(a), apoB, LDL particle number, and remnant cholesterol — support the increasingly granular eligibility criteria of next-generation lipid-lowering studies.
High-sensitivity C-reactive protein (hs-CRP) and IL-6 levels are emerging as stratification biomarkers in inflammation-targeted cardiovascular studies, requiring rapid-turnaround assay capabilities and established specimen processing workflows for central laboratory shipment.
Enrollment Dynamics
Cardiovascular enrollment benefits from large patient populations across most indications, but this advantage is tempered by intense competition among sponsors for the same patient pools and the complexity of enrolling patients already managed on multi-drug background therapies. Understanding these dynamics is critical for realistic enrollment planning and site portfolio management.
Seasonal patterns significantly influence cardiovascular enrollment in ways distinct from most other therapeutic areas. Acute cardiovascular events — including heart failure exacerbations, acute coronary syndromes, and atrial fibrillation episodes — show well-documented winter peaks driven by cold weather, influenza season, and increased physiological stress. Sites in our network that plan enrollment windows to align with these seasonal patterns achieve 15-20% higher enrollment rates during peak months compared to annualized averages. Conversely, summer months typically see lower acute event rates and reduced clinic visit volumes, requiring compensatory enrollment strategies.
Referral pathways from cardiology clinics and primary care networks represent the dominant patient identification channels for cardiovascular studies. Unlike oncology, where tumor board integration serves as a centralized referral mechanism, cardiology referrals are more distributed across outpatient clinics, heart failure programs, electrophysiology practices, and preventive cardiology services. Our network sites that have implemented EHR-based patient identification algorithms — flagging patients meeting preliminary eligibility criteria based on diagnosis codes, laboratory values, and echocardiographic data — achieve 2.1x higher pre-screening volumes compared to sites relying solely on physician referrals.
Medicare and insurance considerations play a larger role in cardiovascular enrollment than in many other therapeutic areas, given the older average age of cardiovascular trial participants. Approximately 62% of heart failure study participants across our network are Medicare beneficiaries, and navigating coverage determinations for protocol-required procedures, hospitalization costs, and concurrent standard-of-care therapies requires experienced financial counseling and benefits verification capabilities at each site.
Key Challenges in Cardiovascular Trial Execution
The increasing complexity of cardiovascular protocols presents operational challenges that require specialized strategies, long-duration infrastructure, and integrated monitoring capabilities.
Outcome-Driven Endpoint Requirements
Major adverse cardiovascular events (MACE) remain the gold standard primary endpoint for cardiovascular outcome trials (CVOTs), encompassing cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. These event-driven endpoints require extended follow-up periods often exceeding 3-5 years, creating substantial operational burden in terms of patient retention, visit compliance, and consistent data collection across long study durations. Our network addresses this through dedicated long-term follow-up coordinators, flexible visit scheduling including home visits and telehealth check-ins, and event adjudication support with standardized documentation of potential endpoint events for central adjudication committees.
Polypharmacy & Background Therapy
Cardiovascular patients typically present on complex multi-drug regimens including beta-blockers, ACE inhibitors or ARBs, diuretics, statins, antiplatelet agents, and anticoagulants. Managing background therapy in the context of clinical trial protocols presents significant challenges: washout periods may be clinically unsafe, dose optimization requirements delay enrollment, and drug-drug interaction assessments must account for extensive concomitant medication lists. Our sites maintain clinical pharmacist support for protocol-specific medication review and coordinate with treating physicians to ensure background therapy management aligns with both protocol requirements and patient safety considerations.
Event-Driven Trial Designs
Cardiovascular outcome trials increasingly employ adaptive event-rate monitoring, where the overall event rate across the study population determines sample size adjustments, study duration modifications, and interim analysis timing. Sites must maintain consistent, high-quality endpoint event capture and reporting to support accurate event-rate estimation. Under-reporting or inconsistent event ascertainment at individual sites can distort study-wide event-rate calculations, potentially leading to premature study termination or unnecessary enrollment extensions. Our network implements standardized endpoint event identification training, regular event-rate reconciliation audits, and centralized medical monitoring to ensure consistent event capture across all participating sites.
Remote Monitoring & Wearable Integration
The integration of digital endpoints and continuous remote monitoring is reshaping cardiovascular trial design. Wearable devices for continuous heart rate and rhythm monitoring, implantable hemodynamic sensors for heart failure management, and smartphone-based applications for blood pressure and symptom tracking are increasingly incorporated as secondary or exploratory endpoints. These technologies introduce operational complexity around device provisioning, patient training, data transmission reliability, technical support, and data quality management. Our network has established device management workflows, dedicated technical support coordinators, and standardized data integration procedures to ensure consistent digital endpoint capture across geographically distributed sites.
Pipeline Analysis
The cardiovascular development pipeline is experiencing a renaissance driven by novel therapeutic modalities, expanded understanding of residual cardiovascular risk, and the convergence of cardiometabolic and inflammatory disease pathways. Several emerging areas are creating significant shifts in trial design, site requirements, and enrollment planning.
Next-Generation Heart Failure Therapies
The heart failure pipeline has expanded dramatically beyond neurohormonal blockade with the success of SGLT2 inhibitors demonstrating benefit across the ejection fraction spectrum. Current pipeline focus areas include SGLT2 inhibitor combination strategies with complementary mechanisms, cardiac myosin activators that directly enhance cardiac contractility without the arrhythmogenic risks of traditional inotropes, and soluble guanylate cyclase (sGC) stimulators targeting the NO-sGC-cGMP pathway in HFpEF. These next-generation therapies require detailed hemodynamic monitoring, serial echocardiographic assessments, and careful safety surveillance for proarrhythmic effects, demanding sites with comprehensive cardiac monitoring infrastructure.
Novel Lipid-Lowering Approaches
The lipid-lowering landscape has evolved far beyond statins and injectable PCSK9 inhibitors. Small interfering RNA (siRNA) therapies targeting PCSK9 mRNA offer the potential for twice-yearly dosing, fundamentally changing adherence dynamics in lipid management. Antisense oligonucleotides (ASOs) targeting Lp(a) — a genetically determined, previously untreatable cardiovascular risk factor — represent an entirely new therapeutic category. Oral PCSK9 inhibitors in development aim to combine the efficacy of injectable anti-PCSK9 therapy with the convenience of daily oral dosing. ANGPTL3 inhibitors targeting triglyceride-rich lipoproteins address residual cardiovascular risk in patients with optimized LDL-cholesterol. These diverse mechanisms require sites with advanced lipid profiling capabilities and long-duration cardiovascular outcome follow-up infrastructure.
Anti-Inflammatory Cardiovascular Agents
The recognition that inflammation plays a causal role in atherosclerotic cardiovascular disease has spawned a growing pipeline of anti-inflammatory agents. IL-1 pathway inhibitors, including canakinumab successors and IL-1 receptor antagonists, target the inflammasome-driven inflammatory cascade. IL-6 pathway modulators aim to reduce downstream inflammatory signaling with potentially fewer immunosuppressive side effects. Colchicine derivatives with improved cardiovascular bioavailability and reduced gastrointestinal toxicity are in mid-stage development. These studies require dual expertise in cardiovascular outcome assessment and inflammatory biomarker monitoring, creating a unique site capability requirement that bridges traditional cardiology and immunology expertise.
Gene Therapy for Cardiomyopathy
Adeno-associated virus (AAV)-based gene therapy is emerging as a transformative approach for genetic cardiomyopathies, including Danon disease, Fabry disease with cardiac involvement, and specific forms of dilated and hypertrophic cardiomyopathy caused by single-gene mutations. These early-phase programs require specialized infrastructure including gene therapy vector handling and administration capabilities, immunosuppressive pre-conditioning regimens, extended post-administration cardiac monitoring, and long-term follow-up protocols spanning 5-15 years. Sites participating in cardiac gene therapy programs must maintain genetic counseling services, molecular diagnostic capabilities for genotype confirmation, and close coordination with cardiac imaging for serial assessment of ventricular remodeling and function.
Site Requirements for Cardiovascular Excellence
The infrastructure, staffing, and operational processes required to execute modern cardiovascular protocols at the highest level of quality and patient safety.
Dedicated research pharmacy with temperature-controlled storage for biologic agents (including siRNA and monoclonal antibody therapies), automated drug accountability systems, and pharmacist oversight for complex multi-drug interaction assessments. Injectable lipid-lowering studies require prefilled syringe management and patient self-injection training infrastructure.
Research-dedicated echocardiography with protocol-specific acquisition sequences, trained sonographers, and core laboratory upload capabilities. Access to cardiac MRI with T1/T2 mapping, late gadolinium enhancement, and stress perfusion protocols. Nuclear perfusion imaging (SPECT/PET) for ischemia-focused studies.
Digital 12-lead ECG with central reading facility transmission capabilities, triplicate ECG acquisition protocols for QTc assessment, 24/48-hour Holter monitoring, extended event monitoring, and continuous telemetry for inpatient cardiovascular safety monitoring. Standardized lead placement and calibration procedures.
Six-minute walk test (6MWT) infrastructure with standardized corridors and monitoring equipment. Cardiopulmonary exercise testing (CPET) with metabolic cart for peak VO2 assessment in heart failure studies. Treadmill and cycle ergometer stress testing with continuous ECG monitoring and emergency resuscitation equipment.
Rapid-turnaround cardiac biomarker panels including NT-proBNP, BNP, high-sensitivity troponin, and hs-CRP. Advanced lipid profiling (Lp(a), apoB, LDL particle number, remnant cholesterol). Comprehensive metabolic panels, coagulation studies, and specimen processing for central laboratory shipment of PK/PD and translational biomarker samples.
Dedicated cardiovascular clinical research coordinators with experience in cardiac imaging protocols, rhythm monitoring procedures, and heart failure management. Research nurses certified in IV infusion administration and cardiac emergency response. Data managers with EDC proficiency and cardiovascular endpoint adjudication documentation experience.
Discuss Your Cardiovascular Program
Connect with our team to explore site capabilities, enrollment strategies, and cardiac imaging infrastructure for your cardiovascular clinical development program.