H. Nassereldine1, E. Tzeng1,3, R.A. Chaer1, J.N. Kennedy2, K.M. Reitz1,3 2University Of Pittsburgh, Critical Care, Pittsburgh, PA, USA 3VA Pittsburgh Healthcare System, Vascular Surgery, Pittsburgh, PA, USA 1University Of Pittsburgh, Vascular Surgery, Pittsburgh, PA, USA
Introduction: Atherosclerotic cardiovascular diseases (ASCVD), with peripheral artery disease (PAD) and coronary artery disease (CAD) being the most common, are leading causes of morbidity and mortality. PAD and CAD affect 114 and 250 million people globally. Despite its high prevalence and contribution to increased risk of ASCVD related death, we hypothesize that PAD is understudied with disproportionally fewer and lower quality clinical trials (CTs) when compared to CAD.
Methods: We queried the ClinicalTrials.gov database for PAD and CAD entries with Embase and PubMed search terms (2000-2024). We excluded observational, expanded access, non-human, and non-adult entries. Our primary outcome was the number of CT entries/year with trends compared using linear regression. Secondary outcomes included CT design (CT evaluation, phase, intervention mode, randomization, blinding, funder) compared with chi-square, Wilcoxon, or t-test. Among entries following Final Rule implementation (mandating CT result reporting in 2017), outcomes included participant enrollment/CT and characteristics (age, sex, race, ethnicity).
Results: We identified 7,651 CTs, including 1,503 (19.6%) PAD and 6,148 (79.4%) CAD entries. CAD CT entries/year were 4x that of PAD (Figure; Beta-coefficient [95% CI]: 3.9[3.5-4.2], P<0.001). Most CTs evaluated treatments (67.2%), but evaluations varied from PAD v CAD (treatment 77.2% v 64.9%, diagnostic 4.5% v 10.9%, prevention 5.8% v 11.1%; P<0.001). Fewer PAD CTs evaluated efficacy or effectiveness: PAD CT were both more commonly Phase I (7.1% v 3.9%, P<0.001) and single arm interventions (31.7% v 20.2%; P<0.001). PAD CT also utilized fewer bias reducing methodologies: less randomization (64.5% v 77.4%; P<0.001), less blinding (43.0% v 46.8%; P=0.006), and more industry funding (35.7% v 20.8%; P<0.001). The proportion of completed CTs (n=4,825) was similar for PAD (62.1%) and CAD (63.7%; P=0.9). Among entries after the Final Rule, PAD CTs enrolled fewer participants/CT (median: 40 [IQR: 16-100] v 60 [25-140]; P<0.001). PAD CT participants were older (66±6 v 62±7 years), more female (36.9% v 34.5%), less non-White race (23.3% v 40.4%), and less Hispanic (10.8% v 20.7%; all P<0.05).
Conclusion: ASCVD CT have increased over time. PAD is half as prevalent as CAD, although likely underestimated, but there were four-fold more CAD than PAD CTs. Further, PAD CT methods less frequently evaluated efficacy or effectiveness, had less rigorous design, and enrolled fewer racial and Ethnic minority patients. Thus, there is less high-quality data informing the care of PAD as compared to CAD. These findings support the need for greater investigation to understand and improve PAD outcomes.