Gaps in Incidence and Design of Peripheral Versus Coronary Artery Disease Clinical Trials

Atherosclerotic cardiovascular diseases, with peripheral artery disease (PAD) and coronary artery disease (CAD) being the most common, are leading causes of morbidity and mortality. Although PAD and CAD have nearly equivalent prevalences, PAD disproportionately affects low resourced and historically marginalized populations and is predominately cared for by surgeons with a growing interest in the PAD pathology by cardiologists. We hypothesize PAD is understudied with fewer and lower quality clinical trials (CTs) than CAD.

We conducted a cross-sectional study and queried the ClinicalTrials.gov database for PAD and CAD entries (2000-2024) and abstracted the structured CT characteristic data available. Our primary outcome was the number of CT entries/year with trends compared CAD and PAD using linear regression. Secondary outcomes included CT design components compared using descriptive statistics.

Of the 7805 CTs included, most were CAD entries (n = 6278 [79.4%]). CAD CT entries/year were 4x that of PAD (beta-coefficient [95% confidence interval]: 3.9 [3.5-4.2], P < 0.001). Overall, CTs most commonly evaluated treatments (67.3%), but diagnostic (4.5% versus 10.8%, P < 0.001) or prevention (5.9% versus 11.1%, P < 0.001) evaluations were more common in CAD trials. Fewer PAD CTs evaluated efficacy or effectiveness: PAD CTs were more commonly phase I (6.9% versus 3.9%, P < 0.001) and single-arm interventions (31.8% versus 20.1%; P < 0.001). PAD CT also utilized fewer bias reducing methods: less randomization (64.5% versus 77.4%; P < 0.001), less blinding (43.2% versus 46.9%; P = 0.006), and more industry funding (35.6% versus 20.6%; P < 0.001). Among completed CTs, PAD CTs enrolled fewer participants/CT (median: 50 [interquartile range: 20-123] versus 92 [38-269]; P < 0.001).

Atherosclerotic cardiovascular disease CTs have increased over time, with CAD having 4-fold more entries than PAD. Further, PAD CT methods less frequently evaluated treatment efficacy or effectiveness and had less rigorous design. Focused efforts targeting quality PAD CT development are needed.