Paclitaxel exposure: Long-term safety and effectiveness of a drug-coated balloon for claudication in pooled randomized trials

Background: Paclitaxel drug-coated balloons (DCB) prevent recurrent claudication after angioplasty, yet data from randomized trials with incomplete follow-up have raised uncertainty regarding long-term mortality. Objectives: To evaluate the effect of paclitaxel exposure on the long-term safety and efficacy of angioplasty of femoropopliteal artery lesions in the combined IN.PACT randomized trials. Methods: The IN.PACT randomized trials (SFA, N = 331 and Japan, N = 100) each compared the DCB with standard percutaneous transluminal angioplasty (PTA) for claudication, and consented patients for 5 and 3 years, respectively. To address long-term safety, sites were requested to obtain vital status follow-up. In the pooled, updated data set, we examined the association between randomized treatment and mortality by cumulative incidence and hazard ratio (HR), and freedom from clinically driven target lesion revascularization (CD-TLR). Multivariable Cox regression with adjustment for baseline characteristics was used to evaluate the dose effect. Causes of death were adjudicated by a blinded clinical events committee that included oncologists with paclitaxel expertise. Results: The rate of long-term vital status ascertainment increased from 81% to 97% for DCB and from 85% to 97% for PTA in the IN.PACT SFA trial. The cumulative incidence of mortality was 14.7% DCB versus 12.0% PTA at 5 years, HR 1.39, log-rank p =.286. Paclitaxel dose (mg) was not an independent predictor of mortality (HR 1.02, p =.381), but was an independent predictor of reduced risk of CD-TLR (HR 0.79; p <.001). Causes of death did not differ by treatment arm. Conclusions: In pooled randomized trial data with updated vital status ascertainment, paclitaxel was associated with improved efficacy but was not associated with increased mortality.