Four-Year Patient-Level Pooled Mortality Analysis of the ILLUMENATE US Pivotal and EU Randomized Controlled Trials.

Abstract

OBJECTIVE\nTo perform a meta-analysis of two concordant randomized controlled trials (RCTs) examining the long-term, four-year safety profile of the Stellarex drug-coated balloon (DCB) versus percutaneous transluminal angioplasty (PTA) for the treatment of peripheral artery disease.\n\n\nMETHODS\nAn independent, third-party, meta-analysis of homogenous, patient-level data from the ILLUMENATE Pivotal and ILLUMENATE EU RCTs was performed to assess mortality (time to death) in patients treated for symptomatic femoropopliteal disease. Kaplan Meier (KM) methodology was used to estimate hazard rates of all-cause mortality and Cox proportional hazard modeling was used to assess predictors of mortality. All serious adverse events, including deaths, were adjudicated by an independent, blinded clinical events committee (CEC).\n\n\nRESULTS\nIn total, 589 (419 DCB; 170 PTA) patients were included in the pooled analysis of the ILLUMENATE Pivotal and ILLUMENATE EU RCTs. The median follow-up was 1735 days (IQR 1434-1829), equivalent to 4.75 years. Vital status compliance was >95% in each RCT. The total number of deaths through four years was 81/589 (13.8%); 58/419 (13.8%) in the DCB arm and 23/170 (13.5%) in the PTA arm. The one-year KM estimate of all-cause mortality was 1.9% ± 0.7% (estimate ± SE) in those treated with DCB versus 1.2 ± 0.9% in those treated with PTA. At two, three, and four years, the respective KM estimates were 6.6 ± 1.2% versus 4.9 ± 1.7%, 9.3 ± 1.4% versus 9.9 ± 2.4%, and 14.0% ± 1.7% versus 14.4% ± 2.8% (P = 0.864). There were no significant differences in CEC-adjudicated deaths between the two cohorts. In multivariate analysis, predictors of four-year mortality were age (HR, 1.048; 95% CI, 1.026 - 1.071; P < 0.0001), renal insufficiency (HR, 2.440; 95% CI, 1.566 - 3.800; P < 0.0001), and lesion length (HR, 1.004; 95% CI, 1.000 - 1.008; P = 0.041). Neither paclitaxel exposure (DCB versus PTA; HR, 1.086; 95% CI, 0.709 - 1.664; P = 0.705) nor dose (mg; HR, 1.043; 95% CI, 0.971 - 1.119; P = 0.248) were predictors of all-cause mortality at four years.\n\n\nCONCLUSIONS\nThis systematic meta-analysis of two concordant ILLUMENATE RCTs shows no difference in all-cause mortality through four-years between Stellarex DCB and PTA, confirming the acceptable, long-term safety profile of the Stellarex DCB.