Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 Trial: Analysis of the Timing and Causes of Death in Participants Randomised to an Infrapopliteal Vein Bypass or Best Endovascular Treatment First Revascularisation Strategy.

Abstract

Objective: The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 trial enrolled participants with chronic limb threatening ischaemia who required an infrapopliteal, with or without a femoropopliteal, revascularisation procedure to restore limb perfusion. Participants randomised to a vein bypass (VB) first revascularisation strategy were over one third more likely than those randomised to a best endovascular treatment (BET) first revascularisation strategy to die from any cause during a median follow up of 40.0 (interquartile range 20.9, 60.6) months. The aim was to describe the timing and causes of death in BASIL-2 as a first step towards trying to better understand why randomisation to a VB first revascularisation strategy was associated with this excess mortality.

Methods: A 10 person international panel comprising vascular and endovascular surgeons as well as vascular interventional radiologists, who had all been principal investigators in BASIL-2, took part in a modified Delphi consensus exercise to adjudicate the primary cause of death and, in particular, whether the cause was primarily cardiac or non-cardiac.

Results: In 151/168 deaths (89.9%) the Delphi panel achieved a consensus regarding the cause of death being probably cardiac or non-cardiac. In the BET group, 16/77 deaths (21%) were classified as probably cardiac compared with 32/91 (35%) in the VB group (unadjusted subdistribution hazard ratio 2.16, 95% confidence interval [CI] 1.20 - 3.87; unadjusted cause specific hazard ratio 2.15, 95% CI 1.19 - 3.90). At the point of randomisation, 64/344 (18.6%), 37/344 (10.8%), and 40/342 (9%) participants had a previous myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG), respectively. There was no evidence of varying treatment effects for cause of death in subgroup analyses of previous PCI, CABG, or MI.

Conclusion: The excess mortality observed in the VB first revascularisation strategy group in BASIL-2 was largely due to deaths that were adjudicated by the Delphi panel as probably primarily cardiac. These excess cardiac deaths were observed throughout follow up and there was no evidence of non-proportional hazards. Further work is ongoing to try to better understand the reasons for these findings.

Keywords: Chronic limb threatening ischaemia; Randomised controlled trial.