Plain balloon angioplasty +/- bare metal stenting versus drug-coated balloon angioplasty +/- bare metal stenting versus primary drug-eluting stenting in patients with chronic limb-threatening ischaemia: BASIL-3, an open-label, three-arm, randomised, multi-centre, phase 3 trial.

内容摘要

To determine which primary endovascular revascularisation strategy represents the most clinical and cost-effective treatment for patients with chronic limb threatening ischaemia who require an endovascular femoro-popliteal, with or without an infra-popliteal revascularisation. Three-arm open-label pragmatic multicentre randomised phase 3 superiority trial. Thirty-five UK NHS vascular units. Patients with chronic limb threatening ischaemia who required an endovascular femoro-popliteal with or without an infra-popliteal revascularisation. Participants were randomly assigned (1 : 1 : 1) to either a femoro-popliteal plain balloon angioplasty with or without bare metal stenting (considered as control or reference), or a drug-coated balloon angioplasty with or without bare metal stenting, or a drug-eluting stenting first revascularisation strategy. The primary outcome was amputation-free survival defined as time to first major amputation or death from any cause. Secondary outcomes included overall survival, limb salvage, major adverse limb events, major adverse cardiac events and other pre-specified clinical and patient reported outcome measures. Serious adverse events were collected up to 30 days following the first revascularisation procedure. Between 29 January 2016 and 31 August 2021, 481 participants [167 (35%) women] of mean age 71.8 years (standard deviation 10.8) were randomised. Major amputation or death occurred in 106 of 160 (66%) participants in the plain balloon angioplasty ± bare metal stenting group, 97 of 161 (60%) participants in the drug-coated balloon angioplasty ± bare metal stenting, and 93 of 159 (58%) participants in the drug-eluting stenting group [adjusted hazard ratios: plain balloon angioplasty ± bare metal stenting vs. drug-coated balloon angioplasty ± bare metal stenting: 0.84 (97.5% confidence interval 0.61 to 1.16), p = 0.22; plain balloon angioplasty ± bare metal stenting vs. drug-eluting stenting: 0.83 (97.5% confidence interval 0.60 to 1.15), p = 0.20]. There were no differences in serious adverse events between the groups. There were no differences in mortality when drug technology arms were pooled versus plain balloon angioplasty ± bare metal stenting. When compared to plain balloon angioplasty, drug-eluting stenting was less costly [-£724 (95% confidence interval -£4975 to £2631)] and resulted in additional 0.048 quality-adjusted life-years (95% confidence interval -0.060 to 0.148). Drug-coated balloon angioplasty was unlikely to be a cost-effective option (probability 52% of being cost-effective at £20,000 per quality-adjusted life-year) while drug-eluting stenting was potentially cost-effective (probability 76% of being cost-effective at £20,000 per quality-adjusted life-year). Neither drug-coated balloon angioplasty ± bare metal stenting, nor drug-eluting stenting, conferred significant clinical benefit over plain balloon angioplasty ± bare metal stenting when used in the femoro-popliteal segment in patients undergoing femoro-popliteal ± infra-popliteal endovascular revascularisation for chronic limb threatening ischaemia. Drug-eluting stenting and drug-coated balloon angioplasty in chronic limb threatening ischaemia patients were found to offer moderate benefits in health economic outcomes particularly when drug-eluting stenting was compared to plain balloon angioplasty. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 13/81/02. Atherosclerosis, or narrowing of the arteries, can be caused by smoking, diabetes, high blood pressure and high blood cholesterol. It can affect any artery in the body. When atherosclerosis happens in the arteries in the leg, it is called peripheral arterial disease. The most severe form of this disease is chronic limb-threatening ischaemia, which causes severe pain in the foot, as well as ulcers and gangrene. People with chronic limb-threatening ischaemia need to have the blood supply to their leg improved or they can be at high risk of amputation or death. Improving the blood supply to the leg is called revascularisation. A technique called ‘endovascular revascularisation’ allows doctors to improve blood flow without major surgery. This involves using a balloon (angioplasty) to squeeze the arteries open or inserting small metal tubes (stents) to keep the artery open. Some devices may be coated with a drug designed to help the artery stay open and stop it becoming narrowed again. The Balloon versus Stenting in Severe Ischaemia of the Leg-3 trial compared how well these drug-coated devices worked against plain balloons. In the trial, 481 people with chronic limb-threatening ischaemia were randomly chosen to be treated with drug-coated balloons, drug-coated stents or plain balloons and were followed up for at least 2 years. The trial found that the amount of amputation and death was similar across the groups, with the drug-coated devices being slightly better. The results, however, did not demonstrate that any one method is better than any other.