Amaze: a double-blind, multicentre randomised controlled trial to investigate the clinical effectiveness and cost-effectiveness of adding an ablation device-based maze procedure as an adjunct to routine cardiac surgery for patients with pre-existing atrial fibrillation

Abstract

BackgroundAtrial fibrillation (AF) can be treated using a maze procedure during planned cardiac surgery, but the effect on clinical patient outcomes, and the cost-effectiveness compared with surgery alone, are uncertain.ObjectivesTo determine whether or not the maze procedure is safe, improves clinical and patient outcomes and is cost-effective for the NHS in patients with AF.DesignMulticentre, Phase III, pragmatic, double-blind, parallel-arm randomised controlled trial. Patients were randomised on a 1 : 1 basis using random permuted blocks, stratified for surgeon and planned procedure.SettingEleven acute NHS specialist cardiac surgical centres.ParticipantsPatients aged ≥ 18 years, scheduled for elective or in-house urgent cardiac surgery, with a documented history (> 3 months) of AF.InterventionsRoutine cardiac surgery with or without an adjunct maze procedure administered by an AF ablation device.Main outcome measuresThe primary outcomes were return to sinus rhythm (SR) at 12 months and quality-adjusted life-years (QALYs) over 2 years after randomisation. Secondary outcomes included return to SR at 2 years, overall and stroke-free survival, drug use, quality of life (QoL), cost-effectiveness and safety.ResultsBetween 25 February 2009 and 6 March 2014, 352 patients were randomised to the control (n = 176) or experimental (n = 176) arms. The odds ratio (OR) for return to SR at 12 months was 2.06 [95% confidence interval (CI) 1.20 to 3.54;p = 0.0091]. The mean difference (95% CI) in QALYs at 2 years between the two trial arms (maze/control) was –0.025 (95% CI 0.129 to 0.078;p = 0.6319). The OR for SR at 2 years was 3.24 (95% CI 1.76 to 5.96). The number of patients requiring anticoagulant drug use was significantly lower in the maze arm from 6 months after the procedure. There were no significant differences between the two arms in operative or overall survival, stroke-free survival, need for cardioversion or permanent pacemaker implants, New York Heart Association Functional Classification (for heart failure), EuroQol-5 Dimensions, three-level version score and Short Form questionnaire-36 items score at any time point. Sixty per cent of patients in each trial arm had a serious adverse event (p = 1.000); most events were mild, but 71 patients (42.5%) in the maze arm and 84 patients (45.5%) in the control arm had moderately severe events; 31 patients (18.6%) in the maze arm and 38 patients (20.5%) in the control arm had severe events. The mean additional cost of the maze procedure was £3533 (95% CI £1321 to £5746); the mean difference in QALYs was –0.022 (95% CI –0.1231 to 0.0791). The maze procedure was not cost-effective at £30,000 per QALY over 2 years in any analysis. In a small substudy, the active left atrial ejection fraction was smaller than that of the control patients (mean difference of –8.03, 95% CI –12.43 to –3.62), but within the predefined clinically equivalent range.LimitationsLow recruitment, early release of trial summaries and intermittent resource-use collection may have introduced bias and imprecise estimates.ConclusionsAblation can be practised safely in routine NHS cardiac surgical settings and increases return to SR rates, but not survival or QoL up to 2 years after surgery. Lower anticoagulant drug use and recovery of left atrial function support anticoagulant drug withdrawal provided that good atrial function is confirmed.Further workContinued follow-up and long-term clinical effectiveness and cost-effectiveness analysis. Comparison of ablation methods.Trial registrationCurrent Controlled Trials ISRCTN82731440.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 19. See the NIHR Journals Library website for further project information.