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

作者：Sharples Linda^*; Everett Colin; Singh Jeshika; Mills Christine; Spyt Tom; Abu Omar Yasir; Fynn Simon; Thorpe Benjamin; Stoneman Victoria; Goddard Hester; Fox Rushby Julia; Nashef Samer

来源：Health Technology Assessment, 2018, 22(19): 1-+.

DOI：10.3310/hta22190

Background: Atrial 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.
Objectives: To 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.
Design: Multicentre, 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.
Setting: Eleven acute NHS specialist cardiac surgical centres.
Participants: Patients aged >= 18 years, scheduled for elective or in-house urgent cardiac surgery, with a documented history (> 3 months) of AF.
Interventions: Routine cardiac surgery with or without an adjunct maze procedure administered by an AF ablation device.
Main outcome measures: The 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.
Results: Between 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 pound (95% CI 1321 pound to 5746); pound 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 pound 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.
Limitations: Low recruitment, early release of trial summaries and intermittent resource-use collection may have introduced bias and imprecise estimates.
Conclusions: Ablation 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.

• 出版日期2018-4