Michael R. Gold

Aims: Apixaban was superior to aspirin for the prevention of stroke or systemic embolism in participants with subclinical atrial fibrillation (SCAF) in the Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation trial. This was especially true for those with CHA2DS2-VASc score > 4. Understanding the cost-effectiveness of treating SCAF is important for decision-makers. Methods and results: Canadian, UK, German, and US direct healthcare costs [in 2023 US dollars (USD)] were applied to hospitalized events (including strokes and bleeds) and study drugs for all participants with a CHA2DS2-VASc score > 4 to determine the mean cost per participant during the trial (mean follow-up 3.5 years). A daily cost of $0.63, $0.11, $2.26, and $6.06 for apixaban in Canada, the UK, Germany, and the USA was used. If in-trial results were not cost-saving (below $0), the prospective plan was to perform a lifetime cost-effectiveness analysis using a Markov model and a willingness-to-pay of 50 000 USD per quality-adjusted life year (QALY). After considering the cost of study medication and clinical events over 3.5 years, apixaban was dominant (cost-saving and more effective) in Canada (−$2301) and the UK (−$902) but cost more in Germany and the USA ($600 and $1990, respectively). Over a lifetime, treatment with apixaban produced a net gain of 0.107 QALYs, but with costs in both Germany ($2623 more) and the USA ($9110 more), yielding an incremental cost-effectiveness ratio of $24 514 per QALY for Germany and $85 140 for the USA. Conclusion: In patients with SCAF and a CHA2DS2-VASc score > 4, apixaban is cost saving in Canada and the UK and cost-effective in Germany. Apixaban was not cost-effective in the USA under the base cost assumption but would be cost-effective at a daily cost of $4.35 and cost saving at $3.59.

Background: Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation. Methods and Results: In this meta‐analysis, we pooled patient‐level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE‐ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all‐cause mortality, and time to all‐cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization‐Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all‐cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64–0.99]; posterior probability or P =0.044), with a similar association with time to all‐cause mortality (aHR, 0.78 [95% CI, 0.59–1.03]; P =0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30–1.27]; P =0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35–1.34]; P =0.27 for all‐cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes. Conclusions: Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.