Event rates of patients with stable heart failure with reduced ejection fraction and newly diagnosed obstructive or central sleep apnoea

AIMS: In patients with heart failure with reduced ejection fraction (HFrEF) and sleep-related breathing disorders, the predominant apnoea type may influence prognosis. The ADVENT-HF trial, which enrolled stable HFrEF patients with newly diagnosed obstructive (OSA) or central (CSA) sleep apnoea, provides a unique opportunity to perform a post-hoc analysis to test this hypothesis. We aimed to compare event rates between those with OSA and those with CSA following randomisation over the course of the trial. METHODS: Cox-proportional hazard ratios (HR) were compared for: the primary composite endpoint (PE); all-cause; and cardiovascular mortality. Proportional-hazards assumption was assessed by Schoenfeld residuals' method. RESULTS: Relative to OSA (n = 533), in unadjusted analyses, over the trial duration, the PE rate was greater in those with CSA (n = 198) (HR 1.38, 95%CI 1.10-1.73; P = .01), as were rates of all-cause (HR 1.72, 95%CI 1.26-2.36; P < .001) and cardiovascular mortality (HR 2.00, 95%CI 1.40-2.85; P < .001). These HRs were not statistically significant after adjustment for clinical characteristics associated with worse prognosis. Importantly, HRs varied over time, with an inflection point at one year. Adjusted HRs before and after 1 year were respectively 1.41 (95%CI 1.00-2.01, P = .051) and .91 (95%CI .65-1.26, P = .562) for the PE, 3.44 (95%CI 1.61-7.36, P = .001) and .89 (95%CI .58-1.37, P = .603) for all-cause mortality and 3.58 (95%CI 1.58-8.12, P = .002) and .92 (95%CI 0.56-1.51, P = 0.741) for cardiovascular mortality. CONCLUSION: Detection of CSA in patients with stable HFrEF identifies a population at increased 1-year risk of adverse events who may benefit from earlier evaluation for advanced therapies or transplantation.