Cardiovascular Benefit of Continuous Positive Airway Pressure in Adults with Coronary Artery Disease and Obstructive Sleep Apnea without Excessive Sleepiness

Rationale: Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (Delta HR). Objectives: Here, in this post hoc analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment Delta HR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. Methods: Delta HR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index >= 15 events/h] with Epworth Sleepiness Scale score, 10; n(CPAP):n(control) = 113:113; male, 85%; age, 66 +/- 8 [mean +/- SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by Delta HR (treatmentby-Delta HR interaction). Measurements and Main Results: The CPAP-related reduction in risk increased progressively with increasing pretreatment Delta HR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in Delta HR; P, 0.05). This means that in patients with a Delta HR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) (P<0.05), but no significant risk reduction was estimated in patients with a mean Delta HR (6 beats/min; CPAP risk reduction, 16% [253% to 54%]; P= 0.6). Conclusions: The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the Delta HR. Specifically, patients with higher Delta HR exhibit greater cardiovascular benefit from CPAP therapy.