Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial.

Original: Lancet Respir Med. 2019. pii: S2213-2600(19)30271-1

Author(s): Sánchez-de-la-Torre M, Sánchez-de-la-Torre A, Bertran S et al Spanish sleep network

Reviewer: Sophia E Schiza, MD

Published: 01 Jan, 2020

The high prevalence and clinical significance of obstructive sleep apnoea (OSA) as well as its effects on a range of cardiovascular conditions have attracted growing interest. In the acute coronary syndrome (ISAACC) study, a multicentre, open-label, parallel-group, randomized controlled trial, the authors investigated whether OSA and its treatment with continuous positive airway pressure (CPAP) would lower the risk of new cardiovascular events of patients with acute coronary syndrome (ACS).

A total of 2551 non-sleepy, mostly men patients with ACS who had respiratory polygraphy during the first 24–72 h after admission was recruited. OSA patients (AHI≥15, n=1264) were randomly assigned to CPAP treatment plus usual care (CPAP group, n=633) or usual care alone (UC group, n=631) and a group of patients with ACS but without OSA (AHI<15, n=603) was included as a reference group. Patients were followed up for a median of 3.35 years. The primary endpoint was the prevalence of new cardiovascular events (cardiovascular death or non-fatal events [Acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalizations for unstable angina or transient ischemic attack]).

Based on the results of the study the prevalence of cardiovascular events was similar in the CPAP and UC groups (98 vs 108 events, p=0.40) during follow-up and between patients in the reference group and the UC group (90 vs 102 events, p=0.93). The median time of CPAP adherence was suboptimal (2.2 h/night), but even after dividing the CPAP group into a poor (mean adherence <4 h/night, n=377) and good (mean adherence ≥4 h/night, n=227) adherence groups the prevalence of cardiovascular events between the groups was similar. The authors concluded that among non-sleepy patients with ACS, the presence of OSA and CPAP treatment failed to show any significant association with the prevalence of new cardiovascular events.

This study addresses a challenging topic – the impact of OSA and CPAP on secondary cardiovascular prevention of patients with ACS – and it has several strengths, including a strong study design, rigorous evaluations of endpoints and a long-term follow-up. There are, however, several concerns, raised by the authors, that should be taken into account. A major concern is that the authors calculated the AHI with a relatively less accurate monitoring system that did not employ an electroencephalogram; therefore there is a tendency to underestimate AHI and subsequently OSA severity, especially in these patients who usually present disrupted sleep with shorter sleep duration that is common during acute cardiac events. An additional consideration concerning the reliable diagnosis of OSA is that the high prevalence of OSA in these patients with ACS may not be indicative of the real picture as a high rate of false-positive diagnoses could exist if the sleep study is performed early after ACS. Furthermore, the use of auto-pap titration in this patient population may raise concerns towards tolerance, adherence and effectiveness. Additionally achieving better CPAP adherence would be desirable, to exceed the lower limit of 4 hours/night of clinical meaningful usage, and stratify patients into subgroups based on different cut-off point of hours of CPAP use. Therefore, the observed neutral effect of OSA on cardiovascular events and CPAP treatment for secondary cardiovascular prevention on ACS patients should be interpreted with caution, until further data are available to overcome these limitations.

Respiratory digests
Sleep and breathing disorders