Effect of Obstructive Sleep Apnea and CPAP Treatment on Cardiovascular Outcomes in Acute Coronary Syndrome in the RICCADSA Trial

Yüksel Peker, Erik Thunström, Helena Glantz, Christine Eulenburg, Yüksel Peker, Erik Thunström, Helena Glantz, Christine Eulenburg

Abstract

We aimed to address the impact of OSA and its treatment with continuous positive airway pressure (CPAP) on major adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS). In this current analysis of the revascularized ACS subgroup (n = 353) of the Randomized Intervention with CPAP in Coronary Artery Disease and Obstructive Sleep Apnea (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT00519597), participants with non-sleepy OSA (apnea-hypopnea-index [AHI] ≥ 15 events/h on a home sleep apnea testing, and Epworth Sleepiness Scale [ESS] score < 10; n = 171) were randomized to CPAP (n = 86) or no-CPAP (n = 85). The sleepy OSA patients (AHI ≥ 15 events/h and ESS ≥ 10) who were offered CPAP, and the ones with no-OSA (AHI < 5 events/h) were included in the observational arm. A post-hoc analysis was done to compare untreated OSA (no-CPAP; n = 78) and nonadherent sleepy/non-sleepy OSA (n = 96) with the reference group without OSA (n = 81). The primary endpoint (the first event of repeat revascularization, myocardial infarction, stroke or cardiovascular mortality) during a median 4.7-year follow-up was evaluated in time-dependent Cox proportional hazards models adjusted for confounding factors. The incidence of MACCE did not differ significantly in intention-to-treat population. On-treatment analysis showed a significant risk reduction in those who used CPAP for ≥4 vs. <4 h/day or did not receive treatment (adjusted hazard ratio [HR] 0.17; 95% confidence interval [CI] 0.03-0.81; p = 0.03). Compared with the reference group, nonadherent/untreated OSA was associated with an increased cardiovascular risk (adjusted HR 1.97, 95% CI 1.03-3.77; p = 0.04). We conclude that OSA is an independent risk factor for adverse cardiovascular outcomes in patients with ACS. CPAP treatment may reduce this risk, if the device is used at least 4 h/day.

Keywords: acute coronary syndrome; cardiovascular outcomes; continuous positive airway pressure; obstructive sleep apnea.

Conflict of interest statement

E.T., H.G., and C.E. report no conflicts of interest; Y.P. declares institutional grants from ResMed Foundation and ResMed Inc.

Figures

Figure 1
Figure 1
Flow of patients through the study: (a) The randomized controlled arm; (b) The final observational arm. Abbreviations: ACS, acute coronary syndrome; AHI, apnea-hypopnea index; CAD; coronary artery disease; CPAP, continuous positive airway pressure; CSA-CSR, central sleep apnea-Cheyne Stokes respiration; ESS, Epworth Sleepiness Scale; OSA, obstructive sleep apnea; RICCADSA, Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea.
Figure 2
Figure 2
Cumulative incidences of the composite endpoint in the intention-to-treat population. CPAP, continuous positive airway pressure; OSA, obstructive sleep apnea.
Figure 3
Figure 3
Cumulative incidences of the composite endpoint in the observational arm. OSA, obstructive sleep apnea.

References

    1. Benjamin E.J., Virani S.S., Callaway C.W., Chamberlain A.M., Chang A.R., Cheng S., Chiuve S.E., Cushman M., Delling F.N., Deo R., et al. Heart Disease and Stroke Statistics-2018 Update: A Report from the American Heart Association. Circulation. 2018;137:e67–e492. doi: 10.1161/CIR.0000000000000558.
    1. Peker Y., Balcan B. Cardiovascular outcomes of continuous positive airway pressure therapy for obstructive sleep apnea. J. Thorac. Dis. 2018;10:S4262–S4279. doi: 10.21037/jtd.2018.11.48.
    1. Zhang J.J., Gao X.F., Ge Z., Jiang X.M., Xiao P.X., Tian N.L., Kan J., Lee C.H., Chen S.L. Obstructive sleep apnea affects the clinical outcomes of patients undergoing percutaneous coronary intervention. Patient Prefer. Adherence. 2016;10:871–878.
    1. Lee C.H., Sethi R., Li R., Ho H.H., Hein T., Jim M.H., Loo G., Koo C.Y., Gao X.F., Chandra S., et al. Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention. Circulation. 2016;133:2008–2017. doi: 10.1161/CIRCULATIONAHA.115.019392.
    1. Uchôa C.H.G., Danzi-Soares N.J., Nunes F.S., de Souza A.A.L., Nerbass F.B., Pedrosa R.P., César L.A.M., Lorenzi-Filho G., Drager L.F. Impact of OSA on cardiovascular events after coronary artery bypass surgery. Chest. 2015;147:1352–1360. doi: 10.1378/chest.14-2152.
    1. Engleman H.M., Martin S.E., Kingshott R.N., Mackay T.W., Deary I.J., Douglas N.J. Randomised placebo controlled trial of daytime function after continuous positive airway pressure (CPAP) therapy for the sleep apnoea/hypopnoea syndrome. Thorax. 1998;53:341–345. doi: 10.1136/thx.53.5.341.
    1. Cassar A., Morgenthaler T.I., Lennon R.J., Rihal C.S., Lerman A. Treatment of obstructive sleep apnea is associated with decreased cardiac death after percutaneous coronary intervention. J. Am. Coll. Cardiol. 2007;50:1310–1314. doi: 10.1016/j.jacc.2007.06.028.
    1. Campos-Rodriguez F., Martinez-Garcia M.A., de la Cruz-Moron I., Almeida-Gonzalez C., Catalan-Serra P., Montserrat J.M. Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: A cohort study. Ann. Intern. Med. 2012;156:115–122. doi: 10.7326/0003-4819-156-2-201201170-00006.
    1. Campos-Rodriguez F., Martinez-Garcia M.A., Reyes-Nunez N., Caballero-Martinez I., Catalan-Serra P., Almeida-Gonzalez C.V. Role of sleep apnea and continuous positive airway pressure therapy in the incidence of stroke or coronary heart disease in women. Am. J. Respir. Crit. Care Med. 2014;189:1544–1550. doi: 10.1164/rccm.201311-2012OC.
    1. Peker Y., Glantz H., Eulenburg C., Wegscheider K., Herlitz J., Thunstrom E. Effect of Positive Airway Pressure on Cardiovascular Outcomes in Coronary Artery Disease Patients with Nonsleepy Obstructive Sleep Apnea. The RICCADSA Randomized Controlled Trial. Am. J. Respir. Crit. Care Med. 2016;194:613–620. doi: 10.1164/rccm.201601-0088OC.
    1. McEvoy R.D., Antic N.A., Heeley E., Luo Y., Ou Q., Zhang X., Mediano O., Chen R., Drager L.F., Liu Z., et al. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N. Engl. J. Med. 2016;375:919–931. doi: 10.1056/NEJMoa1606599.
    1. Sánchez-de-la-Torre M., Sánchez-de-la-Torre A., Bertran S., Abad J., Duran-Cantolla J., Cabriada V., Mediano O., Masdeu M.J., Alonso M.L., Masa J.F., et al. 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. Lancet Respir. Med. 2020;8:359–367. doi: 10.1016/S2213-2600(19)30271-1.
    1. Peker Y., Glantz H., Thunstrom E., Kallryd A., Herlitz J., Ejdeback J. Rationale and design of the Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnoea—RICCADSA trial. Scand. Cardiovasc. J. 2009;43:24–31. doi: 10.1080/14017430802276106.
    1. Peker Y., Thunstrom E., Glantz H., Wegscheider K., Eulenburg C. Outcomes in coronary artery disease patients with sleepy obstructive sleep apnoea on CPAP. Eur. Respir. J. 2017;50 doi: 10.1183/13993003.00749-2017.
    1. Sawyer A.M., Gooneratne N.S., Marcus C.L., Ofer D., Richards K.C., Weaver T.E. A systematic review of CPAP adherence across age groups: Clinical and empiric insights for developing CPAP adherence interventions. Sleep Med. Rev. 2011;15:343–356. doi: 10.1016/j.smrv.2011.01.003.
    1. Lederer D.J., Bell S.C., Branson R.D., Chalmers J.D., Marshall R., Maslove D.M., Ost D.E., Punjabi N.M., Schatz M., Smyth A.R., et al. Control of Confounding and Reporting of Results in Causal Inference Studies. Guidance for Authors from Editors of Respiratory, Sleep, and Critical Care Journals. Ann. Am. Thorac. Soc. 2019;16:22–28. doi: 10.1513/AnnalsATS.201808-564PS.
    1. Peker Y., Wegscheider K., Eulenburg C. Reply: Effect of Continuous Positive Airway Pressure Therapy on Cardiovascular Outcomes: Risk Assessment. Am. J. Respir. Crit. Care Med. 2017;196:662–663. doi: 10.1164/rccm.201702-0420LE.
    1. Yumino D., Tsurumi Y., Takagi A., Suzuki K., Kasanuki H. Impact of obstructive sleep apnea on clinical and angiographic outcomes following percutaneous coronary intervention in patients with acute coronary syndrome. Am. J. Cardiol. 2007;99:26–30. doi: 10.1016/j.amjcard.2006.07.055.
    1. Peker Y. Obstructive sleep apnoea in acute coronary syndrome. Lancet Respir. Med. 2020;8:e14. doi: 10.1016/S2213-2600(20)30042-4.
    1. Schiza S.E., Simantirakis E., Bouloukaki I., Mermigkis C., Kallergis E.M., Chrysostomakis S., Arfanakis D., Tzanakis N., Vardas P., Siafakas N.M. Sleep disordered breathing in patients with acute coronary syndromes. J. Clin. Sleep Med. 2012;8:21–26. doi: 10.5664/jcsm.1652.
    1. Berry R.B., Budhiraja R., Gottlieb D.J., Gozal D., Iber C., Kapur V.K., Marcus C.L., Mehra R., Parthasarathy S., Quan S.F., et al. Rules for scoring respiratory events in sleep: Update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J. Clin. Sleep Med. 2012;8:597–619. doi: 10.5664/jcsm.2172.
    1. Javaheri S., Martinez-Garcia M.A., Campos-Rodriguez F., Muriel A., Peker Y. Continuous Positive Airway Pressure Adherence for Prevention of Major Adverse Cerebrovascular and Cardiovascular Events in Obstructive Sleep Apnea. Am. J. Respir. Crit. Care Med. 2020;201:607–610. doi: 10.1164/rccm.201908-1593LE.
    1. Wise M.S. Objective measures of sleepiness and wakefulness: Application to the real world? J. Clin. Neurophysiol. 2006;23:39–49. doi: 10.1097/01.wnp.0000190416.62482.42.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa