Effects of CPAP on Atherosclerotic Coronary Plaques in Patients with Sleep-Disordered Breathing: the ENTERPRISE Trial

Background The effects of continuous positive airway pressure (CPAP) treatment on coronary atheroma volume and vulnerability in patients with sleep-disordered breathing (SDB) coexisting with coronary artery disease are not well known. Thus, this study aimed to verify how CPAP treatment affects coronary plaques in patients with SDB who underwent percutaneous coronary intervention (PCI). Methods Altogether, fifty-three patients with SDB who underwent elective PCI using near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) were randomly assigned to two groups based on CPAP use. This study evaluated the absolute changes in percentage atheroma volume (PAV) and total atheroma volume by IVUS, and the absolute changes in maximum lipid core burden index calculated for every 4-mm segment (maxLCBI4mm) using NIRS from baseline to 12 months, in addition to major adverse cardiac and cerebrovascular events (MACCE), and all-cause death. Results In the final analysis, 23 patients were allocated to the CPAP group, and 24 patients were allocated to the non-CPAP group. Compared with the non-CPAP group, the CPAP group had a significantly higher absolute change in PAV (−1.90±2.63% vs. 0.82±4.67%, p =0.018) and TAV (−20±35 mm3 vs. −2±21 mm3, p =0.041), and lower incidence rate of MACCE, mainly driven by a decrease in target lesion or non-target lesion target vessel revascularization (4% vs. 25%, p =0.037). In addition, adequate CPAP treatment resulted in greater plaque regression of −2.48%. However, there was no significant difference for absolute change in maxLCBI4mm (0 [−32, 40] vs. 34 [−71, 163], p =0.306) between the both groups, and no all-cause death was observed. Conclusions CPAP treatment for patients with SDB contributed to a decline in coronary plaque volume and prevention of revascularization risk but did not mitigate lipid-rich plaques. Especially, adequate CPAP treatment had a greater effect on coronary plaque regression. Clinical Trial Registration The Ethics Committee of the Juntendo Clinical Research and Trial Center approved this study (reference number 18-021), and which was registered with the UMIN (UMIN ID: R000036293). [https://upload.umin.ac.jp/cgi-open-bin/icdr\_e/ctr\_view.cgi?recptno=R000036293][1] Clinical Perspective The effects of continuous positive airway pressure (CPAP) treatment on coronary atheroma volume and vulnerability in patients with sleep-disordered breathing (SDB) coexisting with coronary artery disease remains unclear. This study revealed that CPAP treatment for patients with SDB who underwent percutaneous coronary intervention contributed to a decline in coronary plaque volume and the prevention of cardiovascular events, mainly driven by a decrease in target vessel revascularization. In particular, adequate CPAP treatment may have a greater effect on coronary plaque regression; thus, it is important to focus on CPAP treatment and subsequent treatment compliance considering coronary plaques and events. In addition, patients with acute coronary syndrome who have greater plaque volume and lipid-rich plaques than those with stable coronary artery disease may benefit from the effects of adding CPAP treatment to optimal medical therapy due to an anti-atherogenic potential effect of CPAP treatment, thus, the further investigations targeting acute coronary syndrome are necessary. ### Competing Interest Statement Tomotaka Dohi has received a research grant from Teijin Pharma Limited. Takatoshi Kasai and Hiroyuki Daida are affiliated with a department endowed by Philips Respironics, ResMed, and Fukuda Denshi. The remaining authors declare no conflicts of interest. ### Clinical Trial This study was registered with the UMIN (UMIN ID: R000036293). https://upload.umin.ac.jp/cgi-open-bin/icdr\_e/ctr\_view.cgi?recptno=R000036293 ### Funding Statement This research was supported by Teijin Pharma Limited and partially funded by KAKENHI (Grant Number 16K19431). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the ethics committee (PR052/08, 07/064/797). The Ethics Committee of the Juntendo Clinical Research and Trial Center approved this study (reference number 18-021), which was registered with the University Hospital Medical Information Network (ID: R000036293). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets during and/or analyzed during the current study are available from the corresponding author with reasonable request. * CPAP : continuous positive airway pressure IVUS : intravascular sound LCBI : lipid core burden index LDL-C : low-density lipoprotein cholesterol MACCE : major adverse cardiac and cerebrovascular events MaxLCBI4mm/10mm : maximum lipid core burden index calculated for every 4-mm / 10-mm segment NIRS : near-infrared spectroscopy PAV : percentage atheroma volume PCI : percutaneous coronary intervention SDB : sleep-disordered breathing [1]: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000036293