TY - JOUR
T1 - Mechanisms underlying increased mortality risk in patients with heart failure and reduced ejection fraction randomly assigned to adaptive servoventilation in the SERVE-HF study
T2 - results of a secondary multistate modelling analysis
AU - Eulenburg, Christine
AU - Wegscheider, Karl
AU - Woehrle, Holger
AU - Angermann, Christiane
AU - d'Ortho, Marie Pia
AU - Erdmann, Erland
AU - Levy, Patrick
AU - Simonds, Anita K.
AU - Somers, Virend K.
AU - Zannad, Faiez
AU - Teschler, Helmut
AU - Cowie, Martin R.
N1 - Funding Information:
MRC's and AKS's salaries are supported by the National Institute for Health Research Cardiovascular and Respiratory Biomedical Research Units, respectively, at the Royal Brompton Hospital, London, UK. VKS was supported by NIH R01HL065176, and receives consulting fees from PricewaterhouseCoopers, Sorin, GlaxoSmithKline, Respicardia, uHealth, Ronda Grey, Philips Respironics, and ResMed, working with Mayo Medical Ventures on intellectual property related to sleep and cardiovascular disease. The content in this Article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CE and KW receive grant support from ResMed. HW is an employee of ResMed. CA receives fees for serving on advisory boards from ResMed, Servier, Boehringer Ingelheim, and Vifor Pharma; fees for serving on a steering committee from ResMed; lecture fees from Servier and Vifor Pharma; grant support from ResMed, Thermo Fisher Scientific, Boehringer Ingelheim, Lundbeck, and Vifor Pharma; financial support for statistical analyses from Thermo Fisher Scientific; and study drugs from Lundbeck. M-Pd'O receives fees for serving on advisory boards from ResMed and IP Santé; lecture fees from ResMed, Philips, IP Santé, and VitalAire; grant support from Fisher and Paykel Healthcare, ResMed, Philips, ADEP Assistance, and IP Santé; and small material donations from VitalAire. EE receives fees for serving on advisory boards and honoraria for lecturing from ResMed. FZ receives fees for serving on steering committees from Janssen Pharmaceutica, Bayer, Pfizer, Novartis, Boston Scientific, ResMed, and Takeda Pharmaceutical; receives consulting fees from Servier, Stealth Peptides, Amgen, and CVRx; and receives lecture fees from Mitsubishi. HT receives consulting fees, grant support, and hardware and software for the development of devices from ResMed. MRC receives consulting fees from ResMed, Servier, Novartis, Pfizer, St Jude Medical, Boston Scientific, Respicardia, and Medtronic; research grants from ResMed; and grant support through his institution from Bayer. PL declares no competing interests outside of the submitted work
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Background A large randomised treatment trial (SERVE-HF) showed that treatment of central sleep apnoea with adaptive servoventilation in patients with heart failure and reduced ejection fraction (HFREF) increased mortality, although the analysis of the composite primary endpoint (time to first event of death from any cause, life-saving cardiovascular intervention, or unplanned hospital admission for worsening heart failure) was neutral. This secondary multistate modelling analysis of SERVE-HF data investigated associations between adaptive servoventilation and individual components of the primary endpoint to try to better understand the mechanisms underlying the observed increased mortality. Methods In SERVE-HF, participants were randomly assigned to receive either optimum medical treatment for heart failure alone (control group), or in combination with adaptive servoventilation. We analysed individual components of the primary SERVE-HF endpoint separately in a multistate model, with and without three covariates suggested for effect modification (implantable cardioverter defibrillator at baseline, left ventricular ejection fraction [LVEF], and proportion of Cheyne-Stokes Respiration [CSR]). The SERVE-HF study is registered with ClinicalTrials.gov, number NCT00733343. Findings Univariate analysis showed an increased risk of both cardiovascular death without previous hospital admission (hazard ratio [HR] 2·59, 95% CI 1·54–4·37, p<0·001) and cardiovascular death after a life-saving event (1·57, 1·01–2·44, p=0·045) in the group receiving adaptive servoventilation versus the control group. Adjusted analysis showed that the increased risk attributed to adaptive servoventilation of cardiovascular death without previous hospital admission for worsening heart failure varied with LVEF and that the risk attributed to adaptive servoventilation of hospital admission for worsening heart failure varied with LVEF and CSR. In patients with LVEF less than or equal to 30%, use of adaptive servoventilation markedly increased the risk of cardiovascular death without previous hospital admission (HR 5·21, 95% CI 2·11–12·89, p=0·026). Interpretation Adaptive servoventilation is associated with an increased risk of cardiovascular death in patients with heart failure and reduced ejection fraction (LVEF ≤45%) treated for predominant central sleep apnoea. This multistate modelling analysis shows that this risk is increased for cardiovascular death in patients not previously admitted to hospital, presumably due to sudden death, and in patients with poor left ventricular function. Funding ResMed.
AB - Background A large randomised treatment trial (SERVE-HF) showed that treatment of central sleep apnoea with adaptive servoventilation in patients with heart failure and reduced ejection fraction (HFREF) increased mortality, although the analysis of the composite primary endpoint (time to first event of death from any cause, life-saving cardiovascular intervention, or unplanned hospital admission for worsening heart failure) was neutral. This secondary multistate modelling analysis of SERVE-HF data investigated associations between adaptive servoventilation and individual components of the primary endpoint to try to better understand the mechanisms underlying the observed increased mortality. Methods In SERVE-HF, participants were randomly assigned to receive either optimum medical treatment for heart failure alone (control group), or in combination with adaptive servoventilation. We analysed individual components of the primary SERVE-HF endpoint separately in a multistate model, with and without three covariates suggested for effect modification (implantable cardioverter defibrillator at baseline, left ventricular ejection fraction [LVEF], and proportion of Cheyne-Stokes Respiration [CSR]). The SERVE-HF study is registered with ClinicalTrials.gov, number NCT00733343. Findings Univariate analysis showed an increased risk of both cardiovascular death without previous hospital admission (hazard ratio [HR] 2·59, 95% CI 1·54–4·37, p<0·001) and cardiovascular death after a life-saving event (1·57, 1·01–2·44, p=0·045) in the group receiving adaptive servoventilation versus the control group. Adjusted analysis showed that the increased risk attributed to adaptive servoventilation of cardiovascular death without previous hospital admission for worsening heart failure varied with LVEF and that the risk attributed to adaptive servoventilation of hospital admission for worsening heart failure varied with LVEF and CSR. In patients with LVEF less than or equal to 30%, use of adaptive servoventilation markedly increased the risk of cardiovascular death without previous hospital admission (HR 5·21, 95% CI 2·11–12·89, p=0·026). Interpretation Adaptive servoventilation is associated with an increased risk of cardiovascular death in patients with heart failure and reduced ejection fraction (LVEF ≤45%) treated for predominant central sleep apnoea. This multistate modelling analysis shows that this risk is increased for cardiovascular death in patients not previously admitted to hospital, presumably due to sudden death, and in patients with poor left ventricular function. Funding ResMed.
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U2 - 10.1016/S2213-2600(16)30244-2
DO - 10.1016/S2213-2600(16)30244-2
M3 - Article
C2 - 27592224
AN - SCOPUS:84994087202
VL - 4
SP - 873
EP - 881
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
SN - 2213-2600
IS - 11
ER -