Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis

Holger Woehrle, Martin R Cowie, Christine Eulenburg, Anna Suling, Christiane Angermann, Marie-Pia d'Ortho, Erland Erdmann, Patrick Levy, Anita K Simonds, Virend K Somers, Faiez Zannad, Helmut Teschler, Karl Wegscheider, Holger Woehrle, Martin R Cowie, Christine Eulenburg, Anna Suling, Christiane Angermann, Marie-Pia d'Ortho, Erland Erdmann, Patrick Levy, Anita K Simonds, Virend K Somers, Faiez Zannad, Helmut Teschler, Karl Wegscheider

Abstract

This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the control group in the SERVE-HF trial.Time-dependent on-treatment analyses were conducted (unadjusted and adjusted for predictive covariates). A comprehensive, time-dependent model was developed to correct for asymmetric selection effects (to minimise bias).The comprehensive model showed increased cardiovascular death hazard ratios during adaptive servo ventilation usage periods, slightly lower than those in the SERVE-HF intention-to-treat analysis. Self-selection bias was evident. Patients randomised to adaptive servo ventilation who crossed over to the control group were at higher risk of cardiovascular death than controls, while control patients with crossover to adaptive servo ventilation showed a trend towards lower risk of cardiovascular death than patients randomised to adaptive servo ventilation. Cardiovascular risk did not increase as nightly adaptive servo ventilation usage increased.On-treatment analysis showed similar results to the SERVE-HF intention-to-treat analysis, with an increased risk of cardiovascular death in heart failure with reduced ejection fraction patients with predominant central sleep apnoea treated with adaptive servo ventilation. Bias is inevitable and needs to be taken into account in any kind of on-treatment analysis in positive airway pressure studies.

Conflict of interest statement

Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com

Copyright ©ERS 2017.

Figures

FIGURE 1
FIGURE 1
Schematic representing different possible patterns of device usage and intervals in the different on-treatment analyses (OTA) (follow-up times are indicative only). Solid lines show periods where treatment was as randomised (control, blue; or ASV, red) and dotted lines show periods were treatment was not as randomised (e.g. no ASV use in the ASV group, or ASV use in the control group). a) Possible usage and adherence patterns to allocated treatment. Patients with continuous use remained in their randomised group and adherent to treatment throughout the study. The intermittent use examples show patients in both the ASV (red line) and control groups (blue line) switching between their allocated treatment (solid lines) and the alternative treatment (dotted lines). Early crossover in the ASV group refers to patient refusal of ASV despite randomisation to the ASV group, and early crossover in the control group refers to initiation of ASV within the first 2 weeks after randomisation in a patient randomised to the control group. Late crossover in the ASV group refers to withdrawal of ASV >2 weeks after randomisation in patients randomised to the ASV group, and late crossover in the control group refers to initiation of ASV >2 weeks after randomisation in patients randomised to the control group. b) Treatment intervals for six different hypothetical patients included in the on-treatment analyses (intention-to-treat, as-treated, as-treated-as-randomised). Intention-to-treat analysis allocates all follow-up intervals to the randomised treatment group, regardless of usage. As-treated analysis includes periods allocated on the basis of actual treatment during different follow-up intervals (ASV, red boxes; or control, blue boxes). As-treated-as-randomised analysis also allocates intervals on the basis of actual treatment received but only includes intervals where patients used the treatment to which they had been initially randomised (ASV, red boxes; or control, blue boxes). For all examples, patients 1 and 2 remained continuously in their randomised group, patients 3 and 4 had intermittent time in their randomised group and patients 5 and 6 crossed over from randomised treatment to the alternative group.

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