Clinical profiles and outcomes in patients with chronic heart failure and chronic obstructive pulmonary disease: an efficacy and safety analysis of SHIFT study

Int J Cardiol. 2013 Dec 10;170(2):182-8. doi: 10.1016/j.ijcard.2013.10.068. Epub 2013 Oct 25.


Background: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist, with undefined prognostic and therapeutic implications. We investigated clinical profile and outcomes of patients with chronic HF and COPD, notably the efficacy and safety of ivabradine, a heart rate-reducing agent.

Methods: 6505 ambulatory patients, in sinus rhythm, heart rate ≥ 70 bpm and stable systolic HF were randomised to placebo or ivabradine (2.5 to 7.5mg bid). Multivariate Cox model analyses were performed to compare the COPD (n=730) and non-COPD subgroups, and the ivabradine and placebo treatment effects.

Results: COPD patients were older and had a poorer risk profile. Beta-blockers were prescribed to 69% of COPD patients and 92% of non-COPD patients. The primary endpoint (PEP) and its component, hospitalisation for worsening HF, were more frequent in COPD patients (HRs f, 1.22 [p=0.006]; and 1.34 [p<0.001]) respectively, but relative risk was reduced similarly by ivabradine in both COPD (14%, and 17%) and non-COPD (18% and 27%) patients (p interaction=0.82, and 0.53, respectively). Similar effect was noted also for cardiovascular death. Adverse events were more common in COPD patients, but similar in treatment subgroups. Bradycardia occurred more frequently in ivabradine subgroups, with similar incidence in patients with or without COPD.

Conclusions: The association of COPD and HF results in a worse prognosis, and COPD represents a barrier to optimisation of beta-blocker therapy. Ivabradine is similarly effective and safe in chronic HF patients with or without COPD, and can be safely combined with beta-blockers in COPD.

Keywords: Beta-blocker; Chronic heart failure; Chronic obstructive pulmonary disease; Heart rate; Ivabradine.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Adrenergic beta-Antagonists / adverse effects
  • Aged
  • Benzazepines / administration & dosage*
  • Benzazepines / adverse effects
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / adverse effects
  • Chronic Disease
  • Female
  • Heart Failure, Systolic / complications
  • Heart Failure, Systolic / drug therapy*
  • Heart Failure, Systolic / mortality*
  • Heart Rate / drug effects*
  • Humans
  • Incidence
  • Ivabradine
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Placebos
  • Prognosis
  • Proportional Hazards Models
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / mortality*
  • Risk Factors
  • Treatment Outcome


  • Adrenergic beta-Antagonists
  • Benzazepines
  • Cardiotonic Agents
  • Placebos
  • Ivabradine