Influence of Cardiovascular and Noncardiovascular Co-morbidities on Outcomes and Treatment Effect of Heart Rate Reduction With Ivabradine in Stable Heart Failure (from the SHIFT Trial)

Am J Cardiol. 2015 Dec 15;116(12):1890-7. doi: 10.1016/j.amjcard.2015.09.029. Epub 2015 Oct 9.

Abstract

Incidence of chronic heart failure (HF) increases with age and cardiovascular (CV) morbidity. Co-morbidities increase hospitalization and mortality in HF, and non-CV co-morbidities may lead to preventable hospitalizations. We studied the impact of co-morbidities on mortality and morbidity in Systolic Heart Failure Treatment with the I(f) Inhibitor Ivabradine Trial, and investigated whether the impact of ivabradine was affected by co-morbidities. We analyzed the Systolic Heart Failure Treatment with the I(f) Inhibitor Ivabradine Trialpopulation, with moderate-to-severe HF and left ventricular dysfunction (in sinus rhythm with heart rate at rest ≥70 beats/min), according to co-morbidity: chronic obstructive pulmonary disease, diabetes mellitus, anemia, stroke, impaired renal function, myocardial infarction, hypertension, and peripheral artery disease. Co-morbidity load was classed as 0, 1, 2, 3, 4+ or 1 to 2 co-morbidities, or 3+ co-morbidities. Co-morbidities were evenly distributed between the placebo and ivabradine groups. Patients with more co-morbidities were likely to be older, women, had more advanced HF, were less likely to be on β blockers, with an even distribution on ivabradine 2.5, 5, or 7.5 mg bid and placebo at all co-morbidity loads. Number of co-morbidities was related to outcomes. Cardiovascular death or HF hospitalization events significantly increased (p <0.0001) with co-morbidity load, with the most events in patients with >3 co-morbidities for both, ivabradine and placebo. There was no interaction between co-morbidity load and the treatment effects of ivabradine. Hospitalization rate was lower at all co-morbidity loads for ivabradine. In conclusion, cardiac and noncardiac co-morbidities significantly affect CV outcomes, particularly if there are >3 co-morbidities. The effect of heart rate reduction with ivabradine is maintained at all co-morbidity loads.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Benzazepines / therapeutic use*
  • Cardiovascular Agents / therapeutic use
  • Comorbidity
  • Cyclic Nucleotide-Gated Cation Channels / antagonists & inhibitors
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Global Health
  • Heart Failure, Systolic / drug therapy*
  • Heart Failure, Systolic / epidemiology
  • Heart Failure, Systolic / physiopathology
  • Heart Rate / drug effects*
  • Humans
  • Incidence
  • Ivabradine
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology*
  • Pulmonary Disease, Chronic Obstructive / epidemiology*
  • Survival Rate / trends
  • Treatment Outcome

Substances

  • Benzazepines
  • Cardiovascular Agents
  • Cyclic Nucleotide-Gated Cation Channels
  • Ivabradine