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).
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.
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg (Saar), Germany. Electronic address: michael.boehm@uks.eu.
Michael
M
Böhm
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
Michele
M
Robertson
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
Ian
I
Ford
Division of Cardiovascular Medicine, The Howard Gilman Institute for Heart Valve Disease and the Schiavone Institute for Cardiovascular Translational Research, State University of New York Downstate Medical Center, New York, New York.
Jeffrey S
JS
Borer
Institute of Cardiometabolism and Nutrition, Pierre et Marie Curie Paris VI University, La Pitié-Salpétrière Hospital, Paris, France.
Michel
M
Komajda
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg (Saar), Germany.
Ingrid
I
Kindermann
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg (Saar), Germany.
Christoph
C
Maack
Department of Cardiology, General Hospital Celje, Celje, Slovenia.
Mitja
M
Lainscak
Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
Karl
K
Swedberg
Maria Cecilia Hospital, Gruppo Villa Maria (GVM) Care and Research, Ettore Sansavini Health Science Foundation, Cotignola, Italy.
Luigi
L
Tavazzi
D000368:Aged; D001552:Benzazepines / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use; D015897:Comorbidity; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D014943:Global Health; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
D001552:Benzazepines; D002317:Cardiovascular Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D000077550:Ivabradine