Heart rate in heart failure: risk marker or risk factor?

Transcription

1 Heart rate in heart failure: risk marker or risk factor? A subanalysis of the SHIFT trial M. Böhm, B K. Swedberg, M. Komajda, J. Borer, I. Ford, L. Tavazzi on behalf of the Investigators

2 Heart rate and outcomes in HF: background Elevated resting heart rate is a marker of CV risk including in HF Ivabradine slows the heart by selective If current inhibition and has no known CV effects other than heart rate reduction SHIFT allows to further explore the prognostic importance and pathophysiological role of heart rate in HF We hypothesised that heart rate is a risk factor for CV events, and tested the effect of isolated HR reduction with ivabradine on outcomes in a HF population

3 Objective of current analysis To determine whether heart rate at baseline and on heart rate-lowering treatment with ivabradine can predict outcomes in SHIFT patients with HF and systolic dysfunction

4 Methods The relationship between risk and heart rate was tested in the placebo group divided by quintiles of baseline heart rate Heart rate achieved at 28 days by ivabradine (end of titration) was related to subsequent outcomes The effect of ivabradine on outcomes, adjusted for prognostic factors at baseline, was estimated by heart rate quintiles Outcomes analysed: primary composite endpoint (CV death and HF hospitalisation) secondary endpoints (all-cause / CV / death from HF; all-cause / CV / HF hospitalisation; composite of CV death, hospitalisation for HF or non-fatal MI)

5 Baseline characteristics in population divided by quintiles of heart rate Heart rate at baseline (bpm) 70 - < < < <87 87 P value* Heart rate (bpm) Age (years) < Caucasian (%) Smoking (%) < Ischaemic cause of HF (%) < NYHA class III/IV (%) < Hypertension (%) Diabetes (%) *p value for interaction (chi-squared test for categorical variables, Kruskal-Wallis test for continuous variables)

6 Baseline characteristics in population divided by quintiles of heart rate Heart rate at baseline (bpm) 70 - < < < <87 87 P value* SBP (mm Hg), mean DBP (mm Hg), mean LVEF (%), mean < Beta-blockers (%) < ACE inhibitors (%) Diuretics (%) Aldosterone antagonists (%) Cardiac glycosides (%) < *p value for interaction (chi-squared test for categorical variables, Kruskal-Wallis test for continuous variables)

7 Baseline heart rate is a predictor of endpoints on placebo Patients with primary composite endpoint (%) P< bpm 80 to <87 bpm 75 to <80 bpm 72 to <75 bpm 70 to <72 bpm Months Primary composite endpoint: risk increases by 2.9% per 1-bpm increase, and by 15.6% per 5-bpm increase Patients with first hospital admission for heart failure (%) P< bpm Patients with cardiovascular death (%) P< to <87 bpm 75 to <80 bpm 72 to <75 bpm 70 to <72 bpm bpm 80 to <87 bpm 75 to <80 bpm 72 to <75 bpm 70 to <72 bpm Months Months

8 Relative risk of primary composite endpoint in the placebo group divided by quintiles of heart rate Heart rate at baseline (bpm) HR Primary composite endpoint HR CV death 70 - < < < < Heart rate at baseline (bpm) HR HF hospitalisation HR Death from HF 70 - < < < <

9 Primary composite endpoint according to heart rate achieved at D28* in the ivabradine group Patients with primary composite endpoint (%) bpm 70-<75 bpm 60-<65 bpm 65-<70 bpm <60 bpm Day Months *Data exclude patients reaching primary composite endpoint in the first 28 days

10 Effect of ivabradine vs placebo according to heart rate at baseline (whole population) HR and 95% CI for primary composite endpoint to <72 72 to <75 75 to <80 80 to <87 87 Heart rate at baseline (bpm) At 28 days (ivabradine group) Heart rate (bpm) Change in heart rate (bpm) At 28 days (placebo group) Heart rate (bpm) Change in heart rate (bpm)

11 Effect of ivabradine vs placebo according to heart rate at baseline (whole population) HR and 95% CI for first hospital admission for heart failure to <72 72 to <75 75 to <80 80 to <87 Heart rate at baseline (bpm) 87 HR and 95% CI for cardiovascular death to <72 72 to <75 75 to <80 80 to<87 Heart rate at baseline (bpm) 87

12 Conclusion Our results indicate that in HF patients in sinus rhythm and heart rate 70 bpm, there is a positive continuous relationship between baseline heart rate and increased risk The risk is modified and significantly decreased by ivabradine, and the effect is related to heart rate at baseline and heart rate achieved at 28 days Patients with lowest heart rates on treatment with ivabradine have the best outcomes

13 Clinical implications Elevated heart rate is a risk factor in HF Heart rate is an important target for therapy in HF Shifting patients to lower heart rate profiles with ivabradine reduces CV events Lower heart rates at baseline and lower heart rates achieved on treatment are associated with better outcomes, with incremental benefit by achieving heart rate 60 bpm when tolerated