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- Bouabdallaoui, Nadia, et al.
(författare)
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Beneficial effects of ivabradine in patients with heart failure, low ejection fraction, and heart rate above 77 b.p.m.
- 2019
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Ingår i: ESC heart failure. - : Wiley. - 2055-5822. ; 6:6, s. 1199-1207
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Tidskriftsartikel (refereegranskat)abstract
- Ivabradine has been approved in heart failure with reduced ejection fraction (HFrEF) and elevated heart rate despite guideline-directed medical therapy (GDMT) to reduce cardiovascular (CV) death and hospitalization for worsening HF. The median value of 77 b.p.m. is the lower bound selected for the regulatory approval in Canada, South Africa, and Australia. Patient-reported outcomes (PROs) including symptoms, quality of life, and global assessment are considered of major interest in the global plan of care of patients with HF. However, the specific impact of GDMT, and specifically ivabradine, on PRO remains poorly studied. In the subgroup of patients from the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) who had heart rate above the median of 77 b.p.m. (pre-specified analysis) and for whom the potential for improvement was expected to be larger, we aimed (i) to evaluate the effects of ivabradine on PRO (symptoms, quality of life, and global assessment); (ii) to consolidate the effects of ivabradine on the primary composite endpoint of CV death and hospitalization for HF; and (iii) to reassess the effects of ivabradine on left ventricular (LV) remodelling.Comparisons were made according to therapy, and proportional hazards models (adjusted for baseline beta-blocker therapy) were used to estimate the association between ivabradine and various outcomes. In SHIFT, n = 3357 (51.6%) patients had a baseline heart rate > 77 b.p.m. After a median follow-up of 22.9 months (inter-quartile range 18-28 months), ivabradine on top of GDMT improved symptoms (28% vs. 23% improvement in New York Heart Association functional class, P = 0.0003), quality of life (5.3 vs. 2.2 improvement in Kansas City Cardiomyopathy Questionnaire overall summary score, P = 0.005), and global assessment [from both patient (improved in 72.3%) and physician (improved in 61.0%) perspectives] significantly more than did placebo (both P < 0.0001). Ivabradine induced a 25% reduction in the combined endpoint of CV death and hospitalization for HF (hazard ratio 0.75; P < 0.0001), which translates into a number of patients needed to be treated for 1 year of 17. Patients under ivabradine treatment demonstrated a significant reduction in LV dimensions when reassessed at 8 months (P < 0.05).In patients with chronic HFrEF, sinus rhythm, and a heart rate > 77 b.p.m. while on GDMT, the present analysis brings novel insights into the role of ivabradine in improving the management of HFrEF, particularly with regard to PRO (ISRCTN70429960).
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| 2. |
- Böhm, Michael, et al.
(författare)
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Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the SHIFT study
- 2013
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Ingår i: Clinical research in cardiology : official journal of the German Cardiac Society. - : Springer Science and Business Media LLC. - 1861-0692. ; 102:1, s. 11-22
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We analysed the effect of ivabradine on outcomes in heart failure (HF) patients on recommended background therapies with heart rates >/=75 bpm and <75 bpm in the SHIFT trial. A cut-off value of >/=75 bpm was chosen by the EMEA for approval for the use of ivabradine in chronic heart failure. METHODS: The SHIFT population was divided by baseline heart rate >/=75 or <75 bpm. The effect of ivabradine was analysed for primary composite endpoint (cardiovascular death or HF hospitalization) and other endpoints. RESULTS: In the >/=75 bpm group, ivabradine reduced primary endpoint (HR 0.76, 95 % CI 0.68-0.85, P < 0.0001), all-cause mortality (HR 0.83, 95 % CI, 0.72-0.96, P = 0.0109), cardiovascular mortality (HR 0.83, 95 % CI, (0.71-0.97, P = 0.0166), HF death (HR 0.61, 95 % CI, 0.46-0.81, P < 0.0006), and HF hospitalization (HR 0.70, 95 % CI, 0.61-0.80, P < 0.0001). Risk reduction depended on heart rate after 28 days, with the best protection for heart rates <60 bpm or reductions >10 bpm. None of the endpoints was significantly reduced in the <75 bpm group, though there were trends for risk reductions in HF death and hospitalization for heart rate <60 bpm and reductions >10 bpm. Ivabradine was tolerated similarly in both groups. CONCLUSION: The effect of ivabradine on outcomes is greater in patients with heart rate >/=75 bpm with heart rates achieved <60 bpm or heart rate reductions >10 bpm predicting best risk reduction. Our findings emphasize the importance of identification of high-risk HF patients by high heart rates and their treatment with heart rate-lowering drugs such as ivabradine.
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| 4. |
- Nikolovska Vukadinović, Aleksandra, et al.
(författare)
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Heart rate and its reduction in chronic heart failure and beyond
- 2017
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 10, s. 1230-41
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 The Authors European Journal of Heart Failure. Heart rate (HR) is associated with cardiovascular outcomes in all the stages of the cardiovascular continuum as well as in patients with pulmonary, cerebrovascular, and renal disease, sepsis, cancer, and erectile dysfunction. In patients with cardiovascular disease, but also in the general population, increased HR represents an important indicator of mortality with each acceleration of HR over 70 b.p.m. increasing the risk. In patients in sinus rhythm with chronic heart failure with reduced ejection fraction (HFrEF), a HR > 70 b.p.m. increased the risk of hospitalization, and > 75 b.p.m. the risk of cardiovascular death as shown in the Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT). Reducing HR with ivabradine by 11 b.p.m. (placebo-controlled) reduced the primary composite endpoint (cardiovascular death and hospitalization for worsening heart failure). Ivabradine was well tolerated showing benefit irrespective of age or diabetes status, and also in the presence of low systolic blood pressure and severe heart failure (SHIFT trial). Therefore, HR qualifies as a modifiable risk factor in heart failure. In patients with stable coronary disease, HR is a risk marker but HR reduction with ivabradine does not improve outcomes. The role of selective HR lowering remains unclear in patients with pulmonary, renal, cerebrovascular, and other diseases, as the potential benefit of interventions on HR has not been explored in these conditions. Future studies should scrutinize if HR reduction improves outcomes, defining HR as a potential risk factor and therapeutic target in other conditions beyond heart failure.
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