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Ian Ford - One of the best experts on this subject based on the ideXlab platform.
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duration of chronic heart failure affects outcomes with preserved effects of heart rate reduction with Ivabradine findings from shift
European Journal of Heart Failure, 2018Co-Authors: Michael Bohm, Christoph Maack, Ian Ford, Jeffrey S Borer, Luigi Tavazzi, Karl Swedberg, M Komajda, Aurelie MoyneAbstract:Aims In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with Ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization. Methods and results It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of ≤35%), in sinus rhythm, heart rate of ≥70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or Ivabradine. Outcomes and the treatment effect of Ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 Ivabradine and 1459 placebo patients had HF duration of ≥4 weeks and <1.5 years; 836 Ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 Ivabradine and 999 placebo patients had HF duration of ≥4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs. 4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of Ivabradine were independent of HF duration. Conclusions Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with Ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials.
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Chronic exposure to Ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post-hoc analysis of SHIFT
European Journal of Heart Failure, 2016Co-Authors: Michel Komajda, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, Karl Swedberg, Aurelie Moyne, Ian FordAbstract:Aims: During the post-discharge phase following a heart failure hospitalization (HFH), patients are at high risk of early readmission despite standard of care therapy. We examined the impact of chronic exposure to Ivabradine on early readmissions in patients hospitalized for heart failure during the course of the SHIFT study (Systolic Heart Failure treatment with the If inhibitor Ivabradine Trial). Methods and results: A total of 1186 of the 6505 randomized patients experienced at least one HFH during the study, and had a more severe profile than those without HFH. Of these 1186 patients, 334 patients (28%) were rehospitalized within 3 months for any reason, mostly for cardiovascular causes (86%), including HFH (61%). Ivabradine was associated with fewer all-cause hospitalizations at 1 month [incidence rate ratio (IRR) 0.70, 95% confidence interval (CI) 0.50–1.00, P < 0.05], 2 months (IRR 0.75, 95% CI 0.58–0.98, P = 0.03), and 3 months (IRR 0.79, 95% CI 0.63–0.99, P = 0.04). A trend for a reduction in cardiovascular and HF hospitalizations was also observed in Ivabradine-treated patients. Conclusion: We demonstrate in this post-hoc analysis that chronic exposure to Ivabradine reduces the incidence of all-cause hospitalizations during the vulnerable phase after a HFH. Further studies are needed to investigate if in-hospital or early post-discharge initiation of Ivabradine could be useful to improve early outcomes in patients hospitalized for HF.
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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
American Journal of Cardiology, 2015Co-Authors: Michael Bohm, Christoph Maack, Ian Ford, Jeffrey S Borer, Michel Komajda, Mitja Lainscak, Karl Swedberg, Michele Robertson, Ingrid Kindermann, Luigi TavazziAbstract: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 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.
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twenty four hour heart rate lowering with Ivabradine in chronic heart failure insights from the shift holter substudy
European Journal of Heart Failure, 2015Co-Authors: Michael Bohm, Ian Ford, Jeffrey S Borer, John Camm, Suzanne M Lloyd, Michel Komajda, Luigi Tavazzi, Mario Talajic, Mitja Lainscak, Janchristian ReilAbstract:Aims Analysis of 24-h Holter recordings was a pre-specified substudy of SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) for exploring the heart rhythm safety of Ivabradine and to determine effects of Ivabradine on 24-h, daytime, and night-time heart rate (HR) compared with resting office HR. Methods and results The 24-h Holter monitoring was performed at baseline and 8 months after randomization to Ivabradine (n = 298) or matching placebo (n = 304) titrated maximally to 7.5 mg b.i.d. in patients with baseline HR ≥70 b.p.m. Patients received guideline-based optimized heart failure therapy including ACE inhibitors and/or ARBs in 93% and beta-blockers at maximally tolerated doses in 93%. After 8 months, HR over 24 h decreased by 9.5 ± 10.0 b.p.m. with Ivabradine, from 75.4 ± 10.3 b.p.m. (P 2.5 s on Ivabradine vs. 4 (1.6%) patients on placebo. No RR intervals >3 s were identified in patients taking Ivabradine. Conclusion Ivabradine safely and significantly lowers HR and improves HR variability in patients with systolic heart failure, without inducing significant bradycardia, ventricular arrhythmias, or supraventricular arrhythmias.
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Ivabradine in stable coronary artery disease without clinical heart failure
The New England Journal of Medicine, 2014Co-Authors: Kim Fox, Michal Tendera, Ian Ford, Jeanclaude Tardif, Philippe Gabriel Steg, Roberto FerrariAbstract:BACKGROUND An elevated heart rate is an established marker of cardiovascular risk. Previous analyses have suggested that Ivabradine, a heart-rate–reducing agent, may improve outcomes in patients with stable coronary artery disease, left ventricular dysfunction, and a heart rate of 70 beats per minute or more. METHODS We conducted a randomized, double-blind, placebo-controlled trial of Ivabradine, added to standard background therapy, in 19,102 patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more (including 12,049 patients with activity-limiting angina [class ≥II on the Canadian Cardiovascular Society scale, which ranges from I to IV, with higher classes indicating greater limitations on physical activity owing to angina]). We randomly assigned patients to placebo or Ivabradine, at a dose of up to 10 mg twice daily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. The primary end point was a composite of death from cardiovascular causes or nonfatal myocardial infarction. RESULTS At 3 months, the mean (±SD) heart rate of the patients was 60.7±9.0 beats per minute in the Ivabradine group versus 70.6±10.1 beats per minute in the placebo group. After a median follow-up of 27.8 months, there was no significant difference between the Ivabradine group and the placebo group in the incidence of the primary end point (6.8% and 6.4%, respectively; hazard ratio, 1.08; 95% confidence interval, 0.96 to 1.20; P = 0.20), nor were there significant differences in the incidences of death from cardiovascular causes and nonfatal myocardial infarction. Ivabradine was associated with an increase in the incidence of the primary end point among patients with activity-limiting angina but not among those without activity-limiting angina (P = 0.02 for interaction). The incidence of bradycardia was higher with Ivabradine than with placebo (18.0% vs. 2.3%, P<0.001). CONCLUSIONS Among patients who had stable coronary artery disease without clinical heart failure, the addition of Ivabradine to standard background therapy to reduce the heart rate did not improve outcomes. (Funded by Servier; SIGNIFY Current Controlled Trials number, ISRCTN61576291.)
Karl Swedberg - One of the best experts on this subject based on the ideXlab platform.
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duration of chronic heart failure affects outcomes with preserved effects of heart rate reduction with Ivabradine findings from shift
European Journal of Heart Failure, 2018Co-Authors: Michael Bohm, Christoph Maack, Ian Ford, Jeffrey S Borer, Luigi Tavazzi, Karl Swedberg, M Komajda, Aurelie MoyneAbstract:Aims In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with Ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization. Methods and results It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of ≤35%), in sinus rhythm, heart rate of ≥70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or Ivabradine. Outcomes and the treatment effect of Ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 Ivabradine and 1459 placebo patients had HF duration of ≥4 weeks and <1.5 years; 836 Ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 Ivabradine and 999 placebo patients had HF duration of ≥4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs. 4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of Ivabradine were independent of HF duration. Conclusions Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with Ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials.
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Chronic exposure to Ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post-hoc analysis of SHIFT
European Journal of Heart Failure, 2016Co-Authors: Michel Komajda, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, Karl Swedberg, Aurelie Moyne, Ian FordAbstract:Aims: During the post-discharge phase following a heart failure hospitalization (HFH), patients are at high risk of early readmission despite standard of care therapy. We examined the impact of chronic exposure to Ivabradine on early readmissions in patients hospitalized for heart failure during the course of the SHIFT study (Systolic Heart Failure treatment with the If inhibitor Ivabradine Trial). Methods and results: A total of 1186 of the 6505 randomized patients experienced at least one HFH during the study, and had a more severe profile than those without HFH. Of these 1186 patients, 334 patients (28%) were rehospitalized within 3 months for any reason, mostly for cardiovascular causes (86%), including HFH (61%). Ivabradine was associated with fewer all-cause hospitalizations at 1 month [incidence rate ratio (IRR) 0.70, 95% confidence interval (CI) 0.50–1.00, P < 0.05], 2 months (IRR 0.75, 95% CI 0.58–0.98, P = 0.03), and 3 months (IRR 0.79, 95% CI 0.63–0.99, P = 0.04). A trend for a reduction in cardiovascular and HF hospitalizations was also observed in Ivabradine-treated patients. Conclusion: We demonstrate in this post-hoc analysis that chronic exposure to Ivabradine reduces the incidence of all-cause hospitalizations during the vulnerable phase after a HFH. Further studies are needed to investigate if in-hospital or early post-discharge initiation of Ivabradine could be useful to improve early outcomes in patients hospitalized for HF.
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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
American Journal of Cardiology, 2015Co-Authors: Michael Bohm, Christoph Maack, Ian Ford, Jeffrey S Borer, Michel Komajda, Mitja Lainscak, Karl Swedberg, Michele Robertson, Ingrid Kindermann, Luigi TavazziAbstract: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 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.
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selective heart rate reduction with Ivabradine unloads the left ventricle in heart failure patients
Journal of the American College of Cardiology, 2013Co-Authors: Janchristia Reil, Suzanne M Lloyd, Michel Komajda, Luigi Tavazzi, Jeanclaude Tardif, Karl Swedberg, Ia Ford, Eilee Omeara, Jeffrey S Ore, Michael OhmAbstract:Objectives The study aimed to determine whether isolated heart rate (HR) reduction with Ivabradine reduces afterload of patients with systolic heart failure. Background The effective arterial elastance (Ea) represents resistive and pulsatile afterload of the heart derived from the pressure volume relation. HR modulates Ea, and, therefore, afterload burden. Methods Among the patients with systolic heart failure (ejection fraction ≤35%) randomized to either placebo or Ivabradine in the SHIFT (Systolic Heart Failure Treatment With the I f Inhibitor Ivabradine Trial), 275 patients (n = 132, placebo; n = 143, Ivabradine 7.5 mg twice a day) were included in the echocardiographic substudy. Ea, total arterial compliance (TAC), and end-systolic elastance (Ees) were calculated at baseline and after 8 months of treatment. Blood pressure was measured by arm cuff; stroke volume (SV), ejection fraction, and end-diastolic volume were assessed by echocardiography. Results At baseline Ea, TAC, HR, and Ees did not differ significantly between Ivabradine- and placebo-treated patients. After 8 months of treatment, HR was significantly reduced in the Ivabradine group (p Conclusions Isolated HR reduction by Ivabradine improves TAC, thus reducing Ea. Because Ees is unaltered, improved ventricular-arterial coupling is responsible for increased SV. Therefore, unloading of the heart may contribute to the beneficial effect of isolated HR reduction in patients with systolic heart failure. (Systolic Heart Failure Treatment With the I f Inhibitor Ivabradine Trial [SHIFT]; ISRCTN70429960 )
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efficacy and safety of Ivabradine in chronic heart failure across the age spectrum insights from the shift study
European Journal of Heart Failure, 2013Co-Authors: Luigi Tavazzi, Michael Bohm, Jeffrey S Borer, Michel Komajda, Mitja Lainscak, Karl Swedberg, Ian FordAbstract:Aims To test whether the efficacy and safety of the selective heart rate-reducing agent Ivabradine changes according to age in chronic heart failure (HF) patients. Methods and results The Ivabradine and placebo arms of SHIFT, which enrolled 6505 chronic HF patients, were combined and age distribution was divided by quartiles to give four groups (<53 years, n = 1522; 53 to <60 years, n = 1521; 60 to <69 years, n = 1750; and ≥69 years, n = 1712). The effects of Ivabradine on cardiovascular outcomes, changes in heart rate, and adverse events, particularly bradycardia, were evaluated according to age group. A subgroup (602 patients) underwent 24 h ambulatory ECG Holter monitoring. The relative risk of the primary endpoint (cardiovascular death or hospitalization for worsening HF) was reduced by Ivabradine in all age groups, ranging from 38% [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.50–0.78, P < 0.001] in the youngest patients <53 years to 16% (HR 0.84, 95% CI 0.71–0.99, P = 0.035) in the oldest patients ≥69 years. Ivabradine up-titration reduced heart rate similarly in all age groups, by 11 b.p.m. As anticipated, bradycardia and phosphenes occurred more frequently with Ivabradine, at a similar rate whatever the age. In the Holter substudy, there were no episodes of severe bradycardia and no clinically relevant pauses with Ivabradine in any age group. Conclusions Age does not limit the appropriate use of Ivabradine in patients with chronic HF and systolic dysfunction. The safety and efficacy of Ivabradine are comparable across all age groups.
Luigi Tavazzi - One of the best experts on this subject based on the ideXlab platform.
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duration of chronic heart failure affects outcomes with preserved effects of heart rate reduction with Ivabradine findings from shift
European Journal of Heart Failure, 2018Co-Authors: Michael Bohm, Christoph Maack, Ian Ford, Jeffrey S Borer, Luigi Tavazzi, Karl Swedberg, M Komajda, Aurelie MoyneAbstract:Aims In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with Ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization. Methods and results It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of ≤35%), in sinus rhythm, heart rate of ≥70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or Ivabradine. Outcomes and the treatment effect of Ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 Ivabradine and 1459 placebo patients had HF duration of ≥4 weeks and <1.5 years; 836 Ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 Ivabradine and 999 placebo patients had HF duration of ≥4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs. 4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of Ivabradine were independent of HF duration. Conclusions Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with Ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials.
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Chronic exposure to Ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post-hoc analysis of SHIFT
European Journal of Heart Failure, 2016Co-Authors: Michel Komajda, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, Karl Swedberg, Aurelie Moyne, Ian FordAbstract:Aims: During the post-discharge phase following a heart failure hospitalization (HFH), patients are at high risk of early readmission despite standard of care therapy. We examined the impact of chronic exposure to Ivabradine on early readmissions in patients hospitalized for heart failure during the course of the SHIFT study (Systolic Heart Failure treatment with the If inhibitor Ivabradine Trial). Methods and results: A total of 1186 of the 6505 randomized patients experienced at least one HFH during the study, and had a more severe profile than those without HFH. Of these 1186 patients, 334 patients (28%) were rehospitalized within 3 months for any reason, mostly for cardiovascular causes (86%), including HFH (61%). Ivabradine was associated with fewer all-cause hospitalizations at 1 month [incidence rate ratio (IRR) 0.70, 95% confidence interval (CI) 0.50–1.00, P < 0.05], 2 months (IRR 0.75, 95% CI 0.58–0.98, P = 0.03), and 3 months (IRR 0.79, 95% CI 0.63–0.99, P = 0.04). A trend for a reduction in cardiovascular and HF hospitalizations was also observed in Ivabradine-treated patients. Conclusion: We demonstrate in this post-hoc analysis that chronic exposure to Ivabradine reduces the incidence of all-cause hospitalizations during the vulnerable phase after a HFH. Further studies are needed to investigate if in-hospital or early post-discharge initiation of Ivabradine could be useful to improve early outcomes in patients hospitalized for HF.
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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
American Journal of Cardiology, 2015Co-Authors: Michael Bohm, Christoph Maack, Ian Ford, Jeffrey S Borer, Michel Komajda, Mitja Lainscak, Karl Swedberg, Michele Robertson, Ingrid Kindermann, Luigi TavazziAbstract: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 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.
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twenty four hour heart rate lowering with Ivabradine in chronic heart failure insights from the shift holter substudy
European Journal of Heart Failure, 2015Co-Authors: Michael Bohm, Ian Ford, Jeffrey S Borer, John Camm, Suzanne M Lloyd, Michel Komajda, Luigi Tavazzi, Mario Talajic, Mitja Lainscak, Janchristian ReilAbstract:Aims Analysis of 24-h Holter recordings was a pre-specified substudy of SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) for exploring the heart rhythm safety of Ivabradine and to determine effects of Ivabradine on 24-h, daytime, and night-time heart rate (HR) compared with resting office HR. Methods and results The 24-h Holter monitoring was performed at baseline and 8 months after randomization to Ivabradine (n = 298) or matching placebo (n = 304) titrated maximally to 7.5 mg b.i.d. in patients with baseline HR ≥70 b.p.m. Patients received guideline-based optimized heart failure therapy including ACE inhibitors and/or ARBs in 93% and beta-blockers at maximally tolerated doses in 93%. After 8 months, HR over 24 h decreased by 9.5 ± 10.0 b.p.m. with Ivabradine, from 75.4 ± 10.3 b.p.m. (P 2.5 s on Ivabradine vs. 4 (1.6%) patients on placebo. No RR intervals >3 s were identified in patients taking Ivabradine. Conclusion Ivabradine safely and significantly lowers HR and improves HR variability in patients with systolic heart failure, without inducing significant bradycardia, ventricular arrhythmias, or supraventricular arrhythmias.
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selective heart rate reduction with Ivabradine unloads the left ventricle in heart failure patients
Journal of the American College of Cardiology, 2013Co-Authors: Janchristia Reil, Suzanne M Lloyd, Michel Komajda, Luigi Tavazzi, Jeanclaude Tardif, Karl Swedberg, Ia Ford, Eilee Omeara, Jeffrey S Ore, Michael OhmAbstract:Objectives The study aimed to determine whether isolated heart rate (HR) reduction with Ivabradine reduces afterload of patients with systolic heart failure. Background The effective arterial elastance (Ea) represents resistive and pulsatile afterload of the heart derived from the pressure volume relation. HR modulates Ea, and, therefore, afterload burden. Methods Among the patients with systolic heart failure (ejection fraction ≤35%) randomized to either placebo or Ivabradine in the SHIFT (Systolic Heart Failure Treatment With the I f Inhibitor Ivabradine Trial), 275 patients (n = 132, placebo; n = 143, Ivabradine 7.5 mg twice a day) were included in the echocardiographic substudy. Ea, total arterial compliance (TAC), and end-systolic elastance (Ees) were calculated at baseline and after 8 months of treatment. Blood pressure was measured by arm cuff; stroke volume (SV), ejection fraction, and end-diastolic volume were assessed by echocardiography. Results At baseline Ea, TAC, HR, and Ees did not differ significantly between Ivabradine- and placebo-treated patients. After 8 months of treatment, HR was significantly reduced in the Ivabradine group (p Conclusions Isolated HR reduction by Ivabradine improves TAC, thus reducing Ea. Because Ees is unaltered, improved ventricular-arterial coupling is responsible for increased SV. Therefore, unloading of the heart may contribute to the beneficial effect of isolated HR reduction in patients with systolic heart failure. (Systolic Heart Failure Treatment With the I f Inhibitor Ivabradine Trial [SHIFT]; ISRCTN70429960 )
Jeffrey S Borer - One of the best experts on this subject based on the ideXlab platform.
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duration of chronic heart failure affects outcomes with preserved effects of heart rate reduction with Ivabradine findings from shift
European Journal of Heart Failure, 2018Co-Authors: Michael Bohm, Christoph Maack, Ian Ford, Jeffrey S Borer, Luigi Tavazzi, Karl Swedberg, M Komajda, Aurelie MoyneAbstract:Aims In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with Ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization. Methods and results It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of ≤35%), in sinus rhythm, heart rate of ≥70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or Ivabradine. Outcomes and the treatment effect of Ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 Ivabradine and 1459 placebo patients had HF duration of ≥4 weeks and <1.5 years; 836 Ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 Ivabradine and 999 placebo patients had HF duration of ≥4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs. 4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of Ivabradine were independent of HF duration. Conclusions Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with Ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials.
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Chronic exposure to Ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post-hoc analysis of SHIFT
European Journal of Heart Failure, 2016Co-Authors: Michel Komajda, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, Karl Swedberg, Aurelie Moyne, Ian FordAbstract:Aims: During the post-discharge phase following a heart failure hospitalization (HFH), patients are at high risk of early readmission despite standard of care therapy. We examined the impact of chronic exposure to Ivabradine on early readmissions in patients hospitalized for heart failure during the course of the SHIFT study (Systolic Heart Failure treatment with the If inhibitor Ivabradine Trial). Methods and results: A total of 1186 of the 6505 randomized patients experienced at least one HFH during the study, and had a more severe profile than those without HFH. Of these 1186 patients, 334 patients (28%) were rehospitalized within 3 months for any reason, mostly for cardiovascular causes (86%), including HFH (61%). Ivabradine was associated with fewer all-cause hospitalizations at 1 month [incidence rate ratio (IRR) 0.70, 95% confidence interval (CI) 0.50–1.00, P < 0.05], 2 months (IRR 0.75, 95% CI 0.58–0.98, P = 0.03), and 3 months (IRR 0.79, 95% CI 0.63–0.99, P = 0.04). A trend for a reduction in cardiovascular and HF hospitalizations was also observed in Ivabradine-treated patients. Conclusion: We demonstrate in this post-hoc analysis that chronic exposure to Ivabradine reduces the incidence of all-cause hospitalizations during the vulnerable phase after a HFH. Further studies are needed to investigate if in-hospital or early post-discharge initiation of Ivabradine could be useful to improve early outcomes in patients hospitalized for HF.
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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
American Journal of Cardiology, 2015Co-Authors: Michael Bohm, Christoph Maack, Ian Ford, Jeffrey S Borer, Michel Komajda, Mitja Lainscak, Karl Swedberg, Michele Robertson, Ingrid Kindermann, Luigi TavazziAbstract: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 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.
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twenty four hour heart rate lowering with Ivabradine in chronic heart failure insights from the shift holter substudy
European Journal of Heart Failure, 2015Co-Authors: Michael Bohm, Ian Ford, Jeffrey S Borer, John Camm, Suzanne M Lloyd, Michel Komajda, Luigi Tavazzi, Mario Talajic, Mitja Lainscak, Janchristian ReilAbstract:Aims Analysis of 24-h Holter recordings was a pre-specified substudy of SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) for exploring the heart rhythm safety of Ivabradine and to determine effects of Ivabradine on 24-h, daytime, and night-time heart rate (HR) compared with resting office HR. Methods and results The 24-h Holter monitoring was performed at baseline and 8 months after randomization to Ivabradine (n = 298) or matching placebo (n = 304) titrated maximally to 7.5 mg b.i.d. in patients with baseline HR ≥70 b.p.m. Patients received guideline-based optimized heart failure therapy including ACE inhibitors and/or ARBs in 93% and beta-blockers at maximally tolerated doses in 93%. After 8 months, HR over 24 h decreased by 9.5 ± 10.0 b.p.m. with Ivabradine, from 75.4 ± 10.3 b.p.m. (P 2.5 s on Ivabradine vs. 4 (1.6%) patients on placebo. No RR intervals >3 s were identified in patients taking Ivabradine. Conclusion Ivabradine safely and significantly lowers HR and improves HR variability in patients with systolic heart failure, without inducing significant bradycardia, ventricular arrhythmias, or supraventricular arrhythmias.
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efficacy and safety of Ivabradine in chronic heart failure across the age spectrum insights from the shift study
European Journal of Heart Failure, 2013Co-Authors: Luigi Tavazzi, Michael Bohm, Jeffrey S Borer, Michel Komajda, Mitja Lainscak, Karl Swedberg, Ian FordAbstract:Aims To test whether the efficacy and safety of the selective heart rate-reducing agent Ivabradine changes according to age in chronic heart failure (HF) patients. Methods and results The Ivabradine and placebo arms of SHIFT, which enrolled 6505 chronic HF patients, were combined and age distribution was divided by quartiles to give four groups (<53 years, n = 1522; 53 to <60 years, n = 1521; 60 to <69 years, n = 1750; and ≥69 years, n = 1712). The effects of Ivabradine on cardiovascular outcomes, changes in heart rate, and adverse events, particularly bradycardia, were evaluated according to age group. A subgroup (602 patients) underwent 24 h ambulatory ECG Holter monitoring. The relative risk of the primary endpoint (cardiovascular death or hospitalization for worsening HF) was reduced by Ivabradine in all age groups, ranging from 38% [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.50–0.78, P < 0.001] in the youngest patients <53 years to 16% (HR 0.84, 95% CI 0.71–0.99, P = 0.035) in the oldest patients ≥69 years. Ivabradine up-titration reduced heart rate similarly in all age groups, by 11 b.p.m. As anticipated, bradycardia and phosphenes occurred more frequently with Ivabradine, at a similar rate whatever the age. In the Holter substudy, there were no episodes of severe bradycardia and no clinically relevant pauses with Ivabradine in any age group. Conclusions Age does not limit the appropriate use of Ivabradine in patients with chronic HF and systolic dysfunction. The safety and efficacy of Ivabradine are comparable across all age groups.
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effect of Ivabradine in patients with heart failure with preserved ejection fraction the edify randomized placebo controlled trial
European Journal of Heart Failure, 2017Co-Authors: Michel Komajda, Piotr Ponikowski, Richard Isnard, Alain Cohensolal, Marco Metra, Burkert Pieske, Adriaan A Voors, Fabienne Dominjon, Cecile Henongoburdhun, Matthieu PannauxAbstract:Aims This randomized, double-blind, placebo-controlled trial assessed whether heart rate (HR) reduction with Ivabradine improves cardiac function in heart failure with preserved ejection fraction (HFpEF). Methods and results The prEserveD left ventricular ejectIon fraction chronic heart Failure with Ivabradine studY (EDIFY) included 179 patients in New York Heart Association (NYHA) classes II and III, in sinus rhythm, with HR of ≥70 b.p.m., NT-proBNP of ≥220 pg/mL (BNP ≥80 pg/mL) and left ventricular ejection fraction of ≥45%. Ivabradine (or placebo) was titrated to 7.5 mg b.i.d. Patients were followed for 8 months on the change and assessed for three co-primary endpoints: echo-Doppler E/e′ ratio, distance on the 6-min walking test (6MWT), and plasma NT-proBNP concentration. At baseline, median E/e′ was 12.8 [interquartile range (IQR): 9.9–16.3], median distance on the 6MWT was 320 m (IQR: 247–375 m), and median NT-proBNP was 375 pg/mL (IQR: 253–701 pg/mL). Baseline median HR was 75 b.p.m. (IQR: 70–107 b.p.m.). A total of 171 patients (87 in the Ivabradine group, 84 in the placebo group) were evaluated for treatment efficacy. After 8 months of treatment, findings showed a median change in HR of −13.0 b.p.m. (IQR: −18.0 to −6.0 b.p.m.) in the Ivabradine group and −3.5 b.p.m. (IQR: −11.5 to 3.0 b.p.m.) in the placebo group [estimated between-group difference: 7.7 b.p.m.; 90% confidence interval (CI) −10 to −5.4; P < 0.0001]. No evidence of improvement was found in any of the three co-primary endpoints. There was almost no change in median E/e′ in either of the two groups [median change: +1.0 (IQR: −0.8 to 2.9) in the Ivabradine group; −0.6 (IQR: −2.2 to 1.4) in the placebo group; estimated between-group difference: 1.4, 90% CI 0.3–2.5; P = 0.135]. There were no meaningful changes in the other co-primary endpoints and no apparent trends. There was no significant safety concern. Conclusions In patients with HFpEF, HR reduction with Ivabradine did not improve outcomes. These findings do not support the use of Ivabradine in HFpEF.
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Chronic exposure to Ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post-hoc analysis of SHIFT
European Journal of Heart Failure, 2016Co-Authors: Michel Komajda, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, Karl Swedberg, Aurelie Moyne, Ian FordAbstract:Aims: During the post-discharge phase following a heart failure hospitalization (HFH), patients are at high risk of early readmission despite standard of care therapy. We examined the impact of chronic exposure to Ivabradine on early readmissions in patients hospitalized for heart failure during the course of the SHIFT study (Systolic Heart Failure treatment with the If inhibitor Ivabradine Trial). Methods and results: A total of 1186 of the 6505 randomized patients experienced at least one HFH during the study, and had a more severe profile than those without HFH. Of these 1186 patients, 334 patients (28%) were rehospitalized within 3 months for any reason, mostly for cardiovascular causes (86%), including HFH (61%). Ivabradine was associated with fewer all-cause hospitalizations at 1 month [incidence rate ratio (IRR) 0.70, 95% confidence interval (CI) 0.50–1.00, P < 0.05], 2 months (IRR 0.75, 95% CI 0.58–0.98, P = 0.03), and 3 months (IRR 0.79, 95% CI 0.63–0.99, P = 0.04). A trend for a reduction in cardiovascular and HF hospitalizations was also observed in Ivabradine-treated patients. Conclusion: We demonstrate in this post-hoc analysis that chronic exposure to Ivabradine reduces the incidence of all-cause hospitalizations during the vulnerable phase after a HFH. Further studies are needed to investigate if in-hospital or early post-discharge initiation of Ivabradine could be useful to improve early outcomes in patients hospitalized for HF.
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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
American Journal of Cardiology, 2015Co-Authors: Michael Bohm, Christoph Maack, Ian Ford, Jeffrey S Borer, Michel Komajda, Mitja Lainscak, Karl Swedberg, Michele Robertson, Ingrid Kindermann, Luigi TavazziAbstract: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 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.
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twenty four hour heart rate lowering with Ivabradine in chronic heart failure insights from the shift holter substudy
European Journal of Heart Failure, 2015Co-Authors: Michael Bohm, Ian Ford, Jeffrey S Borer, John Camm, Suzanne M Lloyd, Michel Komajda, Luigi Tavazzi, Mario Talajic, Mitja Lainscak, Janchristian ReilAbstract:Aims Analysis of 24-h Holter recordings was a pre-specified substudy of SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) for exploring the heart rhythm safety of Ivabradine and to determine effects of Ivabradine on 24-h, daytime, and night-time heart rate (HR) compared with resting office HR. Methods and results The 24-h Holter monitoring was performed at baseline and 8 months after randomization to Ivabradine (n = 298) or matching placebo (n = 304) titrated maximally to 7.5 mg b.i.d. in patients with baseline HR ≥70 b.p.m. Patients received guideline-based optimized heart failure therapy including ACE inhibitors and/or ARBs in 93% and beta-blockers at maximally tolerated doses in 93%. After 8 months, HR over 24 h decreased by 9.5 ± 10.0 b.p.m. with Ivabradine, from 75.4 ± 10.3 b.p.m. (P 2.5 s on Ivabradine vs. 4 (1.6%) patients on placebo. No RR intervals >3 s were identified in patients taking Ivabradine. Conclusion Ivabradine safely and significantly lowers HR and improves HR variability in patients with systolic heart failure, without inducing significant bradycardia, ventricular arrhythmias, or supraventricular arrhythmias.
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selective heart rate reduction with Ivabradine unloads the left ventricle in heart failure patients
Journal of the American College of Cardiology, 2013Co-Authors: Janchristia Reil, Suzanne M Lloyd, Michel Komajda, Luigi Tavazzi, Jeanclaude Tardif, Karl Swedberg, Ia Ford, Eilee Omeara, Jeffrey S Ore, Michael OhmAbstract:Objectives The study aimed to determine whether isolated heart rate (HR) reduction with Ivabradine reduces afterload of patients with systolic heart failure. Background The effective arterial elastance (Ea) represents resistive and pulsatile afterload of the heart derived from the pressure volume relation. HR modulates Ea, and, therefore, afterload burden. Methods Among the patients with systolic heart failure (ejection fraction ≤35%) randomized to either placebo or Ivabradine in the SHIFT (Systolic Heart Failure Treatment With the I f Inhibitor Ivabradine Trial), 275 patients (n = 132, placebo; n = 143, Ivabradine 7.5 mg twice a day) were included in the echocardiographic substudy. Ea, total arterial compliance (TAC), and end-systolic elastance (Ees) were calculated at baseline and after 8 months of treatment. Blood pressure was measured by arm cuff; stroke volume (SV), ejection fraction, and end-diastolic volume were assessed by echocardiography. Results At baseline Ea, TAC, HR, and Ees did not differ significantly between Ivabradine- and placebo-treated patients. After 8 months of treatment, HR was significantly reduced in the Ivabradine group (p Conclusions Isolated HR reduction by Ivabradine improves TAC, thus reducing Ea. Because Ees is unaltered, improved ventricular-arterial coupling is responsible for increased SV. Therefore, unloading of the heart may contribute to the beneficial effect of isolated HR reduction in patients with systolic heart failure. (Systolic Heart Failure Treatment With the I f Inhibitor Ivabradine Trial [SHIFT]; ISRCTN70429960 )
