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Karl Swedberg - One of the best experts on this subject based on the ideXlab platform.
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visit to visit blood pressure variation and outcomes in Heart Failure with reduced ejection fraction findings from the eplerenone in patients with Systolic Heart Failure and mild symptoms trial
Journal of Hypertension, 2020Co-Authors: Luca Monzo, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Michael Bohm, Bertram Pitt, Joao Pedro Ferreira, Paula Abreu, A Szumski, Nicolas GirerdAbstract:BACKGROUND Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with Heart Failure and reduced ejection fraction and the effect of eplerenone on BPV. METHODS AND RESULTS We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or Heart Failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62-2.51), P < 0.001]. The relationship between SBP-CoV and outcomes was not modified by eplerenone (P value for interaction = 0.48). An interaction was detected between mean SBP and SBP-CoV for the primary outcome (P = 0.048) and for HFH (P = 0.018). The effect modification was slight, but lower SBP-CoV was associated with worse outcomes in patients with both low and high SBP, while this interaction was less clear for patients with SBP in the 'normal' range. CONCLUSION In our patients with Heart Failure and reduced ejection fraction and mild symptoms, both a lower and higher SBP-CoV were associated with worse outcomes. SBP-CoV did not modify the benefit of eplerenone. Further studies are warranted to clarify the role of BPV in Heart Failure. CLINICALTRIALS. GOV IDENTIFIER NCT00232180.
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aspirin does not reduce the clinical benefits of the mineralocorticoid receptor antagonist eplerenone in patients with Systolic Heart Failure and mild symptoms an analysis of the emphasis hf study
European Journal of Heart Failure, 2016Co-Authors: Ken Lee Chin, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, T Collier, Eva TurgonyiAbstract:AimsIt is not known whether concomitant use of aspirin might attenuate the beneficial effects of mineralocorticoid receptor antagonists (MRAs). The purpose of this subgroup analysis was to explore the interaction between baseline aspirin treatment and the effect of eplerenone on the primary efficacy outcomes (composite of hospitalization for Heart Failure or cardiovascular mortality), its components, and safety markers [estimated glomerular filtration rate (eGFR), Systolic blood pressure (SBP), and serum potassium >5.5mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). Methods and resultsPatients with chronic Heart Failure, reduced ejection fraction (HFREF), and mild symptoms were enrolled in EMPHASIS-HF. We evaluated baseline characteristics according to aspirin use. We explored the interaction between aspirin and eplerenone, using Cox proportional hazards models providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) and P-values for interaction. Of the 2737 patients randomized, 1605 patients (58.6%) were taking aspirin. The beneficial effects of eplerenone on the primary endpoint were similar in patients not treated (adjusted HR 0.59, 95% CI 0.46-0.75) or treated (adjusted HR 0.71, 95% CI 0.59-0.87) with aspirin at baseline (interaction P-value=0.19). We did not observe any significant modification of the safety markers by aspirin that was clinically meaningful. ConclusionAspirin use in patients with chronic Systolic Heart Failure and mild symptoms did not substantially reduce the overall beneficial effects of the MRA eplerenone contrary to what has been described in some studies with ACE inhibitors.
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effect of visit to visit variation of Heart rate and Systolic blood pressure on outcomes in chronic Systolic Heart Failure results from the Systolic Heart Failure treatment with the if inhibitor ivabradine trial shift trial
Journal of the American Heart Association, 2016Co-Authors: Michael Bohm, Ian Ford, Karl Swedberg, Jeffrey S Borer, Michel Komajda, Michele Robertson, Felix Mahfoud, Sebastian Ewen, Luigi TavazziAbstract:Background Elevated resting Heart rate (HR) and low Systolic blood pressure (SBP) are related to poor outcomes in Heart Failure (HF). The association between visit‐to‐visit variation in SBP and HR and risk in HF is unknown. Methods and Results In Systolic Heart Failure Treatment with the I f inhibitor ivabradine Trial (SHIFT) patients, we evaluated relationships between mean HR, mean SBP, and visit‐to‐visit variations (coefficient of variation [CV]=SD/mean×100%) in SBP and HR (SBP‐CV and HR‐CV, respectively) and primary composite endpoint (cardiovascular mortality or HF hospitalization), its components, all‐cause mortality, and all‐cause hospitalization. High HR and low SBP were closely associated with risk for primary endpoint, all‐cause mortality, and HF hospitalization. The highest number of primary endpoint events occurred in the highest HR tertile (38.8% vs 16.4% lowest tertile; P <0.001). For HR‐CV, patients at highest risk were those in the lowest tertile. Patients in the lowest thirds of mean SBP and SBP‐CV had the highest risk. The combination of high HR and low HR‐CV had an additive deleterious effect on risk, as did that of low SBP and low SBP‐CV. Ivabradine reduced mean HR and increased HR‐CV, and increased SBP and SBP‐CV slightly. Conclusions Beyond high HR and low SBP, low HR‐CV and low SBP‐CV are predictors of cardiovascular outcomes with additive effects on risk in HF, but with an unknown effect size. Beyond HR reduction, ivabradine increases HR‐CV. Low visit‐to‐visit variation of HR and SBP might signal risk of cardiovascular outcomes in Systolic HF. Clinical Trial Registration URL: . Unique identifier: ISRCTN70429960.
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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, Karl Swedberg, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, 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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efficacy and safety of ivabradine in patients with chronic Systolic Heart Failure and diabetes an analysis from the shift trial
European Journal of Heart Failure, 2015Co-Authors: Michel Komajda, Ian Ford, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, Bernard Francq, Karl SwedbergAbstract:Aims: To evaluate clinical profiles and outcomes in patients with Systolic Heart Failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (Heart rate-lowering agent) with respect to diabetic status. Methods and results: This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with Systolic HF, left ventricular ejection fraction ≤35%, and resting Heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07–1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13–1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23–1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68–0.94 and HR 0.84, 95% CI, 0.75–0.95, respectively; interaction P was non-significant) vs. placebo. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo. Conclusions: Comorbid diabetes in chronic HF worsens the prognosis of Systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients.
Luigi Tavazzi - One of the best experts on this subject based on the ideXlab platform.
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effect of visit to visit variation of Heart rate and Systolic blood pressure on outcomes in chronic Systolic Heart Failure results from the Systolic Heart Failure treatment with the if inhibitor ivabradine trial shift trial
Journal of the American Heart Association, 2016Co-Authors: Michael Bohm, Ian Ford, Karl Swedberg, Jeffrey S Borer, Michel Komajda, Michele Robertson, Felix Mahfoud, Sebastian Ewen, Luigi TavazziAbstract:Background Elevated resting Heart rate (HR) and low Systolic blood pressure (SBP) are related to poor outcomes in Heart Failure (HF). The association between visit‐to‐visit variation in SBP and HR and risk in HF is unknown. Methods and Results In Systolic Heart Failure Treatment with the I f inhibitor ivabradine Trial (SHIFT) patients, we evaluated relationships between mean HR, mean SBP, and visit‐to‐visit variations (coefficient of variation [CV]=SD/mean×100%) in SBP and HR (SBP‐CV and HR‐CV, respectively) and primary composite endpoint (cardiovascular mortality or HF hospitalization), its components, all‐cause mortality, and all‐cause hospitalization. High HR and low SBP were closely associated with risk for primary endpoint, all‐cause mortality, and HF hospitalization. The highest number of primary endpoint events occurred in the highest HR tertile (38.8% vs 16.4% lowest tertile; P <0.001). For HR‐CV, patients at highest risk were those in the lowest tertile. Patients in the lowest thirds of mean SBP and SBP‐CV had the highest risk. The combination of high HR and low HR‐CV had an additive deleterious effect on risk, as did that of low SBP and low SBP‐CV. Ivabradine reduced mean HR and increased HR‐CV, and increased SBP and SBP‐CV slightly. Conclusions Beyond high HR and low SBP, low HR‐CV and low SBP‐CV are predictors of cardiovascular outcomes with additive effects on risk in HF, but with an unknown effect size. Beyond HR reduction, ivabradine increases HR‐CV. Low visit‐to‐visit variation of HR and SBP might signal risk of cardiovascular outcomes in Systolic HF. Clinical Trial Registration URL: . Unique identifier: ISRCTN70429960.
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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, Karl Swedberg, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, 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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efficacy and safety of ivabradine in patients with chronic Systolic Heart Failure and diabetes an analysis from the shift trial
European Journal of Heart Failure, 2015Co-Authors: Michel Komajda, Ian Ford, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, Bernard Francq, Karl SwedbergAbstract:Aims: To evaluate clinical profiles and outcomes in patients with Systolic Heart Failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (Heart rate-lowering agent) with respect to diabetic status. Methods and results: This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with Systolic HF, left ventricular ejection fraction ≤35%, and resting Heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07–1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13–1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23–1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68–0.94 and HR 0.84, 95% CI, 0.75–0.95, respectively; interaction P was non-significant) vs. placebo. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo. Conclusions: Comorbid diabetes in chronic HF worsens the prognosis of Systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients.
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beta blocker dosage and use over time in the Systolic Heart Failure treatment with the if inhibitor ivabradine trial shift study
Journal of the American College of Cardiology, 2015Co-Authors: Jeffrey S Borer, Ian Ford, Karl Swedberg, Michel Komajda, Luigi Tavazzi, Michael Boehm, Fabienne Dominjon, Juan Maya, Yuna WuAbstract:In the SHIFT study, ivabradine, a novel selective inhibitor of the cardiac pacemaker f-current (If) that lowers Heart rate, showed significant reduction in cardiovascular mortality or hospitalizations for worsening Heart Failure vs placebo in patients with chronic Systolic Heart Failure, when added
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efficacy and safety of ivabradine in patients with severe chronic Systolic Heart Failure from the shift study
American Journal of Cardiology, 2014Co-Authors: Jeffrey S Borer, Ian Ford, Michael Bohm, Michel Komajda, Luigi Tavazzi, Michele Robertson, Karl SwedbergAbstract:A post hoc analysis of Systolic Heart Failure treatment with the I f inhibitor ivabradine Trial (SHIFT) explored the efficacy and safety of ivabradine in severe Heart Failure (HF) as denoted by left ventricular ejection fraction (LVEF) ≤20% and/or New York Heart Association (NYHA) class IV. The SHIFT population (LVEF ≤35%, Heart rate ≥70 beats/min, and sinus rhythm) comprised 712 patients with severe (defined previously) and 5,973 with less severe (NYHA classes II or III and LVEF >20%) HF, all randomized to ivabradine or placebo on a background of guideline-defined standard care. The rate of primary composite end point of cardiovascular death or HF hospitalization with placebo was higher in severe (42%) than less severe (27%) HF (p
Michel Komajda - One of the best experts on this subject based on the ideXlab platform.
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effect of visit to visit variation of Heart rate and Systolic blood pressure on outcomes in chronic Systolic Heart Failure results from the Systolic Heart Failure treatment with the if inhibitor ivabradine trial shift trial
Journal of the American Heart Association, 2016Co-Authors: Michael Bohm, Ian Ford, Karl Swedberg, Jeffrey S Borer, Michel Komajda, Michele Robertson, Felix Mahfoud, Sebastian Ewen, Luigi TavazziAbstract:Background Elevated resting Heart rate (HR) and low Systolic blood pressure (SBP) are related to poor outcomes in Heart Failure (HF). The association between visit‐to‐visit variation in SBP and HR and risk in HF is unknown. Methods and Results In Systolic Heart Failure Treatment with the I f inhibitor ivabradine Trial (SHIFT) patients, we evaluated relationships between mean HR, mean SBP, and visit‐to‐visit variations (coefficient of variation [CV]=SD/mean×100%) in SBP and HR (SBP‐CV and HR‐CV, respectively) and primary composite endpoint (cardiovascular mortality or HF hospitalization), its components, all‐cause mortality, and all‐cause hospitalization. High HR and low SBP were closely associated with risk for primary endpoint, all‐cause mortality, and HF hospitalization. The highest number of primary endpoint events occurred in the highest HR tertile (38.8% vs 16.4% lowest tertile; P <0.001). For HR‐CV, patients at highest risk were those in the lowest tertile. Patients in the lowest thirds of mean SBP and SBP‐CV had the highest risk. The combination of high HR and low HR‐CV had an additive deleterious effect on risk, as did that of low SBP and low SBP‐CV. Ivabradine reduced mean HR and increased HR‐CV, and increased SBP and SBP‐CV slightly. Conclusions Beyond high HR and low SBP, low HR‐CV and low SBP‐CV are predictors of cardiovascular outcomes with additive effects on risk in HF, but with an unknown effect size. Beyond HR reduction, ivabradine increases HR‐CV. Low visit‐to‐visit variation of HR and SBP might signal risk of cardiovascular outcomes in Systolic HF. Clinical Trial Registration URL: . Unique identifier: ISRCTN70429960.
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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, Karl Swedberg, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, 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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efficacy and safety of ivabradine in patients with chronic Systolic Heart Failure and diabetes an analysis from the shift trial
European Journal of Heart Failure, 2015Co-Authors: Michel Komajda, Ian Ford, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, Bernard Francq, Karl SwedbergAbstract:Aims: To evaluate clinical profiles and outcomes in patients with Systolic Heart Failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (Heart rate-lowering agent) with respect to diabetic status. Methods and results: This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with Systolic HF, left ventricular ejection fraction ≤35%, and resting Heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07–1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13–1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23–1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68–0.94 and HR 0.84, 95% CI, 0.75–0.95, respectively; interaction P was non-significant) vs. placebo. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo. Conclusions: Comorbid diabetes in chronic HF worsens the prognosis of Systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients.
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beta blocker dosage and use over time in the Systolic Heart Failure treatment with the if inhibitor ivabradine trial shift study
Journal of the American College of Cardiology, 2015Co-Authors: Jeffrey S Borer, Ian Ford, Karl Swedberg, Michel Komajda, Luigi Tavazzi, Michael Boehm, Fabienne Dominjon, Juan Maya, Yuna WuAbstract:In the SHIFT study, ivabradine, a novel selective inhibitor of the cardiac pacemaker f-current (If) that lowers Heart rate, showed significant reduction in cardiovascular mortality or hospitalizations for worsening Heart Failure vs placebo in patients with chronic Systolic Heart Failure, when added
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efficacy and safety of ivabradine in patients with severe chronic Systolic Heart Failure from the shift study
American Journal of Cardiology, 2014Co-Authors: Jeffrey S Borer, Ian Ford, Michael Bohm, Michel Komajda, Luigi Tavazzi, Michele Robertson, Karl SwedbergAbstract:A post hoc analysis of Systolic Heart Failure treatment with the I f inhibitor ivabradine Trial (SHIFT) explored the efficacy and safety of ivabradine in severe Heart Failure (HF) as denoted by left ventricular ejection fraction (LVEF) ≤20% and/or New York Heart Association (NYHA) class IV. The SHIFT population (LVEF ≤35%, Heart rate ≥70 beats/min, and sinus rhythm) comprised 712 patients with severe (defined previously) and 5,973 with less severe (NYHA classes II or III and LVEF >20%) HF, all randomized to ivabradine or placebo on a background of guideline-defined standard care. The rate of primary composite end point of cardiovascular death or HF hospitalization with placebo was higher in severe (42%) than less severe (27%) HF (p
Michael Bohm - One of the best experts on this subject based on the ideXlab platform.
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visit to visit blood pressure variation and outcomes in Heart Failure with reduced ejection fraction findings from the eplerenone in patients with Systolic Heart Failure and mild symptoms trial
Journal of Hypertension, 2020Co-Authors: Luca Monzo, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Michael Bohm, Bertram Pitt, Joao Pedro Ferreira, Paula Abreu, A Szumski, Nicolas GirerdAbstract:BACKGROUND Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with Heart Failure and reduced ejection fraction and the effect of eplerenone on BPV. METHODS AND RESULTS We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or Heart Failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62-2.51), P < 0.001]. The relationship between SBP-CoV and outcomes was not modified by eplerenone (P value for interaction = 0.48). An interaction was detected between mean SBP and SBP-CoV for the primary outcome (P = 0.048) and for HFH (P = 0.018). The effect modification was slight, but lower SBP-CoV was associated with worse outcomes in patients with both low and high SBP, while this interaction was less clear for patients with SBP in the 'normal' range. CONCLUSION In our patients with Heart Failure and reduced ejection fraction and mild symptoms, both a lower and higher SBP-CoV were associated with worse outcomes. SBP-CoV did not modify the benefit of eplerenone. Further studies are warranted to clarify the role of BPV in Heart Failure. CLINICALTRIALS. GOV IDENTIFIER NCT00232180.
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effect of visit to visit variation of Heart rate and Systolic blood pressure on outcomes in chronic Systolic Heart Failure results from the Systolic Heart Failure treatment with the if inhibitor ivabradine trial shift trial
Journal of the American Heart Association, 2016Co-Authors: Michael Bohm, Ian Ford, Karl Swedberg, Jeffrey S Borer, Michel Komajda, Michele Robertson, Felix Mahfoud, Sebastian Ewen, Luigi TavazziAbstract:Background Elevated resting Heart rate (HR) and low Systolic blood pressure (SBP) are related to poor outcomes in Heart Failure (HF). The association between visit‐to‐visit variation in SBP and HR and risk in HF is unknown. Methods and Results In Systolic Heart Failure Treatment with the I f inhibitor ivabradine Trial (SHIFT) patients, we evaluated relationships between mean HR, mean SBP, and visit‐to‐visit variations (coefficient of variation [CV]=SD/mean×100%) in SBP and HR (SBP‐CV and HR‐CV, respectively) and primary composite endpoint (cardiovascular mortality or HF hospitalization), its components, all‐cause mortality, and all‐cause hospitalization. High HR and low SBP were closely associated with risk for primary endpoint, all‐cause mortality, and HF hospitalization. The highest number of primary endpoint events occurred in the highest HR tertile (38.8% vs 16.4% lowest tertile; P <0.001). For HR‐CV, patients at highest risk were those in the lowest tertile. Patients in the lowest thirds of mean SBP and SBP‐CV had the highest risk. The combination of high HR and low HR‐CV had an additive deleterious effect on risk, as did that of low SBP and low SBP‐CV. Ivabradine reduced mean HR and increased HR‐CV, and increased SBP and SBP‐CV slightly. Conclusions Beyond high HR and low SBP, low HR‐CV and low SBP‐CV are predictors of cardiovascular outcomes with additive effects on risk in HF, but with an unknown effect size. Beyond HR reduction, ivabradine increases HR‐CV. Low visit‐to‐visit variation of HR and SBP might signal risk of cardiovascular outcomes in Systolic HF. Clinical Trial Registration URL: . Unique identifier: ISRCTN70429960.
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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, Karl Swedberg, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, 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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efficacy and safety of ivabradine in patients with chronic Systolic Heart Failure and diabetes an analysis from the shift trial
European Journal of Heart Failure, 2015Co-Authors: Michel Komajda, Ian Ford, Michael Bohm, Jeffrey S Borer, Luigi Tavazzi, Bernard Francq, Karl SwedbergAbstract:Aims: To evaluate clinical profiles and outcomes in patients with Systolic Heart Failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (Heart rate-lowering agent) with respect to diabetic status. Methods and results: This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with Systolic HF, left ventricular ejection fraction ≤35%, and resting Heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07–1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13–1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23–1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68–0.94 and HR 0.84, 95% CI, 0.75–0.95, respectively; interaction P was non-significant) vs. placebo. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo. Conclusions: Comorbid diabetes in chronic HF worsens the prognosis of Systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients.
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efficacy and safety of ivabradine in patients with severe chronic Systolic Heart Failure from the shift study
American Journal of Cardiology, 2014Co-Authors: Jeffrey S Borer, Ian Ford, Michael Bohm, Michel Komajda, Luigi Tavazzi, Michele Robertson, Karl SwedbergAbstract:A post hoc analysis of Systolic Heart Failure treatment with the I f inhibitor ivabradine Trial (SHIFT) explored the efficacy and safety of ivabradine in severe Heart Failure (HF) as denoted by left ventricular ejection fraction (LVEF) ≤20% and/or New York Heart Association (NYHA) class IV. The SHIFT population (LVEF ≤35%, Heart rate ≥70 beats/min, and sinus rhythm) comprised 712 patients with severe (defined previously) and 5,973 with less severe (NYHA classes II or III and LVEF >20%) HF, all randomized to ivabradine or placebo on a background of guideline-defined standard care. The rate of primary composite end point of cardiovascular death or HF hospitalization with placebo was higher in severe (42%) than less severe (27%) HF (p
John J V Mcmurray - One of the best experts on this subject based on the ideXlab platform.
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visit to visit blood pressure variation and outcomes in Heart Failure with reduced ejection fraction findings from the eplerenone in patients with Systolic Heart Failure and mild symptoms trial
Journal of Hypertension, 2020Co-Authors: Luca Monzo, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Michael Bohm, Bertram Pitt, Joao Pedro Ferreira, Paula Abreu, A Szumski, Nicolas GirerdAbstract:BACKGROUND Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with Heart Failure and reduced ejection fraction and the effect of eplerenone on BPV. METHODS AND RESULTS We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or Heart Failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62-2.51), P < 0.001]. The relationship between SBP-CoV and outcomes was not modified by eplerenone (P value for interaction = 0.48). An interaction was detected between mean SBP and SBP-CoV for the primary outcome (P = 0.048) and for HFH (P = 0.018). The effect modification was slight, but lower SBP-CoV was associated with worse outcomes in patients with both low and high SBP, while this interaction was less clear for patients with SBP in the 'normal' range. CONCLUSION In our patients with Heart Failure and reduced ejection fraction and mild symptoms, both a lower and higher SBP-CoV were associated with worse outcomes. SBP-CoV did not modify the benefit of eplerenone. Further studies are warranted to clarify the role of BPV in Heart Failure. CLINICALTRIALS. GOV IDENTIFIER NCT00232180.
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aspirin does not reduce the clinical benefits of the mineralocorticoid receptor antagonist eplerenone in patients with Systolic Heart Failure and mild symptoms an analysis of the emphasis hf study
European Journal of Heart Failure, 2016Co-Authors: Ken Lee Chin, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, John Vincent, T Collier, Eva TurgonyiAbstract:AimsIt is not known whether concomitant use of aspirin might attenuate the beneficial effects of mineralocorticoid receptor antagonists (MRAs). The purpose of this subgroup analysis was to explore the interaction between baseline aspirin treatment and the effect of eplerenone on the primary efficacy outcomes (composite of hospitalization for Heart Failure or cardiovascular mortality), its components, and safety markers [estimated glomerular filtration rate (eGFR), Systolic blood pressure (SBP), and serum potassium >5.5mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). Methods and resultsPatients with chronic Heart Failure, reduced ejection fraction (HFREF), and mild symptoms were enrolled in EMPHASIS-HF. We evaluated baseline characteristics according to aspirin use. We explored the interaction between aspirin and eplerenone, using Cox proportional hazards models providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) and P-values for interaction. Of the 2737 patients randomized, 1605 patients (58.6%) were taking aspirin. The beneficial effects of eplerenone on the primary endpoint were similar in patients not treated (adjusted HR 0.59, 95% CI 0.46-0.75) or treated (adjusted HR 0.71, 95% CI 0.59-0.87) with aspirin at baseline (interaction P-value=0.19). We did not observe any significant modification of the safety markers by aspirin that was clinically meaningful. ConclusionAspirin use in patients with chronic Systolic Heart Failure and mild symptoms did not substantially reduce the overall beneficial effects of the MRA eplerenone contrary to what has been described in some studies with ACE inhibitors.
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cost effectiveness of eplerenone in patients with Systolic Heart Failure and mild symptoms
Heart, 2014Co-Authors: Dawn Lee, Dirk J Van Veldhuisen, John Vincent, Faiez Zannad, Henry Krum, Koo Wilson, Ron Akehurst, Martin R Cowie, John J V McmurrayAbstract:Aim In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), aldosterone blockade with eplerenone decreased mortality and hospitalisation in patients with mild symptoms (New York Heart Association class II) and chronic Systolic Heart Failure (HF). The present study evaluated the cost-effectiveness of eplerenone in the treatment of these patients in the UK and Spain. Methods and results Results from the EMPHASIS-HF trial were used to develop a discrete-event simulation model estimating lifetime direct costs and effects (life years and quality-adjusted life years (QALYs) gained) of the addition of eplerenone to standard care among patients with chronic Systolic HF and mild symptoms. Eplerenone plus standard care compared with standard care alone increased lifetime direct costs per patient by £4284 for the UK and €7358 for Spain, with additional quality-adjusted life expectancy of 1.22 QALYs for the UK and 1.33 QALYs for Spain. Mean lifetime costs were £3520 per QALY in the UK and €5532 per QALY in Spain. Probabilistic sensitivity analysis suggested a 100% likelihood of eplerenone being regarded as cost-effective at a willingness-to-pay threshold of £20 000 per QALY (UK) or €30 000 per QALY (Spain). Conclusions By currently accepted standards of value for money, the addition of eplerenone to optimal medical therapy for patients with chronic Systolic HF and mild symptoms is likely to be cost-effective.
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the impact of eplerenone at different levels of risk in patients with Systolic Heart Failure and mild symptoms insight from a novel risk score for prognosis derived from the emphasis hf trial
European Heart Journal, 2013Co-Authors: T Collier, Harry Shi, John J V Mcmurray, Dirk J Van Veldhuisen, Karl Swedberg, Stuart J Pocock, Faiez Zannad, Henry Krum, John VincentAbstract:Aims Our objective was to create a simple prognostic risk score for patients with Systolic Heart Failure and mild symptoms. We then assessed the efficacy of eplerenone across different categories of risk. Methods and results The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF) was an international randomized trial, comparing eplerenone with placebo in 2737 patients with Systolic Heart Failure and mild symptoms. The primary outcome was a composite of cardiovascular death or hospitalization for Heart Failure, over a median 2.1 years follow-up. Using multivariable Cox modelling age, sex, Systolic blood pressure, estimated glomerular filtration rate, diabetes, BMI, haemoglobin, prior Heart Failure (HF) hospitalization, prior myocardial infarction/coronary artery bypass surgery (CABG), and Heart rate were identified as strong independent risk factors. Estimates from the model were converted into a simple integer risk score which was categorized into three groups of low-, medium-, and high risk. In placebo patients, the rates (per 100 patient-years) for the primary outcome were 7.6, 19.0, and 39.4 in the low-, medium-, and high-risk groups, respectively. On eplerenone, these rates were reduced to 5.6, 12.2, and 24.2, respectively. Eplerenone was beneficial across all risk categories and the hazard ratios were similar. The absolute treatment benefit was greatest among those at highest risk. Similar patterns emerged for all-cause mortality and for all HF hospitalizations. Conclusion This easy-to-use integer risk score should be of value in quantifying individual patient risk in patients with Systolic HF and mild symptoms. The relative benefits of eplerenone appeared consistent across the whole spectrum of risk, including those at lower risk.
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digoxin reduces 30 day all cause hospital admission in older patients with chronic Systolic Heart Failure
The American Journal of Medicine, 2013Co-Authors: Robert C Bourge, John J V Mcmurray, Dirk J Van Veldhuisen, Gregg C Fonarow, Inmaculada Aban, Kanan Patel, John G F Cleland, Jerome L Fleg, Mihai Gheorghiade, Richard M AllmanAbstract:Abstract Background In the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older Systolic Heart Failure patients. However, this effect has not been studied in older diastolic Heart Failure patients. Methods In the ancillary DIG trial, of the 988 patients with chronic Heart Failure and preserved (> 45%) ejection fraction, 631 were age ≥ 65 years (mean age 73 years, 45% women, 12% non-whites), of whom 311 received digoxin. Results All-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage ( P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day death in the placebo group. Digoxin-associated HRs (95% CIs) for 30-day hospitalizations due to cardiovascular, Heart Failure, and unstable angina causes were 2.82 (1.18-6.69), 0.51 (0.09-2.79), and 6.21 (0.75-51.62), respectively. Digoxin had no significant association with 30-day all-cause hospitalization among younger patients (6% vs 7% for placebo; HR 0.80; 95% CI, 0.36-1.79). Conclusions In older patients with chronic diastolic Heart Failure, digoxin increased the risk of 30-day all-cause hospital admission, but not during longer follow-up. Although chance finding due to small sample size is possible, these data suggest that unlike in Systolic Heart Failure, digoxin may not reduce 30-day all-cause hospitalization in older diastolic Heart Failure patients.
