Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study

Swedberg, Karl; Komajda, Michel; Böhm, Michael; Borer, Jeffrey S.; Ford, Ian; Dubost-Brama, Ariane; Lerebours, Guy; Tavazzi, Luigi

doi:10.1016/s0140-6736(10)61198-1

Cited by 2,229 publications

(1,990 citation statements)

References 26 publications

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“…The mortality observed in our study (60%) in ChD HF is much higher in comparison with that of the SHIFT overall population (~17.5%) and of the recent PARADIGM‐HF trial (~15%) at 750 day follow‐up 11, 25. This finding is in agreement with previous publication 9, 26.…”

Section: Discussionsupporting

confidence: 92%

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Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial

et al. 2017

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AimsThe SHIFT trial showed that ivabradine reduced heart rate (HR) and the risk of cardiovascular outcomes. Concerns remain over the efficacy and safety of ivabradine on heart failure (HF) due to Chagas disease (ChD). We therefore conducted a post hoc analysis of the SHIFT trial to investigate the effect of ivabradine in these patients.Methods and resultsSHIFT was a randomized, double‐blind, placebo‐controlled trial in symptomatic systolic stable HF, HR ≥ 70 b.p.m., and in sinus rhythm. The ChD HF subgroup included 38 patients, 20 on ivabradine, and 18 on placebo. The ChD HF subgroup showed high prevalence of bundle branch right block and, compared with the overall SHIFT population, lower systolic blood pressure; higher use of diuretics, cardiac glycosides, and antialdosterone agents; and lower use of angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker or target daily dose of beta‐blocker. ChD HF presented a poor prognosis (all‐cause mortality at 2 years was ~60%). The mean twice‐daily dose of ivabradine was 6.26 ± 1.15 mg and placebo 6.43 ± 1.55 mg. Ivabradine reduced HR from 77.9 ± 3.8 to 62.3 ± 10.1 b.p.m. (P = 0.005) and improved functional class (P = 0.02). A trend towards reduction in all‐cause death was observed in ivabradine arm vs. placebo (P = 0.07). Ivabradine was not associated with serious bradycardia, atrioventricular block, hypotension, or syncope.ConclusionsChD HF is an advanced form of HF with poor prognosis. Ivabradine was effective in reducing HR in these patients and improving functional class. Although our results are based on a very limited sample and should be interpreted with caution, they suggest that ivabradine may have a favourable benefit–risk profile in ChD HF patients.

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Section: Discussionsupporting

confidence: 92%

“…Therefore, use of ivabradine may be feasible in ChD HF patients fulfilling the SHIFT inclusion criterion. The reduction of HR at 28 days compared with pre‐treatment observed in ChD HF was close to that described in the SHIFT study 11. Our findings disagree with the potential concern about use of ivabradine in ChD HF.…”

Section: Discussionsupporting

confidence: 75%

Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial

et al. 2017

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“…Nevertheless, there is a remarkable lack of evidence regarding the optimal management of patients after haemodynamic stabilization following hospitalization for AHF. The landmark studies in HF have predominantly recruited ambulatory patients with chronic ‘stable’ HF 45, 46, 47, 48, 49, 50. The PARADIGM‐HF trial established sacubitril/valsartan as a new evidence‐based therapy in patients with chronic HF, but in common with other major studies, it enrolled patients who were ambulatory at the time of inclusion 38.…”

Section: Rationale For the Transition Studymentioning

confidence: 99%

Rationale and design of TRANSITION: a randomized trial of pre‐discharge vs. post‐discharge initiation of sacubitril/valsartan

et al. 2017

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AimsThe prognosis after hospitalization for acute decompensated heart failure (ADHF) remains poor, especially <30 days post‐discharge. Evidence‐based medications with prognostic impact administered at discharge improve survival and hospital readmission, but robust studies comparing pre‐discharge with post‐discharge initiation are rare. The PARADIGM‐HF trial established sacubitril/valsartan as a new evidence‐based therapy in patients with heart failure (HF) and reduced left ventricular ejection fraction (<40%) (rEF). In common with other landmark studies, it enrolled patients who were ambulatory at the time of inclusion. In addition, there is also still limited knowledge of initiation and up‐titration of sacubitril/valsartan in ACEi/ARB‐ naïve patients and in de novo HF with rEF patients.Methods and results TRANSITION is a multicentre, open‐label study in which ~1000 adults hospitalized for ADHF with rEF are randomized to start sacubitril/valsartan in a pre‐discharge arm (initiated ≥24 h after haemodynamic stabilization) or a post‐discharge arm (initiated within Days 1–14 after discharge). The protocol allows investigators to select the appropriate starting dose and dose adjustments according to clinical circumstances. Over a 10 week treatment period, the primary and secondary objectives assess the feasibility and safety of starting sacubitril/valsartan in‐hospital, early after haemodynamic stabilization. Exploratory objectives also include assessment of HF signs and symptoms, readmissions, N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity troponin T levels, and health resource utilization parameters.Conclusions TRANSITION will provide new evidence about initiating sacubitril/valsartan following hospitalization for ADHF, occurring either as de novo ADHF or as deterioration of chronic HF, and in patients with or without prior ACEI/ARB therapy. The results of TRANSITION will thus be highly relevant to the management of patients hospitalized for ADHF with rEF.

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“…The primary end point was a composite of time to cardiovascular death or hospitalization for worsening heart failure, which was significantly reduced with ivabradine+background therapy (hazard ratio: 0.82, 95% CI: 0.75, 0.90, P <0.0001). The results of SHIFT also showed that ivabradine+background therapy reduced hospitalizations for worsening HF by 26% (relative risk) 9. While this indicates that ivabradine may improve patient outcomes, the economic implications of adding ivabradine to a standard HF treatment regimen in the United States have not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Cost‐Effectiveness of Ivabradine for Heart Failure in the United States

Kansal

Cowie

Kielhorn

et al. 2016

JAHA

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BackgroundIvabradine is a heart rate–lowering agent approved to reduce the risk of hospitalization for worsening heart failure. This study assessed the cost‐effectiveness of adding ivabradine to background therapy in the United States from the perspective of a commercial or Medicare Advantage payer.Methods and ResultsA cost‐effectiveness, cohort‐based Markov model using a state transition approach tracked a cohort of heart failure patients with heart rate ≥70 beats per minute in sinus rhythm who were treated with ivabradine+background therapy or background therapy alone. Model inputs, including adjusted hazard ratios, rates of hospitalization and mortality, adverse events, and utility‐regression equations, were derived from a large US claims database and SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial). In the commercial population, ivabradine+background therapy was associated with a cost savings of $8594 versus the cost of background therapy alone over a 10‐year time horizon, primarily because of reduced hospitalization. Ivabradine was associated with an incremental benefit of 0.24 quality‐adjusted life years over a 10‐year time horizon. In the Medicare Advantage population, the incremental cost‐effectiveness ratio for ivabradine was estimated to be $24 920/quality‐adjusted life years.ConclusionsThe cost‐effectiveness model suggests that for a commercial population, the addition of ivabradine to background therapy was associated with cost savings and improved clinical outcomes. For a Medicare Advantage population, the analysis indicates that the clinical benefit of ivabradine can be achieved at a reasonable cost.

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Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study

Cited by 2,229 publications

References 26 publications

Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial

Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial

Rationale and design of TRANSITION: a randomized trial of pre‐discharge vs. post‐discharge initiation of sacubitril/valsartan

Cost‐Effectiveness of Ivabradine for Heart Failure in the United States

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