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SHIFT: Systolic Heart failure treatment with the I F inhibitor ivabradine Trial

SHIFT: Systolic Heart failure treatment with the I F inhibitor ivabradine Trial. Purpose

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SHIFT: Systolic Heart failure treatment with the I F inhibitor ivabradine Trial

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  1. SHIFT: Systolic Heart failure treatment with the IF inhibitor ivabradine Trial Purpose To examine the effect of ivabradine in addition to guidelines-based treatment on cardiovascular (CV) outcomes, symptoms, and quality of life in patients with chronic heart failure (CHF) and systolic dysfunction SwedbergK, et al. Lancet 2010;376:875–885.

  2. SHIFT: TRIAL DESIGN Design Randomized trial with a 1:1 design. Patients 6558 patients in sinus rhythm with a resting heart rate of ≥70 beats per minute (bmp), CHF for ≥4 weeks, previous admission for worsening heart failure (HF) within the previous 12 months, and left-ventricular ejection fraction (LVEF) of ≤35%. Follow-up, primary and secondary endpointsThe primary endpoint was a composite of CV death or admission for worsening HF. The principal secondary endpoint was a composite of CV death or admission for worsening HF in patients at ≥50% of the target daily dose of a β blocker. Patients were followed up every 4 months. The median duration of follow-up was 22.9 months. Treatment Patients were randomized to 5 mg twice daily of ivabradine or matching placebo. After 14 days, the dose was adjusted depending on the patients resting heart rate. SwedbergK, et al. Lancet 2010;376:875–885.

  3. SHIFT: Baseline characteristics SwedbergK, et al. Lancet 2010;376:875–885.

  4. SHIFT: RESULTS Primary endpoint and follow-up The primary endpoint occurred in 937 (29%) patients in the placebo group versus 793 (24%) of patients receiving ivabradine (hazard ratio [HR], 0.82; p<0·0001). This result was primarily due to reductions in admissions for worsening HF, at 672 (21%) in patients receiving placebo and 514 (16%) of those given ivabradine (HR, 0.74; p<0.0001). Twenty six patients would need treatment for 1 year in order to prevent one CV death or admission for HF. Interestingly, there was evidence of a significant treatment effect in patients with a baseline heart rate over 77 bpm. Secondary endpoints In patients receiving ≥50% of the target daily dose of a β blocker, the composite endpoint and mortality components were not significantly reduced. However, ivabradine reduced admissions for worsening HF by 19% (HR, 0.81; p=0.021). Safety endpoints Although there were more withdrawals in patients given ivabradine than those given placebo, at 682 (21%) versus 605 (19%), respectively (HR, 1.14; p=0.017), serious adverse events were less common with ivabradine than with placebo (p=0.025). Symptomatic and asymptomatic bradycardia was more frequent with ivabradine than with placebo (both p<0·0001). SwedbergK, et al. Lancet 2010;376:875–885.

  5. SHIFT: Effects on primary and major secondary endpoints SwedbergK, et al. Lancet 2010;376:875–885.

  6. 40 30 20 10 0 0 6 12 18 24 30 Months SHIFT: cumulative event curvesPatients with primary composite endpoint (%) Patients with primary composite endpoint (%) Placebo (937 events) HR, 0.82; 95% Cl, 0.75–0.90; p<0.0001. Ivabradine (793 events) Swedberg K, et al. Lancet 2010;376:875–885. SwedbergK, et al. Lancet 2010;376:875–885.

  7. 30 20 10 0 0 6 12 18 24 30 Months SHIFT: Cumulative event curvesPatients with first hospital admission for worsening HF Patients with first hospital admission for worsening HF (%) Placebo (672 events) Ivabradine (514 events) HR, 0.74; 95% Cl, 0.66–0.83; p<0.0001. Swedberg K, et al. Lancet 2010;376:875–885. SwedbergK, et al. Lancet 2010;376:875–885.

  8. 40 20 10 0 0 6 12 18 24 30 Months SHIFT: cumulative event curves Patients with CVdeath (%) Patients withCVdeath (%) Placebo (491 events) Ivabradine (449 events) HR, 0.91; 95% Cl, 0.80–1.03; p=0.128. Swedberg K, et al. Lancet 2010;376:875–885. SwedbergK, et al. Lancet 2010;376:875–885.

  9. SHIFT: Effect of treatment on primary composite endpoint in prespecified subgroups SwedbergK, et al. Lancet 2010;376:875–885.

  10. SHIFT: Systolic Heart failure treatment with the IF inhibitor ivabradineTrial - SUMMARY - Ivabradine, when added to guideline-based and evidence-based treatment, substantially and significantly reduced the major risks associated with HF.The risk of the primary endpoint reduced by 18% with ivabradine, which was primarily because of a beneficial effect on HF events that became apparent within 3 months of initiating treatment.Patients with heart rates higher than the median were at increased risk of an event and experienced a greater reduction in events with ivabradine than those with lower heart rates. This variation indicates that the magnitude of benefit associated with ivabradine varies directly with pretreatment heart rate. SwedbergK, et al. Lancet 2010;376:875–885.

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