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SHIFT (Systolic Heart Failure Treatment
with the If Inhibitor Ivabradine Trial)
SHIFT (Systolic Heart Failure Treatment with the If
Inhibitor Ivabradine Trial)
M Komajda (Groupe Hospitalier Pitié-Salpêtrière, Paris, France)
European Society of Cardiology 2010 Congress


• Background:
     Ivabradine is a selective inhibitor of a sodium-potassium channel highly
     expressed in the sinoatrial node, on which it has a mild dampening effect
• Population and treatment:
     >6500 patients with NYHA class 2–4 heart failure, an LVEF <35%, a resting
     heart rate >70 bpm, and HF hospitalization within the previous year
     Randomized to placebo or ivabradine at a starting dose of 5 mg twice daily,
     with adjustments to achieve a resting HR of 50 to 60 bpm; all patients were on
     standard HF medications according to guidelines
• Primary outcome:
     Composite of CV death or HF hospitalization


  HR=heart rate
SHIFT: Results

• Significant 18% reduction in HR for CV death or hospitalization for worsening HF
  with ivabradine vs control group—driven by significant 26% HR reductions for the
  individual secondary end points of death from HF and hospitalization for
  worsening HF

Primary and secondary end pointsa
Outcomes                                         Ivabradine    Placebo       HR (95% CI)        p
                                                 (n=3241), %   (n=3264), %

Primary end point                                24            29            0.82 (0.75–0.90)   <0.001

Death from HF                                    3             5             0.74 (0.58–0.94)   0.014

HF hospitalization                               16            21            0.74 (0.66–0.83)   <0.001

CV death, HF hospitalization, or admission for   25            30            0.82 (0.74–0.89)   <0.001
nonfatal MI




 a. Mean follow-up of 23 months
 b. HR=hazard ratio
SHIFT: Commentary*

"SHIFT confirms the importance of heart rate in the pathophysiology of heart failure
and supports the concept that reduction of heart rate contributes significantly to
beneficial outcomes in patients with heart failure. It appears therefore likely that
heart rate is not only a risk factor but may well be a mediator of the progression of
heart failure."

                                                                                           - Dr Inder Anand


"This is a very interesting study that tests a novel concept of heart-rate slowing as
adjunctive therapy for heart failure, but sufficient questions remain regarding whom
it is who would benefit most from this approach."

                                                                                           - Dr Clyde Yancy


 *All comments from SHIFT: Adding HR-slowing agent ivabradine to HF meds cuts mortality,
 hospitalization (http://www.theheart.org/article/1113617.do)
Become a member of http://www.theheart.org
    Become a fan on Facebook: http://www.facebook.com/theheartorg
        Follow us on Twitter: http://www.twitter.com/theheartorg

theheart.org is the leading online source of independent cardiology news.
We are the top provider of news and opinions for over 100 000 physicians.

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SHIFT trial - Summary & Results

  • 1. SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial)
  • 2. SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) M Komajda (Groupe Hospitalier Pitié-Salpêtrière, Paris, France) European Society of Cardiology 2010 Congress • Background: Ivabradine is a selective inhibitor of a sodium-potassium channel highly expressed in the sinoatrial node, on which it has a mild dampening effect • Population and treatment: >6500 patients with NYHA class 2–4 heart failure, an LVEF <35%, a resting heart rate >70 bpm, and HF hospitalization within the previous year Randomized to placebo or ivabradine at a starting dose of 5 mg twice daily, with adjustments to achieve a resting HR of 50 to 60 bpm; all patients were on standard HF medications according to guidelines • Primary outcome: Composite of CV death or HF hospitalization HR=heart rate
  • 3. SHIFT: Results • Significant 18% reduction in HR for CV death or hospitalization for worsening HF with ivabradine vs control group—driven by significant 26% HR reductions for the individual secondary end points of death from HF and hospitalization for worsening HF Primary and secondary end pointsa Outcomes Ivabradine Placebo HR (95% CI) p (n=3241), % (n=3264), % Primary end point 24 29 0.82 (0.75–0.90) <0.001 Death from HF 3 5 0.74 (0.58–0.94) 0.014 HF hospitalization 16 21 0.74 (0.66–0.83) <0.001 CV death, HF hospitalization, or admission for 25 30 0.82 (0.74–0.89) <0.001 nonfatal MI a. Mean follow-up of 23 months b. HR=hazard ratio
  • 4. SHIFT: Commentary* "SHIFT confirms the importance of heart rate in the pathophysiology of heart failure and supports the concept that reduction of heart rate contributes significantly to beneficial outcomes in patients with heart failure. It appears therefore likely that heart rate is not only a risk factor but may well be a mediator of the progression of heart failure." - Dr Inder Anand "This is a very interesting study that tests a novel concept of heart-rate slowing as adjunctive therapy for heart failure, but sufficient questions remain regarding whom it is who would benefit most from this approach." - Dr Clyde Yancy *All comments from SHIFT: Adding HR-slowing agent ivabradine to HF meds cuts mortality, hospitalization (http://www.theheart.org/article/1113617.do)
  • 5. Become a member of http://www.theheart.org Become a fan on Facebook: http://www.facebook.com/theheartorg Follow us on Twitter: http://www.twitter.com/theheartorg theheart.org is the leading online source of independent cardiology news. We are the top provider of news and opinions for over 100 000 physicians.