Latest publications on SHIFT

■ The efficacy and safety of ivabradine is independent of baseline blood pressure

Published in July 2014
Low systolic blood pressure (SBP) is associated with poor outcomes in heart failure. Moreover, it limits the use and/or dose of recommended pharmacological agents in a substantial number of chronic heart failure patients. A SHIFT analysis assessed the efficacy and safety of ivabradine depending on the baseline SBP. The population was composed of 2110 patients with SBP The conclusion was that ivabradine was associated with a similar relative risk reduction of the primary end point of cardiovascular mortality or hospitalization for worsening heart failure in the three SBP groups (SBP 5

■ Ivabradine’s clinical benefits in CHF are maintained with or without renal dysfunction

Published in February 2014
Patients with heart failure commonly have renal dysfunction, which is one of the strongest predictors of mortality in these patients. It has been shown that treatment with ivabradine in patients with chronic heart failure, in sinus rhythm, with heart rate ≥70 beats/minute, did not affect renal function and all outcomes were improved in patients with renal dysfunction (eGFR 1

■ Ivabradine improves clinical outcomes independently of heart failure severity.

Published in February 2014
A recent analysis from SHIFT explored the efficacy and safety of ivabradine in 712 patients with severe heart failure (LVEF ≤20% and/or NYHA class IV) and 5973 with less severe heart failure (NYHA classes II/III and LVEF >20%). Treatment with ivabradine in severe heart failure was associated with relative risk reductions indistinguishable from those of less severe disease for the primary end point (16% reduction), all-cause death (22%), cardiovascular death (22%), heart failure death (37%), and heart failure hospitalization (17%) (all P for interaction nonsignificant). Moreover, in the 272 patients with severe heart failure and baseline heart rate ≥75 bpm (the indication approved by the EMA), ivabradine reduced the primary end point by 25% (P=0.045), heart failure hospitalization by 30% (P=0.042), and cardiovascular death by 32% (P=0.034). Ivabradine’s safety profile in severe heart failure was indistinguishable from that in less severe heart failure. Ivabradine can be safely used in severe heart failure and improves clinical outcomes, independently of heart failure severity.2

■ Ivabradine is similarly effective in chronic heart failure patients with or without COPD.

Published in December 2013
The presence of chronic obstructive pulmonary disease (COPD) is associated with increased risk of cardiovascular outcomes in patients with chronic heart failure and represents the barrier to optimized heart failure therapy including beta-blockers. This analysis assessed the efficacy and safety of ivabradine in the SHIFT study population with and without COPD. 11% of the SHIFT population had COPD (n=730). COPD patients were older and had a poorer risk profile. Beta-blockers were prescribed to 69% of COPD patients and 92% of non-COPD patients. Ivabradine reduced risk of the primary end point and heart failure hospitalization similarly in both COPD (14%, and 17%) and non-COPD (18% and 27%) patients (P interaction=0.82, and 0.53, respectively). A similar effect was also noted for cardiovascular death. Adverse events were more common in COPD patients, but similar in treatment subgroups. Ivabradine is similarly effective and safe in chronic heart failure patients with or without COPD, and can be safely combined with beta-blockers in COPD.3

■ Age does not limit the appropriate use of ivabradine in patients with chronic heart failure and systolic dysfunction.

Published in November 2013
The effects of ivabradine on cardiovascular outcomes, changes in heart rate, and adverse events, particularly bradycardia, were evaluated according to age group in a recent analysis from SHIFT. Age distribution was divided by quartiles to give four groups (4

References
1. Voors AA, et al; SHIFT Investigators. The effect of heart rate reduction with ivabradine on renal function in patients with chronic heart failure: an analysis from SHIFT. Eur J Heart Fail. 2014 Feb 7. [Epub ahead of print]
2. Borer JS, Böhm M, Ford I at al. SHIFT Investigators. Efficacy and Safety of Ivabradine in Patients With Severe Chronic Systolic Heart Failure (from the SHIFT Study). Am J Cardiol. 2014;113(3):497-503.
3. Tavazzi L, Swedberg K, Komajda M et al. SHIFT Investigators. Clinical profiles and outcomes in patients with chronic heart failure and chronic obstructive pulmonary disease: an efficacy and safety analysis of SHIFT study. Int J Cardiol. 2013;170(2):182-188.
4. Tavazzi L, Swedberg K, Komajda M, et al; SHIFT Investigators. Efficacy and safety of ivabradine in chronic heart failure across the age spectrum: insights from the SHIFT study. Eur J Heart Fail. 2013;15(11):1296-1303.
5. Komajda M et al. Efficacy and safety of ivabradine in patients with chronic systolic heart failure according to blood pressure level in SHIFT. Eur J Heart Fail. 2014;16(7):810-816.

NEWS from Heart Failure Congress 2015, Seville, May 2015

■ Ivabradine is effective in chronic heart failure patients whatever the number of comorbidities

An analysis from the SHIFT trial assessed the impact of multiple comorbidities on outcomes and the potential impact on the benefits of ivabradine in heart failure patients. Multimorbidity was associated with a higher risk of outcomes but, whatever the number of comorbidities, did not interfere with the effects of ivabradine in reducing the primary end point of cardiovascular death or hospitalization for heart failure or in reducing other heart failure-related outcomes.

References
1. Böhm M et al. Effect of comorbidities on outcomes and ivabradine effects in patients with chronic systolic heart failure in the SHIFT trial. Eur J Heart Fail. 2015:17(Supplement 1):266. Abstract 1283.

NEWS from the American College of Cardiology Congress 2015, San Diego, March 2015

■ Ivabradine is effective in chronic heart failure patients with or without angina

In order to assess the efficacy of ivabradine in chronic heart failure patients with angina, an analysis was carried out for this subgroup from the SHIFT study (2220 patients [34%] had a history of angina at baseline).1
In those patients, the SHIFT primary end point, cardiovascular death or hospitalization for worsening heart failure was reduced by 15% (P=0.0553). This confirmed ivabradine’s efficacy in reducing cardiovascular death or hospitalization for worsening heart failure in patients with chronic heart failure with or without angina.

References
1. Borer JS et al. Efficacy profile of ivabradine in patients with heart failure plus angina pectoris . J Am Coll Cardiol. 2015;65(10_S):A791. Oral contributions.

NEWS from Heart Failure Congress 2014, Athens, May 2014

■ The efficacy and safety of ivabradine are similar in diabetic and nondiabetic patients

Diabetes mellitus is considered as a common comorbidity in chronic heart failure patients and leads to poorer outcomes. A SHIFT analysis presented at the Heart Failure Congress 2014, Athens, May 2014 concluded that the primary composite end pointof cardiovascular death and hospitalization for worsening heart failure was reduced similarly by ivabradine in patients with and without diabetes mellitus (P for interaction=0.86), as was hospitalization for heart failure. This confirmed that the efficacy and safety of ivabradine are similar in diabetic and non-diabetic patients.1

References
1. Komajda M, Tavazzi L, Swedberg K, et al. Efficacy and safety of ivabradine in patients with chronic heart failure and diabetes: an analysis from the SHIFT trial. European Society of Cardiology. 2014;16(Suppl. 2):42.Abstract P227

NEWS from ESC congress 2013, Amsterdam

■ Ivabradine’s clinical benefits in CHF are maintained with or without renal dysfunction

Patients with heart failure commonly have renal dysfunction, which is one of the strongest predictors of mortality in these patients. It has been shown that treatment with ivabradine in patients with chronic heart failure, in sinus rhythm, with heart rate ≥70 beats/minute, did not affect renal function and all outcomes were improved in patients with renal dysfunction (eGFR 1

■ The benefits and tolerability of ivabradine are similar irrespective of blood pressure

Low blood pressure limits the use and/or dose of recommended pharmacological agents in a substantial number of chronic heart failure patients. In this population, it is associated with worsened outcomes. SHIFT data confirm that clinical profile and outcomes in heart failure patients are influenced by baseline blood pressure. However, the benefits and tolerability of ivabradine are similar irrespective of blood pressure levels.2

■ SHIFT is the basis of a prognostic model for heart failure patients

Prognostic models for death and heart failure hospitalization provide important information for identifying patients at risk. A multivariable statistical model for risk stratification was developed by using clinical parameters that are routinely collected and easily obtained in patients from the SHIFT study. The top 10 predictors for the risk model were high heart rate, reduced left ventricular ejection fraction, abnormal creatinine, NYHA class III/IV, increasing duration of heart failure, older age, decreasing SBP, relatively low total cholesterol, history of left bundle-branch block, and history of atrial fibrillation/flutter (all P<0.001).3

■ Ivabradine’s efficacy and safety are maintained with or without COPD

Chronic obstructive pulmonary disease (COPD) is a barrier to optimization of beta-blocker therapy in heart failure patients, and the association of COPD and CHF results in a worse prognosis. Ivabradine is effective and safe in CHF patients with or without COPD, and can be safely combined with beta-blockers in COPD.4

References – Abstracts of ESC congress 2013
1. Voors AA., van Veldhuisen DJ., Robertson M., Ford I., Borer J., Boehm M., Komajda M., Swedberg K., Tavazzi L. The effect of heart rate reduction with ivabradine on renal function in patients with chronic heart failure: an analysis from SHIFT. European Heart Journal. 2013; 34 ( Suppl. 1 ): 162-163.
2. Komajda M., Böhm M., Borer J., Ford I., Robertson M., Manolis A.,Tavazzi L., Swedberg K. Efficacy and safety of ivabradine in patients with chronic systolic heart failure and low blood pressure in the SHIFT trial. European Heart Journal. 2013;34 ( Suppl. 1 ):610.
3. Ford I., Robertson M., Borer J., Böhm M., Komajda M., Tavazzi L., Swedberg K. The top ten factors related to morbidity and mortality in patients with chronic heart failure and LVSD: a SHIFT prognostic model. European Heart Journal. 2013; 34 ( Suppl. 1 ):286.
4. Tavazzi L., Swedberg K., Komajda M., Böhm M., Borer J., Lainscak M., Robertson M, Ford I. Clinical profiles and outcomes of patients with chronic heart failure and chronic obstructive pulmonary disease: efficacy and safety of Ivabradine. a SHIFT study analysis. European Heart Journal. 2013; 34 ( Suppl. 1 ): 652.