Date: 2014-09-14
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 18th Annual Scientific Meeting of the Heart Failure Society of America (HFSA) in Las Vegas
Company: Amgen (USA - CA)
Product: ivabradine
Action
mechanism: bradycardic agent. Ivabradine is an If inhibitor approved by the European Medicines Agency in 2005 for the symptomatic treatment of stable angina and in 2012 for chronic heart failure, as well as approved in more than 100 other countries, excluding the U.S.
Disease: chronic heart failure
Therapeutic area: Cardiovascular diseases
Country:
Trial
details: SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) is a large, multi-center, randomized, double-blind, placebo-controlled, outcomes study involving more than 6,500 patients in 37 countries. The Phase 3 SHIFT study compared ivabradine to placebo on top of standard-of-care therapies (including beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), diuretics and/or aldosterone antagonists), in patients with symptomatic chronic HF in sinus rhythm with reduced left ventricular function and heart rate >70 bpm. After a run-in period of 14 days without study treatment, eligible patients were randomized to receive ivabradine or placebo, with a starting dose of 5 mg daily. After a 14-day titration period, at Day 14, the dose was increased to 7.5 mg twice daily, unless the resting heart rate was 60 bpm or lower. If resting heart rate fell below 50 bpm or patients experienced signs or symptoms of bradycardia, the dose was reduced to 2.5 mg twice daily. The double-blind treatment period lasted approximately 12-48 months. The primary endpoint was the composite of cardiovascular death or hospitalization for worsening HF. The first secondary endpoint was the composite of cardiovascular death or hospitalization for worsening HF in patients receiving at least 50 percent of the target daily dose of beta blockers at randomization. Other secondary endpoints included all-cause death, any cardiovascular death, hospitalization for worsening HF, all-cause hospitalization, any cardiovascular hospitalization and death from HF, and the composite of cardiovascular death, hospitalization for worsening HF or hospitalization for non-fatal myocardial infarction.
The SHIFT study, which completed in May 2010 , was funded by Les Laboratoires Servier and coordinated by the SHIFT executive committee, an international group of HF experts.
Latest
news: * On September 14, 2014, Amgen announced data from the Phase 3 SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) study evaluating ivabradine in patients with chronic heart failure (HF) were presented at the 18th Annual Scientific Meeting of the Heart Failure Society of America (HFSA) in Las Vegas . A post-hoc analysis from the SHIFT study confirmed low systolic blood pressure (SBP) is associated with poor outcomes in chronic HF, and that ivabradine reduced the primary composite endpoint of cardiovascular death or hospitalization for worsening HF in this subgroup with low baseline SBP. Safety was similar across the three SBP groups. Results were published in the July 2014 issue of the European Journal of Heart Failure. At HFSA, Amgen presented a post-hoc analysis of the SHIFT study that evaluated the efficacy and safety of ivabradine across three different blood pressure groups, divided according to SBP: low SBP (130 mm Hg; n=2,427). The analysis confirmed chronic HF with low SBP is associated with poor outcomes, and that ivabradine reduced the primary composite endpoint of cardiovascular death and hospitalization for worsening HF independent of baseline SBP. Safety was similar across the three SBP groups. The most common adverse events were phosphenes and bradycardia, which occurred more frequently with ivabradine. Additional findings presented at the HFSA meeting included data from a pre-specified Holter electrocardiography sub-study (ECG-Holter sub-study), which evaluated 501 patients from the SHIFT trial to better understand the relationship between heart rate and safety/incidence of adverse events while taking ivabradine on top of optimized HF therapy, including beta blockers. Results showed that at eight months, 24-hour heart rate was significantly reduced by 9.5 + 10.1 bpm in the ivabradine group (n=254) versus 1.2 + 8.9 bpm in the placebo group (n=247) (p<0.0001). Higher rates of at least one episode of heart rate less than 40 bpm were also reported in the ivabradine group (p<0.0001). No increase in significant pauses, second/high degree atrioventricular block or arrhythmias was observed in the ivabradine group in this sub-study. In August 2014 , the FDA granted ivabradine priority review designation, which is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions compared to available therapies.3 FDA will target a priority review Prescription Drug User Fee Act (PDUFA) action date of Feb. 27, 2015 .
