SHIFT: hartfalenrisico bij AF significant gereduceerd met ivabradine

SHIFT: Heart failure risk significantly reduced with ivabradine

29 August 2010

Presentation slides

Stockholm, Sweden -  The risk of cardiovascular death or hospitalization for heart failure (HF) is significantly reduced with ivabradine in moderate to severe chronic HF patients with left ventricular dysfunction, results from the SHIFT study indicate.

Over 6500 patients, who also had a heart rate of ≥70 bpm, were randomly assigned to ivabradine or placebo, alongside currently recommended heart-failure medication, for a median of almost 23 months. In addition to an 18% reduction in the risk of cardiovascular mortality or heart-failure hospitalization, there was a 26% reduction in heart-failure events leading to hospitalization or death.

	Ivabradine (n=3241)*	Placebo (n=3264)*	Hazard ratio (95% CI)	p-value
Primary endpoint Cardiovascular mortality or heart-failure hospitalization	24 (14.5%/year)	29 (17.7%/year)	0.82 (0.75-0.90)	<0.0001
Secondary endpoints Hospitalization for HF Death from HF	16 (9.4%/year) 3 (1.9%/year)	21 (12.7%/year) 5 (2.6%/year)	0.74 (0.66-0.83) 0.74 (0.58-0.94)	<0.0001 <0.0001

* Analysed

“This is a major finding”, said lead researcher Michel Komajda (Pitié Salpetrière Hospital, Paris, France). “The results have been achieved in addition to the effects of other medications. HF and high heart rates are extremely common, so it is very good news for patients and doctors that, even when using the best current drug treatment available, ivabradine further reduces the risk of death or hospitalization by over 25%.”

He added: “Ivabradine has only one known cardiac action, so this opens a fascinating area of research”.

Study details
The Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) involved a total of 6558 patients who were aged ≥18 years old and who had class II–IV New York Heart Association (NYHA) HF, left ventricular ejection fraction ≤35%, a heart rate of ≥70 bpm, sinus rhythm, and documented hospital admission for worsening HF within the previous 12 months.

The participants, who had an average age of approximately 60 years, were randomized to ivabradine 5 mg twice daily (up-titrated to 7.5 mg bid or down-titrated to 2.5 mg bid) or placebo for a median of 22.9 months (maximum 41.7 months). A total of 3241 ivabradine and 3264 placebo patients were available for analysis.

Ninety per cent of patients also received a beta blocker, 91% were treated with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker or both, and 60% received an aldosterone antagonist. In all, 56% of patients in each group received ≥50% of the daily target beta blocker dose, and approximately 25% received the target daily dose.

The primary composite endpoint was cardiovascular death or hospitalization for worsening HF. Secondary endpoints were all-cause cardiovascular/HF death, all-cause cardiovascular/HF hospitalization, a composite of cardiovascular death, HF death and non-fatal myocardial infarction, change in NHYA class, and Physician’s Global Assessment.

Ivabradine was associated with an 18% reduction relative to placebo in the occurrence of cardiovascular mortality or hospitalization for HF (14.5% versus 17.1% per year, respectively for placebo), a 26% reduction in the frequency of hospitalization for HF (9.4% versus 12.7% per year, respectively), and a 26% reduction in the rate of death from HF (1.9% versus 2.6% per year, respectively).

The effect of ivabradine was seen in all prespecified subgroups aside from patients with a baseline heart rate <77 bpm. The number needed to treat for 1 year to prevent one primary endpoint was 26, and the number needed to treat for 1 year to prevent one hospitalization for HF was 27.

There were no significant differences between ivabradine- and placebo-treated patients in overall serious adverse events and adverse events, although symptomatic and asymptomatic bradycardia was increased with ivabradine versus placebo, at 5% versus 1% and 6% versus 1%, respectively (p<0.0001 in both cases).

Lancet 2010; Advance online publication