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Lowering heart rate offers no benefit in stable heart disease

Slowing heart rate with the drug ivabradine did not improve the long-term prognosis of patients with stable coronary artery disease and an elevated heart rate, and was linked to a surprise increase in cardiovascular deaths in those with angina, researchers have said.

Their study – the SIGNIFY clinical trial, reported at the European Society of Cardiology annual congress last week – tested ivabradine against placebo, on top of other standard therapies, in stable coronary artery disease patients with heart rates above 70 bpm.

This was after an earlier study suggested the drug conferred a survival advantage to such patients with elevated heart rates – particular those with angina.

But, despite lowering the heart rate by an average of 10 bpm, ivabradine did not result in any change in the primary endpoint – a combination of death from cardiovascular causes and nonfatal MI – compared with placebo.

A prespecified subgroup analysis also showed the drug was associated with a significant 18% increase in cardiovascular deaths and nonfatal MI among patients with angina (Canadian Cardiovascular Society scale score of two or higher).

The results – also released online in the New England Journal of Medicine during the conference – come after the European medicines regulator announced it had been informed by investigators of the increased heart deaths in angina patients, and would be conducting a review of the drug.

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Dr Terry McCormack, secretary of the British Hypertension Society and a GPSI in cardiology in North Yorkshire, who is also one of the SIGNIFY trial investigators, told Pulse GPs should not be unduly concerned, however, because the doses used in the trial were much higher than usually prescribed – most patients in the trial were uptitrated to the top dose of 10 mg daily to hit the target heart rate of 55-60 bpm.

Dr McCormack emphasised that the drug should continue to be given at lower doses, for symptom relief, and that GPs should wait for the European Medicines Agency review to be completed before reviewing any patient on the drug.

He said: ‘There is going to be a European Medicines Agency statement at some point and people shouldn’t change anything before then.

‘The important point is the dose used in SIGNIFY wasn’t a dose used in primary or secondary care, the drug should be used ideally at 5 mg and definitely should not be given at 10 mg as in the trial.’

NEJM 2014; available online 31 August



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