Update on HF ManagementJan. 5, 2012
Prof. Martin R. Cowie, Imperial College, London, United Kingdom |
“There have been two very important randomized trials in the field of heart failure in the past 12 months”, Cowie starts. The EMPHASIS and SHIFT should in his view have an impact in everybody’s practice, both in general practice and in hospital. These studies analyzed eplerenone, an aldosterone antagonist, and ivabradine, a heart rate lowering drug, respectively. Neither drug is presently licensed for chronic heart failure.
Furthermore, it is important to treat ‘mild’ heart failure. His important message for GPs is: just because a patient is not very symptomatic, this does not mean he/she is not at high risk. “You should be doing everything you can to reduce that risk.”
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Recent data in context
Prof. Martin Cowie - London, United Kingdom
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Update on heart failure management – recent data in context – Prof. Martin Cowie
Quality of life in heart failure has been shown to be very poor: in fact, evidence suggests that this is worse than for those on haemodialysis. Many patients remain symptomatic after discharge from hospital, with 40% classified as NYHF stage 3 or 4 following an inpatient stay. There is already good evidence for the use of ACE inhibitors and beta blockers in heart failure. However, evidence for the use of aldosterone antagonists is also mounting.
The RALES Study (1999) demonstrated the efficacy of spironolactone 25mg vs. placebo in those with NYHA 3 or 4 and an ejection fraction < 35%. Meanwhile, the EPHESUS trial showed the benefit of eplerenone versus placebo in addition to “standard medical therapy” in those with heart failure following a myocardial infarction. Compared with spironolactone, eplerenone was also found to be less likely to cause gynaecomastia or breast tenderness though monitoring of potassium was still required.
However, the EMPHASIS-HF trial showed overwhelming evidence for the use of eplerenone in those with symptoms of mild heart failure (NHYA 2) but a low ejection fraction (<35%). This trial was actually stopped prematurely as the evidence for eplerenone was so significant that it was not deemed ethical to continue. Here eplerenone was shown to result in a 37% relative risk reduction in either death from cardiovascular causes or hospitalisation for heart failure, a 23% relative risk reduction in hospitalisation for any reason and a 42% relative risk reduction in hospitalisation for heart failure.
However, 8% of patients on eplerenone experienced hyperkalaemia compared with 4% of those randomised to placebo. In terms of discontinuation, there was no difference between eplerenone and placebo. This resulted in a number needed to treat of 19 to prevent one primary end point per year of follow-up and 51 to prevent one death per year of follow-up. As a result, eplerenone is soon to be licensed for use in chronic heart failure. This is good news as even those with “mild symptoms of heart failure” (i.e. NYHA 2) have an 18% chance of dying within 2 years.
The SHIFT study considered the use of ivabradine (an If channel blocker which acts purely on the sino-atrial node to slow heart rate) in heart failure. In particular, it compared ivabradine with placebo in those with moderate to severe chronic heart failure who are already on best recommended therapy but have a heart rate greater than 70 bpm in sinus rhythm. The primary composite end point of the study was either cardiovascular death or hospitalisation for worsening heart failure, whilst the median study duration was 22.9 months. Those treated with placebo had a mean heart rate of 75 bpm, whilst those randomised to ivabradine had a mean heart rate of 67 bpm. This resulted in an 18% relative risk reduction in the primary composite end point, a 26% relative risk reduction in hospitalisation from worsening heart failure and a 26% relative risk reduction in death from heart failure.
However, there was a higher incidence of both bradycardias and phosphenes (brief spots of light brought on by eye movements) in those taking ivabradine. Overall, the number needed to treat to prevent one patient from experiencing the primary end point was 26, and to postpone one hospitalisation for heart failure per year of follow-up was 27. This implies that in those with moderate to severe heart failure, ivabradine should be prescribed if the heart rate remains above 70 bpm on maximal beta-blockade.
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