At the American College of Cardiology in March two major trials were presented. The publicity surrounding the two could not have been more different. The LIFE demonstrated clear superiority of
losartan-based
therapy over
atenolol-based
therapy for the treatment of
hypertension. It was published the same week in the Lancet and received major press coverage all over the world. The OVERTURE (
Omapatrilat Versus
Enalapril Randomized Trial of Utility in Reducing Events) study in contrast received a subdued reception, very little publicity and is yet to be published. 5770 NYHA class II-IV
heart failure patients (LVEF<or=30%, recent
heart failure hospital admission) were randomised and uptitrated to either 10 mg BD of
Enalapril or 40 mg once a day
Omapatrilat. The primary end-point of all cause mortality or
heart failure related hospitalisation did not differ significantly: 914/2884 for
Enalapril and 914/2886 for
Omapatrilat (hazard ratio 0.94, CI's 0.86-1.03, P=0.187). Mortality was also similar: 509 for
Enalapril and 477 for
Omapatrilat (hazard ratio 0.94, CI's 0.83-1.07, P=0.339).
Omapatrilat was as good as
Enalapril but not better. The worrying trend was however, that
angioedema was more common with
Omapatrilat; 24 (0.8%) versus 14 cases (0.5%). The OCTAVE (
Omapatrilat Cardiovascular Treatment Assessment Versus
Enalapril) study was also presented at this time. 25,267 hypertensives were randomised to
Omapatrilat or
enalapril and a difference of approximately 3 mmHg in favour of
Omapatrilat was seen. Significantly more cases of
angioedema were seen with
Omapatrilat, 274 (2.17%) compared to 86 (0.68%) with
enalapril. Overall death rates were similar, 0.18% for
enalapril and 0.15% for
Omapatrilat. All adverse events were similar, 51.0% for
Omapatrilat and 50.4% for
enalapril. The rates of
angioedema were much higher in blacks, 5.54% for Ompatrilat and 1.62% for
enalapril and for smokers, 3.93% for
Omapatrilat and 0.81% for
enalapril. We were left with a
drug that was, for
heart failure, not superior to an
ACE inhibitor already off patent, and, as an
anti-hypertensive, with an
angioedema rate more than double that of an
ACE inhibitor in a large head to head comparison. The medical community will be watching to make sure these data are published in full in the medical literature in a timely fashion, in the order of end-points specified in the protocol and with appropriate emphasis on the logical points of presentation.