Drug trios best for hypertension

By Lilian Anekwe

Triple combination antihypertensive therapy is ‘significantly better' than combinations of two blood-pressure lowering drugs, according to the results of two trials of new drugs.

The results may have important implications on future guidance, as Pulse revealed earlier this month that the forthcoming Joint British Societies' hypertension guideline is set to recommend GPs use combination therapies much earlier in treatment.

This may include two triple combination therapies - depending on successful results from efficacy and safety trials – two of which were presented at the American Society for Hypertension annual meeting in New York earlier this month.

The first trial -of a triple combination in development by Daiichi Sankyo - compared a fixed-dose combination of olmesartan 40mg, amlodipine 10mg and hydrochlorothiazide 25mg, with the three combinations of dual therapy.

After three months patients on triple therapy had a mean diastolic blood pressure reduction of 21.8 mmHg compared with 18.0 mmHg in the best-performing dual therapy group. Corresponding figures for systolic blood pressure drops were 37.1 mmHg and 30.0 mmHg.

More patients treated with the triple combination of drugs hit a blood pressure targets of less than 140/90mm Hg – 69.9% compared with the maximum of 53.4% of patients on dual therapy.

The second trial looked at the effect of a triple combination of aliskiren 300mg, hydrocholorothiazide 25mg and amlodipine 10mg developed by Novartis. After 28 weeks blood pressure fell by 34.2mm Hg systolic and 20.3mm Hg diastolic, and 69.1% of patients reached a target of 140/90 mm Hg or below.

After 54 weeks systolic blood pressure was 37.3mm Hg lower and diastolic blood pressure was 21.8mm Hg lower and 77.1% of had reached the blood pressure target.

Serious adverse events were comparable between all four options in the first trial and said to be low - at 2.7% - in the Novartis trial.

Professor Suzanne Oparil, professor of medicine at the University of Alabama, who presented Daiichi-Sankyo's TRINITY study said: ‘Triple combination therapy is a very potent way of lowering blood pressure, appropriate for patients who are already on one or two antihypertensive medications.'

Dr Kathryn Griffith, GP in York and president elect of the Primary Care Cardiovascular Society said: ‘We would get to target more quickly and wouldn't need all the titration steps. But if patients are intolerant you wouldn't know which drug they are intolerant of.

‘There is also an issue of cost and these drugs would have an impact on practices' prescribing budgets.'

Olmesartan/amlodipine/hydrochlorothiazide
BP reduction from baseline: 37.1/21.8mm hg diastolic at week 12
% of patients reaching 140/90 target: 69.9%

Aliskiren/amlodipine/hydrochlorothiazide
BP reduction from baseline: 34.2/20.3mm Hg at week 28 and 37.3/21.8mm Hg at week 54
% of patients reaching 140/90 target: 69.1% at week 25 and 77.1% at week 54

American Society of Hypertension annual scientific meeting 2010 posters 54 & 57