Which combination therapy for hypertension?
Although an ACEI/thiazide combination produced similar reductions in BP compared with an ACEI/ CCB combination, the latter produced better cardiovascular outcomes in the ACCOMPLISH trial.
A total of 11, 506 patients aged 55 years or older with a systolic BP greater than 160 mmHg were enrolled in the trial. All patients were on antihypertensive therapy at entry into the study and more importantly had evidence of cardiovascular or renal disease or target-organ damage. Most patients were obese and nearly two-thirds had diabetes. Only 37% of patients had their BP controlled to <140/90 mmHg at baseline despite 70% being on two or more antihypertensives.
At the start of the trial all patients stopped their medication and were subsequently randomised to combination treatment with benazepril/hydrochlorothiazide or benazepril/amlodipine. The primary endpoint was a composite of death from cardiovascular causes, nonfatal MI, nonfatal stroke, hospitalisation for angina, resuscitation after sudden cardiac arrest, and coronary revascularisation.
The study was terminated after a mean follow up of 36 months with both treatment arms achieving good BP control, 132/73 mmHg with benazepril/amlodipine and 133/74 mmHg with benazepril/hydrochlorothiazide.
A total of 9.6% of patients in the benazepril/amlodipine group had a cardiovascular event compared with 11.8% in the benazepril/hydrochlorothiazide group (HR 0.80, 95% CI 0.72-0.90, P<0.001).
Current hypertension guidelines in the UK recommend that in patients aged 55 and over first-line therapy should be either a CCB or a thiazide-type diuretic. Furthermore, the addition of an ACEI is recommended if satisfactory BP control is not achieved with the first agent alone.
Should this study influence our use of diuretics? Certainly both combinations were highly effective at reducing BP to well below target levels but the ACEI/CCB combination resulted in better cardiovascular outcomes despite similar BP reductions.
However, before we relegate thiazides to the minor leagues in BP control we must remember that not all thiazides are necessarily equal with chlorthalidone and indapamide achieving favourable results in trials such as ALLHAT and HYVET. So my takehome message is not to abandon these drugs just yet.
Jamerson K, Weber MA and Bakris GL. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients N Eng J Med 2008;359:2417-28Reviewer
Dr Peter Savill
GPwSI Cardiology, Southampton