- Prescribing Advice for GPs - https://www.prescriber.org.uk -

Which antihypertensive combination?

The New England Journal of Medicine has published the results of a study that aimed to compare two combination drug therapies for hypertension to find the optimal approach.

The ACCOMPLISH Study recruited 11,506 participants with hypertension who were at high risk for cardiovascular events. They were randomly assigned to treatment with a fixed dose combination of amlodipine 5mg/benazepril 20mg or hydrochlorothiazide 12.5mg/benazepril 20mg. After 1 month, benazepril was titrated to 40 mg in both arms and thereafter the dose of the other agent was doubled. After 3 months additional antihypertensive medication could be added to attain blood pressure targets of <140/90 mmHg, or <130/80 mmHg in patients with diabetes or renal insufficiency.

The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospital admission for angina, resuscitation after sudden cardiac arrest and coronary revascularisation.

The study found a 20% reduction in the primary endpoint in the amlodipine/benazepril arm (Event rate 9.6%) compared with the hydrochlorothiazide/benazepril arm (Event rate 11.8%) (p<0.001). There was a significant reduction in the rate of fatal and nonfatal myocardial infarction (2.2% versus 2.8%, p=0.04) although rates of cardiovascular mortality, stroke, and resuscitated sudden death were similar between the two groups.

The incidence of adverse effects was similar between the two groups for outcomes such as hypotension, cough and angioedema although peripheral oedema was much more common in the amlodipine arm (31.2% vs. 13.4%).

The authors of this study conclude that, "the benazepril/amlodipine combination was superior to the benazepril/hydrochlorothiazide combination in reducing cardiovascular events". However, it should be noted that there was a small but statistically significant difference in blood pressure that favoured the benazepril/amlodipine arm of the study and that these findings are contrary to those from the ALLHAT study that found no difference between amlodipine and chlorthalidone (another thiazide diuretic).

Action: This study needs evaluation in conjunction with the established evidence base and may require a revision of current guidelines. Clinicians should continue to implement the existing guidelines until advisory organisations have reviewed the current advice.