ACE-i + Thiazide Vs. ACE-i + CCB

Nowadays, it is more or less agreed upon that patients with Stage 2 Hypertension (and many with Stage 1) are better served with initial combination therapy as opposed to a solo anti-hypertensive agent. Acknowledging the complexities of individual patients and agreeing that one-size does not fit all as a backdrop.. Overall, which combination is best? It is a tough question and one may argue that is too simplistic. In reality we cannot merely generalize as there are too many variables. Nevertheless, we have a new study to chew on, the ACCOMPLISH trial.

 The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial was a double-blind, randomized trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12·5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min or needing dialysis).

The trial was terminated early (mean follow-up 2·9 years [SD 0·4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide.There were 113 (2·0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3·7%) in the benazepril plus hydrochlorothiazide group (HR 0·52, 0·41—0·65, p<0·0001).

The conclusion the authors offer is that initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent.

There are many questions that remain. Is an ACE-inhibitor and calcium channel blocker really the preferred choice? Is there something special about benazepril and/or amlodipine or can we extrapolate to other ACE i and CCBs? What about the newer ARB plus CCB (amlodipine) combination drugs (Azor, Exforge and Twynsta)? Do these offer similiar benefits? Are there other specific patient populations that need to be considered?  Surely there will be more to follow...