Initial treatment for high blood pressure using benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of chronic kidney disease (CKD) to a greater extent. This is a conclusion of an Article based on the ACCOMPLISH study, published Online First and in an upcoming edition of The Lancet—written by Dr George Bakris, Hypertensive Diseases Unit, University of Chicago Pritzker School of Medicine, Chicago, IL, USA, and colleagues.
The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial treatment for high blood pressure with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular disease and mortality. In today's study, the authors assessed the effects of these drug combinations on progression of CKD.
ACCOMPLISH was a double-blind, randomised 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 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. Progression of CKD, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate* < 15 mL/min/1•73 m² or need for dialysis).
The trial was terminated early (mean follow-up 3 years) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. 2.0% of patients in the benazepril plus amlodipine group experienced CKD progression compared with 3•7% in the benazepril plus hydrochlorothiazide group — meaning that benazepril plus amlopidine patients were only half as likely to experience CKD progression as those given benazepril plus hydrochlorothiazide. The most frequent adverse event in patients with CKD was peripheral oedema (swelling of the legs and ankles) (benazepril plus amlodipine, 34%; benazepril plus hydrochlorothiazide, 16•0%). In patients with CKD, angio-oedema (acute swelling of the throat, lips, and facial area) was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without CKD, dizziness, hypokalaemia, and low blood pressure were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group.
The authors say: "This trial shows that in patients with hypertension at high risk for cardiovascular events, combination treatment with benazepril plus amlodipine reduces progression of chronic kidney disease more effectively than does benazepril plus hydrochlorothiazide. This benefit was also seen when cardiovascular or all-cause mortality were assessed with progression of chronic kidney disease. Differences in blood pressure control throughout the study could not account for these findings... Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy (CKD) to a greater extent."
In an accompanying Comment, Dr Hiddo Lambers Heerspink and Dr Dick de Zeeuw, University Medical Center Groningen, Netherlands, say: "Today's renal analysis of ACCOMPLISH was needed to help to guide the best treatment of high-risk patients for the future. However, design and interpretation of this trial remains crucial before concluding that one drug combination is better than the other."
Dr George Bakris, Hypertensive Diseases Unit, University of Chicago Pritzker School of Medicine, Chicago, IL, USA. T) +1 773 702 7936 E) gbakris@gmail.com
Dr Dick de Zeeuw, University Medical Center Groningen, Netherlands. T) +31 50 3632810 / +31 50 3632838 E) d.de.zeeuw@med.umcg.nl
For full Article and Comment, see: http://press.thelancet.com/accomplish.pdf
Note to editors: *glomerular filtration rate=the flow rate of filtered fluid through the kidney
Journal
The Lancet