title: Amlodipine+benazepril is superior to hydrochlorothiazide+benazepril irrespective of baseline pulse pressure: subanalysis of the ACCOMPLISH trial.
abstract: Pulse pressure (PP) is an independent risk factor for cardiovascular (CV) disease and death but few studies have investigated the effect of antihypertensive treatments in relation to PP levels before treatment. The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial showed that the combination of benazepril+amlodipine (B+A) is superior to benazepril+hydrochlorothiazide (B+H) in reducing CV events. We aimed to investigate whether the treatment effects in the ACCOMPLISH trial were dependent on baseline PP. High-risk hypertensive patients (n=11,499) were randomized to double-blinded treatment with single-pill combinations of either B+A or B+H and followed for 36 months. Patients were divided into tertiles according to their baseline PP and events (CV mortality/myocardial infarction or stroke) were compared. Hazard ratios (HRs) for the treatment effect (B+A over B+H) were calculated in a Cox regression model with age, coronary artery disease, and diabetes mellitus as covariates and were compared across the tertiles. The event rate was increased in the high tertile of PP compared with the low tertile (7.2% vs 4.4% P<.01). In the high and medium PP tertiles, HRs were 0.75 (95% confidence interval [CI], 0.60-0.95; P=.018) and 0.74 (CI, 0.56-0.98, P=.034), respectively, in favor of B+A. There was no significant difference between the treatments in the low tertile and no significant differences in treatment effect when comparing the HRs between tertiles of PP. B+A has superior CV protection over B+H in high-risk hypertensive patients independent of baseline PP although the absolute treatment effect is enhanced in the higher tertiles of PP where event rates are higher.
authors.affiliation: Department of Medicine, Emergency Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Per H
authors.initials: PH
authors.lastname: Skoglund
authors.forename: Per
authors.initials: P
authors.lastname: Svensson
authors.forename: Joline
authors.initials: J
authors.lastname: Asp
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlöf
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jamerson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weber
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.forename: Dion H
authors.initials: DH
authors.lastname: Zappe
authors.forename: Jan
authors.initials: J
authors.lastname: Östergren
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D001552:Benzazepines; D006852:Hydrochlorothiazide; D017311:Amlodipine; C044946:benazepril