title: Initial combination therapy reduces the risk of cardiovascular events in hypertensive patients: a matched cohort study.
abstract: This study evaluated the effects of initial versus delayed treatment with a drug combination on blood pressure (BP) control and the risk of cardiovascular (CV) events in hypertensive patients. Clinical trials suggest that the time to BP control is an important determinant of long-term outcomes, but real-world evidence is scarce. Using electronic medical charts (2005-2009), we retrospectively analyzed 1762 adult patients with BP elevation initiating combination therapy matched 1:1 with similar patients initiating monotherapy and later switched to combination therapy. Incidence rate ratios of CV events (myocardial infarction, stroke/transient ischemic attack, or hospitalization for heart failure) or all-cause death and Kaplan-Meier analyses of time to BP control were compared between cohorts. Hazard ratios indicating the effects of initial treatment on CV events and BP control were estimated using time-varying Cox proportional hazard models. Initial combination therapy was associated with a significant reduction in the risk of CV events or death (incidence rate ratio, 0.66 [95% confidence interval, 0.52-0.84]; P=0.0008). After 6 months of therapy, 40.3% and 32.6% of patients with initial versus delayed combination treatment reached BP control, respectively. Achieving target BP was associated with a statistically significant risk reduction of 23% for CV events or death (hazard ratio, 0.77 [95% confidence interval, 0.61-0.96]; P=0.0223); the residual effect of initial combination therapy did not reach statistical significance (hazard ratio, 0.84 [95% confidence interval, 0.68-1.03]; P=0.0935). Initial combination therapy was associated with a significant risk reduction of cardiovascular events. More rapid achievement of target BP was found to be the main contributor to the estimated risk reduction.
authors.affiliation: Temple University School of Medicine, 1239 Shady Ave, Pittsburgh, PA 15232, USA. gradmana@temple.edu
authors.forename: Alan H
authors.initials: AH
authors.lastname: Gradman
authors.forename: Hélène
authors.initials: H
authors.lastname: Parisé
authors.forename: Patrick
authors.initials: P
authors.lastname: Lefebvre
authors.forename: Heather
authors.initials: H
authors.lastname: Falvey
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lafeuille
authors.forename: Mei Sheng
authors.initials: MS
authors.lastname: Duh
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk
chemical_list: D000959:Antihypertensive Agents