title: Cardiovascular outcomes in hypertensive patients:  comparing single-agent therapy with combination therapy.
abstract: OBJECTIVE
  To determine whether blood pressure (BP) control in hypertensive patients achieved with combination drug therapy provides the same cardiovascular benefits as with single-agent therapy.
  
  
  BACKGROUND
  Drug combinations, most often including hydrochlorothiazide (HCTZ), are now recommended for routine BP management, but their effects on cardiovascular event rates have not been compared with effective monotherapy.
  
  
  METHODS
  We conducted retrospective analyses of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) data. VALUE compared cardiovascular event rates of valsartan and amlodipine. Patients with BPs not controlled (<140/90  mmHg) by the single agents had HCTZ and, if required, additional drugs of different classes, added. Using data pooled from the two treatment arms, we have now divided patients into those controlled on monotherapy and those controlled or not controlled by combination therapy. The primary study endpoint was first occurrence of cardiovascular death or nonfatal myocardial infarction or stroke. Comparisons between groups were by Cox regression, adjusted for on-treatment BP, age, prior cardiovascular events and left ventricular hypertrophy; the comparison between the monotherapy and combination therapy controlled groups was based on events occurring after 3 months by when the decision to use monotherapy or combination therapy was made.
  
  
  RESULTS
  The primary endpoint occurred in 505 of 5924 (8.5%) monotherapy and 511 of 4621 (11.1%) combination therapy controlled patients: hazard ratio was 0.80 [95% confidence interval (CI) 0.70-0.90]. If these two groups were matched for baseline BPs and all events included from study baseline, the hazard ratio was 0.76 (95% CI 0.67-0.86). The difference between combination controlled and uncontrolled [434 of 3390 (12.8%)] groups was not significant [hazard ratio 0.90 (95% CI 0.80-1.03], nor when they were matched for baseline BPs [hazard ratio 0.95 (95% CI 0.81-1.11)].
  
  
  CONCLUSIONS
  Independent of prior cardiovascular history or baseline BP, hypertensive patients requiring combination therapy, which includes a thiazide diuretic for BP control, have a poorer cardiovascular prognosis than those controlled by monotherapy and only a nonsignificantly lower event rate than noncontrolled patients.
authors.affiliation: State University of New York, Downstate College of Medicine, Brooklyn, NY 11203, USA. michaelwebermd@cs.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weber
authors.forename: Stevo
authors.initials: S
authors.lastname: Julius
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.forename: Hans R
authors.initials: HR
authors.lastname: Brunner
authors.forename: Dion H
authors.initials: DH
authors.lastname: Zappe
authors.forename: Tsushung A
authors.initials: TA
authors.lastname: Hua
authors.forename: Gordon T
authors.initials: GT
authors.lastname: McInnes
authors.forename: Anthony
authors.initials: A
authors.lastname: Schork
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.forename: Alberto
authors.initials: A
authors.lastname: Zanchetti
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D011379:Prognosis; D012189:Retrospective Studies; D020521:Stroke / Q000517:prevention & control; D013777:Tetrazoles / Q000008:administration & dosage; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068756:Valsartan
chemical_list: D000959:Antihypertensive Agents; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine