title: Effectiveness of amlodipine-valsartan single-pill combinations: hierarchical modeling of blood pressure and total cardiovascular disease risk outcomes (the EXCELLENT study).
abstract: BACKGROUND
  Both patient- and physician-related factors have been shown to explain variability in the outcomes of antihypertensive treatment. Total cardiovascular risk (TCVR) is increasingly used as a determinant of treatment effectiveness but has also been proposed as a treatment outcome. To our knowledge, no studies have reported how antihypertensive treatment impacts blood pressure and TCVR outcomes.
  
  
  OBJECTIVE
  To examine in patients treated with a regimen including single-pill combinations (SPCs) of amlodipine/valsartan (1) blood pressure (BP) reduction and control, total cardiovascular risk (TCVR) change, and TCVR reduction of 1 class or more; (2) hierarchical patient- and physician-level determinants of these outcomes; and (3) predictors of uncontrolled BP and improved TCVR classification.
  
  
  METHODS
  A prospective (90 days), multicenter, multilevel pharmacoepidemiologic study was conducted in 3546 patients with hypertension treated with SPC amlodipine/valsartan by 698 general practitioners. Statistical analysis included hierarchical linear and logistic modeling of BP and TCVR outcomes.
  
  
  RESULTS
  Mean (SD) systolic BP (SBP) reductions were 20.1 (15.5) mm Hg and diastolic BP (DBP) reductions were 9.8 (10.3) mm Hg, with higher reductions among high-risk patients. SBP, DBP, and SBP/DBP control rates were 33.3%, 45.3%, and 25.5%, respectively, with lower rates among high-risk patients. Mean TCVR improvement was a reduction of 0.73 (0.96) classes (-4 [best] to +4 [worst]), with higher reductions for high-risk patients; 58.2% of patients achieved a TCVR reduction of 1 or more classes, with lower percentages for high-risk patients. Twenty-two percent of systolic variability and 26% of diastolic variability in 90-day BP values were attributable to a physician class effect, as was 16% of TCVR change.
  
  
  CONCLUSIONS
  Regimens that include SPC amlodipine/valsartan formulations are effective in reducing BP and TCVR in a real-world observational setting. Hierarchical modeling identified patient- and physician-related determinants of BP values and TCVR change, as well as independent predictors of uncontrolled BP and reduced TCVR. TCVR is a scientifically feasible and clinically relevant effectiveness outcome of antihypertensive treatment.
authors.affiliation: University of Antwerp and Clinician, Division of Nephrology and Hypertension, ZNA Stuivenberg, Antwerpen, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Lins
authors.forename: Ann
authors.initials: A
authors.lastname: Aerts
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coen
authors.forename: Christine
authors.initials: C
authors.lastname: Hermans
authors.forename: Karen
authors.initials: K
authors.lastname: MacDonald
authors.forename: Heidi
authors.initials: H
authors.lastname: Brié
authors.forename: Christopher
authors.initials: C
authors.lastname: Lee
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Shen
authors.forename: Stefaan
authors.initials: S
authors.lastname: Vancayzeele
authors.forename: Natalie
authors.initials: N
authors.lastname: Mecum
authors.forename: Ivo
authors.initials: I
authors.lastname: Abraham
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D000068838:Amlodipine, Valsartan Drug Combination; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017891:Pharmacoepidemiology; D011446:Prospective Studies; D012307:Risk Factors; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D000068838:Amlodipine, Valsartan Drug Combination; D000959:Antihypertensive Agents; D004338:Drug Combinations; D013777:Tetrazoles; D017311:Amlodipine