title: Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial.
abstract: OBJECTIVE
  Most patients with cardiovascular disease (CVD) do not take recommended medications long-term. The use of fixed-dose combinations (FDCs) improves adherence in several clinical areas. Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment.
  
  
  OBJECTIVE
  To assess whether FDC delivery of aspirin, statin, and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors, systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C).
  
  
  METHODS
  The UMPIRE trial, a randomized, open-label, blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe. The trial follow-up concluded in July 2012.
  
  
  METHODS
  Participants were randomly assigned (1:1) to an FDC-based strategy (n=1002) containing either (1) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or (2) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide or to usual care (n=1002).
  
  
  METHODS
  Adherence to medication (defined as self-reported use of antiplatelet, statin, and ≥2 BP-lowering medications) and changes in SBP and LDL-C from baseline.
  
  
  RESULTS
  At baseline, mean BP was 137/78 mm Hg, LDL-C was 91.5 mg/dL, and 1233 (61.5%) of 2004 participants reported use of antiplatelet, statin, and 2 or more BP-lowering medications. Median follow-up was 15 months (interquartile range, 12-18 months). The FDC group had improved adherence vs usual care (86% vs 65%; relative risk [RR] of being adherent, 1.33; 95% CI, 1.26-1.41; P < .001) with concurrent reductions in SBP (-2.6 mm Hg; 95% CI, -4.0 to -1.1 mm Hg; P < .001) and LDL-C (-4.2 mg/dL; 95% CI, -6.6 to -1.9 mg/dL; P < .001) at the end of the study. Although there was consistency of effects across predefined subgroups, evidence existed of larger benefits in patients with lower adherence at baseline. In this subgroup of 727 participants (36%), adherence at the end of study was 77% vs 23% (RR, 3.35; 95% CI, 2.74-4.09; P < .001 for interaction), SBP was reduced by 4.9 mm Hg (95% CI 7.3-2.6 mm Hg; P = .01 for interaction), and LDL-C was reduced by 6.7 mg/dL (95% CI, 10.5-2.8 mg/dL; P = .11 for interaction). There were no significant differences in serious adverse events or cardiovascular events (50 [5%] in the FDC group and 35 [3.5%] in the usual care group; RR, 1.45; 95% CI, 0.94-2.24; P=.09) between the groups.
  
  
  CONCLUSIONS
  Among patients with or at high risk of CVD, use of an FDC strategy for blood pressure, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01057537.
authors.affiliation: International Centre for Circulatory Health, Imperial College London, London, England. s.thom@imperial.ac.uk
authors.forename: Simon
authors.initials: S
authors.lastname: Thom
authors.forename: Neil
authors.initials: N
authors.lastname: Poulter
authors.forename: Jane
authors.initials: J
authors.lastname: Field
authors.forename: Anushka
authors.initials: A
authors.lastname: Patel
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.forename: Alice
authors.initials: A
authors.lastname: Stanton
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.forename: K Srinath
authors.initials: KS
authors.lastname: Reddy
authors.forename: Raghu
authors.initials: R
authors.lastname: Cidambi
authors.forename: Severine
authors.initials: S
authors.lastname: Bompoint
authors.forename: Laurent
authors.initials: L
authors.lastname: Billot
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodgers
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage; D001262:Atenolol / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D017706:Lisinopril / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage; D016896:Treatment Outcome; D016903:Drug Monitoring
chemical_list: D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D008078:Cholesterol, LDL; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D006852:Hydrochlorothiazide; D001262:Atenolol; D019821:Simvastatin; D017706:Lisinopril; D001241:Aspirin