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Cited by 405Medication Adherence and ComplianceBlood Pressure and Hypertension StudiesLipoproteins and Cardiovascular Health

Effects of a Fixed-Dose Combination Strategy on Adherence and Risk Factors in Patients With or at High Risk of CVD

Thom·2013·JAMA
DOI 10.1001/jama.2013.277064
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Abstract

IMPORTANCE: 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). DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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). MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01057537.

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  • The UMPIRE randomized controlled trial compared a fixed-dose combination containing aspirin, a statin and two blood-pressure-lowering agents with usual care in both primary and secondary prevention in 2004 randomized patients in India and Europe.

    “The Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE) RCT 482 compared an FDC containing aspirin, statin and two blood pressureelowering agents with usual care in both primary and secondary prevention in 2004 randomized patients in India and Europe.”

    From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [482]

  • At 15 months, statistically significant differences between the intervention and usual care were seen in self-reported adherence and changes in systolic blood pressure and LDL-C.

    “At 15 months, statistically significant differences between intervention and usual care were seen in self-reported adherence and changes in systolic blood pressure and LDL-C.”

    From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [482]

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Authors
Thom
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2013-09-04
Volume
310
Issue
9
Pages
918
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2013.277064
OpenAlex
W2097285811
Cited by
405
References
35
Citations by year
2026: 10 · 2025: 13 · 2024: 35 · 2023: 23 · 2022: 24 · 2021: 24 · 2020: 32 · 2019: 21 · 2018: 34 · 2017: 52 · 2016: 39 · 2015: 31 · 2014: 54 · 2013: 11
FWCI
36.71
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
fixed-dose combination, medication adherence, cardiovascular disease, aspirin, simvastatin, lisinopril, atenolol, hydrochlorothiazide
MeSH terms
Assessment of Medication Adherence, Aged, Anticholesteremic Agents, Antihypertensive Agents, Aspirin, Atenolol, Blood Pressure

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