Objective: The 2018 European Society of Cardiology/European Society of Hypertension Guidelines for the management of arterial hypertension raised the need for evidence to support the use of single-pill combination (SPC) therapy in preference to free-dosed therapy for hypertension. This systematic rapid evidence assessment sought to determine if initiating SPC therapy improves adherence, blood pressure (BP) control and/or cardiovascular outcomes vs. initiation of free-dose combination therapy.
Methods: Rapid evidence assessment conducted in MEDLINE, EMBASE, and Cochrane Library (1 January 2013-11 January 2019) to identify studies investigating SPC therapy for adults with hypertension. Information on adherence/persistence, BP lowering/goal attainment, and cardiovascular outcomes/events were extracted via two-phase screening process. Studies not focusing on adherence, persistence, or compliance with SPC therapy were excluded. Methodological quality was assessed using appropriate scales.
Results: Of 863 citations, 752 failed to meet inclusion or were duplicates. Twenty-nine studies remained following full-text screening. Just four studies (14%) were randomized controlled studies; 25 (86%) were observational. A range of SPC therapies were studied, with calcium channel blocker/angiotensin receptor blocker combinations most common (11/29 studies). Adherence and persistence were generally higher with SPC vs. free-dose combination therapy; 15 studies (54%) directly compared adherence and four (14%) compared persistence. Patients achieving BP targets ranged from 25 to 89%. Despite all studies investigating patients with hypertension only 16 (55%) reported change in BP. Few studies reported on cardiovascular outcomes. Methodological reporting was often suboptimal.
Conclusion: Adherence and/or persistence were generally higher in patients taking antihypertensives as SPC vs. free-dose combination; however, methodological reporting was suboptimal to facilitate comparison. Specifically designed, well reported studies are required to determine if the increased adherence/persistence seen in patients on SPC regimen leads to improved BP control and/or cardiovascular outcomes.
Impact of single-pill combination therapy on adherence, blood pressure control, and clinical outcomes: a rapid evidence assessment of recent literature.J Hypertens. 2020 Feb 12. doi: 10.1097/HJH.0000000000002381. Online ahead of print. J Hypertens. 2020. PMID: 32053523
Single Pill Regimen Leads to Better Adherence and Clinical Outcome in Daily Practice in Patients Suffering from Hypertension and/or Dyslipidemia: Results of a Meta-Analysis.High Blood Press Cardiovasc Prev. 2020 Apr;27(2):157-164. doi: 10.1007/s40292-020-00370-5. Epub 2020 Mar 26. High Blood Press Cardiovasc Prev. 2020. PMID: 32219670 Free PMC article.
Comparison of real-world adherence, healthcare resource utilization and costs for newly initiated valsartan/amlodipine single-pill combination versus angiotensin receptor blocker/calcium channel blocker free-combination therapy.J Med Econ. 2011;14(5):576-83. doi: 10.3111/13696998.2011.596873. Epub 2011 Jul 6. J Med Econ. 2011. PMID: 21728914
Fixed-dose combination therapy for the prevention of cardiovascular disease.Cochrane Database Syst Rev. 2014 Apr 16;4(4):CD009868. doi: 10.1002/14651858.CD009868.pub2. Cochrane Database Syst Rev. 2014. PMID: 24737108 Free PMC article. Updated. Review.
Screening for High Blood Pressure in Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force [Internet].Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Dec. Report No.: 13-05194-EF-1. Agency for Healthcare Research and Quality (US). 2014. PMID: 25632496 Free Books & Documents. Review.