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J Hypertens. 2020 Feb 12. doi: 10.1097/HJH.0000000000002381. [Epub ahead of print]

Impact of single-pill combination therapy on adherence, blood pressure control, and clinical outcomes: a rapid evidence assessment of recent literature.

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First Cardiology Clinic, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Klinische Pharmakologie und Toxikologie, Berlin, Germany.
Medical Affairs, Pfizer Upjohn Hellas Ltd, Athens, Greece.
Medical Affairs, Pfizer Upjohn, Cappelle a/d Ijssel, The Netherlands.
Medical Affairs, Pfizer Upjohn, New York, New York, USA.



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.


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.


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.


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.

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