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

Abstract

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 twophase 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. freedose 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. freedose 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.

The Number of Pills, Rather Than the Type of Renin–Angiotensin System Inhibitor, Predicts Ambulatory Blood Pressure Control in Essential Hypertensives on Triple Therapy: A Real-Life Cross-Sectional Study

“…A recent population-based retrospective cohort study found that the risk of primary outcome (composite of death or hospitalization for acute myocardial infarction, heart failure, or stroke) was lower in patients taking single-pill fixed-dose combination treatment in the intention-to-treat analysis only, while if the analysis was limited to patients who remained adherent to medication (on treatment analysis) the significance of the association was lost, stressing the key role of treatment adherence [37]. In a recent review, Tsioufis et al concluded that further evidence is needed to determine if the increase in adherence seen in patients taking single-pill combinations will translate into better BP control and improved CV outcomes [45]. In this context, only three studies have investigated this aspect using ABPM [46][47][48].…”

Adherence to Antihypertensive Therapy: A Systematic Review of Russian Prospective Studies from 2000 to 2019

“…Наиболее часто для повышения приверженности применялась оптимизация режима приема лекарств, которая заключалась в назначении ФК вместо приема нескольких лекарственных препаратов [7,8,11,[16][17][18][20][21][22]26]. Показана эффективность данного подхода -увеличение среднего балла по шкале МГ-4, доли приверженных пациентов по шкале МГ-4 и по данным оригинального опросника, повышение комплаентности при подсчете таблеток, что согласуется результатами аналогичных зарубежных исследований [27].…”

Shunaoxin pills improve the antihypertensive effect of nifedipine and alleviate its renal lipotoxicity in spontaneous hypertension rats

“…In this study, the mRNA expression levels of SREBP‐1 and FASN in kidney were obviously increased in nifedipine‐treated group, but down‐regulated in combination group. In addition, clinical and experimental evidence suggested that dyslipidemia is a cause for the progression of the accumulation of lipid in renal cells and chronic kidney disease 16,25 . SNX significantly reduced the nifedipine‐induced dyslipidemia in SHR.…”

“…Moreover, ligustilide‐rich total lactones isolated from SNX regulated the lipid metabolic disorder 15 . Combination therapy was recognized to apparently alleviate patient adherence, and some evidence suggested combination therapy can improve the antihypertensive effect and cardiovascular outcomes 16 . The aim of this study was to observe the synergistic antihypertensive effect and to explore whether SNX mitigate nifedipine‐induced renal lipotoxicity.…”