Contribution of single-pill combinations in the management of hypertension: perspectives from China, Europe and the USA

Figures & data

Figure 1. Mean differences changes in blood pressure over time in patients with hypertension receiving a single-pill combination vs. a free combination of the same treatments from a meta-analysis. Data shown are mean treatment differences for SPC vs. free combination from a fixed effects model meta-analysis; bars are 95%CI. Negative treatment differences favour the single pill combination (SPC). Drawn from data presented in reference³⁴.

Table 1. Adherence and persistence with antihypertensive therapy with 2-agent single pill combinations (SPC) vs. the corresponding free combination (FC) from a systematic review and meta-analysis.

No. of studies	Adherence (23 studies)	Persistence (16 studies)
Significantly better for SPC vs. FC	18	14
Numerically better for SPC vs. FC^a	1	2
Similar for SPC and FC	3	0
Numerically better for FC vs. SPC^a	0	0
Significantly better for SPC vs. FC	1	0

Data shown in the table are the numbers of studies reporting the outcomes shown. ^aSubstantial numerical benefit shown, but statistical analysis was not performed. Compiled from data presented in reference 35.

Figure 2. Odds of achieving good adherence and persistence with antihypertensive therapy for treatment with a single-pill combination (SPC) vs. free combination of antihypertensive agents from a meta-analysis. Data for adherence show odds ratios of achieving proportion of days covered (PDC) or medication possession ratio (MPR) ≥80% for SPC vs. free combination. Data for persistence = hazard ratios for time to a treatment gap of at least 30 or 60 days for SPC vs. free combination, or for an answer of “yes” to the question “was there a 30 day treatment gap at any time during the study?”. Drawn from data presented in reference³⁵.

Table 2. Overview of key recommendations for the initiation of pharmacologic management of hypertension in guidelines from China, Europe and the USA and from selected global guidelines.

	China^63^,^64	Europe^2,^3	USA^65	Global (ISH)^66	Global (WHO)^67
Initiation of pharmacologic antihypertensive therapy	Any of the main five classes of anti-hypertensive can be used to initiate treatment (use long-acting agents where possible) Start with a low dose in the elderly (may titrate to the full dose, depending on response)	RAAS blockers, CCB, diuretics are usually used for initiation of pharmacotherapy (BB used for specific indications, such as stable IHD, stable CHF)	First-line agents include thiazide diuretics, CCBs, and ACEI/ARB (BB used for specific indications, such as stable IHD, stable CHF)	Consider monotherapy for low-risk stage 1 hypertension or for very elderly (≥80 years) or frail patients Consider BB used for specific indications, such as stable IHD, stable CHF)	Pharmacologic antihypertensive therapy for BP ≥ 140/≥90 mmHg without comorbidities, or with SBP 130–139 mmHg if CVD, diabetes or high CV risk Initiate therapy with diuretic, ACEI/ARB, long-acting CCB or BB (BB for a patient with IHD)
Use of combination therapy	Use where monotherapy is insufficiently effective Consider combination treatment for BP >160/100 mmHg or 20/10 mmHg higher than the patient’s individualised target Consider low-dose combinations for BP >140/90	Use 2-agent combination therapy, ideally within a single tablet, for BP control in most people with hypertension RAAS blocker–CCB or diuretic combination is preferred initially	Initiate with monotherapy for a patient with Stage 1 hypertension and goal BP <130/80 mmHg Initiate with combination therapy (free combination of in a single tablet) for Stage 2 hypertension and BP >20/10 mmHg above target.	Support for initial use of low-dose combination therapy, starting with RAAS blocker + CCB SPCs are preferred to free combinations to reduce polypharmacy and increase adherence	Combination therapy is supported, “preferably in a single pill” and especially where BP is ≥20/10 mmHg above target Choose from thiazide, RAAS blocker, and long-acting dihydropyridine CCB for inclusion in a combination regimen

RAAS (renin-angiotensin-aldosterone system) blockers include angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB). Abbreviations. BB, β-blocker; CCB, dihydropyridine calcium channel blocker; CHF, congestive heat failure; CVD, cardiovascular disease; IHD, ischaemic heart disease; ISH, International Society of Hypertension; WHO, World Health Organization.

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