Triple antihypertensive single-pill combinations achieved higher blood pressure control compared to dual therapy (59% vs. 46%) and provided additional SBP/DBP reduction (5.4/3.2 mmHg).
Systematic Review (n=13,461)
Do triple antihypertensive single-pill combinations improve blood pressure reduction and control compared to dual therapy or usual care in patients with hypertension?
Triple antihypertensive single-pill combinations provide superior blood pressure reduction and control compared to dual therapy or usual care, supporting their inclusion in the WHO Essential Medicines List.
Absolute Event Rate: 59% vs 46%
Objective: Globally, blood pressure (BP) control remains suboptimal, despite the availability of effective therapies. Most patients require two or more medicines to achieve adequate BP control. Building on the 2019 inclusion of dual single-pill combinations (SPCs), the World Health Organization added triple antihypertensive SPCs to the 24th Model Essential Medicines List in 2025. This work aimed to examine the clinical, guideline, and policy rationale supporting the inclusion of triple antihypertensive SPCs as essential medicines. Design and method: We systematically reviewed the evidence base that underpinned our successful application to include triple antihypertensive SPCs (Valsartan/Amlodipine/Hydrochlorothiazide and Perindopril/Amlodipine/Indapamide) as essential medicines. We synthesised evidence on efficacy and safety of triple vs dual therapy, low-dose triple SPCs, adherence benefits of SPCs versus separate pills, recommendations in international guidelines and standardised treatment protocols, and comparative cost and cost-effectiveness. We also summarised policy implications for national formularies, procurement, and primary care integration. Results: Our systematic review of 17 randomized trials (13,461 participants) showed clinically meaningful additional SBP/DBP reduction (5.4/3.2 mmHg) and BP control (59% vs. 46%) with triple vs. dual therapy, with similar tolerability.Next, compared with usual care, ‘low dose’ triple SPC strategies demonstrated superior SBP/DBP reduction (7.2/4.0 mmHg) and additional BP control (80% vs. 65%) in four pragmatic trials, with faster time to control, less visits and fewer discontinuations due to adverse events. Evidence consistently supports improved adherence and persistence with triple SPCs compared to administering the same medicines as separate pills. Cost evidence suggests wide cross-country variation: in settings with robust manufacturing and procurement mechanisms, triple SPCs can be similarly priced to separate pills, with lower dispensing costs; elsewhere, they remain unaffordable. Implementation experience indicates that WHO EML inclusion should be accompanied by coordinated national action to ensure uptake, including guideline and protocol updates, pooled procurement, predictable financing, price regulation, clinician education to reduce treatment inertia, and integration into primary care. Conclusions: Triple antihypertensive SPCs are effective and well tolerated. Their inclusion in the WHO EML is an important policy signal to expand access. Realising the true population impact of triple SPCs requires coordinated national action and uptake.
Satheesh et al. (Fri,) conducted a systematic review in Hypertension (n=13,461). Triple antihypertensive single-pill combinations vs. Dual therapy was evaluated on Blood pressure control. Triple antihypertensive single-pill combinations achieved higher blood pressure control compared to dual therapy (59% vs. 46%) and provided additional SBP/DBP reduction (5.4/3.2 mmHg).