Table 3. Publication summary of the purpose, number of patients, study type, and conclusion.

A+B+C: angiotensin-converting inhibitor + beta-blocker + calcium channel blocker; A+C+D: angiotensin-converting inhibitor + calcium channel blocker + diuretics; BP: blood pressure; FDTC: Family Drug Treatment Court; MACE: major adverse cardiovascular events; n: number; PAINT: Perindopril-Amlodipine plus Indapamide combination for controlled hypertension Non-intervention Trial; RAAS: renin-angiotensin-aldosterone system; RCT: randomized controlled trial; RH: resistant hypertension; SPC: single-pill combination; SR: sustained release; SBP: systolic blood pressure; DBP: diastolic blood pressure.

Author and year of publication	Purpose	Number of patients	Study type	Results
Egan et al., 2022 [1]	This article provides a detailed overview and summary of the current literature regarding the use of SPCs for managing hypertension, with a particular focus on their use as initial therapy compared to monotherapy and multiple pill regimens. The review examines the impact of SPC on adherence, hypertension control, clinical outcomes, population health, and adverse effects. Additionally, an attempt is made to quantify the relative use of SPC compared to monotherapy and free-dose combinations in hypertension management. The barriers and potential pathways to more effective implementation and use of SPC in managing hypertension are also explored.	>250,000	Systematic Review	Research findings indicate that the incorporation of antihypertensive SPCs in national formularies, the endorsement of SPC utilization in national hypertension guidelines, and the convenient accessibility and cost-effectiveness of SPC in the market enhance the adoption of this therapeutic alternative.
Páll et al., 2014 [2]	The PAINT study was primarily designed to investigate the antihypertensive efficacy of a triple combination of antihypertensive drugs, namely perindopril, amlodipine, and indapamide SR, in patients who had previously been treated for hypertension but had not achieved target BP values. As a secondary objective, the study also analyzed changes in metabolic parameters.	6,088	Observational Study	The administration of a triple combination comprising perindopril, amlodipine, and indapamide SR has demonstrated effective control of BP in hypertensive patients who have previously experienced uncontrolled BP while under treatment with either a single antihypertensive drug or a combination therapy that included a RAAS inhibitor and amlodipine or hydrochlorothiazide.
Düsing et al., 2017 [4]	It has been estimated that a significant portion of patients require the use of three or more antihypertensive agents. The combination of agents from different classes has resulted in a notable reduction in BP, approximately five times greater than the effect of doubling the dose of a single agent. Furthermore, the use of drugs with complementary mechanisms of action may offer additional benefits beyond BP reduction, such as improved tolerability and higher rates of adherence to prescribed medication, in comparison with increasing the dose of a single agent.	>500,223	Systematic Review	In conclusion, combination therapy, including drugs from classes having complementary action, is advantageous in terms of BP reduction and control, particularly in high-risk patients, and may be associated with improved tolerability. Administration of combination therapy as SPC is capable of enhancing treatment adherence.
Lin et al., 2015 [5]	RH is strongly correlated with cardiovascular risks. The limitation of enrolling a large number of study participants constrains research on the treatment effects of RH. This research aims to assess the efficiency of treating resistant hypertension in Taiwanese patients using a triple combination therapy of antihypertensive drugs.	13,551	RCT	The A+C+D combination therapy seemed more effective than the A+B+C therapy in preventing MACE among patients with RH.
Volpe et al., 2020 [6]	As aforementioned, one-fourth to one-third of hypertensive patients fail to achieve BP control with dual combination therapies, requiring three or more antihypertensive agents.	>2,271	Systematic Review	Many hypertensive patients do not achieve adequate BP control with monotherapy or dual therapy, with almost one-third of subjects requiring three or more drugs to reach therapeutic targets. Triple combination therapy has been demonstrated to provide better results regarding the percentage of well-controlled subjects, office and 24-hour BP reduction, and time to achieve BP goals compared to dual-combination therapy, without a significant increase in adverse effects events.
Mazza et al., 2017 [7]	The study aimed to determine whether the FDTC or free combination therapy is more effective and easier to tolerate in reducing office and 24-hour BP levels.	92	Observational Study	The study finds administration of fixed-dose triple combination therapy comprising perindopril/indapamide/amlodipine has effectively reduced systolic and pulse pressure levels among patients exhibiting moderate hypertension that remains uncontrolled despite the use of dual fixed combination therapy.
Gorostidi and de la Sierra, 2013 [8]	The review aims to elucidate the benefits of combination therapy in managing hypertension, as well as the effectiveness of various antihypertensive combinations.	>3,666	Systematic Review	For the majority of patients with hypertension, the combination of antihypertensive drugs may be essential to attain satisfactory BP goals. Approaches to enhance BP control include the rapid transition from monotherapy to combination therapy, the primary treatment with a two-drug combination, and the application of fixed-dose combinations in a single pill.
Salam et al., 2014 [9]	The proposed study is a prospective, open, randomized, controlled clinical trial with a sample size of 700. It aims to compare the triple pill–based strategy to usual care in individuals with persistent mild-to-moderate hypertension. The inclusion criteria for the study are SBP of 140 mm Hg and DBP of 90 mm Hg, or SBP of 130 mm Hg and DBP of 80 mm Hg in patients with diabetes or chronic kidney disease, who are not on any or minimal drug therapy.	700	RCT	The present study aims to evaluate the potential benefits of early utilization of a low-dose triple combination therapy in tackling the challenges associated with hypertension control. The study seeks to investigate if such a strategy can aid in achieving BP control earlier, ensuring better adherence, and reducing the occurrence of adverse effects during less intensive clinical follow-up.
Epstein et al., 2013 [10]	The purpose of this review is to assess the efficacy and potential benefits of implementing fixed-dose triple combination therapy for the treatment and control of hypertension.	>407	Systematic Review	The utilization of combination therapy is a widely accepted cornerstone in the management of hypertension. It has been estimated that approximately one in every four patients will necessitate the use of three antihypertensive agents to attain proper BP control.
Konradi et al., 2022 [12]	The present study aims to assess the effectiveness and safety of the triple therapy comprising amlodipine 5 mg, bisoprolol 5 mg, and perindopril 5 mg in both SPC and other combination formats over a period of 12 weeks.	150	RCT	When faced with uncontrolled BP despite monotherapy at the maximum dose or bi-therapy at the initial dose, it may be beneficial to switch to triple therapy of amlodipine 5 mg, bisoprolol 5 mg, and perindopril 5 mg. This approach has resulted in a significant decrease in BP (p < 0.001), improved response to treatment, and a better BP control rate.
Thomopoulos et al., 2019 [13]	A systematic review and meta-analysis of RCTs comparing double-drug and triple-drug BP-lowering combinations support the guideline view that triple-drug combinations reduce BP levels to a greater extent than double-drug combinations.	116	Systematic Review	Until then, triple-drug combination antihypertensive treatments should replace dual-drug combinations whenever patients remain uncontrolled