Efficacy of Single-Pill, Triple Antihypertensive Therapy in Patients with Uncontrolled Hypertension: A Systematic Review and Meta-analysis

Abstract

Introduction: Systemic arterial hypertension is the most common preventable risk factor for all causes of morbidity and mortality worldwide with a prevalence of 35-40% of the adults. Despite the wide variety of effective antihypertensive medications, most hypertensive patients remain uncontrolled. However, the combination of ACE inhibitor, diuretics, and calcium antagonist for the triple therapy in a single Pill Combination (SPC) is an efficient regimen in hypertension management. It is recommended by the ESH 2018 guideline, which offers better efficacy and compliance to treatment.

Aim: To evaluate the efficacy of perindopril/indapamide/amlodipine single-pill combination in patients with uncontrolled hypertension.

Methods: We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL for relevant clinical trials. We conducted the risk of bias assessment using Cochrane's risk of bias tool. We performed the analysis of continuous data using mean difference (MD) and relative 95% confidence interval (CI), while dichotomous data were analyzed using risk ratio (RR) and relative 95% CI. We included the analysis of the following outcomes: systolic blood pressure (SBP), Diastolic blood pressure (DBP), Heart rate (HR), 24 h Ambulatory blood pressure monitoring (ABPM) for SBP, and 24 h ABPM for DBP.

Results: We included six clinical trials. We found that the triple therapy significantly reduces SBP by 24 mmHg (MD = - 24.65 [22.41, 26.89], (P < 0.01)), DBP by 12 mmHg (MD = 12.41 [11.53, 13.29], (P < 0.01)), 24-h ABPM for SBP by 14 mmHg (MD = 14.08 [9.10, 19.05], (P < 0.01)), and ABPM 24 h DBP by 7 mmHg (MD = 7.01 [5.37, 8.65], (P < 0.01)). We noted no significant difference of the single pill on heart rate (MD = 0.81 [- 0.04, 1.67], (P = 0.06).

Conclusion: perindopril/indapamide/amlodipine is effective in reducing systolic and diastolic blood pressures by 24 and 12 mmHg respectively. Over 24 h, the combination reduced systolic and diastolic blood pressures by 14 and 7 mmHg respectively.

Keywords: Hypertension; Meta-analysis; Single-pill therapy; Systematic review; Triple antihypertensive therapy.