P110 Initial Treatment With a Single Capsule Containing Half-Dose Quadruple Therapy vs Standard-Dose Dual Therapy in Hypertensive Patients (Quadual): A Randomized, Blinded, Crossover Trial

Background and Objective: Guidelines recognized the dual combination in initial antihypertensive therapy. Studies demonstrated low-dose quadruple combination antihypertensive was superior to monotherapy. However, whether low-dose quadruple therapy is better than dual combination is unknown. Methods: A randomized blinded crossover trial was conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23·75 mg + amlodipine 2·5 mg + indapamide 1·25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension. Patients were randomly assigned in a 1:1 ratio to two crossover sequences. Each sequence received four-weeks of either half-dose quadruple antihypertensives or standard-dose dual antihypertensives, followed by a two-week washout and crossover for four-weeks. Participants and researchers were blinded, except for randomization and drug coding. The primary outcome was the reduction of mean 24-hour systolic blood pressure in ambulatory blood pressure monitoring. Safety outcomes were adverse events and changes in biochemistry after treatment. Analyses were per intention to treat. This trial was prospectively registered on www.clinicaltrials.gov (NCT05377203), and is now complete. Results: A total of 90 eligible participants were randomized between July 13, 2022, and April 20, 2023. The mean age of the population was 43.88 years, and 25.6% were women. The mean baseline 24-h blood pressure was 145.59/93.84 mm Hg. Half-dose quadruple treatment compared with standard-dose dual treatment further reduced mean 24-hour blood pressure by 4.72/4.17 mm Hg (P < 0.001 for both systolic and diastolic blood pressure). Except for fasting blood glucose (P = 0.029) and blood uric acid increased significantly (P < 0.001) in half-dose quadruple group, other adverse events and changes in laboratory values between the two treatments were not statistical different. Conclusions: Initiating treatment with half-dose quadruple combination therapy was more effective in lowering blood pressure than standard-dose dual therapy. The safety of half-dose quadruple therapy was comparable.