Do sex differences exist in the treatment with single-pill antihypertensive combinations?

There are noticeable sex differences in the treatment response to antihypertensives, with limited data on the response to single pill combinations. The aim of the PRECIOUS trial (Fixed-Dose Combination of Perindopril/Amlodipine and Fixed-Dose Combination of Perindopril/Amlodipine/Indapamide – Contribution to Management in Newly Diagnosed and Uncontrolled Hypertensive Patients) was to assess the treatment response to dual and triple single-pill combination in men and women.

440 adults with essential hypertension were assessed in the 16-week interventional, open-label, prospective, international, multicentre trial. Based on the previous antihypertensive therapy, patients were assigned to either perindopril/amlodipine 4/5 mg or perindopril/amlodipine/indapamide 4/5/1.25 mg, with the initial dose up-titrated in 4-week intervals in case of uncontrolled blood pressure. An additional analysis was performed for sex- and age-related differences on the blood pressure response and arterial stiffness in men and women aged 35–74 years.

Women achieved better overall blood pressure control in all age groups, except for the 35–44 age group. Women presented higher average 24-hour aortic augmentation indexes than men, but had more pronounced decreasing trends. The pulse wave velocity was only age-dependent, with reductions slightly greater in women. Both the aortic augmentation index and pulse wave velocity were significantly decreased in all groups compared to baseline.

The results of the PRECIOUS trial contribute significant data to the expanding body of evidence on sex differences in hypertension, including the aspect of age-related changes during the life course of women. The differences between same-aged men and women tend to be smaller with advancing age, but with a greater treatment response in women in all age groups for all observed blood pressure parameters and arterial stiffness.

ClinicalTrials.gov identifier: NCT03738761

Publications

Brguljan Hitij J, Gaciong Z, Simić D, Vajer P, Zelveian P, Chazova IE, Jelaković B., et al. Precious trial investigators. Differences in sex and age response to single pill combination based antihypertensive therapy reflecting in blood pressure and arterial stiffness. Journal of Hypertension. 2025;43(3):p387-396. https://doi.org/10.1097/HJH.0000000000003901

Brguljan Hitij J, Gaciong Z, Simić D, Vajer P, Zelveian P, Chazova IE, Jelaković B., et al. Hypertension control in men and women: the role of perindopril-based SPC treatment. Cardiol Croat. 2025;20(7-8):204-9.  https://doi.org/10.15836/ccar2025.204