AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
A Randomised Controlled Crossover Trial Evaluating Differential Responses to Anti-Hypertensive Drugs Used as Mono- and Dual-Therapy on the Basis of Ethnicity: The ComparIsoN oF Optimal Hypertension RegiMens; Part of the Ancestry and Biological Informative Markers in HYpertension Program, AIM-HY INFORM
By Faconti L, Chowienczyk PJ, Wilkinson IB
Background: Antihypertensive drug response may vary by ethnicity, potentially reflecting differences in renin-angiotensin-aldosterone system activity. We investigated whether blood pressure (BP) response to lisinopril, amlodipine, chlortalidone, their combinations, and amiloride plus chlortalidone differs by ethnicity, and whether plasma renin predicts response better than ethnicity. Methods: We conducted a prospective, open-label, randomised, blinded-endpoint (PROBE) crossover trial at UK centres in adults aged 18-65 years with primary hypertension who self-identified as black, South Asian, or white. Participants entered either a monotherapy arm (lisinopril, amlodipine, or chlortalidone, each for 8 weeks in random order) or a dual-therapy arm (lisinopril+amlodipine, lisinopril+chlortalidone, amlodipine+chlortalidone, or amiloride+chlortalidone). The primary endpoint was unattended systolic BP at the end of each treatment period. Analyses used mixed-effects models and included participants completing at least one treatment cycle. Findings: Between 2016 and 2024, 929 participants were randomised. In the monotherapy arm, 445 participants (115 black, 100 South Asian, 230 white) completed at least one treatment cycle; in the dual-therapy arm, 385 (137 black, 48 South Asian, 200 white) did so. Significant treatment-ethnicity interactions were observed. In black participants, systolic BP reductions with amlodipine and chlortalidone were greater than with lisinopril, with adjusted differences versus white participants of 11·9 mmHg (95% CI 8·6-15·3; p<0·001) and 13·2 mmHg (9·8-16·5; p<0·001), respectively. In South Asian participants, amlodipine and chlortalidone also produced greater BP reductions than lisinopril, with differences of 5·4 mmHg (1·8-9·1; p=0·004) and 3·9 mmHg (0·2-7·5; p=0·036), respectively, versus white participants. In black participants, lisinopril+chlortalidone reduced systolic BP by 7·8 mmHg (4·0-11·5; p<0·001) more than lisinopril+amlodipine and was the most effective combination across ethnic groups. Plasma renin predicted treatment response at least as well as ethnicity in both trial arms. Imagine 1 shows treatment changes according to ethnicty and plasma renin tertile in the monotherapy arm of the study. Interpretation: These findings support UK recommendations favouring calcium-channel blockers or thiazide-like diuretics as initial therapy in black people with uncomplicated hypertension and suggest similar advantages in South Asian populations. Combinations containing a diuretic were particularly effective in black patients and lisinopril plus chlortalidone was among the most effective regimens across all ethnic groups. Plasma renin may reduce the need for ethnicity-based prescribing. Trial Registration: ClinicalTrials.gov NCT02847338.