Chlorthalidone yielded greater BP-independent reductions in left ventricular mass index than lisinopril (MD -2.9 g/m2; 95% CI -5.6 to -0.2; p=0.035), with effects driven by Black participants.
RCT (n=134)
Does chlorthalidone improve cardiac remodeling independent of blood pressure reduction compared to amlodipine or lisinopril in untreated hypertensive patients?
Chlorthalidone provides greater blood pressure-independent improvements in left ventricular mass and diastolic remodeling compared to amlodipine or lisinopril in untreated hypertension, with effects predominantly driven by Black participants.
Mean Difference: -2.9 (95% CI -5.6–-0.2)
Absolute Event Rate: -3.7% vs -0.8%
p-value: p=0.035
Objective: Whether cardiac remodelling during antihypertensive treatment reflects blood pressure (BP) reduction or drug-specific effects remains uncertain. This study aimed to compare BP-independent effects of amlodipine, chlorthalidone and lisinopril on cardiac structure and function in untreated hypertension. Design and method: A subset of untreated hypertensive participants from the AIM-HY trial underwent transthoracic echocardiography at baseline and after eight weeks of monotherapy with amlodipine 10 mg od, chlorthalidone 25 mg od or lisinopril 20 mg od. Left ventricular mass index (LVMI), systolic function (ejection fraction and tissue Doppler S’), and diastolic indices (left atrial volume LAV and E/E’) were measured. Mixed-effects random-intercept regression models included baseline echocardiographic values, treatment and change in mean arterial pressure (MAP). Treatment-by-ethnicity interactions were tested. Results: A total of 134 participants were analysed (44% White, 42% Black, 14% South Asian; 64% male; mean age 46.5 11.6 years). MAP decreased with all treatments, with a greater reduction with amlodipine (-11.3 -13.0, -9.4 mmHg) than chlorthalidone (-6.7 -8.8, -4.6 mmHg; p=0.001) and lisinopril (-8.4 -10.9, -6.0 mmHg; p=0.07). After adjustment for MAP change, LVMI decreased most with chlorthalidone (-3.7 -6.3, -1.0 g/m2) compared with amlodipine (-1.4 -4.2, 1.4 g/m2) and lisinopril (-0.8 -3.5, 2.0 g/m2); the difference between chlorthalidone and lisinopril was significant (-2.9 -5.6, -0.2 g/m2; p=0.035) (Fig.). LAV decreased with chlorthalidone (-2.6 -5.5, 0.2 mL) but increased with amlodipine (2.8 -0.1, 5.7 mL); chlorthalidone produced greater reductions than amlodipine (-5.4 -8.2, -2.7 mL; p<0.001) and lisinopril (-3.2 -6.1, -0.3 mL; p=0.03). Systolic function did not differ between treatments. Treatment-by-ethnicity interactions were observed for LVMI (p=0.03) and LAV (p=0.05). Overall, treatment effects were predominantly driven by Black participants, with smaller or absent effects in White participants. Conclusions: Chlorthalidone demonstrated greater BP-independent effects on left ventricular mass and diastolic remodelling than amlodipine or lisinopril in untreated hypertension. Treatment-by-ethnicity interactions were observed with effects predominantly driven by Black participants. These findings support consideration of antihypertensive drug choice for cardiac remodelling beyond BP lowering.
Rory et al. (Fri,) conducted a rct in untreated hypertension (n=134). Chlorthalidone vs. Amlodipine (10 mg od) and Lisinopril (20 mg od) was evaluated on Change in left ventricular mass index (LVMI) adjusted for mean arterial pressure change (MD -2.9, 95% CI -5.6 to -0.2, p=0.035). Chlorthalidone yielded greater BP-independent reductions in left ventricular mass index than lisinopril (MD -2.9 g/m2; 95% CI -5.6 to -0.2; p=0.035), with effects driven by Black participants.