Zilebesiran Add-On Treatment for Inadequately Controlled Hypertension—Reply

In Reply In their Letter, Drs Chen and Zhu highlight baseline differences in BMI and prior use of antihypertensive therapy in patients randomized to receive zilebesiran vs placebo in the KARDIA-2 trial. We did not include formal P values for between-group differences in our article’s Table 1 per JAMA style, but we can clarify that observed numerical differences in these variables at baseline were not statistically important for the overall study population or for the individual background therapy cohorts. Our statistical analysis plan prespecified covariate adjustment for baseline systolic blood pressure (SBP) and estimated glomerular filtration rate, but not BMI and number of prior antihypertensive medications for the primary analysis. Importantly, the differences in BMI and prior use of antihypertensives in the zilebesiran and placebo groups were small and unlikely to be clinically important; overall, mean BMI was similar (approximately 32.5) among patients randomized to receive zilebesiran or placebo within and across cohorts, and prior antihypertensive medication ranged from 83% to 89% in patients randomized to the zilebesiran group and 85% to 95% in patients randomized to the placebo group. Of note, the prior phase 1 and KARDIA-1 studies showed no effect of zilebesiran on body weight.