Impact of baseline cardiovascular risk on hypertension treatment with a novel triple single-pill: a subanalysis of the OPTION TREAT Trial

Background Although cardiovascular risk guides initiation of antihypertensive therapy, its influence on the response to single-pill combination regimens remains unclear. Purpose To assess whether baseline cardiovascular risk modifies treatment effects on systolic blood pressure reduction at 12 weeks. Methods The OPTION TREAT trial compared a novel triple single-pill combination (candesartan cilexetil 16 mg, amlodipine 5 mg, and chlorthalidone 12.5 mg) with an active control (valsartan 160 mg, hydrochlorothiazide 12.5 mg, and amlodipine 5 mg) in patients with uncontrolled hypertension. This secondary analysis aimed to assess whether baseline cardiovascular risk, estimated by the PREVENT score, modifies treatment effects on systolic blood pressure (SBP) from baseline to 12 weeks. Patients were stratified into high cardiovascular risk, defined as an estimated 10-year risk >20% by the American Heart Association PREVENT™ Online Calculator, or low/intermediate risk. A mixed-effects model was fitted with random intercepts for center, fixed effects for treatment and cardiovascular risk category, a risk-by-treatment interaction term, and baseline SBP as a covariate. Results Of the 703 randomized participants, 666 had complete data for PREVENT Score calculation and were included in the present analysis. Mean age was 57.6 ± 10.2 years; 62.9% were women. A total 134 (20.1%) were classified as high cardiovascular risk at baseline and 532 (79.9%) as low/intermediate risk. Baseline SBP was higher in the high-risk group (159.0 ± 12.6 mmHg vs. 151.1 ± 9.5 mmHg). In the experimental arm, mean changes in SBP were −22.9 ± 18.9 mmHg in participants at high cardiovascular risk and −24.2 ± 14.7 mmHg in those at low/intermediate risk. In the active control arm, changes in SBP were −19.2 ± 16 mmHg and −19.5 ± 15.3 mmHg, respectively. Pooling data from both treatment arms, participants at low/intermediate cardiovascular risk appeared to achieve greater SBP reduction compared with those at high risk (least-square mean difference: −4.13 mmHg; 95% CI −7.0 to −1.3; p=0.004). The novel triple single-pill combination was associated with SBP least-square means differences of −5.4 mmHg (95% CI −7.9 to −2.9) in participants at low/intermediate cardiovascular risk and of −2.8 mmHg (95% CI −7.7 to 2.2) in those at high cardiovascular risk, compared with the active control (nonsignificant p interaction). Conclusion Patients at low/intermediate cardiovascular risk appeared to achieve greater overall SBP reductions than those at high risk. The treatment effect of the novel triple single-pill relative to active control was consistent across cardiovascular risk strata, with no evidence of effect modification. These findings suggest that risk stratification may help anticipate the magnitude of SBP reduction, supporting a more tailored treatment approach.