Key result
Benazepril/amlodipine combination therapy had a 35% lower variable importance factor for achieved systolic BP at 6-months (0.082) compared to benazepril/hydrochlorothiazide (0.126).
Why the study?
Prior findings suggested benazepril plus amlodipine provides superior cardiovascular protection compared with benazepril plus hydrochlorothiazide potentially in a blood pressure-independent manner, which warranted evaluation using machine learning.
Does benazepril/amlodipine combination reduce the relative importance of in-trial blood pressure control for predicting cardiovascular outcomes compared to benazepril/hydrochlorothiazide in patients with systolic hypertension?
Does benazepril/amlodipine combination reduce the relative importance of in-trial blood pressure control for predicting cardiovascular outcomes compared to benazepril/hydrochlorothiazide in patients with systolic hypertension?
Machine learning analysis of the ACCOMPLISH trial suggests that benazepril/amlodipine provides cardiovascular protection in a more blood pressure-independent manner compared to benazepril/hydrochlorothiazide.
Suggests cardiovascular protection beyond BP lowering with benazepril/amlodipine; hypothesis-generating and should not yet change practice.
Results from the ACCOMPLISH (Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic Hypertension) trial suggest that combining benazepril with amlodipine, rather than hydrochlorothiazide, provides superior cardiovascular protection potentially in a BP-independent manner. We employed random survival forest, a powerful machine learning approach, to compare the relative importance of risk factors (i.e., variable importance factor (VIF)), focusing on in-trial BP control for predicting the primary composite cardiovascular outcome in the 2 treatment limbs. Among the 6 risk factors with significantly different VIFs between treatments, all were lower under benazepril/amlodipine combination. The VIF for achieved systolic BP at 6-months was 35% lower in the benazepril/amlodipine (0.082) versus the benazepril/hydrochlorothiazide (0.126) limb. The fact that in-trial BP control was less important for preventing cardiovascular events during benazepril/amlodipine treatment provides novel support for our contention that this combination regimen provides a degree of clinically-relevant cardio-protective actions in a BP-independent manner.
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Kaciroti et al. (2026) studied Systolic Hypertension. Benazepril with amlodipine vs. Benazepril with hydrochlorothiazide was evaluated on Primary composite cardiovascular outcome. Benazepril/amlodipine combination therapy had a 35% lower variable importance factor for achieved systolic BP at 6-months (0.082) compared to benazepril/hydrochlorothiazide (0.126).
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