Antihypertensive Combinations Modify Cardiovascular Risk Factor Importance: A Machine Learning Analysis of the ACCOMPLISH Trial.

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.