What is the clinical evidence from this study?

Study design: Other. Population: Systolic Hypertension. Intervention: Benazepril with amlodipine vs. Benazepril with hydrochlorothiazide. Primary outcome: Primary composite cardiovascular outcome.

What question did this study set out to answer?

This research aims to determine how antihypertensive combinations impact cardiovascular risk factor significance.

May 16, 2026Open Access

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

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).

Key Points

This research aims to determine how antihypertensive combinations impact cardiovascular risk factor significance.
Applied random survival forest analysis to compare risk factors from ACCOMPLISH trial data.
Focused on the variable importance factor for predicting primary composite cardiovascular outcomes between treatment groups.
Examined differences in blood pressure control between benazepril/amlodipine and benazepril/hydrochlorothiazide.
The variable importance factor for systolic blood pressure at 6-months was 35% lower in the benazepril/amlodipine group (0.082) compared to the benazepril/hydrochlorothiazide group (0.126).
Lower variable importance factors for risk factors were observed under the benazepril/amlodipine combination, indicating a reduced role of BP control in predicting cardiovascular events.
Findings support the theory of clinically relevant cardio-protective actions of the benazepril/amlodipine combination independently of blood pressure.

Structured PICO

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?

Population

Patients living with systolic hypertension from the ACCOMPLISH trial

Intervention

Benazepril/amlodipine combination

Comparator

Benazepril/hydrochlorothiazide combination

Outcome

Primary composite cardiovascular outcomecomposite

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.

Abstract

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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