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

Area of Science:

• Cardiology
• Pharmacology
• Machine Learning

Background:

• The ACCOMPLISH trial compared benazepril/amlodipine with benazepril/hydrochlorothiazide for systolic hypertension.
• Previous findings suggest superior cardiovascular protection with the benazepril/amlodipine combination.

Purpose of the Study:

• To compare the relative importance of risk factors, particularly blood pressure control, in predicting cardiovascular outcomes between the two treatment groups.
• To investigate potential blood pressure-independent cardio-protective effects of benazepril/amlodipine.

Main Methods:

• Utilized random survival forest, a machine learning technique, to determine variable importance factors (VIFs).
• Analyzed VIFs for risk factors, focusing on achieved systolic blood pressure at 6 months, to predict the primary composite cardiovascular outcome.
• Compared VIFs between the benazepril/amlodipine and benazepril/hydrochlorothiazide treatment arms.

Main Results:

• Six risk factors showed significantly different VIFs between the treatment groups.
• All identified risk factors had lower VIFs in the benazepril/amlodipine group.
• The VIF for achieved systolic blood pressure at 6 months was 35% lower with benazepril/amlodipine (0.082) compared to benazepril/hydrochlorothiazide (0.126).

Conclusions:

• Blood pressure control was less critical for preventing cardiovascular events with benazepril/amlodipine.
• These findings support the hypothesis that benazepril/amlodipine offers clinically relevant cardio-protective actions independent of blood pressure reduction.
• The study highlights the potential for combination therapy to provide benefits beyond simple blood pressure lowering.