Analyzing Patient Heterogeneity Upon Antihypertensive Therapy Initiation to Personalize Prognosis
Different responses to antihypertensive treatment were associated with different risk for cardiovascular events.
Heterogeneity exists in response to antihypertensive therapy, according to new data presented at the 66th Annual Scientific Session & Expo of the American College of Cardiology in Washington, DC.
Researchers from the Yale School of Medicine in New Haven, Connecticut, sought to examine patient heterogeneity in antihypertensive treatment responses in order to determine whether these differences have any prognostic implications on cardiovascular outcomes.
They applied growth mixture modeling to identify classes of systolic blood pressure (SBP) trajectories within the first 6 months of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT; ClinicalTrials.gov identifier: NCT00000542). They evaluated the treatment effects associated with each SBP trajectory class as well as the difference in combined cardiovascular disease between classes using log-rank and Cox proportional hazard models. Participants were placed in 1 of 2 responses classes based on their trajectory patterns: immediate responders (85.5%; decreasing SBP) and non-immediate responders (14.5%; an initially increasing SBP followed by a decrease).
Patients in the immediate responders group had a baseline mean SBP of 145 mm Hg, which decreased by 4.8 mm Hg within the first month and then plateaued. Patients in the non-immediate responders group had a baseline mean SBP of 154 mm Hg, which increased by 7.8 mm Hg within the first month following treatment initiation and then decreased.
The odds of being in the non-immediate responder group were higher for patients who were randomly assigned to amlodipine compared with patients assigned to chlorthalidone (odds ratio [OR], 1.20; 95% CI, 1.10-1.31), lisinopril (OR, 1.88; 95% CI, 1.73-2.03), or doxazosin (OR: 1.65; 95% CI, 1.52-1.78).
Non-immediate responders also had higher hazard ratio [HR] of stroke (HR: 1.48; 95% CI, 1.20-1.83), combined cardiovascular disease (HR: 1.21; 95% CI, 1.11-1.31), and heart failure (HR: 1.50; 95% CI, 1.25-1.80) during follow-up between 6 months and 2 years, after multivariable adjustment for baseline SBP, demographics, and past medical history.
“There is heterogeneity in response to initiation of antihypertensive therapies,” the researchers concluded. “Different response patterns are associated with different risk for cardiovascular events.”
Dhruva SS, Huang C, Spatz E, et al. Toward identifying personalized prognosis in hypertension: variation in early responses in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Abstract 1186-033. Presented at: The 66th Annual Scientific Session & Expo of the American College of Cardiology. March 17-19, 2017; Washington, DC.