Impact of antihypertensive drug classes on cardiovascular outcomes: insights from the STEP study

Abstract Background The optimal class of antihypertensive drugs for reducing cardiovascular risk remains unclear. This study investigated whether prolonged exposure to specific antihypertensive drug classes is associated with lower cardiovascular risk in individuals with well-controlled blood pressu...

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Main Authors: Xinyi Peng, Michael Hecht Olsen, Manan Pareek, Jingjing Bai, Yang Liu, Qirui Song, Jun Cai
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Medicine
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Online Access:https://doi.org/10.1186/s12916-025-04158-z
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author Xinyi Peng
Michael Hecht Olsen
Manan Pareek
Jingjing Bai
Yang Liu
Qirui Song
Jun Cai
author_facet Xinyi Peng
Michael Hecht Olsen
Manan Pareek
Jingjing Bai
Yang Liu
Qirui Song
Jun Cai
author_sort Xinyi Peng
collection DOAJ
description Abstract Background The optimal class of antihypertensive drugs for reducing cardiovascular risk remains unclear. This study investigated whether prolonged exposure to specific antihypertensive drug classes is associated with lower cardiovascular risk in individuals with well-controlled blood pressure. Methods This study utilised data from the STEP trial, which enrolled elderly, hypertensive Chinese patients with no history of stroke. After excluding 234 patients lost to follow-up and 20 patients without blood pressure records after randomisation, 8257 patients were included. The relative time on each antihypertensive drug (medication time/event time) was calculated. The primary outcome was a composite of the first occurrence of stroke, acute coronary syndrome (ACS), acute decompensated heart failure, coronary revascularisation, atrial fibrillation, and cardiovascular death. Secondary endpoints included individual components of the primary outcome. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome. Results Over a median 3.34 years follow-up, primary outcome analysis revealed that longer relative exposure to angiotensin II receptor blockers (ARBs) or calcium channel blockers (CCBs) significantly reduced cardiovascular risk. Each unit increase in relative time on ARBs was associated with a 45% lower risk of the primary outcome (HR 0.55, 95% CI 0.43–0.70), whereas CCBs reduced risk by 30% (HR 0.70, 95% CI 0.54–0.92). Diuretics demonstrated neutral results. Conversely, longer relative time on beta-blockers was linked to a higher primary outcome risk (HR 2.20, 95% CI 1.81–2.68). Regarding secondary outcomes, extended exposure to both ARBs and CCBs was significantly associated with lower risks of all-cause and cardiovascular mortality. Longer exposure to ARBs produced additional benefits by reducing risks of stroke, ACS, and major adverse cardiac events (MACE). The HRs for ARBs per-unit increase in relative time remained consistently lower than those of CCBs across the primary outcome, MACE, and stroke (all P < 0.05). Conclusions This post hoc analysis suggested that ARBs and CCBs might be more favourable for composite cardiovascular outcomes than diuretics and beta-blockers. ARBs appeared to offer greater cardiovascular benefits than CCBs. Longer exposure to beta-blockers was associated with a higher cardiovascular risk, which might reflect a selection bias based on medical indications. Trial registration STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.
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spelling doaj-art-c040662c7b224379b26a0836c71b5c8d2025-08-20T03:03:25ZengBMCBMC Medicine1741-70152025-07-0123111010.1186/s12916-025-04158-zImpact of antihypertensive drug classes on cardiovascular outcomes: insights from the STEP studyXinyi Peng0Michael Hecht Olsen1Manan Pareek2Jingjing Bai3Yang Liu4Qirui Song5Jun Cai6State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Clinical Medicine, University of CopenhagenDepartment of Cardiology, Copenhagen University Hospital—Rigshospitalet Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical UniversityDepartment of Epidemiology and Biostatistics, School of Public Health, Peking UniversityState Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background The optimal class of antihypertensive drugs for reducing cardiovascular risk remains unclear. This study investigated whether prolonged exposure to specific antihypertensive drug classes is associated with lower cardiovascular risk in individuals with well-controlled blood pressure. Methods This study utilised data from the STEP trial, which enrolled elderly, hypertensive Chinese patients with no history of stroke. After excluding 234 patients lost to follow-up and 20 patients without blood pressure records after randomisation, 8257 patients were included. The relative time on each antihypertensive drug (medication time/event time) was calculated. The primary outcome was a composite of the first occurrence of stroke, acute coronary syndrome (ACS), acute decompensated heart failure, coronary revascularisation, atrial fibrillation, and cardiovascular death. Secondary endpoints included individual components of the primary outcome. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome. Results Over a median 3.34 years follow-up, primary outcome analysis revealed that longer relative exposure to angiotensin II receptor blockers (ARBs) or calcium channel blockers (CCBs) significantly reduced cardiovascular risk. Each unit increase in relative time on ARBs was associated with a 45% lower risk of the primary outcome (HR 0.55, 95% CI 0.43–0.70), whereas CCBs reduced risk by 30% (HR 0.70, 95% CI 0.54–0.92). Diuretics demonstrated neutral results. Conversely, longer relative time on beta-blockers was linked to a higher primary outcome risk (HR 2.20, 95% CI 1.81–2.68). Regarding secondary outcomes, extended exposure to both ARBs and CCBs was significantly associated with lower risks of all-cause and cardiovascular mortality. Longer exposure to ARBs produced additional benefits by reducing risks of stroke, ACS, and major adverse cardiac events (MACE). The HRs for ARBs per-unit increase in relative time remained consistently lower than those of CCBs across the primary outcome, MACE, and stroke (all P < 0.05). Conclusions This post hoc analysis suggested that ARBs and CCBs might be more favourable for composite cardiovascular outcomes than diuretics and beta-blockers. ARBs appeared to offer greater cardiovascular benefits than CCBs. Longer exposure to beta-blockers was associated with a higher cardiovascular risk, which might reflect a selection bias based on medical indications. Trial registration STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.https://doi.org/10.1186/s12916-025-04158-zAngiotensin II receptor blockerCalcium channel blockerFirst-line antihypertensive drugAntihypertensive drug classCardiovascular outcomes
spellingShingle Xinyi Peng
Michael Hecht Olsen
Manan Pareek
Jingjing Bai
Yang Liu
Qirui Song
Jun Cai
Impact of antihypertensive drug classes on cardiovascular outcomes: insights from the STEP study
BMC Medicine
Angiotensin II receptor blocker
Calcium channel blocker
First-line antihypertensive drug
Antihypertensive drug class
Cardiovascular outcomes
title Impact of antihypertensive drug classes on cardiovascular outcomes: insights from the STEP study
title_full Impact of antihypertensive drug classes on cardiovascular outcomes: insights from the STEP study
title_fullStr Impact of antihypertensive drug classes on cardiovascular outcomes: insights from the STEP study
title_full_unstemmed Impact of antihypertensive drug classes on cardiovascular outcomes: insights from the STEP study
title_short Impact of antihypertensive drug classes on cardiovascular outcomes: insights from the STEP study
title_sort impact of antihypertensive drug classes on cardiovascular outcomes insights from the step study
topic Angiotensin II receptor blocker
Calcium channel blocker
First-line antihypertensive drug
Antihypertensive drug class
Cardiovascular outcomes
url https://doi.org/10.1186/s12916-025-04158-z
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