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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2025-07-01
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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 |
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| 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. |
| format | Article |
| id | doaj-art-c040662c7b224379b26a0836c71b5c8d |
| institution | DOAJ |
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| publishDate | 2025-07-01 |
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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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