Abstract
BACKGROUND: The primary objective of this analysis is to assess if greater exposure to any major antihypertensive drug class was associated with reduced primary composite outcome events in SPRINT (Systolic Blood Pressure Intervention Trial). METHODS: This is a secondary analysis of the SPRINT trial evaluating whether longitudinal, time varying exposure to any major antihypertensive drug class had any impact on primary outcome events, after adjusting for effects of randomization arm, time varying achieved systolic blood pressure, other drug class exposure, and baseline characteristics. RESULTS: Nine thousand two hundred fifty-two participants were included. After adjustments, exposure of one year or greater to thiazide-type diuretics or renin-angiotensin system blockers was associated with significantly fewer primary events than exposure of less than one year (hazard ratio, 0.78 [95% CI, 0.64–0.94]). There was no significant difference with longer versus shorter exposure to calcium channel blockers. Greater exposure to beta-blockers was associated with an increase in primary events compared with exposure of <1 year (hazard ratio, 1.35 [95% CI, 1.13–1.62]). Furthermore, thiazide-type diuretics were associated with a reduction in heart failure events and renin-angiotensin system blockers with reduced myocardial infarction. Both were associated with less cardiovascular deaths. CONCLUSIONS: The SPRINT trial demonstrated a lower target blood pressure led to reductions in adverse cardiovascular events. This analysis suggests greater exposure to thiazide-type diuretics and renin-angiotensin system blockers also contributed to reduced adverse cardiovascular events.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1112-1121 |
| Number of pages | 10 |
| Journal | Hypertension |
| Volume | 79 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2022 |
Bibliographical note
Funding Information:Longer exposure to an RAS blocker was also associated with reduced primary outcome events and notably, fewer myocardial infarctions. This finding is also supported by previous evidence. Numerous experimental studies reveal protective cardiovascular pharmacological effects of RAS blockers considered independent or in addition to their blood-pressure lowering effects. Randomized clinical trials also support blood-pressure independent effects of ACE inhibitors including the HOPE (Heart Outcomes Prevention Evaluation Study) and EUROPA (European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease), both demonstrating substantial improvements in cardiovascular outcomes (including myocardial infarction) with their addition to therapeutic regimens, many already receiving other antihypertensive agents. The inference of RAS blocker pharmacological effects extending beyond blood pressure reduction has also been supported by their wide success in improving outcomes in patients after myocardial infarction or with heart failure or chronic kidney disease. A Blood Pressure Lowering Treatment Trialists’ Collaboration review of the early evidence concluded ACE inhibitors exhibit protective effects independent of a lower blood pressure with a particular effect on reducing risks of future coronary heart disease events, similar to the outcomes measured in SPRINT. There has been less data for the ARB class due to their later discovery and absence from large RCT’s included in previous meta-analyses. However, like the ACE inhibitors, blood-pressure independent benefits of the ARB drug class are supported by randomized clinical trial evidence with positive findings of the ON-TARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global End point Trial) and LIFE (Losartan Intervention For End point reduction in hypertension study) trials. A Cochrane meta-analysis and two recent new-user comparative cohort studies conclude no comparable differences in efficacy between the 2 drug class. Overall, our results are consistent with and contribute further to evidence supporting blood-pressure independent protective vascular effects of RAS blockers showing that longer exposure decreased cardiovascular events (including death) and myocardial infarction after accounting for the effects of achieved blood pressure and randomization arm. , ,
Publisher Copyright:
© 2022 American Heart Association, Inc.
Keywords
- antihypertensive agents
- blood pressure
- clinical outcomes
- hypertension
- thiazide
PubMed: MeSH publication types
- Journal Article
- Randomized Controlled Trial