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Cardiac Effects of Renin-Angiotensin System Inhibitors in Nonproteinuric CKD
Rachel S Shulman1, Wei Yang2, Debbie L Cohen1
1Renal-Electrolyte and Hypertension Division (R.S.S., D.L.C., P.P.R., J.B.C.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Insights
Renin-angiotensin system inhibitors (RASIs) may offer cardioprotective benefits in nonproteinuric chronic kidney disease (CKD). Prioritizing RASIs for hypertension management in nonproteinuric CKD patients could reduce cardiovascular events and mortality.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Cardioprotective effects of antihypertensive medications are well-established in proteinuric chronic kidney disease (CKD).
- The benefits of specific antihypertensive classes in nonproteinuric CKD remain largely unknown.
- This study investigates cardiovascular outcomes in nonproteinuric CKD patients treated with renin-angiotensin system inhibitors (RASIs) versus other antihypertensives.
Purpose of the Study:
- To compare long-term cardiovascular outcomes and mortality in patients with nonproteinuric CKD.
- To evaluate the efficacy of RASIs versus alternative antihypertensive medications in this patient population.
Main Methods:
- Utilized data from the Chronic Renal Insufficiency Cohort (CRIC) study, focusing on participants without proteinuria.
- Employed intention-to-treat, per-protocol, and time-updated analyses with inverse probability of treatment weighting and Cox proportional hazards modeling.
- Assessed a composite cardiovascular outcome (myocardial infarction, stroke, heart failure hospitalization, death) and all-cause mortality.
Main Results:
- Intention-to-treat analyses showed no significant difference between RASIs and other antihypertensives for cardiovascular events or mortality.
- Per-protocol analyses revealed that RASIs were associated with a lower risk of adverse cardiovascular events and mortality.
- Time-updated analyses indicated that increased RASI use over time correlated with a reduced risk of mortality.
Conclusions:
- In nonproteinuric CKD, time-adjusted RASI use is linked to reduced cardiovascular events and mortality compared to other antihypertensives.
- Prioritizing RASIs for hypertension management in nonproteinuric CKD patients may improve cardiovascular outcomes and survival.
- Further research may solidify RASI's role in managing hypertension in nonproteinuric CKD.
Background:
In contrast to proteinuric chronic kidney disease (CKD), the relative cardioprotective benefits of antihypertensive medications in nonproteinuric CKD are unknown. We examined long-term cardiovascular outcomes and mortality in patients with nonproteinuric CKD treated with renin-angiotensin system inhibitors (RASIs) versus other antihypertensive medications.
Methods:
Among participants of the CRIC study (Chronic Renal Insufficiency Cohort) without proteinuria, we used intention-to-treat analyses with inverse probability of treatment weighting and Cox proportional hazards modeling to determine the association of RASIs versus other antihypertensive medications with a composite cardiovascular outcome (myocardial infarction, stroke, heart failure hospitalization, and death) and mortality. Secondary analyses included per-protocol analyses accounting for continuous adherence and time-updated analyses accounting for the proportion of time using RASIs during follow-up.
Results:
A total of 2806 participants met the inclusion criteria. In the intention-to-treat analyses, RASIs versus other antihypertensive medications were not associated with an appreciable difference in cardiovascular events (adjusted hazard ratio [aHR], 0.94 [95% CI, 0.80-1.11]) or mortality (aHR, 1.06 [95% CI, 0.88-1.28]). In the per-protocol analyses, RASIs were associated with a lower risk of adverse cardiovascular events (aHR, 0.78 [95% CI, 0.63-0.97]) and mortality (aHR, 0.64 [95% CI, 0.48-0.85]). Similarly, in the time-updated analyses, a higher proportion of RASI use over time was associated with a lower mortality risk (aHR, 0.33 [95% CI, 0.14-0.86]).
Conclusions:
Among individuals with nonproteinuric CKD, after accounting for time-updated use, RASIs are associated with fewer cardiovascular events and a lower mortality risk compared with other antihypertensive medications. Patients with nonproteinuric CKD may benefit from prioritizing RASIs for hypertension management.
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