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Have we fallen off target with concerns surrounding dual RAAS blockade?
Michael R Lattanzio1, Matthew R Weir
1Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Misinterpretation of the ONTARGET trial data has raised concerns about dual renin-angiotensin-aldosterone system (RAAS) blockade for kidney disease. This analysis clarifies its appropriate use in specific patient groups, particularly those with proteinuric kidney disease.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Pharmacology
Background:
- The ONTARGET trial's results have been misinterpreted, leading to unwarranted concerns about dual renin-angiotensin-aldosterone system (RAAS) blockade efficacy and safety for renal outcomes.
- Concerns primarily stem from the study's specific cohort (non-proteinuric CKD patients) and insufficient statistical power for renal endpoints.
Purpose of the Study:
- To critically analyze the ONTARGET study's findings in the context of dual RAAS blockade.
- To provide evidence-based substantiation for the use of dual RAAS blockade in specific kidney disease populations.
Main Methods:
- Critical review of the ONTARGET trial data.
- Analysis of existing literature on dual RAAS blockade in various patient cohorts.
- Examination of different dual RAAS blockade combinations (ACE inhibitors, ARBs, MRAs, DRIs).
Main Results:
- Dual RAAS blockade demonstrates cardiac and renal protective effects in select populations, notably proteinuric chronic kidney disease (CKD) and congestive heart failure (CHF).
- The study population in ONTARGET (non-proteinuric CKD) was not adequately powered to assess renal outcomes.
- Responses to dual RAAS blockade may vary across different patient groups and drug combinations.
Conclusions:
- Misinterpretation of the ONTARGET trial should not preclude the use of dual RAAS blockade in appropriate patients.
- Dual RAAS blockade is supported by literature for select populations, including those with proteinuric kidney disease.
- Further research and careful patient selection are warranted for optimizing dual RAAS blockade strategies.
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