Dual renin-angiotensin system blockade in the ONTARGET study: clinically relevant risk for the kidney?

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Inhibition of the renin-angiotensin system (RAS) is crucial for managing chronic kidney disease (CKD).
• ACE inhibitors and ARBs slow CKD progression and reduce proteinuria but offer incomplete blockade.
• Combination therapy aims for superior renoprotection and cardioprotection via complete RAS blockade.

Purpose of the Study:

• To review the evidence on combination RAS inhibition strategies for CKD.
• To analyze the findings of the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) regarding renal outcomes.
• To compare combination therapy with monotherapy in terms of renoprotective effects and safety.

Main Methods:

• Review of existing literature on RAS inhibitor combination therapies.
• Detailed analysis of renal outcomes reported in the ONTARGET trial.
• Comparison of adverse renal events between monotherapy and combination therapy groups.

Main Results:

• The ONTARGET trial indicated a higher incidence of adverse renal outcomes with combined ACE inhibitor and ARB therapy compared to monotherapy.
• Evidence suggests that dual RAS blockade may not offer superior renoprotection and can increase risks.
• Incomplete RAS blockade with monotherapy might be associated with better renal safety profiles.

Conclusions:

• Combined ACE inhibitor and ARB therapy may lead to unfavorable renal outcomes.
• Monotherapy with either an ACE inhibitor or an ARB appears safer for renal protection in CKD.
• Further investigation is needed to clarify the role and safety of combination RAS blockade in CKD management.