Recent changes in the landscape of combination RAS blockade

Area of Science:

• Cardiovascular Pharmacology
• Renal Physiology
• Drug Therapy

Background:

• The renin-angiotensin system (RAS) is a key target for cardiovascular and renal disease management.
• ACE inhibitors and ARBs incompletely suppress RAS, leading to residual cardiovascular and renal events.
• Incomplete RAS blockade necessitates exploring alternative therapeutic strategies.

Purpose of the Study:

• To evaluate the efficacy and safety of combined RAS blockade strategies.
• To compare dual blockade with ACE inhibitors and ARBs versus newer combinations involving direct renin inhibitors.
• To determine optimal use of dual RAS blockade in hypertension, heart failure, and renal disease.

Main Methods:

• Review of outcomes studies on ACE inhibitors and ARBs.
• Analysis of clinical trials investigating combined ACE inhibitor/ARB therapy.
• Examination of emerging data on direct renin inhibitor (aliskiren) combinations.

Main Results:

• Combined ACE inhibitor and ARB therapy provides minimal additional blood pressure reduction and no further cardiovascular event reduction in hypertension.
• Dual RAS blockade in heart failure and proteinuric kidney disease shows clinical event reduction in selected patients.
• Dual RAS blockade increases risks of hyperkalemia and worsening renal function.

Conclusions:

• Combined ACE inhibitor and ARB therapy is not recommended for routine hypertension treatment.
• Combination therapy with ACE inhibitors or ARBs and aliskiren shows promise for blood pressure management.
• Dual RAS inhibition may be considered in carefully selected heart failure and kidney disease patients, balancing benefits against risks.