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Dual blockade of the renin-angiotensin system for cardiorenal protection: an update
1Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey. marici@hacettepe.edu.tr
Abstract:
The renin-angiotensin system (RAS) has an important role in hypertension and the continuum of cardiovascular and kidney disease. The inhibition of this system, either with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), has been shown to be beneficial for cardiorenal protection. Dual blockade with an ACE inhibitor and ARB may have additional benefits due to the more complete inhibition of the system. Most published trials, including recent large studies and meta-analyses, have reported either limited or no additional benefit. Dual-blockade therapy seems to have some benefit on proteinuria and blood pressure reduction, and on morbidity and mortality in patients with heart failure, compared with monotherapy. The major issue arising from these published trials and meta-analyses is the increased frequency of dual therapy discontinuation and adverse effects on kidney function. There is a lack of hard end-point data for renal outcomes and long-term safety data in most published trials. Until the results of ongoing trials become available and as further safety data emerge, a wise approach would be to withhold use of ACE inhibitor and ARB combination therapy in general practice. When used in selected conditions, patients need to be closely monitored.
Insights
Dual blockade using angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) offers limited additional cardiorenal protection and increases adverse effects. Current evidence suggests withholding this combination therapy in general practice due to safety concerns.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- The renin-angiotensin system (RAS) is crucial in cardiovascular and kidney diseases, including hypertension.
- Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are established therapies for cardiorenal protection.
- Dual blockade aims for more complete RAS inhibition, potentially enhancing therapeutic benefits.
Purpose of the Study:
- To evaluate the efficacy and safety of dual RAS blockade (ACE inhibitor + ARB) compared to monotherapy.
- To assess the impact of dual blockade on cardiorenal outcomes, proteinuria, blood pressure, and adverse events.
Main Methods:
- Review of published trials, large studies, and meta-analyses on dual ACE inhibitor and ARB therapy.
- Analysis of data regarding proteinuria, blood pressure, heart failure outcomes, and adverse events, particularly renal function.
Main Results:
- Dual blockade shows marginal benefits in reducing proteinuria, blood pressure, and improving outcomes in heart failure patients.
- Significant increases in therapy discontinuation and adverse effects on kidney function were observed with dual blockade.
- Limited hard end-point data for renal outcomes and long-term safety are available.
Conclusions:
- Dual ACE inhibitor and ARB therapy provides limited additional cardiorenal benefits over monotherapy.
- Increased risks of adverse events, especially renal impairment, necessitate caution.
- Withholding dual therapy in general practice is advised pending further trial results and safety data.
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01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
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01:22Heart Failure Drugs: Diuretics
01:29Hypertension II: Pathophysiology