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Blocking the renin-angiotensin system: dual- versus mono-therapy
1Division of Cardiology and Population Health Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Abstract:
The renin-angiotensin system (RAS) plays an important role in the pathogenesis of cardiovascular disease. One of the effects of the activated RAS is target-organ damage, in part due to their effects on causing hypertension. Blocking angiotensin-converting enzyme (ACE) with inhibitors has been shown to attenuate the pathological effects of the RAS. Clinical trials have shown that ACE inhibition improves outcomes in the prevention of acute myocardial infarction, lowering the morbidity and mortality in congestive heart failure, and attenuates renal dysfunction. There is recent evidence to show that angiotensin receptor blockers (ARBs) have similar efficacy to ACE inhibitors in reducing cardiovascular outcomes. The wealth of information obtained regarding the beneficial effects of RAS inhibition on clinical outcome has been focused on monotherapy with either ARB or ACE inhibition. Evidence from some trials suggests that better overall inhibition of RAS by dual therapy may improve clinical outcomes. Combination therapy has been shown to be beneficial in patients with congestive heart failure or renal disease. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) trial showed equal benefit of either ARB or ACE inhibition with reduction in primary end points in postmyocardial infarction patients, but there was no further benefit from dual therapy in reducing outcomes. In the recent ONTARGET study, there was further evidence that ARBs are equal to ACE inhibitors in reducing cardiovascular events. In Ongoing Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events (ONTARGET), combined RAS blockade did not have any added benefit but resulted in increased risk of adverse outcomes. In the Candesartan in Heart Failure (CHARM) and the Valsartan Heart Failure Trial (Val-HeFT) trials of patients with severe heart failure, the addition of an ARB to an ACE inhibitor reduced cardiac mortality and lowered hospital admissions. Whether or not dual therapy is beneficial in patients with diabetic renal failure should be clarified by future studies. Overall, patients receiving dual therapy, if clinically justified, should be monitored closely for potential adverse effects.
Insights
Dual therapy targeting the renin-angiotensin system (RAS) shows mixed results. While beneficial in some heart failure cases, combination therapy did not improve outcomes in post-heart attack patients and increased risks in others.
Area of Science:
- Cardiology
- Pharmacology
- Nephrology
Background:
- The renin-angiotensin system (RAS) is implicated in cardiovascular disease pathogenesis, contributing to hypertension and target-organ damage.
- Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are established therapies for managing RAS-related conditions.
- Monotherapy with ACE inhibitors or ARBs has demonstrated significant clinical benefits in cardiovascular and renal outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of dual renin-angiotensin system (RAS) blockade compared to monotherapy.
- To synthesize evidence on combination therapy with ACE inhibitors and ARBs in various cardiovascular and renal conditions.
- To determine if dual RAS inhibition offers additional benefits beyond monotherapy.
Main Methods:
- Review of clinical trial data, including landmark studies like VALIANT, ONTARGET, CHARM, and Val-HeFT.
- Comparative analysis of outcomes between ACE inhibitor monotherapy, ARB monotherapy, and dual RAS blockade.
- Assessment of cardiovascular events, morbidity, mortality, and adverse effects across different treatment strategies.
Main Results:
- ACE inhibitors and ARBs show similar efficacy in monotherapy for cardiovascular outcomes.
- Dual therapy demonstrated benefits in specific patient groups, such as severe heart failure (reduced mortality and hospitalizations).
- However, combination therapy did not provide additional benefits in post-myocardial infarction patients and increased adverse event risks in high-risk vascular populations (ONT ОнTARGET).
Conclusions:
- Dual RAS blockade offers specific benefits in certain conditions like severe heart failure but lacks broad efficacy in other cardiovascular settings.
- Combination therapy may increase the risk of adverse outcomes, necessitating careful patient selection and monitoring.
- Future research is needed to clarify the role of dual RAS blockade in diabetic renal failure.
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