Angiotensin Receptor Blockers for Aortic Stenosis

(ARBAS Trial)

Recruiting at 1 trial location

Overseen By Krystel Duplain-Bouffard, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Must not be taking: Renin-angiotensin meds, Aliskiren

Disqualifiers: Renal dysfunction, Diabetes, Coronary artery disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how angiotensin receptor blockers (ARBs), a type of medication, affect individuals with mild-to-moderate aortic stenosis, a heart condition where the valve between the heart and the main artery narrows. Participants will receive either ARBs or a placebo (a sugar pill with no active medicine) for two years to determine if ARBs can help manage this condition. Suitable candidates have mild-to-moderate aortic stenosis, normal heart pumping ability, and normal blood pressure. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand its benefits for more patients with this condition.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using or need medications that affect the renin-angiotensin system, like Aliskiren.

What is the safety track record for these treatments?

Research has shown that angiotensin receptor blockers (ARBs) are generally safe for people with aortic stenosis, a condition where the heart's aortic valve narrows. Studies have found that patients taking ARBs had a lower risk of dying from any cause and from heart-related issues, suggesting that ARBs are well-tolerated over time. Additionally, ARBs may help slow the progression of aortic stenosis. These findings are based on studies of ARBs already approved for other uses, indicating a good safety record. Overall, ARBs appear to be a safe option for managing aortic stenosis. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using angiotensin receptor blockers (ARBs) for aortic stenosis because ARBs target the renin-angiotensin system, which plays a role in blood pressure regulation and may help reduce the progression of heart valve narrowing. Unlike standard treatments for aortic stenosis, which typically involve surgical interventions or valve replacement, ARBs offer a non-invasive option that can be taken orally. This approach could provide a significant advantage by potentially delaying the need for surgery, improving patient quality of life, and offering a simpler, long-term management strategy for this heart condition.

What evidence suggests that angiotensin receptor blockers might be an effective treatment for aortic stenosis?

Research has shown that certain medications called angiotensin receptor blockers (ARBs) might help slow aortic stenosis, a condition where the heart's aortic valve narrows. They may achieve this by reducing fibrosis, which occurs when tissue becomes thick and scarred. Some studies suggest that ARBs could also aid in beneficial changes in heart structure for those with aortic stenosis. Additionally, ARBs have been linked to better survival rates and a lower risk of heart problems in patients with similar conditions. In this trial, participants will receive either ARBs or a placebo to evaluate their effectiveness specifically for aortic stenosis. This treatment is already known to work well for other heart and blood pressure issues. ^{3 4 6 7 8}

Who Is on the Research Team?

Marie-Annick Clavel, PhD

Principal Investigator

Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Are You a Good Fit for This Trial?

This trial is for adults with mild to moderate aortic stenosis, normal heart pump function, and stable blood pressure. It's not for those with certain heart valve issues, on specific heart medications, allergic to ARBs, cognitive impairments like Alzheimer's or dementia, severe kidney problems, chronic high potassium levels, serious liver conditions, recent diabetes diagnosis or uncontrolled diabetes, advanced coronary artery disease or recent heart attack.

Inclusion Criteria

Your systolic blood pressure is higher than 110 mmHg.

Your heart is pumping normally, at 50% or higher.

My heart valve narrowing is mild to moderate.

Exclusion Criteria

I have moderate to severe heart valve issues.

I am allergic to or cannot tolerate ARBs.

I have long-term high potassium levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either angiotensin receptor blockers or placebo orally once a day

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Angiotensin Receptor Blockers
• Placebo

Trial Overview The study examines the effects of angiotensin receptor blockers (ARBs) compared to a placebo in patients with mild-to-moderate aortic stenosis. Participants will be randomly assigned to receive either the ARB medication or an inactive substance without any active drug (placebo).

How Is the Trial Designed?

Group I: Angiotensin Receptor Blockers Experimental Treatment 1 Intervention

Angiotensin Receptor Blockers will be given orally once a day for 2 years.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive a matched placebo orally once a day for 2 years.

Angiotensin Receptor Blockers is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as ARBs for:

• Hypertension
• Heart Failure
• Diabetic Nephropathy
• Chronic Kidney Disease

Approved in United States as ARBs for:

• Hypertension
• Heart Failure
• Diabetic Nephropathy
• Chronic Kidney Disease

Approved in Canada as ARBs for:

• Hypertension
• Heart Failure
• Diabetic Nephropathy
• Chronic Kidney Disease

Approved in Japan as ARBs for:

• Hypertension
• Heart Failure
• Diabetic Nephropathy
• Chronic Kidney Disease

Who Is Running the Clinical Trial?

Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Lead Sponsor

Trials

26

Recruited

6,300+

Odense University Hospital

Collaborator

Trials

808

Recruited

1,272,000+

Published Research Related to This Trial

A systematic review of 46 randomized controlled trials involving 13,451 participants found that angiotensin receptor blockers (ARBs) lower blood pressure modestly, with an average reduction of -8 mm Hg for systolic and -5 mm Hg for diastolic blood pressure at maximum recommended doses.

The study indicates that there are no significant differences in blood pressure-lowering efficacy among different ARBs, and that starting doses achieve 60-70% of the maximum effect, suggesting that higher doses may not provide additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood pressure lowering efficacy of angiotensin receptor blockers for primary hypertension. Heran, BS., Wong, MM., Heran, IK., et al.[2022]

Angiotensin receptor blockers (ARBs) are effective and safe antihypertensive medications that work by blocking the angiotensin II type 1 receptor, and they may also stimulate the type 2 receptor, contributing to their therapeutic effects.

In addition to lowering blood pressure, ARBs have shown benefits in treating heart failure, diabetic nephropathy, and preventing strokes, making them a versatile class of drugs with multiple protective actions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pleiotropic effects of angiotensin receptor blockers. Chrysant, SG., Chrysant, GS.[2023]

In a study involving 5,139 heart failure patients, those treated with candesartan had a significantly higher one-year survival rate of 90% compared to 83% for those on losartan.

Candesartan was associated with a 43% lower risk of mortality compared to losartan, indicating it may be a more effective treatment option for reducing mortality in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of candesartan vs losartan with all-cause mortality in patients with heart failure. Eklind-Cervenka, M., Benson, L., Dahlström, U., et al.[2021]

In a study of 2,117 patients with aortic stenosis (AS), those treated with ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) showed a significant reduction in all-cause mortality, with a hazard ratio of 0.76, indicating a 24% lower risk of death compared to those not on these medications.

Patients on ACEIs or ARBs also experienced fewer cardiovascular events, with a hazard ratio of 0.77, suggesting a 23% lower risk of cardiovascular death or hospitalizations, highlighting the potential benefits of these medications in managing AS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis. Nadir, MA., Wei, L., Elder, DH., et al.[2021]

Angiotensin-receptor blockers have been shown to significantly improve outcomes in patients at high cardiovascular risk, beyond just lowering blood pressure.

Clinical trials have led to expanded uses for these medications, indicating their potential benefits in various cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin-receptor blockers: benefits beyond lowering blood pressure. Silverstein, RL., Ram, CV.[2019]

Renin-angiotensin system (RAS) blockade therapy shows promise in improving outcomes for patients with aortic stenosis (AS), potentially slowing the progression of the disease and enhancing survival rates both before and after aortic valve replacement (AVR).

Current evidence suggests that RAS inhibition is associated with significant survival advantages in patients undergoing surgical or transcatheter AVR, highlighting the need for further randomized trials to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renin-Angiotensin System Blockade in Aortic Stenosis: Implications Before and After Aortic Valve Replacement. Goel, SS., Kleiman, NS., Zoghbi, WA., et al.[2021]

In a study of 20 hypertensive patients with aortic valve stenosis, ACE inhibitors significantly lowered systolic blood pressure and improved stroke volume during peak stress, indicating a positive effect on stress haemodynamics.

Despite these benefits, ACE inhibitors also led to an increased mean pressure gradient, suggesting that their afterload relief effect is countered in patients with aortic stenosis, but they should still be continued due to their overall favorable impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of angiotensin converting enzyme inhibitors in hypertensive patients with aortic valve stenosis: a drug withdrawal study. Jiménez-Candil, J., Bermejo, J., Yotti, R., et al.[2018]

Angiotensin II receptor blockers (ARBs) have been shown to effectively reduce cardiovascular events and mortality across various patient populations, from those at risk to post-myocardial infarction patients, based on a review of large, well-designed studies.

ARBs have demonstrated comparable efficacy to ACE inhibitors in certain groups, indicating their potential as a reliable treatment option for cardiovascular disease prevention, with ongoing studies expected to further clarify their benefits in additional populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for the efficacy of ARBs across the cardiovascular continuum. Gupta, M., Honos, GN., Velazquez, EJ., et al.[2010]

In a study of 1873 asymptomatic patients with mild to moderate aortic stenosis, the use of renin-angiotensin system inhibitors (RASI) did not increase the risk of sudden cardiac death, cardiovascular death, or all-cause mortality over a median follow-up of 4.3 years.

RASI treatment was associated with significant benefits, including a greater reduction in systolic blood pressure and less progression of left ventricular mass, suggesting potential advantages for heart health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renin-angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis. Bang, CN., Greve, AM., Køber, L., et al.[2014]

Hypertension significantly accelerates the progression of aortic stenosis (AS) and increases the risk of mortality, as shown in a study of 338 patients over an average follow-up of 6.2 years.

Angiotensin-receptor blockers (ARBs) were associated with slower AS progression and did not increase mortality risk, while angiotensin-converting enzyme inhibitors (ACEIs) did not provide the same protective effect against mortality in hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of hypertension and renin-angiotensin system inhibitors in aortic stenosis. Capoulade, R., Clavel, MA., Mathieu, P., et al.[2013]

Angiotensin II type 1 receptor blockers are well-tolerated cardiovascular agents with side effects occurring at rates similar to placebo, making them a safer option compared to traditional angiotensin converting enzyme inhibitors, particularly regarding cough.

Serious side effects are rare but can include cough, angioneurotic edema, and renal issues; these blockers are not recommended for use in pregnancy or in patients with severe renal or hepatic impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse effects of angiotensin II type 1 receptor blockers ]. Preobrazhenskiĭ, DV., Sidorenko, BA.[2018]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0828282X24002708

Angiotensin II Receptor Blockers Are Associated With ... Angiotensin receptor blockers (ARBs) may slow down the progression of aortic stenosis (AS) through their antifibrotic effect. Women present more valvular ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38518892/

Angiotensin II Receptor Blockers Are Associated With ... Background: Angiotensin receptor blockers (ARBs) may slow down the progression of aortic stenosis (AS) through their antifibrotic effect. Women present more ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04913870?term=AREA%5BConditionSearch%5D(aortic%20valve%20stenosis)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=3

Angiotensin Receptor Blockers in Aortic Stenosis Furthermore recent studies have shown that renin-angiotensin system medication may slow down aortic stenosis progression rate and left ventricle remodeling.

4. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.125.25549

Multidatabase Target Trial Emulation Studies | Hypertension Evidence on the comparative effectiveness of both drugs on long-term death is inconclusive. METHODS: This multidatabase cohort study used a ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2011.01.063

Impact of Renin-Angiotensin System Blockade Therapy on ... This large observational study suggests that ACEI/ARB therapy is associated with an improved survival and a lower risk of CV events in patients ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8204653/

an analysis of from the PARTNER 2 trial and registries Two-year unadjusted clinical outcomes. Crude Kaplan–Meier failure rates according to angiotensin-converting enzyme inhibitor/angiotensin II ...

7. ahajournals.org ahajournals.org/doi/10.1161/JAHA.120.016911

Renin‐Angiotensin System Blockade in Aortic Stenosis Treatment with an ACEI/ARB was associated with lower 2‐year all‐cause mortality (18.6% versus 27.5%; P<0.0001), cardiovascular mortality (12.3% ...

8. jacc.org jacc.org/doi/10.1016/j.jacadv.2024.100927

Angiotensin-Converting Enzyme Inhibitors or ... Patients on ACEIs/ARBs had lower risk of all-cause mortality (RR: 0.74, 95% CI: 0.65-0.86, I2 = 62%, chi-square P < 0.01), cardiovascular mortality (RR: 0.70, ...