PCI vs Medical Management for Aortic Stenosis

(COMPLETE TAVR Trial)

Recruiting at 72 trial locations

Overseen By Charles Resor, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Disqualifiers: Prior CABG, Severe mitral regurgitation, Severe LV dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1-45 days

4000 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients undergoing transcatheter aortic valve replacement (TAVR) often have concomitant coronary artery disease (CAD) which may adversely affect prognosis. There is uncertainty about the benefits and the optimal timing of revascularization for such patients. There is currently clinical equipoise regarding the management of concomitant CAD in patients undergoing TAVR. Some centers perform routine revascularization with percutaneous coronary intervention (PCI) (either before or after TAVR), while others follow an alternative strategy of medical management. The potential benefits and optimal timing of PCI in these patients are unknown. As TAVR expands to lower risk patients, and potentially becomes the preferred therapy for the majority of patients with severe aortic stenosis, the optimal management of concomitant coronary artery disease will be of increasing importance. The COMPLETE TAVR study will determine whether, on a background of guideline-directed medical therapy, a strategy of complete revascularization involving staged PCI using drug eluting stents to treat all suitable coronary artery lesions is superior to a strategy of medical therapy alone in reducing the composite outcome of Cardiovascular Death, new Myocardial Infarction, Ischemia-driven Revascularization or Hospitalization for Unstable Angina or Heart Failure. The study will be a randomized, multicenter, open-label trial with blinded adjudication of outcomes. Patients will be screened and consented for elective transfemoral TAVR and randomized within 96 hours of successful balloon expandable TAVR. Complete Revascularization: Staged PCI using third generation drug eluting stents to treat all suitable coronary artery lesions in vessels that are at least 2.5 mm in diameter and that are amenable to treatment with PCI and have a ≥70% visual angiographic diameter stenosis. Staged PCI can occur any time from 1 to 45 days post successful transfemoral TAVR. Vs. Medical Therapy Alone: No further revascularization of coronary artery lesions. All patients, regardless of randomized treatment allocation, will receive guideline-directed medical therapy consisting of risk factor modification and use of evidence-based therapies. The COMPLETE TAVR study will help address the current lack of evidence in this area. It will likely impact both the global delivery of health care and the management and clinical outcomes of all patients undergoing TAVR with concomitant CAD.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications. However, all participants will receive guideline-directed medical therapy, which includes risk factor modification and evidence-based therapies.

What data supports the effectiveness of the treatment Percutaneous Coronary Intervention (PCI) for aortic stenosis?

Research suggests that PCI can be feasible for patients with both severe aortic stenosis and coronary artery disease, and it may benefit certain patients, especially when combined with other procedures like transcatheter aortic valve implantation (TAVI). However, the outcomes of PCI in these patients are still being studied, and its effectiveness compared to other treatments is not fully known. ^{1 2 3 4 5}

Is PCI safe for patients with aortic stenosis?

Research shows that PCI (Percutaneous Coronary Intervention) is generally safe for patients with aortic stenosis, even when combined with other procedures like TAVR (Transcatheter Aortic Valve Replacement). Studies found no significant increase in risks such as heart attack, stroke, or severe bleeding when PCI is performed alongside TAVR. ^{1 6 7 8 9}

How is the treatment PCI different for aortic stenosis compared to other treatments?

Percutaneous Coronary Intervention (PCI) is unique for aortic stenosis because it can be performed alongside procedures like transcatheter aortic valve implantation (TAVI) to address both valve and coronary artery issues in one session, which is not typical for other treatments. This combined approach can be beneficial for patients with both severe aortic stenosis and coronary artery disease, offering a comprehensive treatment option. ^{1 3 4 10 11}

Research Team

David A Wood, MD

Principal Investigator

CCI-CIC, University of British Columbia

Eligibility Criteria

This trial is for men and women with severe symptomatic aortic valve stenosis who have undergone successful TAVR within the past 96 hours. They must have at least one treatable coronary artery lesion and be deemed suitable for elective transfemoral TAVR by a heart team. Exclusions include recent heart attacks or strokes, severe mitral regurgitation, life expectancy under 5 years, prior bypass surgery or valve replacement, among others.

Inclusion Criteria

My heart team agrees I can have a specific heart valve replacement through my thigh and would get a bypass if I had surgery.

I had a successful heart valve replacement via catheter within the last 4 days without major issues.

I have a significant blockage in one of my heart's arteries that can be treated without surgery.

Exclusion Criteria

I had or will have a PCI procedure close to my TAVR surgery date.

I am scheduled for a procedure to open blocked arteries in my heart.

You have something that would prevent you from being followed up for 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo elective transfemoral TAVR and are randomized to either staged PCI with drug eluting stents or medical therapy alone

1-45 days

Multiple visits for TAVR and PCI procedures

Follow-up

Participants are monitored for safety and effectiveness, including cardiovascular outcomes and quality of life assessments

3.5 years

Regular follow-up visits, including annual assessments

Treatment Details

Interventions

• Percutaneous Coronary Intervention (PCI)

Trial Overview The study tests if complete revascularization using drug eluting stents after TAVR (staged PCI) is better than just medical therapy alone in reducing cardiovascular death and other complications. Patients are randomly assigned to either undergo staged PCI post-TAVR or receive only medical management without further revascularization.

Participant Groups

Group I: Complete Revascularization Experimental Treatment 1 Intervention

Routine PCI (percutaneous coronary intervention) of all suitable coronary artery stenoses of ≥70% in vessels ≥2.5mm in diameter.

Group II: Medical Therapy Alone Active Control 1 Intervention

No revascularization of coronary artery lesions.

Percutaneous Coronary Intervention (PCI) is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Percutaneous Coronary Intervention for:

• Stable angina
• Unstable angina
• Myocardial infarction
• Ischemic heart disease

Approved in United States as Percutaneous Coronary Intervention for:

• Stable angina
• Unstable angina
• Myocardial infarction
• Ischemic heart disease

Approved in Canada as Percutaneous Coronary Intervention for:

• Stable angina
• Unstable angina
• Myocardial infarction
• Ischemic heart disease

Approved in Japan as Percutaneous Coronary Intervention for:

• Stable angina
• Unstable angina
• Myocardial infarction
• Ischemic heart disease

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Findings from Research

Percutaneous coronary intervention (PCI) is a safe and effective treatment for patients with severe aortic stenosis (AS) and significant coronary artery disease (CAD), with 92.1% of patients reporting symptomatic improvement after the procedure.

The study, which analyzed 38 patients aged around 71 years, found that good functional class and single-vessel coronary disease were significant predictors of long-term survival, suggesting that PCI may be particularly beneficial for patients with these characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of percutaneous coronary intervention in aortic valve stenosis with coronary artery disease. Alcalai, R., Viola, N., Mosseri, M., et al.[2010]

Percutaneous coronary intervention (PCI) in patients with severe aortic stenosis (AS) does not increase the risk of 30-day mortality compared to patients without AS, based on a study of 254 AS patients matched with 508 non-AS patients.

However, patients with severe AS who also have a low ejection fraction (≤30%) or a high Society of Thoracic Surgeons score (≥10) face a significantly higher risk of 30-day mortality after PCI, highlighting the need for careful risk assessment in these high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous coronary intervention in patients with severe aortic stenosis: implications for transcatheter aortic valve replacement. Goel, SS., Agarwal, S., Tuzcu, EM., et al.[2012]

In a study of 593 patients undergoing transapical TAVI, those with severe aortic stenosis and significant coronary artery disease (CAD) who received combined TAVI and PCI showed similar survival rates up to 3 years compared to patients without CAD who only received TAVI.

The combined treatment significantly reduced the complexity of coronary lesions, as indicated by a decrease in the mean SYNTAX score from 8.0 to 3.0, while not increasing the risk of acute kidney injury despite higher radiation exposure and contrast use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve implantation combined with elective coronary artery stenting: a simultaneous approach†. Penkalla, A., Pasic, M., Drews, T., et al.[2015]

In patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), the necessity of pre-TAVI revascularization through percutaneous coronary intervention (PCI) is being questioned, suggesting it may not always be required.

Current data indicates that the management of coronary artery disease in TAVI patients can be approached differently, impacting clinical decision-making and potentially reducing unnecessary procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary artery disease in patients undergoing TAVI--why not to treat. Khawaja, MZ., Redwood, SR., Thomas, M.[2022]

In patients with severe aortic stenosis and coronary artery disease, the combined percutaneous approach of TAVI and PCI showed significantly lower risks of major adverse cardiovascular events (MACE) and all-cause mortality during the initial hospitalization compared to the surgical approach of SAVR and CABG.

However, the TAVI+PCI group experienced a higher incidence of complications and mortality within 30 days post-procedure, indicating a trade-off between immediate benefits and short-term risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends and outcomes of combined percutaneous (TAVI+PCI) and surgical approach (SAVR+CABG) for patients with aortic valve and coronary artery disease: A National Readmission Database (NRD) analysis. Ullah, W., Sarvepalli, D., Kumar, A., et al.[2023]

A study involving 51 cardiologists and 54 cardiac surgeons revealed significant differences in how these two groups assess the risks and benefits of percutaneous aortic valve replacement (PAVR), with cardiologists generally viewing the procedure more favorably.

Both groups acknowledged risks associated with PAVR, such as impaired hemodynamic outcomes and embolic events, but cardiologists rated these risks significantly lower than surgeons, suggesting a need for more evidence-based information to align perspectives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Job matters: differences in risk assessment of percutaneous aortic valve replacement between cardiologists and cardiac surgeons. Grebel, T., Schumm, J.[2015]

In a study of 409 patients with severe aortic stenosis, combining balloon aortic valvuloplasty (BAV) with percutaneous coronary intervention (PCI) was found to be safe, with similar rates of serious adverse events compared to BAV alone (13.7% vs. 17.3%).

The combined procedure did not significantly increase mortality rates, with 40% in the BAV/PCI group and 48.6% in the BAV alone group, suggesting that the combination may provide additional protection against myocardial ischemia without increasing risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of concomitant percutaneous coronary intervention and balloon aortic valvuloplasty. Ben-Dor, I., Maluenda, G., Looser, PM., et al.[2015]

Percutaneous aortic valvuloplasty (PAV) can effectively increase aortic valve area and improve heart function in patients with critical aortic stenosis, even in life-threatening situations like cardiogenic shock.

While PAV can be life-saving, especially after complications like a myocardial infarction, it is associated with high rates of morbidity and mortality, highlighting the need for careful patient selection and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined PTCA and aortic valvuloplasty for acute myocardial infarction complicated by severe aortic stenosis and cardiogenic shock. Whisenant, B., Sweeney, J., Ports, TA.[2019]

A meta-analysis evaluating patients undergoing transcatheter aortic valve replacement (TAVR) found that adding percutaneous coronary intervention (PCI) for coronary artery disease (CAD) does not increase the risk of 30-day mortality compared to TAVR alone.

The study also showed no significant differences in major complications such as myocardial infarction, stroke, or life-threatening bleeding between patients receiving TAVR with PCI and those receiving TAVR alone, indicating that PCI is a safe and feasible option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of PCI in patients undergoing TAVR: A systematic review and meta-analysis. Bajaj, A., Pancholy, S., Sethi, A., et al.[2018]

A study of 45,420 patients with aortic stenosis (AS) showed that PCI procedures, including those with atherectomy, increased significantly from 2016 to 2019, indicating a growing trend in treating AS patients with coronary artery disease.

Using intravascular ultrasound (IVUS) during atherectomy and PCI was associated with lower odds of major adverse cardiovascular events (MACE), suggesting that this approach is both safe and effective for patients with AS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Coronary Intervention and Discretionary Atherectomy in Patients with Aortic Stenosis: 2016-2019 National Inpatient Sample. Vedantam, K., Torres, CA., Martinsen, BJ., et al.[2023]

In patients with severe aortic stenosis and significant coronary artery disease, performing percutaneous coronary intervention (PCI) followed immediately by percutaneous aortic valve implantation (PAVI) can be a viable treatment strategy.

The study highlights the complexity of treating these frail patients and proposes an algorithm to guide treatment decisions, emphasizing the need to differentiate between symptoms of ischemic heart disease and severe aortic stenosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous aortic valve implantation in patients with coronary artery disease: review of therapeutic strategies. Dvir, D., Assali, A., Spargias, K., et al.[2010]

References

1. United States pubmed.ncbi.nlm.nih.gov

The value of percutaneous coronary intervention in aortic valve stenosis with coronary artery disease. [2010]

2. United States pubmed.ncbi.nlm.nih.gov

Percutaneous coronary intervention in patients with severe aortic stenosis: implications for transcatheter aortic valve replacement. [2012]

3. Germany pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve implantation combined with elective coronary artery stenting: a simultaneous approach†. [2015]

4. France pubmed.ncbi.nlm.nih.gov

Coronary artery disease in patients undergoing TAVI--why not to treat. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Trends and outcomes of combined percutaneous (TAVI+PCI) and surgical approach (SAVR+CABG) for patients with aortic valve and coronary artery disease: A National Readmission Database (NRD) analysis. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Job matters: differences in risk assessment of percutaneous aortic valve replacement between cardiologists and cardiac surgeons. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Outcomes of concomitant percutaneous coronary intervention and balloon aortic valvuloplasty. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Combined PTCA and aortic valvuloplasty for acute myocardial infarction complicated by severe aortic stenosis and cardiogenic shock. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Safety and feasibility of PCI in patients undergoing TAVR: A systematic review and meta-analysis. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Percutaneous Coronary Intervention and Discretionary Atherectomy in Patients with Aortic Stenosis: 2016-2019 National Inpatient Sample. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Percutaneous aortic valve implantation in patients with coronary artery disease: review of therapeutic strategies. [2010]