Meeting NewsPerspective

COAPT: MitraClip reduces hospitalization, mortality in HF, mitral regurgitation

Gregg W. Stone, MD
Gregg W. Stone

SAN DIEGO — Patients with HF with moderate to severe or severe functional mitral regurgitation who underwent transcatheter mitral valve repair reduced the risk for HF hospitalization and mortality compared with patients treated with medical therapy alone, according to 2-year data from the COAPT trial presented at TCT 2018.

Patients who underwent the procedure with the transcatheter device (MitraClip, Abbott) also had improved exercise tolerance and quality of life.

The findings are contrary to the MITRA-FR trial, in which, as Cardiology Today’s Intervention previously reported, assignment to a procedure with a MitraClip did not improve survival or HF hospitalization in patients with severe secondary mitral regurgitation.

“This is really the first therapy that’s been shown to improve the prognosis in high-risk patients with secondary mitral regurgitation due to underlying left ventricular dysfunction,” Gregg W. Stone, MD, director of cardiovascular research and education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian/Columbia University Irving Medical Center, told Cardiology Today’s Intervention.

Researchers analyzed data from 614 patients from 78 sites in the United States and Canada.

“In this space, it’s the largest randomized trial ever done of any mitral valve technology,” Stone, a member of the Cardiology Today’s Intervention Editorial Board, said in an interview.

Patients had HF with reduced ejection fraction, moderate left ventricular dilatation, secondary mitral regurgitation graded moderate to severe or severe and were symptomatic despite receiving best medical therapies and cardiac resynchronization therapy if appropriate.

Patients were assigned transcatheter mitral valve repair with medical therapy (n = 302; mean age, 72 years; 67% men) or medical therapy alone (n = 312; mean age, 73 years; 62% men).

“The MitraClip is a much safer, less invasive therapy than is surgery,” Stone told Cardiology Today’s Intervention. “It works by basically attaching the tips of the two leaflets of the mitral valve to create ... a double orifice valve; therefore, it reduces mitral regurgitation.”

The primary effectiveness endpoint was HF hospitalization within 24 months. The primary safety endpoint was freedom from complications related to the device at 12 months, which was compared with a prespecified performance goal of 88%.

The rate of HF hospitalization per year was reduced in patients assigned the device vs. the control group (35.8% per year vs. 67.9% per year; HR = 0.53; 95% CI, 0.4-0.7).

At 1 year, the performance goal for the primary safety endpoint was exceeded with a rate of freedom from device-related complications at 96.6% (lower 95% confidence limit, 94.8%; P < .001).

At 2 years, 29.1% of patients in the device group died compared with 46.1% in the control group, which resulted in a 38% reduction in mortality (HR = 0.62; 95% CI, 0.46-0.82). The composite of death or first HF hospitalization was reduced by 43% in patients assigned the device (P < .001), according to a press release from Abbott.

Mitral regurgitation severity was significantly reduced in the device group at 1 year compared with the control group. More patients assigned the device had mitral regurgitation of grade 2 or less compared with those assigned medical therapy alone (94.8% vs. 46.9%; P < .001). Also at 1 year, 72.2% of the device group had NYHA class I or II HF vs. 49.6% in the control group (P < .001).

“Now the MitraClip has become a standard of care approach for these patients,” Stone said in an interview. “It can substantially make them feel better, improve their exercise capacity and quality of life, reduce their need for heart failure hospitalization and improve their survival. Heart failure is the No. 1 cause overall of morbidity and mortality in patients in the United States and in most Westernized countries and has tremendous cost implications for the health resource utilization. This really now has become the new standard of care for patients who fit these criteria.”

Michael J. Mack, MD
Michael J. Mack

“This is one of the most difficult trials I have ever been involved in, ... and this is the most positive trial I’ve been involved in,” Michael J. Mack, MD, FACC, medical director of cardiovascular surgery at Baylor Health Care System in Dallas, chairman of the Heart Hospital Baylor Plano Research Center in Texas and Cardiology Today’s Intervention Editorial Board Member, said during a press conference.

Stone said there are several differences between the COAPT trial and the MITRA-FR trial recently presented at ESC.

In contrast, the MITRA-FR trial found that percutaneous mitral valve repair plus medical therapy offered no advantage over medical therapy alone in patients with HF with reduced ejection fraction and secondary mitral valve regurgitation.

The severity of mitral regurgitation enrolled in COAPT was substantially greater, and the ventricles were not severely dilated in the current trial, Stone said. The HF medications were allowed to vary in the MITRA-FR trial, whereas in COAPT, patients were on maximally tolerated guideline-directed medical therapy at baseline with few major changes during follow-up.

“Today we have two publications in The New England Journal of Medicine and apparently two different outcomes,” Jean-Francois Obadia, MD, PhD, from Hopital Cardiovasculaire Louis Pradel, Lyon, France, who presented data from the MITRA-FR trial at the European Society of Cardiology Congress in August, said during the presentation. “This is the best scenario we could have. ... This difference leads us to go deeper into the analysis ... to try to understand this complex disease. Therefore, we know with COAPT what to do, because it provides an accurate selection of the patients who could really benefit from the clip, and with MITRA-FR, which represents more the real world, in which patients should not receive a clip. The two studies are more complementary than controversial.” – by Darlene Dobkowski

References:

Stone GW, et al. Late-Breaking Trials 3. Presented at: TCT Scientific Symposium; Sept. 21-25, 2018; San Diego.

Stone GW, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1806640.

Disclosures: The trial was funded by Abbott. Stone reports he received grants from Abbott to the Cardiovascular Research Foundation; personal fees from Ablative Solutions, Claret, Gore, HeartFlow, Matrizyme, Miracor, Neovasc, Reva, Robocath, Shockwave, TherOx, V-wave, Valfix and Vascular Dynamics; and other support from Ancora, Aria, Biostar, Cagent, Caliber, MedFocus, Qool Therapeutics, SpectraWave; and his employer, Columbia University, receives royalties from Abbott for sales of the MitraClip. Please see the study for all other authors’ relevant financial disclosures.

Gregg W. Stone, MD
Gregg W. Stone

SAN DIEGO — Patients with HF with moderate to severe or severe functional mitral regurgitation who underwent transcatheter mitral valve repair reduced the risk for HF hospitalization and mortality compared with patients treated with medical therapy alone, according to 2-year data from the COAPT trial presented at TCT 2018.

Patients who underwent the procedure with the transcatheter device (MitraClip, Abbott) also had improved exercise tolerance and quality of life.

The findings are contrary to the MITRA-FR trial, in which, as Cardiology Today’s Intervention previously reported, assignment to a procedure with a MitraClip did not improve survival or HF hospitalization in patients with severe secondary mitral regurgitation.

“This is really the first therapy that’s been shown to improve the prognosis in high-risk patients with secondary mitral regurgitation due to underlying left ventricular dysfunction,” Gregg W. Stone, MD, director of cardiovascular research and education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian/Columbia University Irving Medical Center, told Cardiology Today’s Intervention.

Researchers analyzed data from 614 patients from 78 sites in the United States and Canada.

“In this space, it’s the largest randomized trial ever done of any mitral valve technology,” Stone, a member of the Cardiology Today’s Intervention Editorial Board, said in an interview.

Patients had HF with reduced ejection fraction, moderate left ventricular dilatation, secondary mitral regurgitation graded moderate to severe or severe and were symptomatic despite receiving best medical therapies and cardiac resynchronization therapy if appropriate.

Patients were assigned transcatheter mitral valve repair with medical therapy (n = 302; mean age, 72 years; 67% men) or medical therapy alone (n = 312; mean age, 73 years; 62% men).

“The MitraClip is a much safer, less invasive therapy than is surgery,” Stone told Cardiology Today’s Intervention. “It works by basically attaching the tips of the two leaflets of the mitral valve to create ... a double orifice valve; therefore, it reduces mitral regurgitation.”

The primary effectiveness endpoint was HF hospitalization within 24 months. The primary safety endpoint was freedom from complications related to the device at 12 months, which was compared with a prespecified performance goal of 88%.

The rate of HF hospitalization per year was reduced in patients assigned the device vs. the control group (35.8% per year vs. 67.9% per year; HR = 0.53; 95% CI, 0.4-0.7).

At 1 year, the performance goal for the primary safety endpoint was exceeded with a rate of freedom from device-related complications at 96.6% (lower 95% confidence limit, 94.8%; P < .001).

PAGE BREAK

At 2 years, 29.1% of patients in the device group died compared with 46.1% in the control group, which resulted in a 38% reduction in mortality (HR = 0.62; 95% CI, 0.46-0.82). The composite of death or first HF hospitalization was reduced by 43% in patients assigned the device (P < .001), according to a press release from Abbott.

Mitral regurgitation severity was significantly reduced in the device group at 1 year compared with the control group. More patients assigned the device had mitral regurgitation of grade 2 or less compared with those assigned medical therapy alone (94.8% vs. 46.9%; P < .001). Also at 1 year, 72.2% of the device group had NYHA class I or II HF vs. 49.6% in the control group (P < .001).

“Now the MitraClip has become a standard of care approach for these patients,” Stone said in an interview. “It can substantially make them feel better, improve their exercise capacity and quality of life, reduce their need for heart failure hospitalization and improve their survival. Heart failure is the No. 1 cause overall of morbidity and mortality in patients in the United States and in most Westernized countries and has tremendous cost implications for the health resource utilization. This really now has become the new standard of care for patients who fit these criteria.”

Michael J. Mack, MD
Michael J. Mack

“This is one of the most difficult trials I have ever been involved in, ... and this is the most positive trial I’ve been involved in,” Michael J. Mack, MD, FACC, medical director of cardiovascular surgery at Baylor Health Care System in Dallas, chairman of the Heart Hospital Baylor Plano Research Center in Texas and Cardiology Today’s Intervention Editorial Board Member, said during a press conference.

Stone said there are several differences between the COAPT trial and the MITRA-FR trial recently presented at ESC.

In contrast, the MITRA-FR trial found that percutaneous mitral valve repair plus medical therapy offered no advantage over medical therapy alone in patients with HF with reduced ejection fraction and secondary mitral valve regurgitation.

The severity of mitral regurgitation enrolled in COAPT was substantially greater, and the ventricles were not severely dilated in the current trial, Stone said. The HF medications were allowed to vary in the MITRA-FR trial, whereas in COAPT, patients were on maximally tolerated guideline-directed medical therapy at baseline with few major changes during follow-up.

“Today we have two publications in The New England Journal of Medicine and apparently two different outcomes,” Jean-Francois Obadia, MD, PhD, from Hopital Cardiovasculaire Louis Pradel, Lyon, France, who presented data from the MITRA-FR trial at the European Society of Cardiology Congress in August, said during the presentation. “This is the best scenario we could have. ... This difference leads us to go deeper into the analysis ... to try to understand this complex disease. Therefore, we know with COAPT what to do, because it provides an accurate selection of the patients who could really benefit from the clip, and with MITRA-FR, which represents more the real world, in which patients should not receive a clip. The two studies are more complementary than controversial.” – by Darlene Dobkowski

PAGE BREAK

References:

Stone GW, et al. Late-Breaking Trials 3. Presented at: TCT Scientific Symposium; Sept. 21-25, 2018; San Diego.

Stone GW, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1806640.

Disclosures: The trial was funded by Abbott. Stone reports he received grants from Abbott to the Cardiovascular Research Foundation; personal fees from Ablative Solutions, Claret, Gore, HeartFlow, Matrizyme, Miracor, Neovasc, Reva, Robocath, Shockwave, TherOx, V-wave, Valfix and Vascular Dynamics; and other support from Ancora, Aria, Biostar, Cagent, Caliber, MedFocus, Qool Therapeutics, SpectraWave; and his employer, Columbia University, receives royalties from Abbott for sales of the MitraClip. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    B. Hadley Wilson

    B. Hadley Wilson

    This may be one of the most exciting trials presented here at TCT 2018. The reason is that this was an anticipated study to see whether or not the MitraClip procedure would be a viable procedure that can be used in patients who are symptomatic with moderate to severe or severe mitral regurgitation or leakage of the mitral valve. These are not because of an anatomical issue, but because of a functional mitral regurgitation from antecedent HF.

    In the past, these patients honestly were mostly treated with medical therapy. There were some pacemaker devices and other novel devices that were used to try and help these HF patients and to perhaps reduce the leakage of the mitral valve, but aside from surgery, it was not considered necessarily that MitraClip would be a therapy that can be used with these patients.

    What is encouraging and exciting is that with this large group of patients who were randomly assigned to medical therapy or to the MitraClip procedure for functional mitral regurgitation from previous or antecedent HF after being followed for 2 years with successful MitraClip therapy, those patients actually did significantly better and specifically they had less hospitalizations for HF and lower all-cause mortality at the end of 2 years compared with the medical therapy group.

    This opens up MitraClip as a viable and encouraging procedure that can be used for these patients that previously were relegated to the best medical therapy they can have, but not necessarily in a way that was improving their clinical situation. It did appear that this improves these patients’ clinical situation.

    It was also exciting that the device failure or complication rate was lower than expected. Again, that points to anytime you have a new therapy, particularly if it is a device, a minor surgery or what have you that regards something that is potentially invasive, that is always a concern of complications, but this had very low, several percentage complication rate and less than what they expected on the front end of the procedures.

    Several of the studies that have been presented here really knocked it out of the park because it showed a new therapy for an indication for something that we have not had optimal treatments for in the past. This is a large group of patients with HF, and then with secondary mitral regurgitation that can now be treated with the MitraClip.

    This trial is encouraging, and we do have to take everything in totality, but this may impact the guidelines for use of this therapy. It may not be that it is going to be a Ia guideline recommendation, but it may be a IIb or perhaps even a IIa, meaning that it is one that can be considered for use in these patients.

    We have seen that MitraClip has been a successful therapy in patients who were high surgical risk before. Now this gives another group of patients that can be treated with MitraClip. That is great because that means that they have other options if they are at high surgical risk, which these HF patients are, other than medical therapy. They are going to feel better.

    • B. Hadley Wilson, MD, FACC
    • Interventional Cardiologist
      Sanger Heart & Vascular Institute, Atrium Health
      Clinical Professor of Medicine
      UNC School of Medicine
      Member, Board of Trustees
      American College of Cardiology

    Disclosures: Wilson reports no relevant financial disclosures.

    Perspective
    Dharam J. Kumbhani

    Dharam J. Kumbhani

    COAPT is an incredible trial. It is probably one of the biggest trials in our field in a really long time. There have been a lot of very important trials, but as a structural interventionalist, probably after PARTNER, this is probably the biggest trial in the field. It has been 8 to 10 years since we had another blockbuster like that. Off the bat, it suggests that transcatheter mitral valve approximation using the MitraClip is superior to medical therapy alone for selected patients with HF and moderate-to-severe or severe mitral regurgitation. The striking thing is that all the endpoints are completely concordant. The primary endpoint of HF hospitalizations was reduced, but so was mortality. The MitraClip provided a durable result at 1 year in this trial, and as a result, the left ventricles didn’t dilate further, and patients also felt better. Only CV mortality and hospitalization, and that too, the portion related to HF, got better; non-CV mortality and hospitalization rates were similar between the two arms. The overall story is thus very convincing, even though this was an open-label study.

    There have been a lot of sessions and a lot of discussions at TCT about how to best reconcile COAPT with the trial at ESC, MITRA-FR, and what this means for the field in general. There are key differences between the trials as far as identifying which patients would benefit the most. For example, COAPT suggests that you have to catch patients with cardiomyopathy and severe MR that are not too far gone when their left ventricles are really dilated, which was the case for many patients in MITRA-FR. You could argue that those patients are too far gone for the MitraClip to actually help them.

    Another difference is that the severity of MR was higher in COAPT. The sweet spot is thus probably patients with not very dilated ventricles, but low ejection fraction — 31% was average in the trial — and at least having moderate-to-severe to severe mitral regurgitation.

    Regarding optimal medical therapy, in the MITRA-FR trial, you had to be on medical therapy, but you could have some changes made as you went through the trial on both sides. In COAPT, this was minimal (< 5%).

    Everyone is asking where we go from here after MITRA-FR and COAPT. There is at least one other trial called RESHAPE-HF2 that is ongoing in Europe. My feeling is that, because the two trials enrolled different patient populations, we do not necessarily need another trial in this space. In some ways, given the results of COAPT, some may say that it would be unethical to randomize patients with the same criteria as COAPT to medical therapy alone, knowing that there is also a mortality benefit.

    I do not know if there will be a tiebreaking trial ever in this space, but going forward, this is likely to be the gold standard with the caveat that it is not yet FDA-approved for that indication. That would need to come.

    Probably in a good way, this complicates the field for the other devices. There are so many devices that are being tested in many different stages of development. Unless they are not MitraClip candidates, it may be unethical again for the same reason to randomly assign them to the new device vs. medical therapy. They would need to have potentially a tiered approach.

    • Dharam J. Kumbhani, MD, SM
    • Cardiology Today Next Gen Innovator
      Associate Professor, Department of Internal Medicine
      UTSouthwestern Medical Center, Dallas

    Disclosures: Kumbhani reports no relevant financial disclosures.

    Perspective

    The results of this trial have been described as spectacular and breathtaking. It is an amazing trial and is extremely important because this is a difficult population of patients with a high underlying mortality and morbidity.

    The implication is, for this group of patients with HF and mitral regurgitation who have hit the limit as far as medical therapy, there is another option, which this trial conclusively shows will improve their quality of life and improve their survival.

    There are significant differences in COAPT and MITRA-FR. A very important part of COAPT, for which I was a principal site investigator, was the participation of HF doctors and achievement of maximum medical therapy before a patient was accepted into the trial. As a result, the patients that were in the trial had more mitral regurgitation and were sicker. From what I understand with MITRA-FR, there was no such requirement, and their HF treatment was allowed to change before and after their MitraClip.

    The reason that is important is that mitral regurgitation is very sensitive to variations in medications, BP, etc. We had many patients that started out with severe mitral regurgitation, but by the time they reached their maximum medical therapy, it was no longer as severe, and they were excluded from the trial.

    An important outcome of the trial was how safe the procedure is. The complication rate was only about 3% in a very sick population. That is important because if you are having an invasive intervention in a sick population, you want to know that it is safe. It has been shown to be safe.

    • Lawrence Ong, MD
    • Chair, Department of Cardiology
      Southside Hospital, Bay Shore, New York

    Disclosures: Ong reports he was a principal site investigator for COAPT.

    Perspective
    Vinod H. Thourani

    Vinod H. Thourani

    The outcomes of COAPT were staggering. As a surgeon who deals with this in the cath lab and also in the operating room, the management of patients with severe functional mitral regurgitation has been moderately successful at best. We were anticipating some pathway that would give us better outcomes in addition to guideline-directed medical therapy.

    In these high-risk patients with an ejection fraction of approximately 30%, surgical outcome has been good, but not phenomenal. Therefore, a lot of these patients have been treated with guideline medical therapy with or without CRT. What this study shows is that in addition to guideline-directed medical therapy, decreasing that mitral regurgitation is a safe procedure that significantly reduces mortality, and more importantly, decreases hospitalization and improves quality of life. This is extremely impactful for a patient. Not only the individual patient, but for health care resources for this very sick patient population. I am exceedingly encouraged and optimistic of the future management in these complex patients.

    It would have been nice to have both COAPT and MITRA-FR] have positive results, but there are differences between the studies. The rigor that was performed with COAPT, especially with guideline-directed medical therapy, was like no other and has a 2-year follow-up. When I look at both studies, I am more impacted by COAPT, especially since I know the rigors of what it took to perform.

    We would hope that MitraClip will become approved in the U.S. for this patient population. Going forward, it will be important to tease out which patient cohorts had a successful recovery and those who did not. This will be important from anatomic considerations and patient preoperative characteristics. We have just now gotten to the tip of the iceberg in treating patients with functional mitral regurgitation. This is a very exciting time indeed.

    • Vinod H. Thourani, MD, FACS, FACC
    • Chairman, Department of Cardiac Surgery
      MedStar Heart & Vascular Institute
      Georgetown University School of Medicine
      Washington, D.C.

    Disclosures: Thourani reports he has relationships with Abbott Vascular, Boston Scientific, Edwards Lifesciences, Gore Vascular, JenaValve and Medtronic.

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