Heart surgeons get serious about RCTs

SAN DIEGO – The days when cardiologists could look down their noses at cardiac surgeons as primitive when it comes to conducting high-quality clinical research have come and gone.

“Cardiologists have been much more sophisticated than we have in doing randomized controlled trials. But cardiac surgeons are finally making strong progress in conducting randomized clinical trials, an area we’re not typically known for,” Dr. Vinod H. Thourani asserted at the annual meeting of the American College of Cardiology.

Much of this progress can be credited to the relatively recent creation of the Cardiothoracic Surgical Trials Network (CSTN), funded by the U.S. National Institutions of Health and the Canadian Institutes of Health Research. This surgical network is carrying out cutting-edge RCTs that will change the practice of cardiology as well as heart surgery, said Dr. Thourani, professor of surgery and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.

To illustrate the breadth of current research in cardiothoracic surgery, he presented thumbnail sketches of RCTs due to report findings as early as this spring and no later than the latter part of next year or early 2017. The trials he selected, some conducted by the CSTN and others with industry sponsorship, address the aortic valve, the mitral valve, postoperative atrial fibrillation, revascularization in patients with unprotected left main coronary artery disease, and advanced heart failure.

• Heart failure: Outcomes of the ENDURANCE destination trial are due to be presented this spring at the annual meeting of the International Society for Heart and Lung Transplantation in Nice, France. This study will compare 12-month outcomes of continuous-flow ventricular assist devices as destination therapy in advanced heart failure. In this HeartWare-sponsored study, 310 patients received the investigational HeartWare ventricular assist system and 155 controls were implanted with the FDA-approved HeartMate II device marketed by Thoratec.

• Atrial fibrillation: The Rate Control Versus Rhythm Control for Postoperative Atrial Fibrillation trial compares the two management strategies in patients with new-onset AF following cardiac surgery. This CSTN-conducted study, to be presented next year, looks at which treatment approach results in fewer days in the hospital, as well as heart rhythm at discharge and through 60 days of follow-up, economic costs, and the incidence of postoperative clinical events.

• Coronary artery disease: The EXCEL trial has randomized 2,600 patients with unprotected left main coronary artery disease to coronary artery bypass surgery or percutaneous intervention with a XIENCE everolimus-eluting stent. The primary outcome is the composite of all-cause mortality, acute MI, or stroke. First results of this Abbott Vascular–sponsored trial are due to be reported next year.“This is a study that will clearly be impactful for you,” Dr. Thourani observed.

• Aortic valve disease: Two major RCTs are looking at the impact of extending transcatheter aortic valve replacement (TAVR) to an intermediate-surgical-risk population of patients with symptomatic severe aortic stenosis. The PARTNER II trial compares transfemoral or transapical/transaortic TAVR with a SAPIEN XT valve to surgical aortic valve replacement in patients with a Society of Thoracic Surgeons mortality risk score of 4%-8%. The primary endpoint is all-cause mortality and disabling stroke at 2 years. Results of this Edwards Lifesciences–sponsored trial will be presented by early 2016.

The Medtronic-sponsored SURTAVI trial compares TAVR using the company’s CoreValve alone or with PCI if revascularization is indicated versus surgical aortic valve replacement alone or with coronary artery bypass grafting if revascularization is indicated. This is a randomized trial involving 2,500 intermediate-risk patients. Of note, the SURTAVI investigators have revised the study protocol to open the trial to patients who are age 75 years or older or have an STS score of 2%-10%, which really redefines the concept of intermediate risk, Dr. Thourani said. Results will be presented by early 2017.

• Mitral valve disease: The Evaluation of Outcomes Following Mitral Valve Repair/Replacement in Severe Chronic Ischemic Mitral Regurgitation trial, carried out by the CSTN, will present 2-year outcome data later this year or in early 2016. The 1-year results caused major consternation in the surgical world. The eye opener was that 33% of patients in the repair group had moderate or severe mitral regurgitation at 12 months, compared with just 2% in the replacement group (N. Engl. J. Med. 2014;370:23-32). Mitral valve repair has traditionally been by far the more popular strategy. If the 2-year results show a growing disparity in terms of rates of severe mitral regurgitation, that may change.

Another CSTN study, the Surgical Intervention in Moderate Ischemic Mitral Regurgitation trial, found no demonstrable clinical benefit in adding a mitral valve repair operation to CABG surgery at 1 year of follow-up. The incidence of moderate or severe mitral regurgitation was lower at 1 year with concomitant valve repair and CABG, but this was offset by more neurologic events, longer ICU and total hospital stays, and no differences in the degree of reverse remodeling, mortality, or quality of life (N. Engl. J. Med. 2014;371:2178-88).

“Two-year follow-up is ongoing. It really becomes very important that later this year or next year we’re going to have the results available for you to determine if the lower incidence of moderate or severe mitral regurgitation at 1 year translates into a net clinical benefit for patients undergoing CABG and mitral repair. This study has big implications for the practice of thoracic surgery and for how cardiologists refer patients,” according to Dr. Thourani.

The COAPT trial is randomizing patients with symptomatic functional mitral regurgitation and very high surgical risk to percutaneous catheter-based treatment with the MitraClip or to a standard-care control group. One-year outcomes will be presented in 2016, and follow-up out to 5 years is planned.

“You can see now that in cardiac surgery there’s a lot going on,” Dr. Thourani concluded. “It’s not only good for us, but it’s good for you. As a cardiovascular community, we need to work together more.”

He reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott Medical, Boston Scientific, Medtronic, and Sorin.

[email protected]

SAN DIEGO – The days when cardiologists could look down their noses at cardiac surgeons as primitive when it comes to conducting high-quality clinical research have come and gone.

“Cardiologists have been much more sophisticated than we have in doing randomized controlled trials. But cardiac surgeons are finally making strong progress in conducting randomized clinical trials, an area we’re not typically known for,” Dr. Vinod H. Thourani asserted at the annual meeting of the American College of Cardiology.

Much of this progress can be credited to the relatively recent creation of the Cardiothoracic Surgical Trials Network (CSTN), funded by the U.S. National Institutions of Health and the Canadian Institutes of Health Research. This surgical network is carrying out cutting-edge RCTs that will change the practice of cardiology as well as heart surgery, said Dr. Thourani, professor of surgery and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.

To illustrate the breadth of current research in cardiothoracic surgery, he presented thumbnail sketches of RCTs due to report findings as early as this spring and no later than the latter part of next year or early 2017. The trials he selected, some conducted by the CSTN and others with industry sponsorship, address the aortic valve, the mitral valve, postoperative atrial fibrillation, revascularization in patients with unprotected left main coronary artery disease, and advanced heart failure.

• Heart failure: Outcomes of the ENDURANCE destination trial are due to be presented this spring at the annual meeting of the International Society for Heart and Lung Transplantation in Nice, France. This study will compare 12-month outcomes of continuous-flow ventricular assist devices as destination therapy in advanced heart failure. In this HeartWare-sponsored study, 310 patients received the investigational HeartWare ventricular assist system and 155 controls were implanted with the FDA-approved HeartMate II device marketed by Thoratec.

• Atrial fibrillation: The Rate Control Versus Rhythm Control for Postoperative Atrial Fibrillation trial compares the two management strategies in patients with new-onset AF following cardiac surgery. This CSTN-conducted study, to be presented next year, looks at which treatment approach results in fewer days in the hospital, as well as heart rhythm at discharge and through 60 days of follow-up, economic costs, and the incidence of postoperative clinical events.

• Coronary artery disease: The EXCEL trial has randomized 2,600 patients with unprotected left main coronary artery disease to coronary artery bypass surgery or percutaneous intervention with a XIENCE everolimus-eluting stent. The primary outcome is the composite of all-cause mortality, acute MI, or stroke. First results of this Abbott Vascular–sponsored trial are due to be reported next year.“This is a study that will clearly be impactful for you,” Dr. Thourani observed.

• Aortic valve disease: Two major RCTs are looking at the impact of extending transcatheter aortic valve replacement (TAVR) to an intermediate-surgical-risk population of patients with symptomatic severe aortic stenosis. The PARTNER II trial compares transfemoral or transapical/transaortic TAVR with a SAPIEN XT valve to surgical aortic valve replacement in patients with a Society of Thoracic Surgeons mortality risk score of 4%-8%. The primary endpoint is all-cause mortality and disabling stroke at 2 years. Results of this Edwards Lifesciences–sponsored trial will be presented by early 2016.

The Medtronic-sponsored SURTAVI trial compares TAVR using the company’s CoreValve alone or with PCI if revascularization is indicated versus surgical aortic valve replacement alone or with coronary artery bypass grafting if revascularization is indicated. This is a randomized trial involving 2,500 intermediate-risk patients. Of note, the SURTAVI investigators have revised the study protocol to open the trial to patients who are age 75 years or older or have an STS score of 2%-10%, which really redefines the concept of intermediate risk, Dr. Thourani said. Results will be presented by early 2017.

• Mitral valve disease: The Evaluation of Outcomes Following Mitral Valve Repair/Replacement in Severe Chronic Ischemic Mitral Regurgitation trial, carried out by the CSTN, will present 2-year outcome data later this year or in early 2016. The 1-year results caused major consternation in the surgical world. The eye opener was that 33% of patients in the repair group had moderate or severe mitral regurgitation at 12 months, compared with just 2% in the replacement group (N. Engl. J. Med. 2014;370:23-32). Mitral valve repair has traditionally been by far the more popular strategy. If the 2-year results show a growing disparity in terms of rates of severe mitral regurgitation, that may change.

Another CSTN study, the Surgical Intervention in Moderate Ischemic Mitral Regurgitation trial, found no demonstrable clinical benefit in adding a mitral valve repair operation to CABG surgery at 1 year of follow-up. The incidence of moderate or severe mitral regurgitation was lower at 1 year with concomitant valve repair and CABG, but this was offset by more neurologic events, longer ICU and total hospital stays, and no differences in the degree of reverse remodeling, mortality, or quality of life (N. Engl. J. Med. 2014;371:2178-88).

“Two-year follow-up is ongoing. It really becomes very important that later this year or next year we’re going to have the results available for you to determine if the lower incidence of moderate or severe mitral regurgitation at 1 year translates into a net clinical benefit for patients undergoing CABG and mitral repair. This study has big implications for the practice of thoracic surgery and for how cardiologists refer patients,” according to Dr. Thourani.

The COAPT trial is randomizing patients with symptomatic functional mitral regurgitation and very high surgical risk to percutaneous catheter-based treatment with the MitraClip or to a standard-care control group. One-year outcomes will be presented in 2016, and follow-up out to 5 years is planned.

“You can see now that in cardiac surgery there’s a lot going on,” Dr. Thourani concluded. “It’s not only good for us, but it’s good for you. As a cardiovascular community, we need to work together more.”

He reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott Medical, Boston Scientific, Medtronic, and Sorin.

[email protected]

SAN DIEGO – The days when cardiologists could look down their noses at cardiac surgeons as primitive when it comes to conducting high-quality clinical research have come and gone.

“Cardiologists have been much more sophisticated than we have in doing randomized controlled trials. But cardiac surgeons are finally making strong progress in conducting randomized clinical trials, an area we’re not typically known for,” Dr. Vinod H. Thourani asserted at the annual meeting of the American College of Cardiology.

Much of this progress can be credited to the relatively recent creation of the Cardiothoracic Surgical Trials Network (CSTN), funded by the U.S. National Institutions of Health and the Canadian Institutes of Health Research. This surgical network is carrying out cutting-edge RCTs that will change the practice of cardiology as well as heart surgery, said Dr. Thourani, professor of surgery and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.

To illustrate the breadth of current research in cardiothoracic surgery, he presented thumbnail sketches of RCTs due to report findings as early as this spring and no later than the latter part of next year or early 2017. The trials he selected, some conducted by the CSTN and others with industry sponsorship, address the aortic valve, the mitral valve, postoperative atrial fibrillation, revascularization in patients with unprotected left main coronary artery disease, and advanced heart failure.

• Heart failure: Outcomes of the ENDURANCE destination trial are due to be presented this spring at the annual meeting of the International Society for Heart and Lung Transplantation in Nice, France. This study will compare 12-month outcomes of continuous-flow ventricular assist devices as destination therapy in advanced heart failure. In this HeartWare-sponsored study, 310 patients received the investigational HeartWare ventricular assist system and 155 controls were implanted with the FDA-approved HeartMate II device marketed by Thoratec.

• Atrial fibrillation: The Rate Control Versus Rhythm Control for Postoperative Atrial Fibrillation trial compares the two management strategies in patients with new-onset AF following cardiac surgery. This CSTN-conducted study, to be presented next year, looks at which treatment approach results in fewer days in the hospital, as well as heart rhythm at discharge and through 60 days of follow-up, economic costs, and the incidence of postoperative clinical events.

• Coronary artery disease: The EXCEL trial has randomized 2,600 patients with unprotected left main coronary artery disease to coronary artery bypass surgery or percutaneous intervention with a XIENCE everolimus-eluting stent. The primary outcome is the composite of all-cause mortality, acute MI, or stroke. First results of this Abbott Vascular–sponsored trial are due to be reported next year.“This is a study that will clearly be impactful for you,” Dr. Thourani observed.

• Aortic valve disease: Two major RCTs are looking at the impact of extending transcatheter aortic valve replacement (TAVR) to an intermediate-surgical-risk population of patients with symptomatic severe aortic stenosis. The PARTNER II trial compares transfemoral or transapical/transaortic TAVR with a SAPIEN XT valve to surgical aortic valve replacement in patients with a Society of Thoracic Surgeons mortality risk score of 4%-8%. The primary endpoint is all-cause mortality and disabling stroke at 2 years. Results of this Edwards Lifesciences–sponsored trial will be presented by early 2016.

The Medtronic-sponsored SURTAVI trial compares TAVR using the company’s CoreValve alone or with PCI if revascularization is indicated versus surgical aortic valve replacement alone or with coronary artery bypass grafting if revascularization is indicated. This is a randomized trial involving 2,500 intermediate-risk patients. Of note, the SURTAVI investigators have revised the study protocol to open the trial to patients who are age 75 years or older or have an STS score of 2%-10%, which really redefines the concept of intermediate risk, Dr. Thourani said. Results will be presented by early 2017.

• Mitral valve disease: The Evaluation of Outcomes Following Mitral Valve Repair/Replacement in Severe Chronic Ischemic Mitral Regurgitation trial, carried out by the CSTN, will present 2-year outcome data later this year or in early 2016. The 1-year results caused major consternation in the surgical world. The eye opener was that 33% of patients in the repair group had moderate or severe mitral regurgitation at 12 months, compared with just 2% in the replacement group (N. Engl. J. Med. 2014;370:23-32). Mitral valve repair has traditionally been by far the more popular strategy. If the 2-year results show a growing disparity in terms of rates of severe mitral regurgitation, that may change.

Another CSTN study, the Surgical Intervention in Moderate Ischemic Mitral Regurgitation trial, found no demonstrable clinical benefit in adding a mitral valve repair operation to CABG surgery at 1 year of follow-up. The incidence of moderate or severe mitral regurgitation was lower at 1 year with concomitant valve repair and CABG, but this was offset by more neurologic events, longer ICU and total hospital stays, and no differences in the degree of reverse remodeling, mortality, or quality of life (N. Engl. J. Med. 2014;371:2178-88).

“Two-year follow-up is ongoing. It really becomes very important that later this year or next year we’re going to have the results available for you to determine if the lower incidence of moderate or severe mitral regurgitation at 1 year translates into a net clinical benefit for patients undergoing CABG and mitral repair. This study has big implications for the practice of thoracic surgery and for how cardiologists refer patients,” according to Dr. Thourani.

The COAPT trial is randomizing patients with symptomatic functional mitral regurgitation and very high surgical risk to percutaneous catheter-based treatment with the MitraClip or to a standard-care control group. One-year outcomes will be presented in 2016, and follow-up out to 5 years is planned.

“You can see now that in cardiac surgery there’s a lot going on,” Dr. Thourani concluded. “It’s not only good for us, but it’s good for you. As a cardiovascular community, we need to work together more.”

He reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott Medical, Boston Scientific, Medtronic, and Sorin.

[email protected]