ACC 2012

CHICAGO – Two-year follow-up results on transcatheter aortic valve replacement identified for the first time the critical role that even mild paravalvular aortic regurgitation can play in patient survival and highlighted a new problem the percutaneous procedure needs to overcome in contending with aortic valve replacement by open surgery.

In the PARTNER (Placement of Aortic Transcatheter Valves) trial, which compared the performance of one system of transcatheter aortic valve replacement (TAVR) against aortic valve replacement by open surgery, patients with mild paravalvular aortic regurgitation (a leak around the outer edges of the inserted valve) had a 33% 2-year morality, compared with a 26% rate in TAVR patients with no leak or a trace leak, Dr. Susheel K. Kodali reported at the meeting. Patients with a moderate or severe leak had a 51% mortality rate at 2-year follow-up, a statistically significant difference, compared with patients with a trace or no leak.

The data Dr. Kodali reported also showed that the incidence of paravalvular leaks, which generally appeared during the first 30 days following intervention, occurred substantially more often in the TAVR patients, compared with those who underwent open valve replacement. In the TAVR group of the PARTNER trial, about 48% of patients had a trace or no leak at 2 years, compared with a roughly 90% rate in the surgery patients. By 2 years after treatment, 7% of the TAVR patients had a moderate or severe leak, compared with 1% of the open-surgery patients.

"The trend was to say that grade 1, grade 2 leaks didn’t matter. Now you show that aortic regurgitation, especially moderate or severe, is not acceptable," commented Dr. G. Alain Cribier, professor of cardiology at Charles Nicolle Hospital in Rouen, France. "The good part is that you can do something about them. We can do a lot more to assess the anatomy of the annulus and use more valve sizes. In my experience, the trend is to reduce the [number of] leaks," said Dr. Cribier, who performs TAVR.

Dr. Kodali agreed. "Paravalvular aortic regurgitation is an important target for us to improve. Factors that go into paravalvular aortic regurgitation include valve size and position. Two recent reports said that we have systematically undersized the valve 35%-40% of the time," when TAVR had been performed in the past. "We need to better understand valve anatomy," said Dr. Kodali, an interventional cardiologist and codirector of the transcatheter aortic valve program at Columbia University in New York.

Another step he and his associates have taken to cut leak incidence and severity has been valve dilatation following placement. "If we see a paravalvular leak that is mild or worse, we tend to reballoon the valve," he said. He cited a separate report he and his associates made at the meeting that documented the ability of balloon dilatation following valve placement to significantly reduce the volume of paravalvular regurgitation in 36 patients who began with moderate or severe regurgitation.

"But ideally, if we better size the valve up front we won’t need to do postimplant dilatation," he said.

"Leaks are significantly improved by improved techniques. There will probably be about a 50% improvement in leak" incidence and severity, predicted Dr. Robert A. Guyton, professor of surgery and chief of cardiothoracic surgery at Emory University in Atlanta and a collaborator on the PARTNER trial. "But I don’t think we’ll get rid of it." The incidence of mild or worse paravalvular leaks following TAVR may drop to perhaps 25% of patients, he predicted, "but that’s still a big number," compared with the rate following open surgery, he said in an interview.

The data Dr. Kodali reported showed the powerful impact that paravalvular leaks had on overall outcomes in the study. Although the overall 1- and 2-year outcome results from PARTNER showed essentially superimposable mortality rates for TAVR and open surgery, among those patients who emerged from TAVR with a trace or no paravalvular leak, 1-year mortality was 13% with TAVR, compared with 24% with open surgery, and 2-year mortality was 26% with TAVR, compared with 30% with open surgery, differences that approached statistically significance. In other words, patients who came through TAVR with a trace or mild leak had better outcomes than did the surgery patients, but because many TAVR patients had mild, moderate, or severe leaks, the poor prognosis of those patients counterbalanced the relatively good outcomes of the patients who had ideal TAVR outcomes.

And the problem, said Dr. Guyton, is that "going into the cath lab, you can’t predict which patients will have a leak and which won’t. But maybe [in the future] we can look at how much calcium there is on a valve and predict which patients may have leaks" and perform open surgery on those patients instead of TAVR.

The PARTNER trial used the SAPIEN Heart Valve System marketed by Edwards Lifesciences. The trial was sponsored by Edwards. Concurrent with Dr. Kodali’s report at the meeting, the results he presented appeared online (N. Engl. J. Med. 2012, March 26;366 [doi:10.1056/NEJMoa1200384]).

The PARTNER trial was sponsored by Edwards Lifesciences. Dr. Cribier said that he is a consultant to Edwards Lifesciences. Dr. Kodali said that he has been a consultant to Edwards Lifesciences, Medtronic, and St. Jude Medical, that he serves on an advisory board for Paieon Medical, and that he owns stock in Thubrikar Aortic Valve. Dr. Guyton said that he had no disclosures.

*Correction, 4/3/2012: An earlier version of this story mischaracterized the findings.

CHICAGO – Two-year follow-up results on transcatheter aortic valve replacement identified for the first time the critical role that even mild paravalvular aortic regurgitation can play in patient survival and highlighted a new problem the percutaneous procedure needs to overcome in contending with aortic valve replacement by open surgery.

In the PARTNER (Placement of Aortic Transcatheter Valves) trial, which compared the performance of one system of transcatheter aortic valve replacement (TAVR) against aortic valve replacement by open surgery, patients with mild paravalvular aortic regurgitation (a leak around the outer edges of the inserted valve) had a 33% 2-year morality, compared with a 26% rate in TAVR patients with no leak or a trace leak, Dr. Susheel K. Kodali reported at the meeting. Patients with a moderate or severe leak had a 51% mortality rate at 2-year follow-up, a statistically significant difference, compared with patients with a trace or no leak.

The data Dr. Kodali reported also showed that the incidence of paravalvular leaks, which generally appeared during the first 30 days following intervention, occurred substantially more often in the TAVR patients, compared with those who underwent open valve replacement. In the TAVR group of the PARTNER trial, about 48% of patients had a trace or no leak at 2 years, compared with a roughly 90% rate in the surgery patients. By 2 years after treatment, 7% of the TAVR patients had a moderate or severe leak, compared with 1% of the open-surgery patients.

"The trend was to say that grade 1, grade 2 leaks didn’t matter. Now you show that aortic regurgitation, especially moderate or severe, is not acceptable," commented Dr. G. Alain Cribier, professor of cardiology at Charles Nicolle Hospital in Rouen, France. "The good part is that you can do something about them. We can do a lot more to assess the anatomy of the annulus and use more valve sizes. In my experience, the trend is to reduce the [number of] leaks," said Dr. Cribier, who performs TAVR.

Dr. Kodali agreed. "Paravalvular aortic regurgitation is an important target for us to improve. Factors that go into paravalvular aortic regurgitation include valve size and position. Two recent reports said that we have systematically undersized the valve 35%-40% of the time," when TAVR had been performed in the past. "We need to better understand valve anatomy," said Dr. Kodali, an interventional cardiologist and codirector of the transcatheter aortic valve program at Columbia University in New York.

Another step he and his associates have taken to cut leak incidence and severity has been valve dilatation following placement. "If we see a paravalvular leak that is mild or worse, we tend to reballoon the valve," he said. He cited a separate report he and his associates made at the meeting that documented the ability of balloon dilatation following valve placement to significantly reduce the volume of paravalvular regurgitation in 36 patients who began with moderate or severe regurgitation.

"But ideally, if we better size the valve up front we won’t need to do postimplant dilatation," he said.

"Leaks are significantly improved by improved techniques. There will probably be about a 50% improvement in leak" incidence and severity, predicted Dr. Robert A. Guyton, professor of surgery and chief of cardiothoracic surgery at Emory University in Atlanta and a collaborator on the PARTNER trial. "But I don’t think we’ll get rid of it." The incidence of mild or worse paravalvular leaks following TAVR may drop to perhaps 25% of patients, he predicted, "but that’s still a big number," compared with the rate following open surgery, he said in an interview.

The data Dr. Kodali reported showed the powerful impact that paravalvular leaks had on overall outcomes in the study. Although the overall 1- and 2-year outcome results from PARTNER showed essentially superimposable mortality rates for TAVR and open surgery, among those patients who emerged from TAVR with a trace or no paravalvular leak, 1-year mortality was 13% with TAVR, compared with 24% with open surgery, and 2-year mortality was 26% with TAVR, compared with 30% with open surgery, differences that approached statistically significance. In other words, patients who came through TAVR with a trace or mild leak had better outcomes than did the surgery patients, but because many TAVR patients had mild, moderate, or severe leaks, the poor prognosis of those patients counterbalanced the relatively good outcomes of the patients who had ideal TAVR outcomes.

And the problem, said Dr. Guyton, is that "going into the cath lab, you can’t predict which patients will have a leak and which won’t. But maybe [in the future] we can look at how much calcium there is on a valve and predict which patients may have leaks" and perform open surgery on those patients instead of TAVR.

The PARTNER trial used the SAPIEN Heart Valve System marketed by Edwards Lifesciences. The trial was sponsored by Edwards. Concurrent with Dr. Kodali’s report at the meeting, the results he presented appeared online (N. Engl. J. Med. 2012, March 26;366 [doi:10.1056/NEJMoa1200384]).

The PARTNER trial was sponsored by Edwards Lifesciences. Dr. Cribier said that he is a consultant to Edwards Lifesciences. Dr. Kodali said that he has been a consultant to Edwards Lifesciences, Medtronic, and St. Jude Medical, that he serves on an advisory board for Paieon Medical, and that he owns stock in Thubrikar Aortic Valve. Dr. Guyton said that he had no disclosures.

*Correction, 4/3/2012: An earlier version of this story mischaracterized the findings.

CHICAGO – Two-year follow-up results on transcatheter aortic valve replacement identified for the first time the critical role that even mild paravalvular aortic regurgitation can play in patient survival and highlighted a new problem the percutaneous procedure needs to overcome in contending with aortic valve replacement by open surgery.

In the PARTNER (Placement of Aortic Transcatheter Valves) trial, which compared the performance of one system of transcatheter aortic valve replacement (TAVR) against aortic valve replacement by open surgery, patients with mild paravalvular aortic regurgitation (a leak around the outer edges of the inserted valve) had a 33% 2-year morality, compared with a 26% rate in TAVR patients with no leak or a trace leak, Dr. Susheel K. Kodali reported at the meeting. Patients with a moderate or severe leak had a 51% mortality rate at 2-year follow-up, a statistically significant difference, compared with patients with a trace or no leak.

The data Dr. Kodali reported also showed that the incidence of paravalvular leaks, which generally appeared during the first 30 days following intervention, occurred substantially more often in the TAVR patients, compared with those who underwent open valve replacement. In the TAVR group of the PARTNER trial, about 48% of patients had a trace or no leak at 2 years, compared with a roughly 90% rate in the surgery patients. By 2 years after treatment, 7% of the TAVR patients had a moderate or severe leak, compared with 1% of the open-surgery patients.

"The trend was to say that grade 1, grade 2 leaks didn’t matter. Now you show that aortic regurgitation, especially moderate or severe, is not acceptable," commented Dr. G. Alain Cribier, professor of cardiology at Charles Nicolle Hospital in Rouen, France. "The good part is that you can do something about them. We can do a lot more to assess the anatomy of the annulus and use more valve sizes. In my experience, the trend is to reduce the [number of] leaks," said Dr. Cribier, who performs TAVR.

Dr. Kodali agreed. "Paravalvular aortic regurgitation is an important target for us to improve. Factors that go into paravalvular aortic regurgitation include valve size and position. Two recent reports said that we have systematically undersized the valve 35%-40% of the time," when TAVR had been performed in the past. "We need to better understand valve anatomy," said Dr. Kodali, an interventional cardiologist and codirector of the transcatheter aortic valve program at Columbia University in New York.

Another step he and his associates have taken to cut leak incidence and severity has been valve dilatation following placement. "If we see a paravalvular leak that is mild or worse, we tend to reballoon the valve," he said. He cited a separate report he and his associates made at the meeting that documented the ability of balloon dilatation following valve placement to significantly reduce the volume of paravalvular regurgitation in 36 patients who began with moderate or severe regurgitation.

"But ideally, if we better size the valve up front we won’t need to do postimplant dilatation," he said.

"Leaks are significantly improved by improved techniques. There will probably be about a 50% improvement in leak" incidence and severity, predicted Dr. Robert A. Guyton, professor of surgery and chief of cardiothoracic surgery at Emory University in Atlanta and a collaborator on the PARTNER trial. "But I don’t think we’ll get rid of it." The incidence of mild or worse paravalvular leaks following TAVR may drop to perhaps 25% of patients, he predicted, "but that’s still a big number," compared with the rate following open surgery, he said in an interview.

The data Dr. Kodali reported showed the powerful impact that paravalvular leaks had on overall outcomes in the study. Although the overall 1- and 2-year outcome results from PARTNER showed essentially superimposable mortality rates for TAVR and open surgery, among those patients who emerged from TAVR with a trace or no paravalvular leak, 1-year mortality was 13% with TAVR, compared with 24% with open surgery, and 2-year mortality was 26% with TAVR, compared with 30% with open surgery, differences that approached statistically significance. In other words, patients who came through TAVR with a trace or mild leak had better outcomes than did the surgery patients, but because many TAVR patients had mild, moderate, or severe leaks, the poor prognosis of those patients counterbalanced the relatively good outcomes of the patients who had ideal TAVR outcomes.

And the problem, said Dr. Guyton, is that "going into the cath lab, you can’t predict which patients will have a leak and which won’t. But maybe [in the future] we can look at how much calcium there is on a valve and predict which patients may have leaks" and perform open surgery on those patients instead of TAVR.

The PARTNER trial used the SAPIEN Heart Valve System marketed by Edwards Lifesciences. The trial was sponsored by Edwards. Concurrent with Dr. Kodali’s report at the meeting, the results he presented appeared online (N. Engl. J. Med. 2012, March 26;366 [doi:10.1056/NEJMoa1200384]).

The PARTNER trial was sponsored by Edwards Lifesciences. Dr. Cribier said that he is a consultant to Edwards Lifesciences. Dr. Kodali said that he has been a consultant to Edwards Lifesciences, Medtronic, and St. Jude Medical, that he serves on an advisory board for Paieon Medical, and that he owns stock in Thubrikar Aortic Valve. Dr. Guyton said that he had no disclosures.

*Correction, 4/3/2012: An earlier version of this story mischaracterized the findings.

CHICAGO – The CORONARY trial provides new insights into the benefits of performing coronary artery bypass grafting on a beating heart, but falls short of delivering a knockout victory for the off-pump technique.

There were no significant differences in the rate of the composite coprimary outcome of death, stroke, nonfatal myocardial infarction (MI), or new renal failure at 30 days between off-pump CABG and bypass with the induction of ischemic cardiac arrest (on-pump) (9.8% vs. 10.3%; P = .59; hazard ratio, 0.95), or in any of its individual components.

Off-pump CABG was associated with fewer transfusions, reoperations for bleeding, acute kidney injuries, and respiratory infections or failure, but more early repeat revascularizations.

"We believe that in experienced hands, both procedures are reasonable options based on short-term results," principal investigator Dr. André Lamy said in a late-breaking session at the annual meeting of the American College of Cardiology. The difference in 30-day morbidity in the CORONARY (Coronary Artery Bypass Grafting Off or On Pump Revascularization) study may or may not lead to significant differences during ongoing follow-up, he added.

Invited discussant Dr. Robert Guyton, with the adult cardiac surgery team at Emory University in Atlanta, said CORONARY is larger by a factor of two than any other prospective randomized trial comparing on-pump versus off-pump surgery and is well executed.

"However, it is a superiority trial that failed to show a superiority of off-pump surgery," he said. "Therefore the conclusion probably needs to be stated that there is no significant difference detected. You can’t claim that there’s no difference between the two in this trial."

Dr. Guyton also highlighted a Cochrane systematic review, published just days before the meeting, of 86 trials involving 10,716 patients that showed a mortality benefit with on-pump CABG. The review failed to demonstrate any significant benefit of off-pump CABG with regard to mortality, stroke, or myocardial infarction, and concluded that on-pump CABG should remain the standard surgical treatment (Cochrane Database Syst. Rev. 2012 Mar 14;3:CD007224).

Dr. Lamy said he was not well versed in the details of the review but pointed out that one of its studies reported an inordinately high mortality rate of 25% with off-pump CABG that may have shifted the review results.

A New England Journal of Medicine editorial (10.1056/NEJMe1203194) that accompanied simultaneous publication of the CORONARY study (10.1056/NEJMoa1200388) called the lack of postoperative coronary arteriography an important limitation of CORONARY, and noted that the true relative efficacy and durability of off-pump CABG will probably be determined by longer-term follow-up.

Editorialist Dr. Frederick L. Grover, chair of the department of surgery at the University of Colorado in Denver, wrote that forthcoming neurocognitive data will have a major influence on the interpretation of the primary trial results.

He observed that unlike the recent Randomized On/Off Bypass trial (N. Engl. J. Med. 2009;361:1827-37) that reported worse outcomes at 1 year with off-pump than with on-pump CABG among veterans, CORONARY was limited to surgeons with more extensive off-pump experience, and did not allow trainees to act as primary surgeons. CORONARY also included a somewhat higher-risk population of patients, who may derive a greater relative benefit from the off-pump technique. Although these differences did not significantly influence short-term outcomes between the two trials, their long-term outcome remains to be seen, said Dr. Grover, also of the cardiothoracic surgery section of the Denver Veterans Affairs Medical Center.

CORONARY randomly assigned 4,752 patients from 79 centers in 19 countries to undergo CABG either off-pump or on-pump. Patients had to be at least 70 years of age, or 60-69 years old with at least one prespecified risk factor, or 55-59 years old with at least two of the prespecified risk factors of diabetes, urgent revascularization, recent smoking history, or a left ventricular ejection fraction of no more than 35%. Only staff cardiac surgeons with more than 2 years of experience who had completed 100 cases of one or both techniques were allowed. The mean patient age was 67 years, one-third had a prior MI, and roughly 20% had a EuroSCORE (European System for Cardiac Operative Risk Evaluation) of more than 5.

Incomplete revascularization was significantly more frequent in the off-pump group, while operating time and initial ventilation were significantly higher in the on-pump group, said Dr. Lamy, with the Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont.

The need for any blood transfusion was significantly higher at 63.3% of the on-pump group versus 50.7% in the off-pump group (P less than .001), as was the need for antifibrinolytics (37% vs. 26%; P less than .001), and reoperation for bleeding (2.4% vs. 1.4%; P = .02).

At 30 days, there was no difference between the off-pump and on-pump groups in the coprimary outcome components of death (2.5% for both; hazard ratio, 1.02), stroke (1.0% vs 1.1%; HR, 0.89), nonfatal MI (6.7% vs. 7.2%; HR, 0.93), and new renal failure (1.2% vs. 1.1%; HR, 1.04).

Respiratory infection or failure was reported in 6% of the off-pump group and 7.5% of the on-pump group (P = .03; relative risk, 0.79), acute kidney injury stage 1 in 28% vs. 32% (P = .01; RR, 0.87) and RIFLE (risk, injury, failure, loss, and end-stage kidney disease) risk in 17% vs. 19.6% (P = .02; RR, 0.87), he said.

A subgroup analysis found no differences between the two techniques by age, cerebrovascular or peripheral arterial disease, EuroSCORE, left ventricular ejection fraction, region, or experience of the surgeon, Dr. Lamy said.

Both approaches are valid, and surgeons will need to tailor surgery for each individual patient, he said in an interview. For example, the off-pump technique may be best in a frail elderly patient to avoid transfusions and massive fluid infusion, whereas the on-pump technique may be best for a very large patient with the heart deeply placed within the chest.

Neurological outcomes and a cost-effectiveness analysis will be forthcoming. Five-year data on the coprimary end point plus repeat coronary revascularization over 5 years of follow-up are expected in 2016, Dr. Lamy said.

This study is funded by the Canadian Institutes of Health Research. Dr. Lamy reported consulting fees and honoraria from AstraZeneca.

CHICAGO – The CORONARY trial provides new insights into the benefits of performing coronary artery bypass grafting on a beating heart, but falls short of delivering a knockout victory for the off-pump technique.

There were no significant differences in the rate of the composite coprimary outcome of death, stroke, nonfatal myocardial infarction (MI), or new renal failure at 30 days between off-pump CABG and bypass with the induction of ischemic cardiac arrest (on-pump) (9.8% vs. 10.3%; P = .59; hazard ratio, 0.95), or in any of its individual components.

Off-pump CABG was associated with fewer transfusions, reoperations for bleeding, acute kidney injuries, and respiratory infections or failure, but more early repeat revascularizations.

"We believe that in experienced hands, both procedures are reasonable options based on short-term results," principal investigator Dr. André Lamy said in a late-breaking session at the annual meeting of the American College of Cardiology. The difference in 30-day morbidity in the CORONARY (Coronary Artery Bypass Grafting Off or On Pump Revascularization) study may or may not lead to significant differences during ongoing follow-up, he added.

Invited discussant Dr. Robert Guyton, with the adult cardiac surgery team at Emory University in Atlanta, said CORONARY is larger by a factor of two than any other prospective randomized trial comparing on-pump versus off-pump surgery and is well executed.

"However, it is a superiority trial that failed to show a superiority of off-pump surgery," he said. "Therefore the conclusion probably needs to be stated that there is no significant difference detected. You can’t claim that there’s no difference between the two in this trial."

Dr. Guyton also highlighted a Cochrane systematic review, published just days before the meeting, of 86 trials involving 10,716 patients that showed a mortality benefit with on-pump CABG. The review failed to demonstrate any significant benefit of off-pump CABG with regard to mortality, stroke, or myocardial infarction, and concluded that on-pump CABG should remain the standard surgical treatment (Cochrane Database Syst. Rev. 2012 Mar 14;3:CD007224).

Dr. Lamy said he was not well versed in the details of the review but pointed out that one of its studies reported an inordinately high mortality rate of 25% with off-pump CABG that may have shifted the review results.

A New England Journal of Medicine editorial (10.1056/NEJMe1203194) that accompanied simultaneous publication of the CORONARY study (10.1056/NEJMoa1200388) called the lack of postoperative coronary arteriography an important limitation of CORONARY, and noted that the true relative efficacy and durability of off-pump CABG will probably be determined by longer-term follow-up.

Editorialist Dr. Frederick L. Grover, chair of the department of surgery at the University of Colorado in Denver, wrote that forthcoming neurocognitive data will have a major influence on the interpretation of the primary trial results.

He observed that unlike the recent Randomized On/Off Bypass trial (N. Engl. J. Med. 2009;361:1827-37) that reported worse outcomes at 1 year with off-pump than with on-pump CABG among veterans, CORONARY was limited to surgeons with more extensive off-pump experience, and did not allow trainees to act as primary surgeons. CORONARY also included a somewhat higher-risk population of patients, who may derive a greater relative benefit from the off-pump technique. Although these differences did not significantly influence short-term outcomes between the two trials, their long-term outcome remains to be seen, said Dr. Grover, also of the cardiothoracic surgery section of the Denver Veterans Affairs Medical Center.

CORONARY randomly assigned 4,752 patients from 79 centers in 19 countries to undergo CABG either off-pump or on-pump. Patients had to be at least 70 years of age, or 60-69 years old with at least one prespecified risk factor, or 55-59 years old with at least two of the prespecified risk factors of diabetes, urgent revascularization, recent smoking history, or a left ventricular ejection fraction of no more than 35%. Only staff cardiac surgeons with more than 2 years of experience who had completed 100 cases of one or both techniques were allowed. The mean patient age was 67 years, one-third had a prior MI, and roughly 20% had a EuroSCORE (European System for Cardiac Operative Risk Evaluation) of more than 5.

Incomplete revascularization was significantly more frequent in the off-pump group, while operating time and initial ventilation were significantly higher in the on-pump group, said Dr. Lamy, with the Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont.

The need for any blood transfusion was significantly higher at 63.3% of the on-pump group versus 50.7% in the off-pump group (P less than .001), as was the need for antifibrinolytics (37% vs. 26%; P less than .001), and reoperation for bleeding (2.4% vs. 1.4%; P = .02).

At 30 days, there was no difference between the off-pump and on-pump groups in the coprimary outcome components of death (2.5% for both; hazard ratio, 1.02), stroke (1.0% vs 1.1%; HR, 0.89), nonfatal MI (6.7% vs. 7.2%; HR, 0.93), and new renal failure (1.2% vs. 1.1%; HR, 1.04).

Respiratory infection or failure was reported in 6% of the off-pump group and 7.5% of the on-pump group (P = .03; relative risk, 0.79), acute kidney injury stage 1 in 28% vs. 32% (P = .01; RR, 0.87) and RIFLE (risk, injury, failure, loss, and end-stage kidney disease) risk in 17% vs. 19.6% (P = .02; RR, 0.87), he said.

A subgroup analysis found no differences between the two techniques by age, cerebrovascular or peripheral arterial disease, EuroSCORE, left ventricular ejection fraction, region, or experience of the surgeon, Dr. Lamy said.

Both approaches are valid, and surgeons will need to tailor surgery for each individual patient, he said in an interview. For example, the off-pump technique may be best in a frail elderly patient to avoid transfusions and massive fluid infusion, whereas the on-pump technique may be best for a very large patient with the heart deeply placed within the chest.

Neurological outcomes and a cost-effectiveness analysis will be forthcoming. Five-year data on the coprimary end point plus repeat coronary revascularization over 5 years of follow-up are expected in 2016, Dr. Lamy said.

This study is funded by the Canadian Institutes of Health Research. Dr. Lamy reported consulting fees and honoraria from AstraZeneca.

CHICAGO – The CORONARY trial provides new insights into the benefits of performing coronary artery bypass grafting on a beating heart, but falls short of delivering a knockout victory for the off-pump technique.

There were no significant differences in the rate of the composite coprimary outcome of death, stroke, nonfatal myocardial infarction (MI), or new renal failure at 30 days between off-pump CABG and bypass with the induction of ischemic cardiac arrest (on-pump) (9.8% vs. 10.3%; P = .59; hazard ratio, 0.95), or in any of its individual components.

Off-pump CABG was associated with fewer transfusions, reoperations for bleeding, acute kidney injuries, and respiratory infections or failure, but more early repeat revascularizations.

"We believe that in experienced hands, both procedures are reasonable options based on short-term results," principal investigator Dr. André Lamy said in a late-breaking session at the annual meeting of the American College of Cardiology. The difference in 30-day morbidity in the CORONARY (Coronary Artery Bypass Grafting Off or On Pump Revascularization) study may or may not lead to significant differences during ongoing follow-up, he added.

Invited discussant Dr. Robert Guyton, with the adult cardiac surgery team at Emory University in Atlanta, said CORONARY is larger by a factor of two than any other prospective randomized trial comparing on-pump versus off-pump surgery and is well executed.

"However, it is a superiority trial that failed to show a superiority of off-pump surgery," he said. "Therefore the conclusion probably needs to be stated that there is no significant difference detected. You can’t claim that there’s no difference between the two in this trial."

Dr. Guyton also highlighted a Cochrane systematic review, published just days before the meeting, of 86 trials involving 10,716 patients that showed a mortality benefit with on-pump CABG. The review failed to demonstrate any significant benefit of off-pump CABG with regard to mortality, stroke, or myocardial infarction, and concluded that on-pump CABG should remain the standard surgical treatment (Cochrane Database Syst. Rev. 2012 Mar 14;3:CD007224).

Dr. Lamy said he was not well versed in the details of the review but pointed out that one of its studies reported an inordinately high mortality rate of 25% with off-pump CABG that may have shifted the review results.

A New England Journal of Medicine editorial (10.1056/NEJMe1203194) that accompanied simultaneous publication of the CORONARY study (10.1056/NEJMoa1200388) called the lack of postoperative coronary arteriography an important limitation of CORONARY, and noted that the true relative efficacy and durability of off-pump CABG will probably be determined by longer-term follow-up.

Editorialist Dr. Frederick L. Grover, chair of the department of surgery at the University of Colorado in Denver, wrote that forthcoming neurocognitive data will have a major influence on the interpretation of the primary trial results.

He observed that unlike the recent Randomized On/Off Bypass trial (N. Engl. J. Med. 2009;361:1827-37) that reported worse outcomes at 1 year with off-pump than with on-pump CABG among veterans, CORONARY was limited to surgeons with more extensive off-pump experience, and did not allow trainees to act as primary surgeons. CORONARY also included a somewhat higher-risk population of patients, who may derive a greater relative benefit from the off-pump technique. Although these differences did not significantly influence short-term outcomes between the two trials, their long-term outcome remains to be seen, said Dr. Grover, also of the cardiothoracic surgery section of the Denver Veterans Affairs Medical Center.

CORONARY randomly assigned 4,752 patients from 79 centers in 19 countries to undergo CABG either off-pump or on-pump. Patients had to be at least 70 years of age, or 60-69 years old with at least one prespecified risk factor, or 55-59 years old with at least two of the prespecified risk factors of diabetes, urgent revascularization, recent smoking history, or a left ventricular ejection fraction of no more than 35%. Only staff cardiac surgeons with more than 2 years of experience who had completed 100 cases of one or both techniques were allowed. The mean patient age was 67 years, one-third had a prior MI, and roughly 20% had a EuroSCORE (European System for Cardiac Operative Risk Evaluation) of more than 5.

Incomplete revascularization was significantly more frequent in the off-pump group, while operating time and initial ventilation were significantly higher in the on-pump group, said Dr. Lamy, with the Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont.

The need for any blood transfusion was significantly higher at 63.3% of the on-pump group versus 50.7% in the off-pump group (P less than .001), as was the need for antifibrinolytics (37% vs. 26%; P less than .001), and reoperation for bleeding (2.4% vs. 1.4%; P = .02).

At 30 days, there was no difference between the off-pump and on-pump groups in the coprimary outcome components of death (2.5% for both; hazard ratio, 1.02), stroke (1.0% vs 1.1%; HR, 0.89), nonfatal MI (6.7% vs. 7.2%; HR, 0.93), and new renal failure (1.2% vs. 1.1%; HR, 1.04).

Respiratory infection or failure was reported in 6% of the off-pump group and 7.5% of the on-pump group (P = .03; relative risk, 0.79), acute kidney injury stage 1 in 28% vs. 32% (P = .01; RR, 0.87) and RIFLE (risk, injury, failure, loss, and end-stage kidney disease) risk in 17% vs. 19.6% (P = .02; RR, 0.87), he said.

A subgroup analysis found no differences between the two techniques by age, cerebrovascular or peripheral arterial disease, EuroSCORE, left ventricular ejection fraction, region, or experience of the surgeon, Dr. Lamy said.

Both approaches are valid, and surgeons will need to tailor surgery for each individual patient, he said in an interview. For example, the off-pump technique may be best in a frail elderly patient to avoid transfusions and massive fluid infusion, whereas the on-pump technique may be best for a very large patient with the heart deeply placed within the chest.

Neurological outcomes and a cost-effectiveness analysis will be forthcoming. Five-year data on the coprimary end point plus repeat coronary revascularization over 5 years of follow-up are expected in 2016, Dr. Lamy said.

This study is funded by the Canadian Institutes of Health Research. Dr. Lamy reported consulting fees and honoraria from AstraZeneca.

CHICAGO – A triple-antiplatelet regimen that added cilostazol to the standard combination of clopidogrel and aspirin proved noninferior to a double-dose clopidogrel plus aspirin regimen during 30 days following placement of drug-eluting coronary stents in a randomized trial with 3,755 patients conducted in South Korea.

Results from the HOST-ASSURE (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Safety and Effectiveness of Drug-Eluting Stents and Anti-Platelet Regimen) trial showed that both the triple, cilostazol-containing regimen and the double-dose clopidogrel regimen were "slightly stronger than conventional-dose clopidogrel, effective, and safe," Dr. Hyo-Soo Kim said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

During the first 30 days following placement of either everolimus- or zotarolimus-eluting coronary stents, daily, oral treatment with 100 mg aspirin, 75 mg clopidogrel, and 100 mg cilostazol taken twice daily led to a 1.2% cardiovascular event rate, compared with a 1.4% rate among patients who received 100 mg aspirin plus 150 mg clopidogrel once daily, reported Dr. Kim, director of coronary catheterization at Seoul (South Korea) National University Hospital.

Although these results come from the largest, controlled test of cilostazol as part of an antiplatelet regimen following the placement of drug-eluting coronary stents, the generalizability and definitiveness of the findings came under question for three reasons, experts said.

First, by being studied in Korea, a population known to have a high prevalence of genetic unresponsiveness to clopidogrel, the results probably do not directly apply to other populations with higher levels of clopidogrel responsiveness. Second, the unexpectedly low rate of adverse coronary events during the 30 days of treatment that was roughly half the expected rate made the study underpowered by about half in its ability to clearly prove a noninferior relationship between the two treatments. And third, in the United States, initial treatment of patients following drug-eluting stent use in percutaneous coronary intervention (PCI) increasingly involves the newer drugs prasugrel (Effient) or ticagrelor (Brilinta), a development that makes comparison of cilostazol to double-dose clopidogrel (Plavix) less relevant.

The study is "a very hard to interpret, underpowered noninferiority trial," commented Dr. E. Magnus Ohman, an interventional cardiologist and professor of medicine at Duke University in Durham, N.C.

"Cilostazol is extensively used [in Korea and elsewhere in East Asia], but has not really been tested, so for Korea this is an important trial. If you do a noninferiority trial, it needs to be sized to be sure of the effect you see, but their result is very comforting because their point estimate is on the right side," Dr. Ohman noted, with the cilostazol-containing regimen leading to fewer events than the comparator regimen.

"Cilostazol has not caught on in the United States," in part because "before this study, there was not a lot of evidence on cilostazol, so this study solves that problem, but it is hard to predict how this study might translate into U.S. practice," Dr. Ohman said in an interview.

"Cilostazol is a relatively weak anti-platelet agent, and more and more people are becoming aware that clopidogrel, although it has been terrific, also has limitations," he noted.

As a result of problems with clopidogrel’s potency and reliable efficacy in all patients, many U.S. physicians increasingly prescribe prasugrel plus aspirin or ticagrelor plus aspirin for the first weeks following PCI, said Dr. Ohman and other cardiologists. "There has been slow adoption" of prasugrel and ticagrelor into U.S. practice, but more recently U.S. physicians "have become more comfortable with the trade-off" of reduced coronary events with either prasugrel or ticagrelor despite the small increase in bleeding complications both drugs cause, he said.

"Prasugrel and ticagrelor have become the standard of care [for U.S. practice following PCI] for patients who are not at excessive risk for bleeding," commented Dr. Gregg W. Stone, an interventional cardiologist and professor of medicine at Columbia University in New York.

The HOST-ASSURE results "are very applicable for Korea and East Asian populations, and is not generalizable to the United States," commented Dr. George D. Dangas, professor of medicine and director of cardiovascular innovation at Mount Sinai Medical Center in New York. In the United States, "prasugrel and ticagrelor are steadily becoming more used, mostly in the first month [following PCI] in higher-risk patients. The trend is to go with prasugrel or ticagrelor rather than try different dosages of clopidogrel," he said in an interview.

The HOST-ASSURE trial enrolled patients with an average age of about 63 years; about two-thirds were men. The primary efficacy endpoint after 1 month of treatment was a composite of cardiac death, nonfatal myocardial infarction, stroke, definite or probable stent thrombosis, and major bleeding events. The 1,879 patients randomized to the cilostazol arm received a 200-mg loading dose of cilostazol when they started their regimen. The 1,876 patients randomized to the double-dose clopidogrel arm received no loading dose of the drug.

Dr. Kim said he had no relevant financial disclosures. Dr. Ohman said that he has been a consultant to a wide variety of pharmaceutical companies, including Sanofi-Aventis, Merck, Bristol-Myers Squibb, AstraZeneca, and Boehringer Ingelheim. He has received research support from Eli Lilly, Maquet, and Daiichi Sankyo. Dr. Stone said that he has also been a consultant to a variety of pharmaceutical companies. Dr. Dangas said that he has been a consultant to AstraZeneca and has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, Eli Lilly, and Daiichi Sankyo.

CHICAGO – A triple-antiplatelet regimen that added cilostazol to the standard combination of clopidogrel and aspirin proved noninferior to a double-dose clopidogrel plus aspirin regimen during 30 days following placement of drug-eluting coronary stents in a randomized trial with 3,755 patients conducted in South Korea.

Results from the HOST-ASSURE (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Safety and Effectiveness of Drug-Eluting Stents and Anti-Platelet Regimen) trial showed that both the triple, cilostazol-containing regimen and the double-dose clopidogrel regimen were "slightly stronger than conventional-dose clopidogrel, effective, and safe," Dr. Hyo-Soo Kim said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

During the first 30 days following placement of either everolimus- or zotarolimus-eluting coronary stents, daily, oral treatment with 100 mg aspirin, 75 mg clopidogrel, and 100 mg cilostazol taken twice daily led to a 1.2% cardiovascular event rate, compared with a 1.4% rate among patients who received 100 mg aspirin plus 150 mg clopidogrel once daily, reported Dr. Kim, director of coronary catheterization at Seoul (South Korea) National University Hospital.

Although these results come from the largest, controlled test of cilostazol as part of an antiplatelet regimen following the placement of drug-eluting coronary stents, the generalizability and definitiveness of the findings came under question for three reasons, experts said.

First, by being studied in Korea, a population known to have a high prevalence of genetic unresponsiveness to clopidogrel, the results probably do not directly apply to other populations with higher levels of clopidogrel responsiveness. Second, the unexpectedly low rate of adverse coronary events during the 30 days of treatment that was roughly half the expected rate made the study underpowered by about half in its ability to clearly prove a noninferior relationship between the two treatments. And third, in the United States, initial treatment of patients following drug-eluting stent use in percutaneous coronary intervention (PCI) increasingly involves the newer drugs prasugrel (Effient) or ticagrelor (Brilinta), a development that makes comparison of cilostazol to double-dose clopidogrel (Plavix) less relevant.

The study is "a very hard to interpret, underpowered noninferiority trial," commented Dr. E. Magnus Ohman, an interventional cardiologist and professor of medicine at Duke University in Durham, N.C.

"Cilostazol is extensively used [in Korea and elsewhere in East Asia], but has not really been tested, so for Korea this is an important trial. If you do a noninferiority trial, it needs to be sized to be sure of the effect you see, but their result is very comforting because their point estimate is on the right side," Dr. Ohman noted, with the cilostazol-containing regimen leading to fewer events than the comparator regimen.

"Cilostazol has not caught on in the United States," in part because "before this study, there was not a lot of evidence on cilostazol, so this study solves that problem, but it is hard to predict how this study might translate into U.S. practice," Dr. Ohman said in an interview.

"Cilostazol is a relatively weak anti-platelet agent, and more and more people are becoming aware that clopidogrel, although it has been terrific, also has limitations," he noted.

As a result of problems with clopidogrel’s potency and reliable efficacy in all patients, many U.S. physicians increasingly prescribe prasugrel plus aspirin or ticagrelor plus aspirin for the first weeks following PCI, said Dr. Ohman and other cardiologists. "There has been slow adoption" of prasugrel and ticagrelor into U.S. practice, but more recently U.S. physicians "have become more comfortable with the trade-off" of reduced coronary events with either prasugrel or ticagrelor despite the small increase in bleeding complications both drugs cause, he said.

"Prasugrel and ticagrelor have become the standard of care [for U.S. practice following PCI] for patients who are not at excessive risk for bleeding," commented Dr. Gregg W. Stone, an interventional cardiologist and professor of medicine at Columbia University in New York.

The HOST-ASSURE results "are very applicable for Korea and East Asian populations, and is not generalizable to the United States," commented Dr. George D. Dangas, professor of medicine and director of cardiovascular innovation at Mount Sinai Medical Center in New York. In the United States, "prasugrel and ticagrelor are steadily becoming more used, mostly in the first month [following PCI] in higher-risk patients. The trend is to go with prasugrel or ticagrelor rather than try different dosages of clopidogrel," he said in an interview.

The HOST-ASSURE trial enrolled patients with an average age of about 63 years; about two-thirds were men. The primary efficacy endpoint after 1 month of treatment was a composite of cardiac death, nonfatal myocardial infarction, stroke, definite or probable stent thrombosis, and major bleeding events. The 1,879 patients randomized to the cilostazol arm received a 200-mg loading dose of cilostazol when they started their regimen. The 1,876 patients randomized to the double-dose clopidogrel arm received no loading dose of the drug.

Dr. Kim said he had no relevant financial disclosures. Dr. Ohman said that he has been a consultant to a wide variety of pharmaceutical companies, including Sanofi-Aventis, Merck, Bristol-Myers Squibb, AstraZeneca, and Boehringer Ingelheim. He has received research support from Eli Lilly, Maquet, and Daiichi Sankyo. Dr. Stone said that he has also been a consultant to a variety of pharmaceutical companies. Dr. Dangas said that he has been a consultant to AstraZeneca and has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, Eli Lilly, and Daiichi Sankyo.

CHICAGO – A triple-antiplatelet regimen that added cilostazol to the standard combination of clopidogrel and aspirin proved noninferior to a double-dose clopidogrel plus aspirin regimen during 30 days following placement of drug-eluting coronary stents in a randomized trial with 3,755 patients conducted in South Korea.

Results from the HOST-ASSURE (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Safety and Effectiveness of Drug-Eluting Stents and Anti-Platelet Regimen) trial showed that both the triple, cilostazol-containing regimen and the double-dose clopidogrel regimen were "slightly stronger than conventional-dose clopidogrel, effective, and safe," Dr. Hyo-Soo Kim said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

During the first 30 days following placement of either everolimus- or zotarolimus-eluting coronary stents, daily, oral treatment with 100 mg aspirin, 75 mg clopidogrel, and 100 mg cilostazol taken twice daily led to a 1.2% cardiovascular event rate, compared with a 1.4% rate among patients who received 100 mg aspirin plus 150 mg clopidogrel once daily, reported Dr. Kim, director of coronary catheterization at Seoul (South Korea) National University Hospital.

Although these results come from the largest, controlled test of cilostazol as part of an antiplatelet regimen following the placement of drug-eluting coronary stents, the generalizability and definitiveness of the findings came under question for three reasons, experts said.

First, by being studied in Korea, a population known to have a high prevalence of genetic unresponsiveness to clopidogrel, the results probably do not directly apply to other populations with higher levels of clopidogrel responsiveness. Second, the unexpectedly low rate of adverse coronary events during the 30 days of treatment that was roughly half the expected rate made the study underpowered by about half in its ability to clearly prove a noninferior relationship between the two treatments. And third, in the United States, initial treatment of patients following drug-eluting stent use in percutaneous coronary intervention (PCI) increasingly involves the newer drugs prasugrel (Effient) or ticagrelor (Brilinta), a development that makes comparison of cilostazol to double-dose clopidogrel (Plavix) less relevant.

The study is "a very hard to interpret, underpowered noninferiority trial," commented Dr. E. Magnus Ohman, an interventional cardiologist and professor of medicine at Duke University in Durham, N.C.

"Cilostazol is extensively used [in Korea and elsewhere in East Asia], but has not really been tested, so for Korea this is an important trial. If you do a noninferiority trial, it needs to be sized to be sure of the effect you see, but their result is very comforting because their point estimate is on the right side," Dr. Ohman noted, with the cilostazol-containing regimen leading to fewer events than the comparator regimen.

"Cilostazol has not caught on in the United States," in part because "before this study, there was not a lot of evidence on cilostazol, so this study solves that problem, but it is hard to predict how this study might translate into U.S. practice," Dr. Ohman said in an interview.

"Cilostazol is a relatively weak anti-platelet agent, and more and more people are becoming aware that clopidogrel, although it has been terrific, also has limitations," he noted.

As a result of problems with clopidogrel’s potency and reliable efficacy in all patients, many U.S. physicians increasingly prescribe prasugrel plus aspirin or ticagrelor plus aspirin for the first weeks following PCI, said Dr. Ohman and other cardiologists. "There has been slow adoption" of prasugrel and ticagrelor into U.S. practice, but more recently U.S. physicians "have become more comfortable with the trade-off" of reduced coronary events with either prasugrel or ticagrelor despite the small increase in bleeding complications both drugs cause, he said.

"Prasugrel and ticagrelor have become the standard of care [for U.S. practice following PCI] for patients who are not at excessive risk for bleeding," commented Dr. Gregg W. Stone, an interventional cardiologist and professor of medicine at Columbia University in New York.

The HOST-ASSURE results "are very applicable for Korea and East Asian populations, and is not generalizable to the United States," commented Dr. George D. Dangas, professor of medicine and director of cardiovascular innovation at Mount Sinai Medical Center in New York. In the United States, "prasugrel and ticagrelor are steadily becoming more used, mostly in the first month [following PCI] in higher-risk patients. The trend is to go with prasugrel or ticagrelor rather than try different dosages of clopidogrel," he said in an interview.

The HOST-ASSURE trial enrolled patients with an average age of about 63 years; about two-thirds were men. The primary efficacy endpoint after 1 month of treatment was a composite of cardiac death, nonfatal myocardial infarction, stroke, definite or probable stent thrombosis, and major bleeding events. The 1,879 patients randomized to the cilostazol arm received a 200-mg loading dose of cilostazol when they started their regimen. The 1,876 patients randomized to the double-dose clopidogrel arm received no loading dose of the drug.

Dr. Kim said he had no relevant financial disclosures. Dr. Ohman said that he has been a consultant to a wide variety of pharmaceutical companies, including Sanofi-Aventis, Merck, Bristol-Myers Squibb, AstraZeneca, and Boehringer Ingelheim. He has received research support from Eli Lilly, Maquet, and Daiichi Sankyo. Dr. Stone said that he has also been a consultant to a variety of pharmaceutical companies. Dr. Dangas said that he has been a consultant to AstraZeneca and has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, Eli Lilly, and Daiichi Sankyo.

CHICAGO – Bolus intracoronary abciximab delivered directly to the infarct lesion site in patients undergoing primary percutaneous coronary intervention for a large anterior myocardial infarction significantly reduced infarct size at 30 days in the INFUSE-AMI randomized trial.

In contrast, manual aspiration thrombectomy, also studied in INFUSE-AMI, proved to have no impact on infarct size, Dr. Gregg W. Stone reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/IMNG Medical Media

INFUSE-AMI was a 37-site, 6-nation prospective clinical trial. It involved 452 patients who presented within 4 hours after onset of symptoms, because of an ST-segment elevation MI involving occlusion of the proximal or midleft anterior descending coronary artery with no or minimal flow.

Participants underwent primary percutaneous coronary intervention (PCI) with bivalirudin anticoagulation. Under the 2 x 2 factorial study design, patients were randomized to aspiration plus a 0.25-mg/kg bolus of intracoronary abciximab, aspiration without abciximab, abciximab with no aspiration, or neither intervention. The goal was to find out whether either or both interventions reduce distal embolization of atherothrombotic debris resulting from primary PCI, which can lead to large infarcts despite prompt revascularization.

The primary endpoint in INFUSE-AMI was infarct size at 30 days as assessed by cardiac MRI. Most prior trials have measured infarct size at 3-5 days, when transitory myocardial edema typically makes the infarcts more than twice as large as they are at 30 days, explained Dr. Stone, director of cardiovascular research and education at Columbia University Medical Center/New York–Presbyterian Hospital.

The median 30-day infarct size in patients who got intracoronary abciximab was 15.1%, compared with 17.9% in those who did not. That’s roughly a 15% relative reduction. The abciximab group also had a significantly smaller median absolute infarct mass: 18.4 g, compared with 24 g. In addition, they showed a trend for a lower abnormal wall motion score that didn’t reach significance.

In contrast, 30-day infarct size and the other endpoints were almost identical, regardless of whether patients got aspiration thrombectomy or not.

The combined rate of TIMI (Thrombolysis in Myocardial Infarction) major or minor bleeding was 2.2% in patients who received intracoronary abciximab and 1.8% in those who did not, a nonsignificant difference.

Dr. Stone said that while it might now be reasonable based on the INFUSE-AMI findings to use an intracoronary bolus of abciximab during primary PCI in a highly select patient subset – those who present early with a particularly large occlusion of the proximal left anterior descending artery and are at low bleeding risk – he doesn’t consider INFUSE-AMI to be a definitive trial.

"The reduction in infarct size, while significant, was modest. Going into the study we considered that an absolute 6% reduction would be clinically relevant. We got about half of that. We really need a large outcomes trial to see if that amount of infarct size reduction improves clinical outcomes," the cardiologist said.

Currently, there are no plans for such a study, since INFUSE-AMI was just completed, and the findings are still being scrutinized. But Dr. Stone indicated that a decision to undertake a big clinical outcomes trial is by no means a slam dunk.

"If you studied 10,000 patients and you had exactly these results, there probably would be a clinical benefit, but it would be modest. And there is the possibility that bleeding would offset some of that," he commented.

Discussant Dr. Erik Magnus Ohman of Duke University, Durham, N.C., noted that a recent report from the AIDA STEMI (Abciximab IV versus IC in ST-Elevation Myocardial Infarction) trial, which with 2,065 randomized patients was powered for clinical outcomes, reported nearly identical infarct sizes and cardiovascular event rates with bolus intracoronary abciximab, compared with intravenous abciximab (Lancet 2012;379:875-7).

Dr. Stone replied that AIDA-STEMI and all other studies prior to INFUSE-AMI had a major limitation: Intracoronary abciximab was infused through the guide catheter. That’s highly inefficient in terms of getting the agent into the thrombus.

"Most of the drug probably goes down the circumflex artery or just blows back into the aorta," he explained.

In contrast, INFUSE-AMI utilized the ClearWay Rx local therapeutic infusion catheter, a low-profile "weeping" balloon that delivers abciximab directly to the infarct lesion.

As for aspiration thrombectomy, a practice now encouraged with a IIb recommendation in the ACC/American Heart Association guidelines, Dr. Stone noted that this intervention is the subject of two ongoing multithousand-patient randomized trials, TOTAL and TASTE, which should provide the final word on this procedure.

"I will say, though, that it’s hard for me to understand how aspiration can work as a routine therapy if it doesn’t decrease infarct size. I would predict that these trials might not be positive," Dr. Stone said.

The INFUSE-AMI trial was published in JAMA (2012;307([7];doi:10.1001/jama.2012.421) at the same time the study results were presented at the ACC meeting.

INFUSE-AMI was sponsored by Atrium Medical with support from Medtronic and the Medicines Co. Dr. Stone reported having served as a consultant to those three companies and more than a dozen others.

CHICAGO – Bolus intracoronary abciximab delivered directly to the infarct lesion site in patients undergoing primary percutaneous coronary intervention for a large anterior myocardial infarction significantly reduced infarct size at 30 days in the INFUSE-AMI randomized trial.

In contrast, manual aspiration thrombectomy, also studied in INFUSE-AMI, proved to have no impact on infarct size, Dr. Gregg W. Stone reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/IMNG Medical Media

INFUSE-AMI was a 37-site, 6-nation prospective clinical trial. It involved 452 patients who presented within 4 hours after onset of symptoms, because of an ST-segment elevation MI involving occlusion of the proximal or midleft anterior descending coronary artery with no or minimal flow.

Participants underwent primary percutaneous coronary intervention (PCI) with bivalirudin anticoagulation. Under the 2 x 2 factorial study design, patients were randomized to aspiration plus a 0.25-mg/kg bolus of intracoronary abciximab, aspiration without abciximab, abciximab with no aspiration, or neither intervention. The goal was to find out whether either or both interventions reduce distal embolization of atherothrombotic debris resulting from primary PCI, which can lead to large infarcts despite prompt revascularization.

The primary endpoint in INFUSE-AMI was infarct size at 30 days as assessed by cardiac MRI. Most prior trials have measured infarct size at 3-5 days, when transitory myocardial edema typically makes the infarcts more than twice as large as they are at 30 days, explained Dr. Stone, director of cardiovascular research and education at Columbia University Medical Center/New York–Presbyterian Hospital.

The median 30-day infarct size in patients who got intracoronary abciximab was 15.1%, compared with 17.9% in those who did not. That’s roughly a 15% relative reduction. The abciximab group also had a significantly smaller median absolute infarct mass: 18.4 g, compared with 24 g. In addition, they showed a trend for a lower abnormal wall motion score that didn’t reach significance.

In contrast, 30-day infarct size and the other endpoints were almost identical, regardless of whether patients got aspiration thrombectomy or not.

The combined rate of TIMI (Thrombolysis in Myocardial Infarction) major or minor bleeding was 2.2% in patients who received intracoronary abciximab and 1.8% in those who did not, a nonsignificant difference.

Dr. Stone said that while it might now be reasonable based on the INFUSE-AMI findings to use an intracoronary bolus of abciximab during primary PCI in a highly select patient subset – those who present early with a particularly large occlusion of the proximal left anterior descending artery and are at low bleeding risk – he doesn’t consider INFUSE-AMI to be a definitive trial.

"The reduction in infarct size, while significant, was modest. Going into the study we considered that an absolute 6% reduction would be clinically relevant. We got about half of that. We really need a large outcomes trial to see if that amount of infarct size reduction improves clinical outcomes," the cardiologist said.

Currently, there are no plans for such a study, since INFUSE-AMI was just completed, and the findings are still being scrutinized. But Dr. Stone indicated that a decision to undertake a big clinical outcomes trial is by no means a slam dunk.

"If you studied 10,000 patients and you had exactly these results, there probably would be a clinical benefit, but it would be modest. And there is the possibility that bleeding would offset some of that," he commented.

Discussant Dr. Erik Magnus Ohman of Duke University, Durham, N.C., noted that a recent report from the AIDA STEMI (Abciximab IV versus IC in ST-Elevation Myocardial Infarction) trial, which with 2,065 randomized patients was powered for clinical outcomes, reported nearly identical infarct sizes and cardiovascular event rates with bolus intracoronary abciximab, compared with intravenous abciximab (Lancet 2012;379:875-7).

Dr. Stone replied that AIDA-STEMI and all other studies prior to INFUSE-AMI had a major limitation: Intracoronary abciximab was infused through the guide catheter. That’s highly inefficient in terms of getting the agent into the thrombus.

"Most of the drug probably goes down the circumflex artery or just blows back into the aorta," he explained.

In contrast, INFUSE-AMI utilized the ClearWay Rx local therapeutic infusion catheter, a low-profile "weeping" balloon that delivers abciximab directly to the infarct lesion.

As for aspiration thrombectomy, a practice now encouraged with a IIb recommendation in the ACC/American Heart Association guidelines, Dr. Stone noted that this intervention is the subject of two ongoing multithousand-patient randomized trials, TOTAL and TASTE, which should provide the final word on this procedure.

"I will say, though, that it’s hard for me to understand how aspiration can work as a routine therapy if it doesn’t decrease infarct size. I would predict that these trials might not be positive," Dr. Stone said.

The INFUSE-AMI trial was published in JAMA (2012;307([7];doi:10.1001/jama.2012.421) at the same time the study results were presented at the ACC meeting.

INFUSE-AMI was sponsored by Atrium Medical with support from Medtronic and the Medicines Co. Dr. Stone reported having served as a consultant to those three companies and more than a dozen others.

CHICAGO – Bolus intracoronary abciximab delivered directly to the infarct lesion site in patients undergoing primary percutaneous coronary intervention for a large anterior myocardial infarction significantly reduced infarct size at 30 days in the INFUSE-AMI randomized trial.

In contrast, manual aspiration thrombectomy, also studied in INFUSE-AMI, proved to have no impact on infarct size, Dr. Gregg W. Stone reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/IMNG Medical Media

INFUSE-AMI was a 37-site, 6-nation prospective clinical trial. It involved 452 patients who presented within 4 hours after onset of symptoms, because of an ST-segment elevation MI involving occlusion of the proximal or midleft anterior descending coronary artery with no or minimal flow.

Participants underwent primary percutaneous coronary intervention (PCI) with bivalirudin anticoagulation. Under the 2 x 2 factorial study design, patients were randomized to aspiration plus a 0.25-mg/kg bolus of intracoronary abciximab, aspiration without abciximab, abciximab with no aspiration, or neither intervention. The goal was to find out whether either or both interventions reduce distal embolization of atherothrombotic debris resulting from primary PCI, which can lead to large infarcts despite prompt revascularization.

The primary endpoint in INFUSE-AMI was infarct size at 30 days as assessed by cardiac MRI. Most prior trials have measured infarct size at 3-5 days, when transitory myocardial edema typically makes the infarcts more than twice as large as they are at 30 days, explained Dr. Stone, director of cardiovascular research and education at Columbia University Medical Center/New York–Presbyterian Hospital.

The median 30-day infarct size in patients who got intracoronary abciximab was 15.1%, compared with 17.9% in those who did not. That’s roughly a 15% relative reduction. The abciximab group also had a significantly smaller median absolute infarct mass: 18.4 g, compared with 24 g. In addition, they showed a trend for a lower abnormal wall motion score that didn’t reach significance.

In contrast, 30-day infarct size and the other endpoints were almost identical, regardless of whether patients got aspiration thrombectomy or not.

The combined rate of TIMI (Thrombolysis in Myocardial Infarction) major or minor bleeding was 2.2% in patients who received intracoronary abciximab and 1.8% in those who did not, a nonsignificant difference.

Dr. Stone said that while it might now be reasonable based on the INFUSE-AMI findings to use an intracoronary bolus of abciximab during primary PCI in a highly select patient subset – those who present early with a particularly large occlusion of the proximal left anterior descending artery and are at low bleeding risk – he doesn’t consider INFUSE-AMI to be a definitive trial.

"The reduction in infarct size, while significant, was modest. Going into the study we considered that an absolute 6% reduction would be clinically relevant. We got about half of that. We really need a large outcomes trial to see if that amount of infarct size reduction improves clinical outcomes," the cardiologist said.

Currently, there are no plans for such a study, since INFUSE-AMI was just completed, and the findings are still being scrutinized. But Dr. Stone indicated that a decision to undertake a big clinical outcomes trial is by no means a slam dunk.

"If you studied 10,000 patients and you had exactly these results, there probably would be a clinical benefit, but it would be modest. And there is the possibility that bleeding would offset some of that," he commented.

Discussant Dr. Erik Magnus Ohman of Duke University, Durham, N.C., noted that a recent report from the AIDA STEMI (Abciximab IV versus IC in ST-Elevation Myocardial Infarction) trial, which with 2,065 randomized patients was powered for clinical outcomes, reported nearly identical infarct sizes and cardiovascular event rates with bolus intracoronary abciximab, compared with intravenous abciximab (Lancet 2012;379:875-7).

Dr. Stone replied that AIDA-STEMI and all other studies prior to INFUSE-AMI had a major limitation: Intracoronary abciximab was infused through the guide catheter. That’s highly inefficient in terms of getting the agent into the thrombus.

"Most of the drug probably goes down the circumflex artery or just blows back into the aorta," he explained.

In contrast, INFUSE-AMI utilized the ClearWay Rx local therapeutic infusion catheter, a low-profile "weeping" balloon that delivers abciximab directly to the infarct lesion.

As for aspiration thrombectomy, a practice now encouraged with a IIb recommendation in the ACC/American Heart Association guidelines, Dr. Stone noted that this intervention is the subject of two ongoing multithousand-patient randomized trials, TOTAL and TASTE, which should provide the final word on this procedure.

"I will say, though, that it’s hard for me to understand how aspiration can work as a routine therapy if it doesn’t decrease infarct size. I would predict that these trials might not be positive," Dr. Stone said.

The INFUSE-AMI trial was published in JAMA (2012;307([7];doi:10.1001/jama.2012.421) at the same time the study results were presented at the ACC meeting.

INFUSE-AMI was sponsored by Atrium Medical with support from Medtronic and the Medicines Co. Dr. Stone reported having served as a consultant to those three companies and more than a dozen others.

Rivaroxaban was noninferior to standard treatment at preventing a recurrence of pulmonary embolism in an international open-label trial reported online in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American College of Cardiology.

Rates of adverse bleeding events with rivaroxaban were similar to those with the more complex standard therapy of enoxaparin plus a vitamin K antagonist, a regimen that requires INR (international normalized ratio) monitoring, said Dr. Harry R. Buller of the department of vascular medicine at the University of Amsterdam and his associated in the EINSTEIN-PE clinical trial.

The study, sponsored by Bayer HealthCare and Janssen Pharmaceuticals, involved 4,832 adults with acute symptomatic pulmonary embolism (PE), with or without deep vein thrombosis (DVT), who were treated at 263 sites in 38 countries in 2007-2011. In all, 2,419 study subjects were randomly assigned to receive oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) and 2,413 to receive enoxaparin (1 mg/kg twice daily, which was discontinued when the INR reached 2.0 or greater for 2 consecutive days after at least 5 days of therapy) plus either warfarin or acenocoumarol at a dosage adjusted to maintain an INR of 2.0-3.0.

All study subjects were treated for durations of 3, 6, or 12 months, according to the wishes of their treating physicians and in keeping with current practice. The mean duration of treatment was approximately 9 months.

In the standard treatment group, the INR was in the therapeutic range 62.7% of the time. The INR was not measured in the rivaroxaban group, but adherence to therapy was high in 94.2% of patients.

The primary efficacy outcome was symptomatic recurrent venous thromboembolism, a composite of fatal and nonfatal PE or DVT. This occurred in 50 patients (2.1%) receiving rivaroxaban and 44 (1.8%) receiving standard therapy, which met the criterion for noninferiority, the investigators said (N. Engl. J. Med. 2012 March 26 [doi:10.1056/NEJMoa1113572]).

During the initial 3-week period of intensive rivaroxaban therapy, the primary efficacy outcome occurred in 18 patients (0.7%) of the rivaroxaban group and in 21 patients (0.9%) in the standard therapy group.

The efficacy results were similar in a per-protocol analysis and in an intention-to-treat analysis.

The primary safety outcome was clinically relevant bleeding, and it occurred in 249 subjects (10.3%) in the rivaroxaban group and in 274 (11.4%) in the standard treatment group. In particular, major bleeding events occurred in 26 patients (1.1%) taking rivaroxaban and 52 (2.2%) taking standard treatment.

During the initial 3-week period of intensive rivaroxaban therapy, bleeding rates were similar between the two study groups. Over the full course of treatment, "there were fewer episodes of intracranial bleeding or bleeding in critical areas in the rivaroxaban group than in the standard therapy group," Dr. Buller and his colleagues said.

With regard to other safety outcomes, the rates of acute coronary events were similar between the two study groups, at 0.6% with rivaroxaban and 0.9% with standard therapy. And abnormal findings on liver function tests were seen in 0.2% of both groups.

"The suggestion that rivaroxaban can be administered at the same dose in all patients without laboratory monitoring has raised concern," so the researchers performed multiple subgroup analyses to examine whether any particular patient group was at increased risk while taking the drug. They found that the rates of recurrent venous thromboembolism and of adverse bleeding events were similar between patients taking rivaroxaban and those on standard therapy regardless of age, sex, obesity status, level of renal function, and the extent of initial PE.

"We believe that our population is representative of the spectrum of patients who present with symptomatic PE," the investigators said, noting that nearly 25% of the study population had extensive PE and 13% had limited PE. Moreover, almost 25% also had concomitant DVT.

This study was supported by Bayer HealthCare and Janssen Pharmaceuticals. Dr. Buller reported ties to ICTOM/Bayer HealthCare, Sanofi-Aventis, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, and Daiichi Sankyo, and his associates reported ties to numerous industry sources.

Rivaroxaban was noninferior to standard treatment at preventing a recurrence of pulmonary embolism in an international open-label trial reported online in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American College of Cardiology.

Rates of adverse bleeding events with rivaroxaban were similar to those with the more complex standard therapy of enoxaparin plus a vitamin K antagonist, a regimen that requires INR (international normalized ratio) monitoring, said Dr. Harry R. Buller of the department of vascular medicine at the University of Amsterdam and his associated in the EINSTEIN-PE clinical trial.

The study, sponsored by Bayer HealthCare and Janssen Pharmaceuticals, involved 4,832 adults with acute symptomatic pulmonary embolism (PE), with or without deep vein thrombosis (DVT), who were treated at 263 sites in 38 countries in 2007-2011. In all, 2,419 study subjects were randomly assigned to receive oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) and 2,413 to receive enoxaparin (1 mg/kg twice daily, which was discontinued when the INR reached 2.0 or greater for 2 consecutive days after at least 5 days of therapy) plus either warfarin or acenocoumarol at a dosage adjusted to maintain an INR of 2.0-3.0.

All study subjects were treated for durations of 3, 6, or 12 months, according to the wishes of their treating physicians and in keeping with current practice. The mean duration of treatment was approximately 9 months.

In the standard treatment group, the INR was in the therapeutic range 62.7% of the time. The INR was not measured in the rivaroxaban group, but adherence to therapy was high in 94.2% of patients.

The primary efficacy outcome was symptomatic recurrent venous thromboembolism, a composite of fatal and nonfatal PE or DVT. This occurred in 50 patients (2.1%) receiving rivaroxaban and 44 (1.8%) receiving standard therapy, which met the criterion for noninferiority, the investigators said (N. Engl. J. Med. 2012 March 26 [doi:10.1056/NEJMoa1113572]).

During the initial 3-week period of intensive rivaroxaban therapy, the primary efficacy outcome occurred in 18 patients (0.7%) of the rivaroxaban group and in 21 patients (0.9%) in the standard therapy group.

The efficacy results were similar in a per-protocol analysis and in an intention-to-treat analysis.

The primary safety outcome was clinically relevant bleeding, and it occurred in 249 subjects (10.3%) in the rivaroxaban group and in 274 (11.4%) in the standard treatment group. In particular, major bleeding events occurred in 26 patients (1.1%) taking rivaroxaban and 52 (2.2%) taking standard treatment.

During the initial 3-week period of intensive rivaroxaban therapy, bleeding rates were similar between the two study groups. Over the full course of treatment, "there were fewer episodes of intracranial bleeding or bleeding in critical areas in the rivaroxaban group than in the standard therapy group," Dr. Buller and his colleagues said.

With regard to other safety outcomes, the rates of acute coronary events were similar between the two study groups, at 0.6% with rivaroxaban and 0.9% with standard therapy. And abnormal findings on liver function tests were seen in 0.2% of both groups.

"The suggestion that rivaroxaban can be administered at the same dose in all patients without laboratory monitoring has raised concern," so the researchers performed multiple subgroup analyses to examine whether any particular patient group was at increased risk while taking the drug. They found that the rates of recurrent venous thromboembolism and of adverse bleeding events were similar between patients taking rivaroxaban and those on standard therapy regardless of age, sex, obesity status, level of renal function, and the extent of initial PE.

"We believe that our population is representative of the spectrum of patients who present with symptomatic PE," the investigators said, noting that nearly 25% of the study population had extensive PE and 13% had limited PE. Moreover, almost 25% also had concomitant DVT.

This study was supported by Bayer HealthCare and Janssen Pharmaceuticals. Dr. Buller reported ties to ICTOM/Bayer HealthCare, Sanofi-Aventis, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, and Daiichi Sankyo, and his associates reported ties to numerous industry sources.

Rivaroxaban was noninferior to standard treatment at preventing a recurrence of pulmonary embolism in an international open-label trial reported online in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American College of Cardiology.

Rates of adverse bleeding events with rivaroxaban were similar to those with the more complex standard therapy of enoxaparin plus a vitamin K antagonist, a regimen that requires INR (international normalized ratio) monitoring, said Dr. Harry R. Buller of the department of vascular medicine at the University of Amsterdam and his associated in the EINSTEIN-PE clinical trial.

The study, sponsored by Bayer HealthCare and Janssen Pharmaceuticals, involved 4,832 adults with acute symptomatic pulmonary embolism (PE), with or without deep vein thrombosis (DVT), who were treated at 263 sites in 38 countries in 2007-2011. In all, 2,419 study subjects were randomly assigned to receive oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) and 2,413 to receive enoxaparin (1 mg/kg twice daily, which was discontinued when the INR reached 2.0 or greater for 2 consecutive days after at least 5 days of therapy) plus either warfarin or acenocoumarol at a dosage adjusted to maintain an INR of 2.0-3.0.

All study subjects were treated for durations of 3, 6, or 12 months, according to the wishes of their treating physicians and in keeping with current practice. The mean duration of treatment was approximately 9 months.

In the standard treatment group, the INR was in the therapeutic range 62.7% of the time. The INR was not measured in the rivaroxaban group, but adherence to therapy was high in 94.2% of patients.

The primary efficacy outcome was symptomatic recurrent venous thromboembolism, a composite of fatal and nonfatal PE or DVT. This occurred in 50 patients (2.1%) receiving rivaroxaban and 44 (1.8%) receiving standard therapy, which met the criterion for noninferiority, the investigators said (N. Engl. J. Med. 2012 March 26 [doi:10.1056/NEJMoa1113572]).

During the initial 3-week period of intensive rivaroxaban therapy, the primary efficacy outcome occurred in 18 patients (0.7%) of the rivaroxaban group and in 21 patients (0.9%) in the standard therapy group.

The efficacy results were similar in a per-protocol analysis and in an intention-to-treat analysis.

The primary safety outcome was clinically relevant bleeding, and it occurred in 249 subjects (10.3%) in the rivaroxaban group and in 274 (11.4%) in the standard treatment group. In particular, major bleeding events occurred in 26 patients (1.1%) taking rivaroxaban and 52 (2.2%) taking standard treatment.

During the initial 3-week period of intensive rivaroxaban therapy, bleeding rates were similar between the two study groups. Over the full course of treatment, "there were fewer episodes of intracranial bleeding or bleeding in critical areas in the rivaroxaban group than in the standard therapy group," Dr. Buller and his colleagues said.

With regard to other safety outcomes, the rates of acute coronary events were similar between the two study groups, at 0.6% with rivaroxaban and 0.9% with standard therapy. And abnormal findings on liver function tests were seen in 0.2% of both groups.

"The suggestion that rivaroxaban can be administered at the same dose in all patients without laboratory monitoring has raised concern," so the researchers performed multiple subgroup analyses to examine whether any particular patient group was at increased risk while taking the drug. They found that the rates of recurrent venous thromboembolism and of adverse bleeding events were similar between patients taking rivaroxaban and those on standard therapy regardless of age, sex, obesity status, level of renal function, and the extent of initial PE.

"We believe that our population is representative of the spectrum of patients who present with symptomatic PE," the investigators said, noting that nearly 25% of the study population had extensive PE and 13% had limited PE. Moreover, almost 25% also had concomitant DVT.

This study was supported by Bayer HealthCare and Janssen Pharmaceuticals. Dr. Buller reported ties to ICTOM/Bayer HealthCare, Sanofi-Aventis, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, and Daiichi Sankyo, and his associates reported ties to numerous industry sources.

CHICAGO – Clinical outcomes of elective percutaneous coronary intervention are similar at hospitals with or without on-site cardiac surgery, results of the CPORT-E trial show.

Mortality at 6 weeks was 0.9% at hospitals without on-site surgery, compared with 1% at those with on-site surgery, meeting the prespecified values for noninferiority.

At 9 months, major adverse cardiac event (MACE) rates were 12.1% and 11.2%, respectively. These also met the noninferiority criteria.

The need for target vessel revascularization (TVR) was slightly higher at hospitals without on-site cardiac surgery, but other adverse events such as bleeding, stroke, renal failure, and need for surgical revascularization were the same at hospitals with and without on-site surgery, Dr. Thomas Aversano reported at the annual meeting of the American College of Cardiology.

Session comoderator Dr. Robert Harrington, director of Duke Clinical Research Institute in Durham, N.C, asked whether every hospital should now offer elective PCI based on the results of the CPORT-E (Cardiovascular Patient Outcomes Research Team Nonprimary PCI) trial.

Dr. Aversano replied without hesitation "No, this study was not undertaken with the express idea of expansion of angioplasty programs. Really, the fundamental question was whether or not health care regulators, policy makers, and national organizations could use angioplasty in hospitals without on-site cardiac surgery as a tool. Is this possible? Is this safe?"

Invited discussant Dr. Gilles Montalescot, professor of cardiology at Hôpital Pitié-Salpétrière in Paris, said it’s always good for a study to confirm current practice, but that "the big difference is that you have excluded all high-risk patients and the temptation is to take all patients who come to the cath lab."

Dr. Aversano, the lead investigator of CPORT-E and associate professor of cardiology at Johns Hopkins University, Baltimore, emphasized that participating hospitals without on-site cardiac surgery undertook a formal PCI development program prior to study participation that took roughly 3-6 months to complete. It included detailed care plans and pathways, order sets, and training of staff in the care of PCI patients. Interventionalists were also required to meet criteria for competency developed by the ACC, the American Heart Association, and the Society for Cardiac Angiography and Interventions.

"What didn’t come out in the [online NEJM] article or the presentation is that these hospitals didn’t simply buy stents and guidewires and start doing this; it was a full development program," he said.

When asked whether the results could serve as a model for hospitals that may be considering offering PCI, Dr. Aversano said he was hesitant to make such a recommendation because each institution has its own unique political and logistical issues that prevent a "cookbook" approach.

ACC past president Dr. Ralph Brindis said results from the randomized trial support recent guideline changes by the ACC stating that it is reasonable for hospitals without cardiac surgery to perform elective PCI, not just emergency PCI.

"How policy makers at a state or government level utilize this in terms of offering PCI to local populations is yet to be determined," Dr. Brindis, clinical professor of medicine at the University of California, San Francisco, said in an interview. "Certainly every hospital shouldn’t be doing this, but there are issues of access in terms of having PCI available for our populations, particularly rural areas."

The 60 CPORT-E hospitals were located in 10 states and had a median annual PCI procedural volume of 150.

In all, 14,149 patients were randomly assigned to undergo PCI at a hospital without on-site cardiac surgery, and 4,718 were assigned to undergo PCI at a hospital with cardiac surgery, with 14,010 and 4,538 patients, respectively, ultimately undergoing the procedure. Patients were well matched, although prior PCI was more common among those randomized to hospitals without cardiac surgery (32% vs. 30.4%), Dr. Aversano said. Their average age was 64 years (N. Engl. J. Med. 2012 March 25 [doi: 10.1056/NEJMoa1114540]).

Staged procedures, meaning those performed on a different day than the initial cath lab visit, were more common at hospitals with on-site cardiac surgery than those without (68% vs. 26%), resulting in more catheterization laboratory visits (1.7 vs. 1.3).

Index PCI failure, however, was higher at hospitals without surgery on site (SOS) than those with SOS both per patient (3.4% vs. 2.5%) and per lesion (6.6% vs. 5.9%), he said. Use of bare metal stents was also higher at hospitals without SOS (24.2% vs. 23%).

At 9 months, there was no difference between hospitals without or with SOS in the composite elements of MACE including death (3.2% for both), Q-wave myocardial infarction (3.1% both) and TVR (6.5% vs. 5.4%, respectively), which included any unplanned PCI or coronary artery bypass grafting (CABG) after randomization.

Rates for hospitals without and with SOS were 5.2% vs. 5.3% for bleeding, 1.2% vs. 1.1% for vascular repair, 0.5% vs. 0.6% for stroke and 0.8% vs. 0.9% for renal insufficiency, respectively.

CABG was performed significantly more often at hospitals without SOS than those with SOS (2.3% vs. 1.5%).

An exploratory analysis of the intention-to-treat population that excluded CABG as part of TVR showed that MACE rates were 11.9% at hospitals without SOS and 10.5% at those with SOS.

An exploratory per protocol analysis also showed higher MACE rates at hospitals without SOS than at those with SOS (12% and 10.4% respectively), although these differences are within the range of noninferiority used in other recent stent trials, Dr. Aversano noted.

TVR may be higher in patients having PCI at hospitals without cardiac surgery because of a higher rate of bare metal stents used, which is a more conservative approach to PCI at relatively inexperienced hospitals, and a lack of a full complement of interventional devices, he suggested.

Johns Hopkins University and participating sites provided support for this trial. Dr. Brindis is a consultant to Ivivi Health Sciences. Dr. Harrington disclosed ties with numerous pharmaceutical companies. Dr. Aversano reported that he has no conflicts of interest.

CHICAGO – Clinical outcomes of elective percutaneous coronary intervention are similar at hospitals with or without on-site cardiac surgery, results of the CPORT-E trial show.

Mortality at 6 weeks was 0.9% at hospitals without on-site surgery, compared with 1% at those with on-site surgery, meeting the prespecified values for noninferiority.

At 9 months, major adverse cardiac event (MACE) rates were 12.1% and 11.2%, respectively. These also met the noninferiority criteria.

The need for target vessel revascularization (TVR) was slightly higher at hospitals without on-site cardiac surgery, but other adverse events such as bleeding, stroke, renal failure, and need for surgical revascularization were the same at hospitals with and without on-site surgery, Dr. Thomas Aversano reported at the annual meeting of the American College of Cardiology.

Session comoderator Dr. Robert Harrington, director of Duke Clinical Research Institute in Durham, N.C, asked whether every hospital should now offer elective PCI based on the results of the CPORT-E (Cardiovascular Patient Outcomes Research Team Nonprimary PCI) trial.

Dr. Aversano replied without hesitation "No, this study was not undertaken with the express idea of expansion of angioplasty programs. Really, the fundamental question was whether or not health care regulators, policy makers, and national organizations could use angioplasty in hospitals without on-site cardiac surgery as a tool. Is this possible? Is this safe?"

Invited discussant Dr. Gilles Montalescot, professor of cardiology at Hôpital Pitié-Salpétrière in Paris, said it’s always good for a study to confirm current practice, but that "the big difference is that you have excluded all high-risk patients and the temptation is to take all patients who come to the cath lab."

Dr. Aversano, the lead investigator of CPORT-E and associate professor of cardiology at Johns Hopkins University, Baltimore, emphasized that participating hospitals without on-site cardiac surgery undertook a formal PCI development program prior to study participation that took roughly 3-6 months to complete. It included detailed care plans and pathways, order sets, and training of staff in the care of PCI patients. Interventionalists were also required to meet criteria for competency developed by the ACC, the American Heart Association, and the Society for Cardiac Angiography and Interventions.

"What didn’t come out in the [online NEJM] article or the presentation is that these hospitals didn’t simply buy stents and guidewires and start doing this; it was a full development program," he said.

When asked whether the results could serve as a model for hospitals that may be considering offering PCI, Dr. Aversano said he was hesitant to make such a recommendation because each institution has its own unique political and logistical issues that prevent a "cookbook" approach.

ACC past president Dr. Ralph Brindis said results from the randomized trial support recent guideline changes by the ACC stating that it is reasonable for hospitals without cardiac surgery to perform elective PCI, not just emergency PCI.

"How policy makers at a state or government level utilize this in terms of offering PCI to local populations is yet to be determined," Dr. Brindis, clinical professor of medicine at the University of California, San Francisco, said in an interview. "Certainly every hospital shouldn’t be doing this, but there are issues of access in terms of having PCI available for our populations, particularly rural areas."

The 60 CPORT-E hospitals were located in 10 states and had a median annual PCI procedural volume of 150.

In all, 14,149 patients were randomly assigned to undergo PCI at a hospital without on-site cardiac surgery, and 4,718 were assigned to undergo PCI at a hospital with cardiac surgery, with 14,010 and 4,538 patients, respectively, ultimately undergoing the procedure. Patients were well matched, although prior PCI was more common among those randomized to hospitals without cardiac surgery (32% vs. 30.4%), Dr. Aversano said. Their average age was 64 years (N. Engl. J. Med. 2012 March 25 [doi: 10.1056/NEJMoa1114540]).

Staged procedures, meaning those performed on a different day than the initial cath lab visit, were more common at hospitals with on-site cardiac surgery than those without (68% vs. 26%), resulting in more catheterization laboratory visits (1.7 vs. 1.3).

Index PCI failure, however, was higher at hospitals without surgery on site (SOS) than those with SOS both per patient (3.4% vs. 2.5%) and per lesion (6.6% vs. 5.9%), he said. Use of bare metal stents was also higher at hospitals without SOS (24.2% vs. 23%).

At 9 months, there was no difference between hospitals without or with SOS in the composite elements of MACE including death (3.2% for both), Q-wave myocardial infarction (3.1% both) and TVR (6.5% vs. 5.4%, respectively), which included any unplanned PCI or coronary artery bypass grafting (CABG) after randomization.

Rates for hospitals without and with SOS were 5.2% vs. 5.3% for bleeding, 1.2% vs. 1.1% for vascular repair, 0.5% vs. 0.6% for stroke and 0.8% vs. 0.9% for renal insufficiency, respectively.

CABG was performed significantly more often at hospitals without SOS than those with SOS (2.3% vs. 1.5%).

An exploratory analysis of the intention-to-treat population that excluded CABG as part of TVR showed that MACE rates were 11.9% at hospitals without SOS and 10.5% at those with SOS.

An exploratory per protocol analysis also showed higher MACE rates at hospitals without SOS than at those with SOS (12% and 10.4% respectively), although these differences are within the range of noninferiority used in other recent stent trials, Dr. Aversano noted.

TVR may be higher in patients having PCI at hospitals without cardiac surgery because of a higher rate of bare metal stents used, which is a more conservative approach to PCI at relatively inexperienced hospitals, and a lack of a full complement of interventional devices, he suggested.

Johns Hopkins University and participating sites provided support for this trial. Dr. Brindis is a consultant to Ivivi Health Sciences. Dr. Harrington disclosed ties with numerous pharmaceutical companies. Dr. Aversano reported that he has no conflicts of interest.

CHICAGO – Clinical outcomes of elective percutaneous coronary intervention are similar at hospitals with or without on-site cardiac surgery, results of the CPORT-E trial show.

Mortality at 6 weeks was 0.9% at hospitals without on-site surgery, compared with 1% at those with on-site surgery, meeting the prespecified values for noninferiority.

At 9 months, major adverse cardiac event (MACE) rates were 12.1% and 11.2%, respectively. These also met the noninferiority criteria.

The need for target vessel revascularization (TVR) was slightly higher at hospitals without on-site cardiac surgery, but other adverse events such as bleeding, stroke, renal failure, and need for surgical revascularization were the same at hospitals with and without on-site surgery, Dr. Thomas Aversano reported at the annual meeting of the American College of Cardiology.

Session comoderator Dr. Robert Harrington, director of Duke Clinical Research Institute in Durham, N.C, asked whether every hospital should now offer elective PCI based on the results of the CPORT-E (Cardiovascular Patient Outcomes Research Team Nonprimary PCI) trial.

Dr. Aversano replied without hesitation "No, this study was not undertaken with the express idea of expansion of angioplasty programs. Really, the fundamental question was whether or not health care regulators, policy makers, and national organizations could use angioplasty in hospitals without on-site cardiac surgery as a tool. Is this possible? Is this safe?"

Invited discussant Dr. Gilles Montalescot, professor of cardiology at Hôpital Pitié-Salpétrière in Paris, said it’s always good for a study to confirm current practice, but that "the big difference is that you have excluded all high-risk patients and the temptation is to take all patients who come to the cath lab."

Dr. Aversano, the lead investigator of CPORT-E and associate professor of cardiology at Johns Hopkins University, Baltimore, emphasized that participating hospitals without on-site cardiac surgery undertook a formal PCI development program prior to study participation that took roughly 3-6 months to complete. It included detailed care plans and pathways, order sets, and training of staff in the care of PCI patients. Interventionalists were also required to meet criteria for competency developed by the ACC, the American Heart Association, and the Society for Cardiac Angiography and Interventions.

"What didn’t come out in the [online NEJM] article or the presentation is that these hospitals didn’t simply buy stents and guidewires and start doing this; it was a full development program," he said.

When asked whether the results could serve as a model for hospitals that may be considering offering PCI, Dr. Aversano said he was hesitant to make such a recommendation because each institution has its own unique political and logistical issues that prevent a "cookbook" approach.

ACC past president Dr. Ralph Brindis said results from the randomized trial support recent guideline changes by the ACC stating that it is reasonable for hospitals without cardiac surgery to perform elective PCI, not just emergency PCI.

"How policy makers at a state or government level utilize this in terms of offering PCI to local populations is yet to be determined," Dr. Brindis, clinical professor of medicine at the University of California, San Francisco, said in an interview. "Certainly every hospital shouldn’t be doing this, but there are issues of access in terms of having PCI available for our populations, particularly rural areas."

The 60 CPORT-E hospitals were located in 10 states and had a median annual PCI procedural volume of 150.

In all, 14,149 patients were randomly assigned to undergo PCI at a hospital without on-site cardiac surgery, and 4,718 were assigned to undergo PCI at a hospital with cardiac surgery, with 14,010 and 4,538 patients, respectively, ultimately undergoing the procedure. Patients were well matched, although prior PCI was more common among those randomized to hospitals without cardiac surgery (32% vs. 30.4%), Dr. Aversano said. Their average age was 64 years (N. Engl. J. Med. 2012 March 25 [doi: 10.1056/NEJMoa1114540]).

Staged procedures, meaning those performed on a different day than the initial cath lab visit, were more common at hospitals with on-site cardiac surgery than those without (68% vs. 26%), resulting in more catheterization laboratory visits (1.7 vs. 1.3).

Index PCI failure, however, was higher at hospitals without surgery on site (SOS) than those with SOS both per patient (3.4% vs. 2.5%) and per lesion (6.6% vs. 5.9%), he said. Use of bare metal stents was also higher at hospitals without SOS (24.2% vs. 23%).

At 9 months, there was no difference between hospitals without or with SOS in the composite elements of MACE including death (3.2% for both), Q-wave myocardial infarction (3.1% both) and TVR (6.5% vs. 5.4%, respectively), which included any unplanned PCI or coronary artery bypass grafting (CABG) after randomization.

Rates for hospitals without and with SOS were 5.2% vs. 5.3% for bleeding, 1.2% vs. 1.1% for vascular repair, 0.5% vs. 0.6% for stroke and 0.8% vs. 0.9% for renal insufficiency, respectively.

CABG was performed significantly more often at hospitals without SOS than those with SOS (2.3% vs. 1.5%).

An exploratory analysis of the intention-to-treat population that excluded CABG as part of TVR showed that MACE rates were 11.9% at hospitals without SOS and 10.5% at those with SOS.

An exploratory per protocol analysis also showed higher MACE rates at hospitals without SOS than at those with SOS (12% and 10.4% respectively), although these differences are within the range of noninferiority used in other recent stent trials, Dr. Aversano noted.

TVR may be higher in patients having PCI at hospitals without cardiac surgery because of a higher rate of bare metal stents used, which is a more conservative approach to PCI at relatively inexperienced hospitals, and a lack of a full complement of interventional devices, he suggested.

Johns Hopkins University and participating sites provided support for this trial. Dr. Brindis is a consultant to Ivivi Health Sciences. Dr. Harrington disclosed ties with numerous pharmaceutical companies. Dr. Aversano reported that he has no conflicts of interest.

CHICAGO – Patients with high platelet reactivity on standard-dose clopidogrel in conjunction with a drug-eluting stent for stable coronary disease obtain markedly greater platelet inhibition by switching to prasugrel at 10 mg/day than by doubling the clopidogrel dose to 150 mg/day, according to the Italian RESET trial.

This was a central finding in RESET. Another key finding was that high platelet reactivity on standard maintenance-dose clopidogrel was a common occurrence, affecting 23% of the 180 patients screened for the study, Dr. Gennaro Sardella, professor of cardiology at the University of Rome, reported at the annual meeting of the American College of Cardiology.

Thirty-two nonresponders to clopidogrel at 75 mg/day participated in the crossover portion of the study. They were randomized to 15 days of prasugrel at the standard dose of 10 mg/day or to clopidogrel at 150 mg/day, then underwent platelet activity testing using the Multiplate P2Y12 assay. Next came crossover to 15 days on the opposite therapy, followed by repeat platelet activity testing.

Twenty-eight percent of subjects were poor responders to double-dose clopidogrel as defined by high platelet reactivity, with an area under the curve in excess of 450/minute. In contrast, none of the subjects displayed high platelet reactivity while on prasugrel.

Moreover, inhibition of platelet aggregation was significantly greater during prasugrel therapy: 50% compared with 9% during double-dose clopidogrel therapy, the cardiologist continued.

Fourteen subjects were hetero- or homozygous for the allelic variant of CYP2C19 previously linked to high platelet reactivity in patients on clopidogrel. These were the patients who experienced high platelet reactivity on clopidogrel at 150 mg/day. Noncarriers had a similarly low level of platelet reactivity whether on prasugrel or clopidogrel.

An area under the curve greater than 600/minute on the Multiplate assay had 75% sensitivity and 72% specificity for the presence of genetic variation of the CYP2C19 allele. This is a novel observation which, if confirmed in larger studies, might obviate the need for genotyping of clopidogrel candidates, according to Dr. Sardella.

Session cochair Dr. George D. Dangas noted that while RESET and other small studies show that variants in CYP2C19 are related to clopidogrel responsiveness, a large meta-analysis by investigators at University College London found no significant association between genotype and cardiovascular events. The meta-analysis (JAMA 2011;306:2704-14) included more than 42,000 patients in 32 studies with 3,545 cardiovascular events, observed Dr. Dangas, professor of medicine at Mount Sinai School of Medicine, New York.

Dr. Sardella reported having no financial disclosures. Dr. Dangas serves as a consultant to Johnson & Johnson and Astra-Zeneca.

CHICAGO – Patients with high platelet reactivity on standard-dose clopidogrel in conjunction with a drug-eluting stent for stable coronary disease obtain markedly greater platelet inhibition by switching to prasugrel at 10 mg/day than by doubling the clopidogrel dose to 150 mg/day, according to the Italian RESET trial.

This was a central finding in RESET. Another key finding was that high platelet reactivity on standard maintenance-dose clopidogrel was a common occurrence, affecting 23% of the 180 patients screened for the study, Dr. Gennaro Sardella, professor of cardiology at the University of Rome, reported at the annual meeting of the American College of Cardiology.

Thirty-two nonresponders to clopidogrel at 75 mg/day participated in the crossover portion of the study. They were randomized to 15 days of prasugrel at the standard dose of 10 mg/day or to clopidogrel at 150 mg/day, then underwent platelet activity testing using the Multiplate P2Y12 assay. Next came crossover to 15 days on the opposite therapy, followed by repeat platelet activity testing.

Twenty-eight percent of subjects were poor responders to double-dose clopidogrel as defined by high platelet reactivity, with an area under the curve in excess of 450/minute. In contrast, none of the subjects displayed high platelet reactivity while on prasugrel.

Moreover, inhibition of platelet aggregation was significantly greater during prasugrel therapy: 50% compared with 9% during double-dose clopidogrel therapy, the cardiologist continued.

Fourteen subjects were hetero- or homozygous for the allelic variant of CYP2C19 previously linked to high platelet reactivity in patients on clopidogrel. These were the patients who experienced high platelet reactivity on clopidogrel at 150 mg/day. Noncarriers had a similarly low level of platelet reactivity whether on prasugrel or clopidogrel.

An area under the curve greater than 600/minute on the Multiplate assay had 75% sensitivity and 72% specificity for the presence of genetic variation of the CYP2C19 allele. This is a novel observation which, if confirmed in larger studies, might obviate the need for genotyping of clopidogrel candidates, according to Dr. Sardella.

Session cochair Dr. George D. Dangas noted that while RESET and other small studies show that variants in CYP2C19 are related to clopidogrel responsiveness, a large meta-analysis by investigators at University College London found no significant association between genotype and cardiovascular events. The meta-analysis (JAMA 2011;306:2704-14) included more than 42,000 patients in 32 studies with 3,545 cardiovascular events, observed Dr. Dangas, professor of medicine at Mount Sinai School of Medicine, New York.

Dr. Sardella reported having no financial disclosures. Dr. Dangas serves as a consultant to Johnson & Johnson and Astra-Zeneca.

CHICAGO – Patients with high platelet reactivity on standard-dose clopidogrel in conjunction with a drug-eluting stent for stable coronary disease obtain markedly greater platelet inhibition by switching to prasugrel at 10 mg/day than by doubling the clopidogrel dose to 150 mg/day, according to the Italian RESET trial.

This was a central finding in RESET. Another key finding was that high platelet reactivity on standard maintenance-dose clopidogrel was a common occurrence, affecting 23% of the 180 patients screened for the study, Dr. Gennaro Sardella, professor of cardiology at the University of Rome, reported at the annual meeting of the American College of Cardiology.

Thirty-two nonresponders to clopidogrel at 75 mg/day participated in the crossover portion of the study. They were randomized to 15 days of prasugrel at the standard dose of 10 mg/day or to clopidogrel at 150 mg/day, then underwent platelet activity testing using the Multiplate P2Y12 assay. Next came crossover to 15 days on the opposite therapy, followed by repeat platelet activity testing.

Twenty-eight percent of subjects were poor responders to double-dose clopidogrel as defined by high platelet reactivity, with an area under the curve in excess of 450/minute. In contrast, none of the subjects displayed high platelet reactivity while on prasugrel.

Moreover, inhibition of platelet aggregation was significantly greater during prasugrel therapy: 50% compared with 9% during double-dose clopidogrel therapy, the cardiologist continued.

Fourteen subjects were hetero- or homozygous for the allelic variant of CYP2C19 previously linked to high platelet reactivity in patients on clopidogrel. These were the patients who experienced high platelet reactivity on clopidogrel at 150 mg/day. Noncarriers had a similarly low level of platelet reactivity whether on prasugrel or clopidogrel.

An area under the curve greater than 600/minute on the Multiplate assay had 75% sensitivity and 72% specificity for the presence of genetic variation of the CYP2C19 allele. This is a novel observation which, if confirmed in larger studies, might obviate the need for genotyping of clopidogrel candidates, according to Dr. Sardella.

Session cochair Dr. George D. Dangas noted that while RESET and other small studies show that variants in CYP2C19 are related to clopidogrel responsiveness, a large meta-analysis by investigators at University College London found no significant association between genotype and cardiovascular events. The meta-analysis (JAMA 2011;306:2704-14) included more than 42,000 patients in 32 studies with 3,545 cardiovascular events, observed Dr. Dangas, professor of medicine at Mount Sinai School of Medicine, New York.

Dr. Sardella reported having no financial disclosures. Dr. Dangas serves as a consultant to Johnson & Johnson and Astra-Zeneca.

CHICAGO – Frailty and three common chronic health conditions place patients at greater risk of late mortality following transcatheter aortic valve replacement, according to extended follow-up of 339 patients in the Multicenter Canadian Experience study.

The overall survival rate was 57% after a median follow-up of 3 years (interquartile range 26-44 months) following transcatheter aortic valve implantation (TAVI).

Importantly, two-thirds of deaths (67%) were of noncardiac origin, 26% were due to cardiac causes, and 7% were of unknown causes, principal investigator Dr. Josep Rodés-Cabau said at the i2 Summit, a conference sponsored by the American College of Cardiology. Nearly half of noncardiac deaths were from respiratory failure (49%).

In multivariate analysis, a history of chronic obstructive pulmonary disease (hazard ratio, 1.99), chronic kidney disease (HR, 1.62), chronic atrial fibrillation (HR 1.82), and frailty (HR, 1.76) emerged as significant independent predictors of all-cause mortality more than 30 days after TAVI.

Surprisingly, there was no difference in survival between the transfemoral and transapical approaches in the multicenter TAVI program using a balloon-expandable valve, said Dr. Rodés-Cabau of the Quebec Heart and Lung Institute, Laval University, Quebec City, Canada. At 48 months follow-up, 45% of patients were free from death and stroke, as were 47% of those treated with the transfemoral approach and 44% treated with the transapical approach.

Causes of cumulative cardiac death included cardiac failure (65.5%), sudden death (13.8%), myocardial infarction (13.8%), endocarditis (3.4%), and postmitral replacement (3.4%).

Two patients required valve explantation because of endocarditis at 7 months and 13 months following TAVI, but no cases of structural valve failure occurred during follow-up, Dr. Rodés-Cabau stressed.

At 48 months, 76% of patients were free from cardiac death, as were 78% of transfemoral patients and 75% of transapical patients.

In multivariate analysis, pulmonary hypertension (HR, 1.92) and chronic kidney disease (HR, 2.30) were significant predictors of late cardiac death.

Although the data are compelling, the patient numbers are not sufficient to use to guide patient selection for TAVI, but instead represent a first step toward TAVI risk stratification, Dr. Rodés-Cabau said. After the introduction of TAVI, the focus was on technique, and many very-sick patients underwent the procedure only to die within the first year. Now, when a patient arrives at his center with these comorbidities, they are evaluated very carefully, including involvement of specialists such as respiratory or dietary specialists.

"I have to say that, based on the results of this study and also in our own daily experience, we have been refusing more patients now than we were in the past," he told reporters at a press briefing.

When asked during the formal study presentation why late mortality was similar with the two TAVI approaches, Dr. Rodés-Cabau said there could be several factors, but that the transapical approach is very well developed in Canada.

"These data were concentrated in a few number of centers with a huge experience in transapical approach, and this could explain the absence of difference between the two approaches," he said.

The investigators also evaluated regurgitation but found no association with late mortality, Dr. Rodés-Cabau said in an interview. The rate of moderate or severe regurgitation was relatively low at 8% at discharge. Studies have found a suggestion that mild regurgitation may be related to late mortality, but the Canadian data clearly show no difference in left ventricular diameter or LV ejection fraction changes between patients with and without mild regurgitation at 3 years, he said.

Overall, valve function remained stable up to 4 years of follow-up, with only mild, nonsignificant changes in transvalvular gradient and valve area.

"Mild aortic regurgitation, mostly paravalvular, was frequent after TAVI but had no impact on left ventricular diameters and function," Dr. Rodés-Cabau said at the meeting, also sponsored by the Cardiovascular Research Foundation.

Thirty-day mortality results from the Canadian experience were previously published in 2010 (J. Am. Coll. Cardiol. 2010;55:1080-90). Overall mortality was 10.4%, with pulmonary hypertension associated with a significantly higher rate of periprocedural death. Notably, patients with either porcelain aorta or frailty had acute outcomes similar to the rest of the study population.

Dr. Rodés-Cabau stressed that data in the study was analyzed at the Echo Core Lab and that only those patients with serial echocardiographic exams were included in the analysis. In all, 158 echocardiographic exams were analyzed at 1 year follow-up, 86 at 2 years, 34 at 3 years, and 11 exams at 4 years.

The median age of the patients was 81 years, 34% had prior cardiac bypass grafting, and 91% had a New York Heart Association functional class III-IV. The majority of patients received the Edwards Sapien valve (275 patients), with 57 implanted with the Cribier-Edwards valve, and 7 with the Sapien XT valve. The transfemoral approach was performed in 162 and transapical in 177 patients.

Dr. Rodés-Cabau is a consultant for Edwards Lifesciences and St. Jude Medical.

CHICAGO – Frailty and three common chronic health conditions place patients at greater risk of late mortality following transcatheter aortic valve replacement, according to extended follow-up of 339 patients in the Multicenter Canadian Experience study.

The overall survival rate was 57% after a median follow-up of 3 years (interquartile range 26-44 months) following transcatheter aortic valve implantation (TAVI).

Importantly, two-thirds of deaths (67%) were of noncardiac origin, 26% were due to cardiac causes, and 7% were of unknown causes, principal investigator Dr. Josep Rodés-Cabau said at the i2 Summit, a conference sponsored by the American College of Cardiology. Nearly half of noncardiac deaths were from respiratory failure (49%).

In multivariate analysis, a history of chronic obstructive pulmonary disease (hazard ratio, 1.99), chronic kidney disease (HR, 1.62), chronic atrial fibrillation (HR 1.82), and frailty (HR, 1.76) emerged as significant independent predictors of all-cause mortality more than 30 days after TAVI.

Surprisingly, there was no difference in survival between the transfemoral and transapical approaches in the multicenter TAVI program using a balloon-expandable valve, said Dr. Rodés-Cabau of the Quebec Heart and Lung Institute, Laval University, Quebec City, Canada. At 48 months follow-up, 45% of patients were free from death and stroke, as were 47% of those treated with the transfemoral approach and 44% treated with the transapical approach.

Causes of cumulative cardiac death included cardiac failure (65.5%), sudden death (13.8%), myocardial infarction (13.8%), endocarditis (3.4%), and postmitral replacement (3.4%).

Two patients required valve explantation because of endocarditis at 7 months and 13 months following TAVI, but no cases of structural valve failure occurred during follow-up, Dr. Rodés-Cabau stressed.

At 48 months, 76% of patients were free from cardiac death, as were 78% of transfemoral patients and 75% of transapical patients.

In multivariate analysis, pulmonary hypertension (HR, 1.92) and chronic kidney disease (HR, 2.30) were significant predictors of late cardiac death.

Although the data are compelling, the patient numbers are not sufficient to use to guide patient selection for TAVI, but instead represent a first step toward TAVI risk stratification, Dr. Rodés-Cabau said. After the introduction of TAVI, the focus was on technique, and many very-sick patients underwent the procedure only to die within the first year. Now, when a patient arrives at his center with these comorbidities, they are evaluated very carefully, including involvement of specialists such as respiratory or dietary specialists.

"I have to say that, based on the results of this study and also in our own daily experience, we have been refusing more patients now than we were in the past," he told reporters at a press briefing.

When asked during the formal study presentation why late mortality was similar with the two TAVI approaches, Dr. Rodés-Cabau said there could be several factors, but that the transapical approach is very well developed in Canada.

"These data were concentrated in a few number of centers with a huge experience in transapical approach, and this could explain the absence of difference between the two approaches," he said.

The investigators also evaluated regurgitation but found no association with late mortality, Dr. Rodés-Cabau said in an interview. The rate of moderate or severe regurgitation was relatively low at 8% at discharge. Studies have found a suggestion that mild regurgitation may be related to late mortality, but the Canadian data clearly show no difference in left ventricular diameter or LV ejection fraction changes between patients with and without mild regurgitation at 3 years, he said.

Overall, valve function remained stable up to 4 years of follow-up, with only mild, nonsignificant changes in transvalvular gradient and valve area.

"Mild aortic regurgitation, mostly paravalvular, was frequent after TAVI but had no impact on left ventricular diameters and function," Dr. Rodés-Cabau said at the meeting, also sponsored by the Cardiovascular Research Foundation.

Thirty-day mortality results from the Canadian experience were previously published in 2010 (J. Am. Coll. Cardiol. 2010;55:1080-90). Overall mortality was 10.4%, with pulmonary hypertension associated with a significantly higher rate of periprocedural death. Notably, patients with either porcelain aorta or frailty had acute outcomes similar to the rest of the study population.

Dr. Rodés-Cabau stressed that data in the study was analyzed at the Echo Core Lab and that only those patients with serial echocardiographic exams were included in the analysis. In all, 158 echocardiographic exams were analyzed at 1 year follow-up, 86 at 2 years, 34 at 3 years, and 11 exams at 4 years.

The median age of the patients was 81 years, 34% had prior cardiac bypass grafting, and 91% had a New York Heart Association functional class III-IV. The majority of patients received the Edwards Sapien valve (275 patients), with 57 implanted with the Cribier-Edwards valve, and 7 with the Sapien XT valve. The transfemoral approach was performed in 162 and transapical in 177 patients.

Dr. Rodés-Cabau is a consultant for Edwards Lifesciences and St. Jude Medical.

CHICAGO – Frailty and three common chronic health conditions place patients at greater risk of late mortality following transcatheter aortic valve replacement, according to extended follow-up of 339 patients in the Multicenter Canadian Experience study.

The overall survival rate was 57% after a median follow-up of 3 years (interquartile range 26-44 months) following transcatheter aortic valve implantation (TAVI).

Importantly, two-thirds of deaths (67%) were of noncardiac origin, 26% were due to cardiac causes, and 7% were of unknown causes, principal investigator Dr. Josep Rodés-Cabau said at the i2 Summit, a conference sponsored by the American College of Cardiology. Nearly half of noncardiac deaths were from respiratory failure (49%).

In multivariate analysis, a history of chronic obstructive pulmonary disease (hazard ratio, 1.99), chronic kidney disease (HR, 1.62), chronic atrial fibrillation (HR 1.82), and frailty (HR, 1.76) emerged as significant independent predictors of all-cause mortality more than 30 days after TAVI.

Surprisingly, there was no difference in survival between the transfemoral and transapical approaches in the multicenter TAVI program using a balloon-expandable valve, said Dr. Rodés-Cabau of the Quebec Heart and Lung Institute, Laval University, Quebec City, Canada. At 48 months follow-up, 45% of patients were free from death and stroke, as were 47% of those treated with the transfemoral approach and 44% treated with the transapical approach.

Causes of cumulative cardiac death included cardiac failure (65.5%), sudden death (13.8%), myocardial infarction (13.8%), endocarditis (3.4%), and postmitral replacement (3.4%).

Two patients required valve explantation because of endocarditis at 7 months and 13 months following TAVI, but no cases of structural valve failure occurred during follow-up, Dr. Rodés-Cabau stressed.

At 48 months, 76% of patients were free from cardiac death, as were 78% of transfemoral patients and 75% of transapical patients.

In multivariate analysis, pulmonary hypertension (HR, 1.92) and chronic kidney disease (HR, 2.30) were significant predictors of late cardiac death.

Although the data are compelling, the patient numbers are not sufficient to use to guide patient selection for TAVI, but instead represent a first step toward TAVI risk stratification, Dr. Rodés-Cabau said. After the introduction of TAVI, the focus was on technique, and many very-sick patients underwent the procedure only to die within the first year. Now, when a patient arrives at his center with these comorbidities, they are evaluated very carefully, including involvement of specialists such as respiratory or dietary specialists.

"I have to say that, based on the results of this study and also in our own daily experience, we have been refusing more patients now than we were in the past," he told reporters at a press briefing.

When asked during the formal study presentation why late mortality was similar with the two TAVI approaches, Dr. Rodés-Cabau said there could be several factors, but that the transapical approach is very well developed in Canada.

"These data were concentrated in a few number of centers with a huge experience in transapical approach, and this could explain the absence of difference between the two approaches," he said.

The investigators also evaluated regurgitation but found no association with late mortality, Dr. Rodés-Cabau said in an interview. The rate of moderate or severe regurgitation was relatively low at 8% at discharge. Studies have found a suggestion that mild regurgitation may be related to late mortality, but the Canadian data clearly show no difference in left ventricular diameter or LV ejection fraction changes between patients with and without mild regurgitation at 3 years, he said.

Overall, valve function remained stable up to 4 years of follow-up, with only mild, nonsignificant changes in transvalvular gradient and valve area.

"Mild aortic regurgitation, mostly paravalvular, was frequent after TAVI but had no impact on left ventricular diameters and function," Dr. Rodés-Cabau said at the meeting, also sponsored by the Cardiovascular Research Foundation.

Thirty-day mortality results from the Canadian experience were previously published in 2010 (J. Am. Coll. Cardiol. 2010;55:1080-90). Overall mortality was 10.4%, with pulmonary hypertension associated with a significantly higher rate of periprocedural death. Notably, patients with either porcelain aorta or frailty had acute outcomes similar to the rest of the study population.

Dr. Rodés-Cabau stressed that data in the study was analyzed at the Echo Core Lab and that only those patients with serial echocardiographic exams were included in the analysis. In all, 158 echocardiographic exams were analyzed at 1 year follow-up, 86 at 2 years, 34 at 3 years, and 11 exams at 4 years.

The median age of the patients was 81 years, 34% had prior cardiac bypass grafting, and 91% had a New York Heart Association functional class III-IV. The majority of patients received the Edwards Sapien valve (275 patients), with 57 implanted with the Cribier-Edwards valve, and 7 with the Sapien XT valve. The transfemoral approach was performed in 162 and transapical in 177 patients.

Dr. Rodés-Cabau is a consultant for Edwards Lifesciences and St. Jude Medical.

CHICAGO – Vorapaxar, a new type of platelet inhibitor drug, showed unequivocal efficacy for preventing new cardiovascular events in patients with a history of myocardial infarction, stroke, or peripheral artery disease already on a standard antiplatelet regimen in a pivotal study with 26,449 patients.

Treatment with vorapaxar also led to worrisome adverse effects of moderate or severe bleeding, as well as an excess of intracranial hemorrhage, in all treated patients, raising concerns about the drug’s safety.

Mitchel L. Zoler/IMNG Medical Media

But a series of prespecified analyses showed that the hazard from vorapaxar focused in patients with a history of stroke, while in patients with a history of myocardial infarction and no history of cerebrovascular disease, the risk for bleeding or intracranial hemorrhage was modest. In addition, the efficacy findings showed that it was the post-MI patients who gained the most from adding vorapaxar to their standard treatment with aspirin and a thienopyridine, usually clopidogrel.

The study’s analysis also identified another key modifier of bleeding risk, body weight of at least 60 kg (132 lbs.).

Among the 18,966 patients in the study who had no history of stroke and body weight of at least 60 kg (72% of the total study population), treatment with vorapaxar over a median of 2.5 years led to an absolute 1.9% reduction in the incidence of new MI, stroke, or cardiovascular death, while causing a 0.2% excess of intracranial hemorrhages and a 1% excess of other moderate or severe bleeding events, Dr. David A. Morrow reported at the meeting. This level of benefit and risk appeared primarily in the patients with a history of MI.

"Our data showed that these patients did very well with respect to risk and benefit," said Dr. Morrow, director of the cardiac unit at Brigham and Women’s Hospital in Boston. "This is a reasonable group to treat. The results are clear and exciting. We have been able to identify simple demographic and historic features that allow us to identify patients where the benefit from reducing clotting outweighs the smaller increase in bleeds. We think this is an important advance."

Concurrent with Dr. Morrow’s report, the results appears online (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1200933]).

Experts who heard the results agreed that the potential benefit could be important to post-MI patients, but if vorapaxar was approved for this indication, it would require very careful prescribing.

"It’s exciting that we have found something that moves the needle, even a little bit, for secondary prevention. For selected patients, this is an important addition to treatment," commented Dr. Patrick T. O’Gara, professor of medicine at Harvard Medical School and director of clinical cardiology at Brigham and Women’s Hospital, both in Boston, who had no involvement in the study. But he cautioned that if vorapaxar were approved, its use would have to be carefully assessed for each patient’s bleeding risk, based not only on weight and history of cerebrovascular events, but also on patient frailty and other global assessments of appropriateness, he said in an interview.

Vorapaxar looks like a drug that should only be used "in very selected patients, and in selected medical centers" in which physicians will take the time and have the experience to adequately judge the risk-to-benefit ratio, commented Dr. David R. Holmes Jr., president of the ACC and a cardiologist and professor of medicine at the Mayo Clinic in Rochester, Minn.

The Food and Drug Administration would likely decide either that vorapaxar needs further testing in MI patients with no history of cerebrovascular disease or that it could receive conditional approval but with need for a follow-up trial or collection of data to validate it safety in routine practice, commented Dr. Elliott M. Antman, a cardiologist and professor of medicine at Harvard Medical School.

The TRA 2P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events – Thrombolysis in Myocardial Infarction) study enrolled patients at 1,032 sites in 32 countries during September 2007–November 2009. Patients received either 2.5 mg oral vorapaxar daily or placebo. Other medications enrolled patients received included aspirin, in 98%, and a thienopyridine, in 78%. The study’s primary end point was the combined rate of cardiovascular death, myocardial infarction, or stroke. For the entire study population, addition of vorapaxar reduced this rate by 1.2 percentage points, a relative reduction of 13% that was statistically significant. For the entire study, vorapaxar increased the incidence of intracranial hemorrhage by 0.5 percentage points, a 94% risk increase that was statistically significant. The drug also increased moderate or severe bleeds by 1.7 percentage points, a relative hazard increase of 66% that was statistically significant.

Vorapaxar is a selective antagonist for the protease-activated receptor-1 on platelets that inhibits platelet aggregation by thrombin by a route that is independent of the action of other antiplatelet drugs, such as aspirin and clopidogrel. Study results from a prior major study of vorapaxar in nearly 13,000 patients with non–ST-elevation acute coronary syndrome had shown no efficacy benefit from adding the drug in this patient population and showed a similar increased rate of moderate and severe bleeds and intracranial hemorrhage. At the time these results from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial were reported last November at the American Heart Association annual meeting, experts concluded that, in TRACER, treatment with vorapaxar had failed to balance safety and efficacy, at least with the dosage regimen tested in that study.

The study was sponsored by Merck. Dr. Morrow said that he has received research support from and has served as an unpaid consultant to Merck and to several other drug companies. Dr. O’Gara, Dr. Holmes, and Dr. Antman said that they had no relevant disclosures.

CHICAGO – Vorapaxar, a new type of platelet inhibitor drug, showed unequivocal efficacy for preventing new cardiovascular events in patients with a history of myocardial infarction, stroke, or peripheral artery disease already on a standard antiplatelet regimen in a pivotal study with 26,449 patients.

Treatment with vorapaxar also led to worrisome adverse effects of moderate or severe bleeding, as well as an excess of intracranial hemorrhage, in all treated patients, raising concerns about the drug’s safety.

Mitchel L. Zoler/IMNG Medical Media

But a series of prespecified analyses showed that the hazard from vorapaxar focused in patients with a history of stroke, while in patients with a history of myocardial infarction and no history of cerebrovascular disease, the risk for bleeding or intracranial hemorrhage was modest. In addition, the efficacy findings showed that it was the post-MI patients who gained the most from adding vorapaxar to their standard treatment with aspirin and a thienopyridine, usually clopidogrel.

The study’s analysis also identified another key modifier of bleeding risk, body weight of at least 60 kg (132 lbs.).

Among the 18,966 patients in the study who had no history of stroke and body weight of at least 60 kg (72% of the total study population), treatment with vorapaxar over a median of 2.5 years led to an absolute 1.9% reduction in the incidence of new MI, stroke, or cardiovascular death, while causing a 0.2% excess of intracranial hemorrhages and a 1% excess of other moderate or severe bleeding events, Dr. David A. Morrow reported at the meeting. This level of benefit and risk appeared primarily in the patients with a history of MI.

"Our data showed that these patients did very well with respect to risk and benefit," said Dr. Morrow, director of the cardiac unit at Brigham and Women’s Hospital in Boston. "This is a reasonable group to treat. The results are clear and exciting. We have been able to identify simple demographic and historic features that allow us to identify patients where the benefit from reducing clotting outweighs the smaller increase in bleeds. We think this is an important advance."

Concurrent with Dr. Morrow’s report, the results appears online (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1200933]).

Experts who heard the results agreed that the potential benefit could be important to post-MI patients, but if vorapaxar was approved for this indication, it would require very careful prescribing.

"It’s exciting that we have found something that moves the needle, even a little bit, for secondary prevention. For selected patients, this is an important addition to treatment," commented Dr. Patrick T. O’Gara, professor of medicine at Harvard Medical School and director of clinical cardiology at Brigham and Women’s Hospital, both in Boston, who had no involvement in the study. But he cautioned that if vorapaxar were approved, its use would have to be carefully assessed for each patient’s bleeding risk, based not only on weight and history of cerebrovascular events, but also on patient frailty and other global assessments of appropriateness, he said in an interview.

Vorapaxar looks like a drug that should only be used "in very selected patients, and in selected medical centers" in which physicians will take the time and have the experience to adequately judge the risk-to-benefit ratio, commented Dr. David R. Holmes Jr., president of the ACC and a cardiologist and professor of medicine at the Mayo Clinic in Rochester, Minn.

The Food and Drug Administration would likely decide either that vorapaxar needs further testing in MI patients with no history of cerebrovascular disease or that it could receive conditional approval but with need for a follow-up trial or collection of data to validate it safety in routine practice, commented Dr. Elliott M. Antman, a cardiologist and professor of medicine at Harvard Medical School.

The TRA 2P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events – Thrombolysis in Myocardial Infarction) study enrolled patients at 1,032 sites in 32 countries during September 2007–November 2009. Patients received either 2.5 mg oral vorapaxar daily or placebo. Other medications enrolled patients received included aspirin, in 98%, and a thienopyridine, in 78%. The study’s primary end point was the combined rate of cardiovascular death, myocardial infarction, or stroke. For the entire study population, addition of vorapaxar reduced this rate by 1.2 percentage points, a relative reduction of 13% that was statistically significant. For the entire study, vorapaxar increased the incidence of intracranial hemorrhage by 0.5 percentage points, a 94% risk increase that was statistically significant. The drug also increased moderate or severe bleeds by 1.7 percentage points, a relative hazard increase of 66% that was statistically significant.

Vorapaxar is a selective antagonist for the protease-activated receptor-1 on platelets that inhibits platelet aggregation by thrombin by a route that is independent of the action of other antiplatelet drugs, such as aspirin and clopidogrel. Study results from a prior major study of vorapaxar in nearly 13,000 patients with non–ST-elevation acute coronary syndrome had shown no efficacy benefit from adding the drug in this patient population and showed a similar increased rate of moderate and severe bleeds and intracranial hemorrhage. At the time these results from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial were reported last November at the American Heart Association annual meeting, experts concluded that, in TRACER, treatment with vorapaxar had failed to balance safety and efficacy, at least with the dosage regimen tested in that study.

The study was sponsored by Merck. Dr. Morrow said that he has received research support from and has served as an unpaid consultant to Merck and to several other drug companies. Dr. O’Gara, Dr. Holmes, and Dr. Antman said that they had no relevant disclosures.

CHICAGO – Vorapaxar, a new type of platelet inhibitor drug, showed unequivocal efficacy for preventing new cardiovascular events in patients with a history of myocardial infarction, stroke, or peripheral artery disease already on a standard antiplatelet regimen in a pivotal study with 26,449 patients.

Treatment with vorapaxar also led to worrisome adverse effects of moderate or severe bleeding, as well as an excess of intracranial hemorrhage, in all treated patients, raising concerns about the drug’s safety.

Mitchel L. Zoler/IMNG Medical Media

But a series of prespecified analyses showed that the hazard from vorapaxar focused in patients with a history of stroke, while in patients with a history of myocardial infarction and no history of cerebrovascular disease, the risk for bleeding or intracranial hemorrhage was modest. In addition, the efficacy findings showed that it was the post-MI patients who gained the most from adding vorapaxar to their standard treatment with aspirin and a thienopyridine, usually clopidogrel.

The study’s analysis also identified another key modifier of bleeding risk, body weight of at least 60 kg (132 lbs.).

Among the 18,966 patients in the study who had no history of stroke and body weight of at least 60 kg (72% of the total study population), treatment with vorapaxar over a median of 2.5 years led to an absolute 1.9% reduction in the incidence of new MI, stroke, or cardiovascular death, while causing a 0.2% excess of intracranial hemorrhages and a 1% excess of other moderate or severe bleeding events, Dr. David A. Morrow reported at the meeting. This level of benefit and risk appeared primarily in the patients with a history of MI.

"Our data showed that these patients did very well with respect to risk and benefit," said Dr. Morrow, director of the cardiac unit at Brigham and Women’s Hospital in Boston. "This is a reasonable group to treat. The results are clear and exciting. We have been able to identify simple demographic and historic features that allow us to identify patients where the benefit from reducing clotting outweighs the smaller increase in bleeds. We think this is an important advance."

Concurrent with Dr. Morrow’s report, the results appears online (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1200933]).

Experts who heard the results agreed that the potential benefit could be important to post-MI patients, but if vorapaxar was approved for this indication, it would require very careful prescribing.

"It’s exciting that we have found something that moves the needle, even a little bit, for secondary prevention. For selected patients, this is an important addition to treatment," commented Dr. Patrick T. O’Gara, professor of medicine at Harvard Medical School and director of clinical cardiology at Brigham and Women’s Hospital, both in Boston, who had no involvement in the study. But he cautioned that if vorapaxar were approved, its use would have to be carefully assessed for each patient’s bleeding risk, based not only on weight and history of cerebrovascular events, but also on patient frailty and other global assessments of appropriateness, he said in an interview.

Vorapaxar looks like a drug that should only be used "in very selected patients, and in selected medical centers" in which physicians will take the time and have the experience to adequately judge the risk-to-benefit ratio, commented Dr. David R. Holmes Jr., president of the ACC and a cardiologist and professor of medicine at the Mayo Clinic in Rochester, Minn.

The Food and Drug Administration would likely decide either that vorapaxar needs further testing in MI patients with no history of cerebrovascular disease or that it could receive conditional approval but with need for a follow-up trial or collection of data to validate it safety in routine practice, commented Dr. Elliott M. Antman, a cardiologist and professor of medicine at Harvard Medical School.

The TRA 2P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events – Thrombolysis in Myocardial Infarction) study enrolled patients at 1,032 sites in 32 countries during September 2007–November 2009. Patients received either 2.5 mg oral vorapaxar daily or placebo. Other medications enrolled patients received included aspirin, in 98%, and a thienopyridine, in 78%. The study’s primary end point was the combined rate of cardiovascular death, myocardial infarction, or stroke. For the entire study population, addition of vorapaxar reduced this rate by 1.2 percentage points, a relative reduction of 13% that was statistically significant. For the entire study, vorapaxar increased the incidence of intracranial hemorrhage by 0.5 percentage points, a 94% risk increase that was statistically significant. The drug also increased moderate or severe bleeds by 1.7 percentage points, a relative hazard increase of 66% that was statistically significant.

Vorapaxar is a selective antagonist for the protease-activated receptor-1 on platelets that inhibits platelet aggregation by thrombin by a route that is independent of the action of other antiplatelet drugs, such as aspirin and clopidogrel. Study results from a prior major study of vorapaxar in nearly 13,000 patients with non–ST-elevation acute coronary syndrome had shown no efficacy benefit from adding the drug in this patient population and showed a similar increased rate of moderate and severe bleeds and intracranial hemorrhage. At the time these results from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial were reported last November at the American Heart Association annual meeting, experts concluded that, in TRACER, treatment with vorapaxar had failed to balance safety and efficacy, at least with the dosage regimen tested in that study.

The study was sponsored by Merck. Dr. Morrow said that he has received research support from and has served as an unpaid consultant to Merck and to several other drug companies. Dr. O’Gara, Dr. Holmes, and Dr. Antman said that they had no relevant disclosures.

CHICAGO  – Transcatheter aortic valve implantation using the CoreValve system improved hemodynamics with a very low incidence of stroke in 1,015 consecutive patients with severe aortic stenosis in the real-world ADVANCE study.

The 30-day stroke rate was 2.9% (1.2% major and 1.7% minor), and 3.4% at 6 months (1.6% major and 1.8% minor). Transient ischemic attack rates were 0.4% and 1.2%, respectively, as adjudicated by an independent neurologist.

Mean aortic valve gradient decreased from 45.6 mm Hg at baseline to 9.3 mm Hg at 30 days and to 9.5 mm Hg at 6 months, while effective orifice area increased from 0.7 cm² at baseline to 1.7 cm² at both 30 days and 6 months.

"The CoreValve ADVANCE study, which is the largest, multicenter, prospective, fully monitored TAVI study, shows that treatment of real-world inoperable and frail high-risk patients with the Medtronic CoreValve is safe and associated with an improvement in aortic valve function and low stroke and mortality rates at 1 month and 6 months follow-up," principal investigator Dr. Axel Linke said at the i2 Summit, a conference sponsored by the American College of Cardiology.

Medtronic’s transcatheter CoreValve System, which features a porcine pericardial tissue valve that is sutured into a self-expanding nitinol frame, is currently limited to investigational use in the United States.

The 1,015 patients, mean age 81 years, were considered inoperable or high risk and were enrolled from March 2010 to July 2011 at 44 centers in 12 countries in Western Europe, Asia, and South America. All centers had conducted at least 40 TAVI procedures prior to the study and had a heart team in place. Clinical end points were reported according to Valve Academic Research Consortium (VARC) criteria.

Among the 996 patients in whom implantation was attempted, the procedural success rate was 98%, said Dr. Linke, professor of medicine at the University of Leipzig (Germany) Heart Center.

The study’s primary end point of major adverse cardiac and cerebrovascular events occurred in 8.3%, with all-cause mortality at 4.5%, myocardial infarctions 0.2%, and emergent cardiac surgery or percutaneous reintervention 1.7%. MACE events were adjudicated by an independent clinical events committee consisting of TAVI-experienced interventional cardiologists and cardiac surgeons, Dr. Linke pointed out at the meeting, also sponsored by the Cardiovascular Research Foundation.

Additional 30-day VARC end points included cardiovascular mortality at 3.4%, major bleeding in 9.7%, life-threatening bleeding in 4%, major vascular complications in 10.7%, and acute stage III kidney injury in 0.4%.

New pacemaker implantation was required in 26.3% of patients, due largely to significant bradycardia or higher grade AV block. The timing of the implantation was left to the discretion of the surgeon, with some implantations occurring during TAVI and others at postoperative day 1 or 2. Although the pacemaker placement rate is consistent with what has been reported in European registries, Dr. Linke noted during a press briefing at the meeting that rates in the study varied widely among countries, from 8% to 30%.

Survival rates were high at both 30 days (95.5%) and 6 months (87.2%). A prespecified subgroup analysis by logistic EuroScore revealed a 6-month survival rate of 95.7% for those with a score of 0-10, 92.4% with a score of 10-20, and 88.1% with a score greater than 20.

Session co-moderator Dr. George Dangas of the senior cardiology faculty at the Mount Sinai Medical School in New York, said the consensus is that bleeding rates with TAVI have improved over time, but remarked that "a 10% bleeding rate is still not that small."

Dr. Linke said further investigation is still needed, but that "despite the fact we have relatively high bleeding rates, they have lost their impact on mortality in the latest registries.

"I believe we still have bleeding, but we have gained so much experience to get control of the bleeding, therefore we have fewer cases of bleeding related-death."

Audience members also questioned what may have contributed to the low incidence of stroke in ADVANCE. Dr. Linke said they don’t yet have an explanation for the very low stroke rates, but that valve expansion may be at play.

One contributor may be "really aggressive oversizing with the cobalt rim that might crush the calcium and release the calcium into those bloodstream," he said. "Here, it’s a rather passive expansion and it might be that the calcium is still covered by fibrotic tissue and endothelium and not exposed to the bloodstream. This might be one reason, but we are still in the process of understanding what is going on."

At baseline, 31% of ADVANCE patients were diagnosed with diabetes, 20% had peripheral vascular disease, and 21% had undergone previous CABG. Their mean logistic EuroSCORE was 19.2. Roughly 80% were New York Heart Association class III and IV. At 6 months post-TAVI, 1% were class IV, 12% class III, 44% class II, and 43% class I.

This study was sponsored by Medtronic Bakken Research Center. Dr. Linke reported serving as a proctor for and receiving customary travel and expenses from Medtronic. Dr. Dangas serves as a consultant to AstraZeneca and Cordis.

CHICAGO  – Transcatheter aortic valve implantation using the CoreValve system improved hemodynamics with a very low incidence of stroke in 1,015 consecutive patients with severe aortic stenosis in the real-world ADVANCE study.

The 30-day stroke rate was 2.9% (1.2% major and 1.7% minor), and 3.4% at 6 months (1.6% major and 1.8% minor). Transient ischemic attack rates were 0.4% and 1.2%, respectively, as adjudicated by an independent neurologist.

Mean aortic valve gradient decreased from 45.6 mm Hg at baseline to 9.3 mm Hg at 30 days and to 9.5 mm Hg at 6 months, while effective orifice area increased from 0.7 cm² at baseline to 1.7 cm² at both 30 days and 6 months.

"The CoreValve ADVANCE study, which is the largest, multicenter, prospective, fully monitored TAVI study, shows that treatment of real-world inoperable and frail high-risk patients with the Medtronic CoreValve is safe and associated with an improvement in aortic valve function and low stroke and mortality rates at 1 month and 6 months follow-up," principal investigator Dr. Axel Linke said at the i2 Summit, a conference sponsored by the American College of Cardiology.

Medtronic’s transcatheter CoreValve System, which features a porcine pericardial tissue valve that is sutured into a self-expanding nitinol frame, is currently limited to investigational use in the United States.

The 1,015 patients, mean age 81 years, were considered inoperable or high risk and were enrolled from March 2010 to July 2011 at 44 centers in 12 countries in Western Europe, Asia, and South America. All centers had conducted at least 40 TAVI procedures prior to the study and had a heart team in place. Clinical end points were reported according to Valve Academic Research Consortium (VARC) criteria.

Among the 996 patients in whom implantation was attempted, the procedural success rate was 98%, said Dr. Linke, professor of medicine at the University of Leipzig (Germany) Heart Center.

The study’s primary end point of major adverse cardiac and cerebrovascular events occurred in 8.3%, with all-cause mortality at 4.5%, myocardial infarctions 0.2%, and emergent cardiac surgery or percutaneous reintervention 1.7%. MACE events were adjudicated by an independent clinical events committee consisting of TAVI-experienced interventional cardiologists and cardiac surgeons, Dr. Linke pointed out at the meeting, also sponsored by the Cardiovascular Research Foundation.

Additional 30-day VARC end points included cardiovascular mortality at 3.4%, major bleeding in 9.7%, life-threatening bleeding in 4%, major vascular complications in 10.7%, and acute stage III kidney injury in 0.4%.

New pacemaker implantation was required in 26.3% of patients, due largely to significant bradycardia or higher grade AV block. The timing of the implantation was left to the discretion of the surgeon, with some implantations occurring during TAVI and others at postoperative day 1 or 2. Although the pacemaker placement rate is consistent with what has been reported in European registries, Dr. Linke noted during a press briefing at the meeting that rates in the study varied widely among countries, from 8% to 30%.

Survival rates were high at both 30 days (95.5%) and 6 months (87.2%). A prespecified subgroup analysis by logistic EuroScore revealed a 6-month survival rate of 95.7% for those with a score of 0-10, 92.4% with a score of 10-20, and 88.1% with a score greater than 20.

Session co-moderator Dr. George Dangas of the senior cardiology faculty at the Mount Sinai Medical School in New York, said the consensus is that bleeding rates with TAVI have improved over time, but remarked that "a 10% bleeding rate is still not that small."

Dr. Linke said further investigation is still needed, but that "despite the fact we have relatively high bleeding rates, they have lost their impact on mortality in the latest registries.

"I believe we still have bleeding, but we have gained so much experience to get control of the bleeding, therefore we have fewer cases of bleeding related-death."

Audience members also questioned what may have contributed to the low incidence of stroke in ADVANCE. Dr. Linke said they don’t yet have an explanation for the very low stroke rates, but that valve expansion may be at play.

One contributor may be "really aggressive oversizing with the cobalt rim that might crush the calcium and release the calcium into those bloodstream," he said. "Here, it’s a rather passive expansion and it might be that the calcium is still covered by fibrotic tissue and endothelium and not exposed to the bloodstream. This might be one reason, but we are still in the process of understanding what is going on."

At baseline, 31% of ADVANCE patients were diagnosed with diabetes, 20% had peripheral vascular disease, and 21% had undergone previous CABG. Their mean logistic EuroSCORE was 19.2. Roughly 80% were New York Heart Association class III and IV. At 6 months post-TAVI, 1% were class IV, 12% class III, 44% class II, and 43% class I.

This study was sponsored by Medtronic Bakken Research Center. Dr. Linke reported serving as a proctor for and receiving customary travel and expenses from Medtronic. Dr. Dangas serves as a consultant to AstraZeneca and Cordis.

CHICAGO  – Transcatheter aortic valve implantation using the CoreValve system improved hemodynamics with a very low incidence of stroke in 1,015 consecutive patients with severe aortic stenosis in the real-world ADVANCE study.

The 30-day stroke rate was 2.9% (1.2% major and 1.7% minor), and 3.4% at 6 months (1.6% major and 1.8% minor). Transient ischemic attack rates were 0.4% and 1.2%, respectively, as adjudicated by an independent neurologist.

Mean aortic valve gradient decreased from 45.6 mm Hg at baseline to 9.3 mm Hg at 30 days and to 9.5 mm Hg at 6 months, while effective orifice area increased from 0.7 cm² at baseline to 1.7 cm² at both 30 days and 6 months.

"The CoreValve ADVANCE study, which is the largest, multicenter, prospective, fully monitored TAVI study, shows that treatment of real-world inoperable and frail high-risk patients with the Medtronic CoreValve is safe and associated with an improvement in aortic valve function and low stroke and mortality rates at 1 month and 6 months follow-up," principal investigator Dr. Axel Linke said at the i2 Summit, a conference sponsored by the American College of Cardiology.

Medtronic’s transcatheter CoreValve System, which features a porcine pericardial tissue valve that is sutured into a self-expanding nitinol frame, is currently limited to investigational use in the United States.

The 1,015 patients, mean age 81 years, were considered inoperable or high risk and were enrolled from March 2010 to July 2011 at 44 centers in 12 countries in Western Europe, Asia, and South America. All centers had conducted at least 40 TAVI procedures prior to the study and had a heart team in place. Clinical end points were reported according to Valve Academic Research Consortium (VARC) criteria.

Among the 996 patients in whom implantation was attempted, the procedural success rate was 98%, said Dr. Linke, professor of medicine at the University of Leipzig (Germany) Heart Center.

The study’s primary end point of major adverse cardiac and cerebrovascular events occurred in 8.3%, with all-cause mortality at 4.5%, myocardial infarctions 0.2%, and emergent cardiac surgery or percutaneous reintervention 1.7%. MACE events were adjudicated by an independent clinical events committee consisting of TAVI-experienced interventional cardiologists and cardiac surgeons, Dr. Linke pointed out at the meeting, also sponsored by the Cardiovascular Research Foundation.

Additional 30-day VARC end points included cardiovascular mortality at 3.4%, major bleeding in 9.7%, life-threatening bleeding in 4%, major vascular complications in 10.7%, and acute stage III kidney injury in 0.4%.

New pacemaker implantation was required in 26.3% of patients, due largely to significant bradycardia or higher grade AV block. The timing of the implantation was left to the discretion of the surgeon, with some implantations occurring during TAVI and others at postoperative day 1 or 2. Although the pacemaker placement rate is consistent with what has been reported in European registries, Dr. Linke noted during a press briefing at the meeting that rates in the study varied widely among countries, from 8% to 30%.

Survival rates were high at both 30 days (95.5%) and 6 months (87.2%). A prespecified subgroup analysis by logistic EuroScore revealed a 6-month survival rate of 95.7% for those with a score of 0-10, 92.4% with a score of 10-20, and 88.1% with a score greater than 20.

Session co-moderator Dr. George Dangas of the senior cardiology faculty at the Mount Sinai Medical School in New York, said the consensus is that bleeding rates with TAVI have improved over time, but remarked that "a 10% bleeding rate is still not that small."

Dr. Linke said further investigation is still needed, but that "despite the fact we have relatively high bleeding rates, they have lost their impact on mortality in the latest registries.

"I believe we still have bleeding, but we have gained so much experience to get control of the bleeding, therefore we have fewer cases of bleeding related-death."

Audience members also questioned what may have contributed to the low incidence of stroke in ADVANCE. Dr. Linke said they don’t yet have an explanation for the very low stroke rates, but that valve expansion may be at play.

One contributor may be "really aggressive oversizing with the cobalt rim that might crush the calcium and release the calcium into those bloodstream," he said. "Here, it’s a rather passive expansion and it might be that the calcium is still covered by fibrotic tissue and endothelium and not exposed to the bloodstream. This might be one reason, but we are still in the process of understanding what is going on."

At baseline, 31% of ADVANCE patients were diagnosed with diabetes, 20% had peripheral vascular disease, and 21% had undergone previous CABG. Their mean logistic EuroSCORE was 19.2. Roughly 80% were New York Heart Association class III and IV. At 6 months post-TAVI, 1% were class IV, 12% class III, 44% class II, and 43% class I.

This study was sponsored by Medtronic Bakken Research Center. Dr. Linke reported serving as a proctor for and receiving customary travel and expenses from Medtronic. Dr. Dangas serves as a consultant to AstraZeneca and Cordis.