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Restrictive transfusions do not increase long-term CV surgery risk
MUNICH – in a large, randomized trial presented at the annual congress of the European Society of Cardiology, and published simultaneously in the New England Journal of Medicine.
The investigators previously reported that 28 day outcomes were non-inferior with the restrictive approach, but they wanted to look into 6 month results to rule out latent problems, such as sequelae from perioperative organ hypoxia.
The new outcomes from the study, dubbed the Transfusion Requirements in Cardiac Surgery (TRICS) III trial, offer some reassurance at a time when cardiac surgeons are shifting towards more restrictive transfusion policies (N Engl J Med. 2018 Aug 26.doi: 10.1056/NEJMoa1808561).
The trial randomized 2,317 patients to red cell transfusions if their hemoglobin concentrations fell below 7.5 g/dL intraoperatively or postoperatively. Another 2,347 were randomized to the liberal approach, with transfusions below 9.5 g/dL in the operating room and ICU, and below 8.5 g/dL outside of the ICU. The arms were well matched, with a mean score of 8 in both groups on the 47-point European System for Cardiac Operative Risk Evaluation I score.
At 6 months, 17.4% of patients in the restrictive arm, versus 17.1% in the liberal-threshold group, met the primary composite outcome of death from any cause, myocardial infarction, stroke, or new onset renal failure with dialysis (P = .006 for noninferiority with the restrictive threshold); 6.2% of patients in the restrictive-threshold group, versus 6.4% in the liberal-arm, had died at that point, a statistically insignificant difference.
Also at 6 months, 43.8% of patients in the restrictive-threshold group, versus 42.8% in the liberal arm, met the study’s secondary composite outcome, which included the components of the primary outcome plus hospital readmissions, ED visits, and coronary revascularization. The difference was again statistically insignificant.
The restrictive strategy saved a lot of blood. Just over half of the patients, versus almost three-quarters in the liberal arm, were transfused during their index admissions. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units.
Unexpectedly, patients 75 years and older had a lower risk of poor outcomes with the restrictive strategy, while the liberal strategy was associated with lower risk in younger subjects. The findings “appear to contradict” current practice, “in which a liberal transfusion strategy is used in older patients undergoing cardiac or noncardiac surgery,” said investigators led by C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
“One could hypothesize that older patients may have unacceptable adverse effects related to transfusion (e.g., volume overload and inflammatory and infectious complications) or that there may be age-related differences in the adverse-effect profile of transfusion or anemia. ... Whether transfusion thresholds should differ according to age” needs to be determined, they said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded. The trial was conducted in 19 countries, including China and India; results were consistent across study sites.
The work was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer had no relevant disclosures.
SOURCE: Mazer CD et al. N Engl J Med. 2018 Aug 26. doi:10.1056/NEJMoa1808561
MUNICH – in a large, randomized trial presented at the annual congress of the European Society of Cardiology, and published simultaneously in the New England Journal of Medicine.
The investigators previously reported that 28 day outcomes were non-inferior with the restrictive approach, but they wanted to look into 6 month results to rule out latent problems, such as sequelae from perioperative organ hypoxia.
The new outcomes from the study, dubbed the Transfusion Requirements in Cardiac Surgery (TRICS) III trial, offer some reassurance at a time when cardiac surgeons are shifting towards more restrictive transfusion policies (N Engl J Med. 2018 Aug 26.doi: 10.1056/NEJMoa1808561).
The trial randomized 2,317 patients to red cell transfusions if their hemoglobin concentrations fell below 7.5 g/dL intraoperatively or postoperatively. Another 2,347 were randomized to the liberal approach, with transfusions below 9.5 g/dL in the operating room and ICU, and below 8.5 g/dL outside of the ICU. The arms were well matched, with a mean score of 8 in both groups on the 47-point European System for Cardiac Operative Risk Evaluation I score.
At 6 months, 17.4% of patients in the restrictive arm, versus 17.1% in the liberal-threshold group, met the primary composite outcome of death from any cause, myocardial infarction, stroke, or new onset renal failure with dialysis (P = .006 for noninferiority with the restrictive threshold); 6.2% of patients in the restrictive-threshold group, versus 6.4% in the liberal-arm, had died at that point, a statistically insignificant difference.
Also at 6 months, 43.8% of patients in the restrictive-threshold group, versus 42.8% in the liberal arm, met the study’s secondary composite outcome, which included the components of the primary outcome plus hospital readmissions, ED visits, and coronary revascularization. The difference was again statistically insignificant.
The restrictive strategy saved a lot of blood. Just over half of the patients, versus almost three-quarters in the liberal arm, were transfused during their index admissions. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units.
Unexpectedly, patients 75 years and older had a lower risk of poor outcomes with the restrictive strategy, while the liberal strategy was associated with lower risk in younger subjects. The findings “appear to contradict” current practice, “in which a liberal transfusion strategy is used in older patients undergoing cardiac or noncardiac surgery,” said investigators led by C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
“One could hypothesize that older patients may have unacceptable adverse effects related to transfusion (e.g., volume overload and inflammatory and infectious complications) or that there may be age-related differences in the adverse-effect profile of transfusion or anemia. ... Whether transfusion thresholds should differ according to age” needs to be determined, they said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded. The trial was conducted in 19 countries, including China and India; results were consistent across study sites.
The work was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer had no relevant disclosures.
SOURCE: Mazer CD et al. N Engl J Med. 2018 Aug 26. doi:10.1056/NEJMoa1808561
MUNICH – in a large, randomized trial presented at the annual congress of the European Society of Cardiology, and published simultaneously in the New England Journal of Medicine.
The investigators previously reported that 28 day outcomes were non-inferior with the restrictive approach, but they wanted to look into 6 month results to rule out latent problems, such as sequelae from perioperative organ hypoxia.
The new outcomes from the study, dubbed the Transfusion Requirements in Cardiac Surgery (TRICS) III trial, offer some reassurance at a time when cardiac surgeons are shifting towards more restrictive transfusion policies (N Engl J Med. 2018 Aug 26.doi: 10.1056/NEJMoa1808561).
The trial randomized 2,317 patients to red cell transfusions if their hemoglobin concentrations fell below 7.5 g/dL intraoperatively or postoperatively. Another 2,347 were randomized to the liberal approach, with transfusions below 9.5 g/dL in the operating room and ICU, and below 8.5 g/dL outside of the ICU. The arms were well matched, with a mean score of 8 in both groups on the 47-point European System for Cardiac Operative Risk Evaluation I score.
At 6 months, 17.4% of patients in the restrictive arm, versus 17.1% in the liberal-threshold group, met the primary composite outcome of death from any cause, myocardial infarction, stroke, or new onset renal failure with dialysis (P = .006 for noninferiority with the restrictive threshold); 6.2% of patients in the restrictive-threshold group, versus 6.4% in the liberal-arm, had died at that point, a statistically insignificant difference.
Also at 6 months, 43.8% of patients in the restrictive-threshold group, versus 42.8% in the liberal arm, met the study’s secondary composite outcome, which included the components of the primary outcome plus hospital readmissions, ED visits, and coronary revascularization. The difference was again statistically insignificant.
The restrictive strategy saved a lot of blood. Just over half of the patients, versus almost three-quarters in the liberal arm, were transfused during their index admissions. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units.
Unexpectedly, patients 75 years and older had a lower risk of poor outcomes with the restrictive strategy, while the liberal strategy was associated with lower risk in younger subjects. The findings “appear to contradict” current practice, “in which a liberal transfusion strategy is used in older patients undergoing cardiac or noncardiac surgery,” said investigators led by C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
“One could hypothesize that older patients may have unacceptable adverse effects related to transfusion (e.g., volume overload and inflammatory and infectious complications) or that there may be age-related differences in the adverse-effect profile of transfusion or anemia. ... Whether transfusion thresholds should differ according to age” needs to be determined, they said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded. The trial was conducted in 19 countries, including China and India; results were consistent across study sites.
The work was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer had no relevant disclosures.
SOURCE: Mazer CD et al. N Engl J Med. 2018 Aug 26. doi:10.1056/NEJMoa1808561
REPORTING FROM THE ESC CONGRESS 2018
Key clinical point: A restrictive transfusion strategy during cardiovascular surgery, versus a more traditional liberal approach, did not increase the risk of poor outcomes at 6 months.
Major finding: At 6 months, 17.4% of patients in the restrictive arm, versus 17.1% in the liberal-threshold group, met the primary composite outcome of death from any cause, myocardial infarction, stroke, or new onset renal failure with dialysis (P = .006 for noninferiority with the restrictive approach).
Study details: Randomized, multicenter trial with over 5,000 surgery patients
Disclosures: The work was funded by the Canadian Institutes of Health Research, among others. The lead investigator had no relevant disclosures.
Source: Mazer CD et al. N Engl J Med. 2018 Aug 26. doi:10.1056/NEJMoa1808561
FFR-guided PCI in stable CAD beats medical management
DENVER – Percutaneous coronary intervention plus optimal medical therapy in stable coronary artery disease (CAD) patients with at least one coronary lesion having an abnormal fractional flow reserve measurement resulted in superior clinical outcomes, better quality of life, and virtually identical cost, compared with optimal medical management alone over 3 years of follow-up in the FAME 2 trial.
“These results reinforce the point that the greater the burden of ischemia, the greater the benefit of revascularization with PCI [percutaneous coronary intervention],” William F. Fearon, MD, said while presenting the FAME 2 findings at the Transcatheter Cardiovascular Therapeutics annual meeting.
FAME 2 was a randomized, multicenter trial designed to help bring clarity regarding the optimal treatment strategy for patients with stable angina and CAD. This is an issue surrounded by considerable controversy. The fog descended a decade ago, when the COURAGE trial created a stir with its conclusion that optimal medical therapy (OMT) alone was as good as PCI plus OMT in terms of clinical outcome and quality of life – and was considerably less expensive as well. And the British ORBITA trial, presented earlier in the same session at TCT 2017 as Dr. Fearon’s report on FAME 2, caused an uproar with its finding that PCI plus OMT was no more effective than sham PCI plus OMT in the setting of stable CAD.
However, FAME 2 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) differed from those studies in a crucial aspect: randomization in FAME 2 was restricted to patients with physiologically significant cardiac ischemia as evidenced by a fractional flow reserve (FFR) measurement of 0.80 or less.
In contrast, COURAGE and ORBITA randomized patients without FFR guidance. As a result, in those trials PCI was performed in a substantial proportion of patients who actually should not have undergone the intervention because they didn’t have physiologic evidence of clinically important ischemia. The non–physiologically based approach to PCI utilized in COURAGE and ORBITA – disappointingly commonplace in daily clinical practice – diluted any true benefit of the procedure when applied appropriately, explained Dr. Fearon, professor of medicine and director of interventional cardiology at Stanford (Calif.) University.
FAME 2 randomized 888 patients with stable single- or multivessel CAD and an FFR of 0.80 or less to PCI plus OMT or an initial strategy of OMT alone at 28 European and North American sites. The primary outcome was the rate of major adverse cardiac events – death, MI, and urgent revascularization – at 3 years. The rate was 10.1% in the PCI group, compared with 22% in the medically managed cohort, Dr. Fearon reported at the meeting sponsored by the Cardiovascular Research Foundation.
Death or MI occurred in 8.3% of the PCI group versus 10.4% in the OMT group, a trend that didn’t reach significance. Of note, however, fully 44% of patients in the OMT group crossed over to PCI during the 3-year study. In the prespecified intent-to-treat analysis they were counted in the OMT group, whereas an as-treated analysis might well have shown statistically significant reductions in death and MI in the PCI group.
The proportion of patients with class II-IV angina was significantly lower in the PCI plus medical therapy group at every time point, including 5.9% versus 15.2% for OMT alone at 1 year, 5.9% versus 12% at 2 years, and 5.2% versus 9.7% at 3 years. This was the case even though the OMT group received significantly more antianginal therapy in an effort to control symptoms.
FAME 2 featured a first-of-its-kind comprehensive cost-effectiveness analysis of OMT vs. PCI over a 3-year period. It showed that, while mean initial costs were as expected higher in the PCI group ($9,944 versus $4,440), by 3 years the cumulative costs were near identical at $16,792 in the PCI group and $16,737 in the initial OMT group. The incremental cost-effectiveness ratio for PCI, compared with OMT at 3 years was attractive at $1,600 per quality-adjusted life-year gained.
The question on TCT attendees’ minds following presentation of the bombshell ORBITA findings was, what would have happened had FAME 2 featured a sham PCI arm? Could the advantageous outcomes for the initial PCI strategy seen in FAME 2 possibly have been due to a placebo effect?
Extremely unlikely, according to Dr. Fearon. For one thing, when he and his coinvestigators broke down the FFR values in the OMT group into quintiles, they saw a clear dose-response effect: The clinical event rate rose further with worsening quintile of FFR. Also, the study endpoints were death, MI, and urgent revascularization – triggered by ACS in half of cases – which are less susceptible to a placebo effect than, say, treadmill exercise time, the primary endpoint in ORBITA.
Moreover, as noted by Gary S. Mintz, MD, who moderated a press conference highlighting the ORBITA and FAME 2 results, placebo effects don’t last for years.
“Most people would say the placebo effect wanes over time. That’s why these 3-year data, analyzed by intent-to-treat, which allow for crossovers to still be analyzed in the medical therapy arm, are pretty compelling to me,” commented Dr. Mintz, chief medical officer for the Cardiovascular Research Foundation in New York.
FAME 2 was supported by St. Jude Medical. Dr. Fearon reported receiving institutional research support from Medtronic, Abbott Vascular, ACIST Medical, CathWorks, and Edwards LifeSciences.
DENVER – Percutaneous coronary intervention plus optimal medical therapy in stable coronary artery disease (CAD) patients with at least one coronary lesion having an abnormal fractional flow reserve measurement resulted in superior clinical outcomes, better quality of life, and virtually identical cost, compared with optimal medical management alone over 3 years of follow-up in the FAME 2 trial.
“These results reinforce the point that the greater the burden of ischemia, the greater the benefit of revascularization with PCI [percutaneous coronary intervention],” William F. Fearon, MD, said while presenting the FAME 2 findings at the Transcatheter Cardiovascular Therapeutics annual meeting.
FAME 2 was a randomized, multicenter trial designed to help bring clarity regarding the optimal treatment strategy for patients with stable angina and CAD. This is an issue surrounded by considerable controversy. The fog descended a decade ago, when the COURAGE trial created a stir with its conclusion that optimal medical therapy (OMT) alone was as good as PCI plus OMT in terms of clinical outcome and quality of life – and was considerably less expensive as well. And the British ORBITA trial, presented earlier in the same session at TCT 2017 as Dr. Fearon’s report on FAME 2, caused an uproar with its finding that PCI plus OMT was no more effective than sham PCI plus OMT in the setting of stable CAD.
However, FAME 2 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) differed from those studies in a crucial aspect: randomization in FAME 2 was restricted to patients with physiologically significant cardiac ischemia as evidenced by a fractional flow reserve (FFR) measurement of 0.80 or less.
In contrast, COURAGE and ORBITA randomized patients without FFR guidance. As a result, in those trials PCI was performed in a substantial proportion of patients who actually should not have undergone the intervention because they didn’t have physiologic evidence of clinically important ischemia. The non–physiologically based approach to PCI utilized in COURAGE and ORBITA – disappointingly commonplace in daily clinical practice – diluted any true benefit of the procedure when applied appropriately, explained Dr. Fearon, professor of medicine and director of interventional cardiology at Stanford (Calif.) University.
FAME 2 randomized 888 patients with stable single- or multivessel CAD and an FFR of 0.80 or less to PCI plus OMT or an initial strategy of OMT alone at 28 European and North American sites. The primary outcome was the rate of major adverse cardiac events – death, MI, and urgent revascularization – at 3 years. The rate was 10.1% in the PCI group, compared with 22% in the medically managed cohort, Dr. Fearon reported at the meeting sponsored by the Cardiovascular Research Foundation.
Death or MI occurred in 8.3% of the PCI group versus 10.4% in the OMT group, a trend that didn’t reach significance. Of note, however, fully 44% of patients in the OMT group crossed over to PCI during the 3-year study. In the prespecified intent-to-treat analysis they were counted in the OMT group, whereas an as-treated analysis might well have shown statistically significant reductions in death and MI in the PCI group.
The proportion of patients with class II-IV angina was significantly lower in the PCI plus medical therapy group at every time point, including 5.9% versus 15.2% for OMT alone at 1 year, 5.9% versus 12% at 2 years, and 5.2% versus 9.7% at 3 years. This was the case even though the OMT group received significantly more antianginal therapy in an effort to control symptoms.
FAME 2 featured a first-of-its-kind comprehensive cost-effectiveness analysis of OMT vs. PCI over a 3-year period. It showed that, while mean initial costs were as expected higher in the PCI group ($9,944 versus $4,440), by 3 years the cumulative costs were near identical at $16,792 in the PCI group and $16,737 in the initial OMT group. The incremental cost-effectiveness ratio for PCI, compared with OMT at 3 years was attractive at $1,600 per quality-adjusted life-year gained.
The question on TCT attendees’ minds following presentation of the bombshell ORBITA findings was, what would have happened had FAME 2 featured a sham PCI arm? Could the advantageous outcomes for the initial PCI strategy seen in FAME 2 possibly have been due to a placebo effect?
Extremely unlikely, according to Dr. Fearon. For one thing, when he and his coinvestigators broke down the FFR values in the OMT group into quintiles, they saw a clear dose-response effect: The clinical event rate rose further with worsening quintile of FFR. Also, the study endpoints were death, MI, and urgent revascularization – triggered by ACS in half of cases – which are less susceptible to a placebo effect than, say, treadmill exercise time, the primary endpoint in ORBITA.
Moreover, as noted by Gary S. Mintz, MD, who moderated a press conference highlighting the ORBITA and FAME 2 results, placebo effects don’t last for years.
“Most people would say the placebo effect wanes over time. That’s why these 3-year data, analyzed by intent-to-treat, which allow for crossovers to still be analyzed in the medical therapy arm, are pretty compelling to me,” commented Dr. Mintz, chief medical officer for the Cardiovascular Research Foundation in New York.
FAME 2 was supported by St. Jude Medical. Dr. Fearon reported receiving institutional research support from Medtronic, Abbott Vascular, ACIST Medical, CathWorks, and Edwards LifeSciences.
DENVER – Percutaneous coronary intervention plus optimal medical therapy in stable coronary artery disease (CAD) patients with at least one coronary lesion having an abnormal fractional flow reserve measurement resulted in superior clinical outcomes, better quality of life, and virtually identical cost, compared with optimal medical management alone over 3 years of follow-up in the FAME 2 trial.
“These results reinforce the point that the greater the burden of ischemia, the greater the benefit of revascularization with PCI [percutaneous coronary intervention],” William F. Fearon, MD, said while presenting the FAME 2 findings at the Transcatheter Cardiovascular Therapeutics annual meeting.
FAME 2 was a randomized, multicenter trial designed to help bring clarity regarding the optimal treatment strategy for patients with stable angina and CAD. This is an issue surrounded by considerable controversy. The fog descended a decade ago, when the COURAGE trial created a stir with its conclusion that optimal medical therapy (OMT) alone was as good as PCI plus OMT in terms of clinical outcome and quality of life – and was considerably less expensive as well. And the British ORBITA trial, presented earlier in the same session at TCT 2017 as Dr. Fearon’s report on FAME 2, caused an uproar with its finding that PCI plus OMT was no more effective than sham PCI plus OMT in the setting of stable CAD.
However, FAME 2 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) differed from those studies in a crucial aspect: randomization in FAME 2 was restricted to patients with physiologically significant cardiac ischemia as evidenced by a fractional flow reserve (FFR) measurement of 0.80 or less.
In contrast, COURAGE and ORBITA randomized patients without FFR guidance. As a result, in those trials PCI was performed in a substantial proportion of patients who actually should not have undergone the intervention because they didn’t have physiologic evidence of clinically important ischemia. The non–physiologically based approach to PCI utilized in COURAGE and ORBITA – disappointingly commonplace in daily clinical practice – diluted any true benefit of the procedure when applied appropriately, explained Dr. Fearon, professor of medicine and director of interventional cardiology at Stanford (Calif.) University.
FAME 2 randomized 888 patients with stable single- or multivessel CAD and an FFR of 0.80 or less to PCI plus OMT or an initial strategy of OMT alone at 28 European and North American sites. The primary outcome was the rate of major adverse cardiac events – death, MI, and urgent revascularization – at 3 years. The rate was 10.1% in the PCI group, compared with 22% in the medically managed cohort, Dr. Fearon reported at the meeting sponsored by the Cardiovascular Research Foundation.
Death or MI occurred in 8.3% of the PCI group versus 10.4% in the OMT group, a trend that didn’t reach significance. Of note, however, fully 44% of patients in the OMT group crossed over to PCI during the 3-year study. In the prespecified intent-to-treat analysis they were counted in the OMT group, whereas an as-treated analysis might well have shown statistically significant reductions in death and MI in the PCI group.
The proportion of patients with class II-IV angina was significantly lower in the PCI plus medical therapy group at every time point, including 5.9% versus 15.2% for OMT alone at 1 year, 5.9% versus 12% at 2 years, and 5.2% versus 9.7% at 3 years. This was the case even though the OMT group received significantly more antianginal therapy in an effort to control symptoms.
FAME 2 featured a first-of-its-kind comprehensive cost-effectiveness analysis of OMT vs. PCI over a 3-year period. It showed that, while mean initial costs were as expected higher in the PCI group ($9,944 versus $4,440), by 3 years the cumulative costs were near identical at $16,792 in the PCI group and $16,737 in the initial OMT group. The incremental cost-effectiveness ratio for PCI, compared with OMT at 3 years was attractive at $1,600 per quality-adjusted life-year gained.
The question on TCT attendees’ minds following presentation of the bombshell ORBITA findings was, what would have happened had FAME 2 featured a sham PCI arm? Could the advantageous outcomes for the initial PCI strategy seen in FAME 2 possibly have been due to a placebo effect?
Extremely unlikely, according to Dr. Fearon. For one thing, when he and his coinvestigators broke down the FFR values in the OMT group into quintiles, they saw a clear dose-response effect: The clinical event rate rose further with worsening quintile of FFR. Also, the study endpoints were death, MI, and urgent revascularization – triggered by ACS in half of cases – which are less susceptible to a placebo effect than, say, treadmill exercise time, the primary endpoint in ORBITA.
Moreover, as noted by Gary S. Mintz, MD, who moderated a press conference highlighting the ORBITA and FAME 2 results, placebo effects don’t last for years.
“Most people would say the placebo effect wanes over time. That’s why these 3-year data, analyzed by intent-to-treat, which allow for crossovers to still be analyzed in the medical therapy arm, are pretty compelling to me,” commented Dr. Mintz, chief medical officer for the Cardiovascular Research Foundation in New York.
FAME 2 was supported by St. Jude Medical. Dr. Fearon reported receiving institutional research support from Medtronic, Abbott Vascular, ACIST Medical, CathWorks, and Edwards LifeSciences.
REPORTING FROM TCT 2017
Key clinical point:
Major finding: The rate of major adverse cardiac events at 3 years was 10.1% in the PCI group and 22% in the medically managed cohort.
Data source: The FAME 2 trial randomized 888 patients with stable single- or multivessel CAD and an FFR of 0.80 or less to PCI plus optimal medical therapy or an initial strategy of optimal medical management alone.
Disclosures: The trial was supported by St. Jude Medical. The presenter reported receiving institutional research support from Medtronic, Abbott Vascular, ACIST Medical, CathWorks, and Edwards LifeSciences.
Intractable VT halted by noninvasive radiation ablation
who had failed to respond to medical management and, in some cases, catheter ablation, according to a report in the New England Journal of Medicine.
During the 3 months before the procedure, the five subjects had 6,577 episodes of VT, ranging from 5 to 4,312 per patient. In addition to failing to respond to medications, three had failed catheter ablation; that procedure was contraindicated in the other two.
During the 6-week postablation blanking period, when inflammation can trigger arrhythmias, there were 680 VT episodes. After the first 6 weeks, there were four episodes over 46 patient-months, for a reduction from baseline of 99.9%.
The oldest subject, an 83-year-old woman who had had 4,312 pretreatment episodes, had a fatal stroke 3 weeks after the procedure, with no clear relationship to treatment on autopsy. In the 3 weeks before she died, her VT burden was reduced 82%.
Among the rest – all men aged 60-65 years, with pretreatment episodes numbering from 5 to 2,210 – there was no decline in left-ventricular ejection fraction during the 12-month follow-up; mild adjacent lung inflammatory changes noted at 3 months resolved during that follow-up period.
The investigators have launched a phase 1-2 trial called ENCORE-VT to further evaluate the technique.
“Although catheter ablation is the current state-of-the-art treatment for drug-refractory ventricular arrhythmias in patients with structural heart disease, it is not curative for many patients” because of inadequate ablation and other problems. Radiation ablation “has the potential to overcome these challenges. ... If a noninvasive approach to ablation of ventricular tachycardia is shown to be safe and effective, it would be a potentially important therapeutic advance,” said investigators led by Washington University cardiologist Phillip Cuculich, MD. However, “because of the novelty of noninvasive radioablation, its potential for harm, and the limited number of patients who were included in this analysis, this procedure should not be considered to be suitable for clinical use, pending the results of further research studies,” they said.
The long-term effects of high-dose radiation to previously injured heart tissue is unknown. “The volumes of myocardium that are subjected to radiotherapy in these patients (from 17 to 81 mL) are large enough that effects on specialized cardiac structures (papillary muscles, coronary arteries, conduction system, and valves) are of potential concern, as is the risk of overall effects on ventricular function, although no such effects were seen during the 12-month follow-up,” they said.
Of the four patients who were alive at 12 months, three were no longer on antiarrhythmic medications. One restarted amiodarone at 9 months after the first posttreatment episode of antitachycardia pacing. One patient had catheter ablation 4 weeks after treatment because of incomplete VT cessation, with no further episodes during follow-up.
In the 3 months before treatment, patients had an aggregate number of 55 implantable cardioverter defibrillator shocks and 6,577 episodes of antitachycardia pacing. Over the following 12 months, there was just one shock and three pacing episodes. After the blanking period, one patient had three VT episodes, one had one, and two didn’t have any, including a man who had 2,210 in the 3 months before treatment; he was the subject who had the secondary catheter ablation.
The work was funded by the Barnes-Jewish Hospital Foundation, Washington University, and the National Institutes of Health. Dr. Cuculich and another author have a patent pending on electrocardiographic imaging and stereotactic body radiation therapy for cardiac arrhythmia. Several authors reported receiving personal fees from and other involvement with a number of companies, including ViewRay, Varian, Elekta, and Medtronic.
SOURCE: Cuculich P et al. N Engl J Med. 2017 Dec 13. doi: 10.1056/NEJMoa1613773.
who had failed to respond to medical management and, in some cases, catheter ablation, according to a report in the New England Journal of Medicine.
During the 3 months before the procedure, the five subjects had 6,577 episodes of VT, ranging from 5 to 4,312 per patient. In addition to failing to respond to medications, three had failed catheter ablation; that procedure was contraindicated in the other two.
During the 6-week postablation blanking period, when inflammation can trigger arrhythmias, there were 680 VT episodes. After the first 6 weeks, there were four episodes over 46 patient-months, for a reduction from baseline of 99.9%.
The oldest subject, an 83-year-old woman who had had 4,312 pretreatment episodes, had a fatal stroke 3 weeks after the procedure, with no clear relationship to treatment on autopsy. In the 3 weeks before she died, her VT burden was reduced 82%.
Among the rest – all men aged 60-65 years, with pretreatment episodes numbering from 5 to 2,210 – there was no decline in left-ventricular ejection fraction during the 12-month follow-up; mild adjacent lung inflammatory changes noted at 3 months resolved during that follow-up period.
The investigators have launched a phase 1-2 trial called ENCORE-VT to further evaluate the technique.
“Although catheter ablation is the current state-of-the-art treatment for drug-refractory ventricular arrhythmias in patients with structural heart disease, it is not curative for many patients” because of inadequate ablation and other problems. Radiation ablation “has the potential to overcome these challenges. ... If a noninvasive approach to ablation of ventricular tachycardia is shown to be safe and effective, it would be a potentially important therapeutic advance,” said investigators led by Washington University cardiologist Phillip Cuculich, MD. However, “because of the novelty of noninvasive radioablation, its potential for harm, and the limited number of patients who were included in this analysis, this procedure should not be considered to be suitable for clinical use, pending the results of further research studies,” they said.
The long-term effects of high-dose radiation to previously injured heart tissue is unknown. “The volumes of myocardium that are subjected to radiotherapy in these patients (from 17 to 81 mL) are large enough that effects on specialized cardiac structures (papillary muscles, coronary arteries, conduction system, and valves) are of potential concern, as is the risk of overall effects on ventricular function, although no such effects were seen during the 12-month follow-up,” they said.
Of the four patients who were alive at 12 months, three were no longer on antiarrhythmic medications. One restarted amiodarone at 9 months after the first posttreatment episode of antitachycardia pacing. One patient had catheter ablation 4 weeks after treatment because of incomplete VT cessation, with no further episodes during follow-up.
In the 3 months before treatment, patients had an aggregate number of 55 implantable cardioverter defibrillator shocks and 6,577 episodes of antitachycardia pacing. Over the following 12 months, there was just one shock and three pacing episodes. After the blanking period, one patient had three VT episodes, one had one, and two didn’t have any, including a man who had 2,210 in the 3 months before treatment; he was the subject who had the secondary catheter ablation.
The work was funded by the Barnes-Jewish Hospital Foundation, Washington University, and the National Institutes of Health. Dr. Cuculich and another author have a patent pending on electrocardiographic imaging and stereotactic body radiation therapy for cardiac arrhythmia. Several authors reported receiving personal fees from and other involvement with a number of companies, including ViewRay, Varian, Elekta, and Medtronic.
SOURCE: Cuculich P et al. N Engl J Med. 2017 Dec 13. doi: 10.1056/NEJMoa1613773.
who had failed to respond to medical management and, in some cases, catheter ablation, according to a report in the New England Journal of Medicine.
During the 3 months before the procedure, the five subjects had 6,577 episodes of VT, ranging from 5 to 4,312 per patient. In addition to failing to respond to medications, three had failed catheter ablation; that procedure was contraindicated in the other two.
During the 6-week postablation blanking period, when inflammation can trigger arrhythmias, there were 680 VT episodes. After the first 6 weeks, there were four episodes over 46 patient-months, for a reduction from baseline of 99.9%.
The oldest subject, an 83-year-old woman who had had 4,312 pretreatment episodes, had a fatal stroke 3 weeks after the procedure, with no clear relationship to treatment on autopsy. In the 3 weeks before she died, her VT burden was reduced 82%.
Among the rest – all men aged 60-65 years, with pretreatment episodes numbering from 5 to 2,210 – there was no decline in left-ventricular ejection fraction during the 12-month follow-up; mild adjacent lung inflammatory changes noted at 3 months resolved during that follow-up period.
The investigators have launched a phase 1-2 trial called ENCORE-VT to further evaluate the technique.
“Although catheter ablation is the current state-of-the-art treatment for drug-refractory ventricular arrhythmias in patients with structural heart disease, it is not curative for many patients” because of inadequate ablation and other problems. Radiation ablation “has the potential to overcome these challenges. ... If a noninvasive approach to ablation of ventricular tachycardia is shown to be safe and effective, it would be a potentially important therapeutic advance,” said investigators led by Washington University cardiologist Phillip Cuculich, MD. However, “because of the novelty of noninvasive radioablation, its potential for harm, and the limited number of patients who were included in this analysis, this procedure should not be considered to be suitable for clinical use, pending the results of further research studies,” they said.
The long-term effects of high-dose radiation to previously injured heart tissue is unknown. “The volumes of myocardium that are subjected to radiotherapy in these patients (from 17 to 81 mL) are large enough that effects on specialized cardiac structures (papillary muscles, coronary arteries, conduction system, and valves) are of potential concern, as is the risk of overall effects on ventricular function, although no such effects were seen during the 12-month follow-up,” they said.
Of the four patients who were alive at 12 months, three were no longer on antiarrhythmic medications. One restarted amiodarone at 9 months after the first posttreatment episode of antitachycardia pacing. One patient had catheter ablation 4 weeks after treatment because of incomplete VT cessation, with no further episodes during follow-up.
In the 3 months before treatment, patients had an aggregate number of 55 implantable cardioverter defibrillator shocks and 6,577 episodes of antitachycardia pacing. Over the following 12 months, there was just one shock and three pacing episodes. After the blanking period, one patient had three VT episodes, one had one, and two didn’t have any, including a man who had 2,210 in the 3 months before treatment; he was the subject who had the secondary catheter ablation.
The work was funded by the Barnes-Jewish Hospital Foundation, Washington University, and the National Institutes of Health. Dr. Cuculich and another author have a patent pending on electrocardiographic imaging and stereotactic body radiation therapy for cardiac arrhythmia. Several authors reported receiving personal fees from and other involvement with a number of companies, including ViewRay, Varian, Elekta, and Medtronic.
SOURCE: Cuculich P et al. N Engl J Med. 2017 Dec 13. doi: 10.1056/NEJMoa1613773.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: A one-time dose of radiation to arrhythmogenic scars nearly eliminated ventricular tachycardia in five patients who had failed to respond to medical management and, in some cases, catheter ablation.
Major finding: VT episodes were slashed by 99.9% from baseline.
Study details: Case series in 5 patients
Disclosures: The work was funded by the Barnes-Jewish Hospital Foundation, Washington University in St. Louis, and the National Institutes of Health. Dr. Cuculich and another author have a patent pending on electrocardiographic imaging and stereotactic body radiation therapy for cardiac arrhythmia. Several authors reported receiving personal fees from and other involvement with a number of companies, including ViewRay, Varian, Elekta, and Medtronic.
Source: Cuculich P et al. N Engl J Med. 2017 Dec 13. doi: 10.1056/NEJMoa1613773
Novel metabolic biomarkers linked to CHD
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with hazard ratios ranging from 1.09 to 1.13.
Data source: More than 10,000 subjects in the BiomarCaRE consortium.
Disclosures: BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
EXCEL: Quality of life better after PCI than CABG
DENVER – Several key validated measures of health status were significantly more favorable a full year after percutaneous coronary intervention using an everolimus-eluting stent than with coronary artery bypass surgery in patients with unprotected left main CAD in the prespecified quality-of-life analysis of the landmark EXCEL trial.
By 3 years of follow-up, there was no longer a difference between the PCI and CABG groups in terms of the various quality-of-life measures, Suzanne J. Baron, MD, reported at the Transcatheter Cardiovascular Therapeutics annual educational meeting. Nor as previously reported was there any significant difference in the primary composite endpoint comprised of all-cause mortality, stroke, or MI.
“My take away from this is that these results provide an ideal opportunity to give patients a choice about which choice they would want: An earlier recovery with angioplasty versus really similar outcomes long-term with either procedure. For me, these EXCEL results make me feel that angioplasty for less complex coronary disease is really probably the preferred option,” said John A. Spertus, MD, director of health outcomes research at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City.
“The faster recovery with PCI, the similar angina relief after 3 years, and also the less depression with PCI, which is an important finding, I think – all this goes in favor of PCI for left main disease,” commented Evald H. Christiansen, MD, a cardiologist at Aarhus (Denmark) University and senior investigator in the NOBLE trial (Lancet. 2016 Dec 3;388[10061]:2743-52), which randomized patients to CABG or a stent that’s no longer marketed.
The previously published clinical outcomes of EXCEL (N Engl J Med. 2016 Dec 8;375[23]:2223-35) were based upon a median 3 years of follow-up. Dr. Baron presented updated outcomes in which all study participants had completed the full 3 years of follow-up. The results were little changed: The primary composite endpoint of all-cause mortality, stroke, or MI occurred in 15.2% of the group treated with the everolimus-eluting Xience stent and was closely similar at 14.7% of the CABG patients, while the 12.5% repeat revascularization rate in the PCI arm was significantly greater than the 7.4% rate with CABG.
But the prespecified EXCEL quality-of-life substudy with assessments at baseline, 1 month, 1 year, and 3 years in 1,788 participants is all new information. Among the highlights: The proportion of patients with clinically significant depression as defined by a Patient Health Questionnaire 8 (PHQ-8) score of 10 or more was 21% at baseline in both groups; 8% in the PCI group, compared with 19% in the CABG arm at 1 month; and 8% in the PCI arm versus 12% with CABG at 12 months of follow-up, with the differences at both time points being significant. By 3 years, the rate was 8%-9% in both groups, reported Dr. Baron of Saint Luke’s Mid America Health Institute and the University of Missouri-Kansas City.
“We now have a new treatment for depression: PCI,” quipped session moderator Gregg W. Stone, MD, professor of medicine at Columbia University in New York, who was lead investigator in EXCEL.
Also, scores on the SF-12 physical summary scale improved sharply from a baseline of 39 points in the PCI group during the first month of follow-up while worsening in the CABG group, such that at 1 month the between-group difference averaged 8.2 points. The gap narrowed over the next 11 months, and by 1 year the CABG patients had caught up.
Scores on the Seattle Angina Questionnaire and the Rose Dyspnea Scale were significantly better in the PCI group than the CABG arm at 1 month, but at 12 and 36 months the two groups were indistinguishable in these domains.
Dr. Spertus, who is credited with inventing both the Seattle Angina Questionnaire and the Kansas City Cardiomyopathy Questionnaire, said that in the context of EXCEL he puts more stock in the SF-12 and PHQ-8 results than the angina and dyspnea measures.
Jonathan Hill, MD, an interventional cardiologist at King’s College London, said the EXCEL quality-of-life substudy provides a valuable picture of the real-life impact of sternotomy.
“We mustn’t underplay that, the months and even up to a year of your life for recovery from the revascularization procedure, compared with days of recovery time with PCI. Patients want the option of PCI if it’s available. This data really vindicates that decision making,” he said.
“I think we minimize the recovery period from CABG. People talk a lot about outcomes at 3 years and 5 years, but look at this prolonged recovery. I think that’s very, very important,” said Dr. Grines, chair of cardiology at Hofstra University, Hempstead, N.Y.
The updated full 3-year data show a trend, albeit not statistically significant, for higher all-cause mortality in the PCI group, by a margin of 8% versus 5.8% with CABG. When asked about it, Dr. Baron said she and her coinvestigators took a closer look and determined that the cardiovascular death rate was virtually identical in the two groups.
“You have to wonder if this was just a random signal regarding the non-cardiovascular-associated deaths,” she added.
The EXCEL trial was supported by Abbott Vascular. Dr. Baron reported serving as a consultant to Edwards Lifesciences and St. Jude Medical.
DENVER – Several key validated measures of health status were significantly more favorable a full year after percutaneous coronary intervention using an everolimus-eluting stent than with coronary artery bypass surgery in patients with unprotected left main CAD in the prespecified quality-of-life analysis of the landmark EXCEL trial.
By 3 years of follow-up, there was no longer a difference between the PCI and CABG groups in terms of the various quality-of-life measures, Suzanne J. Baron, MD, reported at the Transcatheter Cardiovascular Therapeutics annual educational meeting. Nor as previously reported was there any significant difference in the primary composite endpoint comprised of all-cause mortality, stroke, or MI.
“My take away from this is that these results provide an ideal opportunity to give patients a choice about which choice they would want: An earlier recovery with angioplasty versus really similar outcomes long-term with either procedure. For me, these EXCEL results make me feel that angioplasty for less complex coronary disease is really probably the preferred option,” said John A. Spertus, MD, director of health outcomes research at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City.
“The faster recovery with PCI, the similar angina relief after 3 years, and also the less depression with PCI, which is an important finding, I think – all this goes in favor of PCI for left main disease,” commented Evald H. Christiansen, MD, a cardiologist at Aarhus (Denmark) University and senior investigator in the NOBLE trial (Lancet. 2016 Dec 3;388[10061]:2743-52), which randomized patients to CABG or a stent that’s no longer marketed.
The previously published clinical outcomes of EXCEL (N Engl J Med. 2016 Dec 8;375[23]:2223-35) were based upon a median 3 years of follow-up. Dr. Baron presented updated outcomes in which all study participants had completed the full 3 years of follow-up. The results were little changed: The primary composite endpoint of all-cause mortality, stroke, or MI occurred in 15.2% of the group treated with the everolimus-eluting Xience stent and was closely similar at 14.7% of the CABG patients, while the 12.5% repeat revascularization rate in the PCI arm was significantly greater than the 7.4% rate with CABG.
But the prespecified EXCEL quality-of-life substudy with assessments at baseline, 1 month, 1 year, and 3 years in 1,788 participants is all new information. Among the highlights: The proportion of patients with clinically significant depression as defined by a Patient Health Questionnaire 8 (PHQ-8) score of 10 or more was 21% at baseline in both groups; 8% in the PCI group, compared with 19% in the CABG arm at 1 month; and 8% in the PCI arm versus 12% with CABG at 12 months of follow-up, with the differences at both time points being significant. By 3 years, the rate was 8%-9% in both groups, reported Dr. Baron of Saint Luke’s Mid America Health Institute and the University of Missouri-Kansas City.
“We now have a new treatment for depression: PCI,” quipped session moderator Gregg W. Stone, MD, professor of medicine at Columbia University in New York, who was lead investigator in EXCEL.
Also, scores on the SF-12 physical summary scale improved sharply from a baseline of 39 points in the PCI group during the first month of follow-up while worsening in the CABG group, such that at 1 month the between-group difference averaged 8.2 points. The gap narrowed over the next 11 months, and by 1 year the CABG patients had caught up.
Scores on the Seattle Angina Questionnaire and the Rose Dyspnea Scale were significantly better in the PCI group than the CABG arm at 1 month, but at 12 and 36 months the two groups were indistinguishable in these domains.
Dr. Spertus, who is credited with inventing both the Seattle Angina Questionnaire and the Kansas City Cardiomyopathy Questionnaire, said that in the context of EXCEL he puts more stock in the SF-12 and PHQ-8 results than the angina and dyspnea measures.
Jonathan Hill, MD, an interventional cardiologist at King’s College London, said the EXCEL quality-of-life substudy provides a valuable picture of the real-life impact of sternotomy.
“We mustn’t underplay that, the months and even up to a year of your life for recovery from the revascularization procedure, compared with days of recovery time with PCI. Patients want the option of PCI if it’s available. This data really vindicates that decision making,” he said.
“I think we minimize the recovery period from CABG. People talk a lot about outcomes at 3 years and 5 years, but look at this prolonged recovery. I think that’s very, very important,” said Dr. Grines, chair of cardiology at Hofstra University, Hempstead, N.Y.
The updated full 3-year data show a trend, albeit not statistically significant, for higher all-cause mortality in the PCI group, by a margin of 8% versus 5.8% with CABG. When asked about it, Dr. Baron said she and her coinvestigators took a closer look and determined that the cardiovascular death rate was virtually identical in the two groups.
“You have to wonder if this was just a random signal regarding the non-cardiovascular-associated deaths,” she added.
The EXCEL trial was supported by Abbott Vascular. Dr. Baron reported serving as a consultant to Edwards Lifesciences and St. Jude Medical.
DENVER – Several key validated measures of health status were significantly more favorable a full year after percutaneous coronary intervention using an everolimus-eluting stent than with coronary artery bypass surgery in patients with unprotected left main CAD in the prespecified quality-of-life analysis of the landmark EXCEL trial.
By 3 years of follow-up, there was no longer a difference between the PCI and CABG groups in terms of the various quality-of-life measures, Suzanne J. Baron, MD, reported at the Transcatheter Cardiovascular Therapeutics annual educational meeting. Nor as previously reported was there any significant difference in the primary composite endpoint comprised of all-cause mortality, stroke, or MI.
“My take away from this is that these results provide an ideal opportunity to give patients a choice about which choice they would want: An earlier recovery with angioplasty versus really similar outcomes long-term with either procedure. For me, these EXCEL results make me feel that angioplasty for less complex coronary disease is really probably the preferred option,” said John A. Spertus, MD, director of health outcomes research at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City.
“The faster recovery with PCI, the similar angina relief after 3 years, and also the less depression with PCI, which is an important finding, I think – all this goes in favor of PCI for left main disease,” commented Evald H. Christiansen, MD, a cardiologist at Aarhus (Denmark) University and senior investigator in the NOBLE trial (Lancet. 2016 Dec 3;388[10061]:2743-52), which randomized patients to CABG or a stent that’s no longer marketed.
The previously published clinical outcomes of EXCEL (N Engl J Med. 2016 Dec 8;375[23]:2223-35) were based upon a median 3 years of follow-up. Dr. Baron presented updated outcomes in which all study participants had completed the full 3 years of follow-up. The results were little changed: The primary composite endpoint of all-cause mortality, stroke, or MI occurred in 15.2% of the group treated with the everolimus-eluting Xience stent and was closely similar at 14.7% of the CABG patients, while the 12.5% repeat revascularization rate in the PCI arm was significantly greater than the 7.4% rate with CABG.
But the prespecified EXCEL quality-of-life substudy with assessments at baseline, 1 month, 1 year, and 3 years in 1,788 participants is all new information. Among the highlights: The proportion of patients with clinically significant depression as defined by a Patient Health Questionnaire 8 (PHQ-8) score of 10 or more was 21% at baseline in both groups; 8% in the PCI group, compared with 19% in the CABG arm at 1 month; and 8% in the PCI arm versus 12% with CABG at 12 months of follow-up, with the differences at both time points being significant. By 3 years, the rate was 8%-9% in both groups, reported Dr. Baron of Saint Luke’s Mid America Health Institute and the University of Missouri-Kansas City.
“We now have a new treatment for depression: PCI,” quipped session moderator Gregg W. Stone, MD, professor of medicine at Columbia University in New York, who was lead investigator in EXCEL.
Also, scores on the SF-12 physical summary scale improved sharply from a baseline of 39 points in the PCI group during the first month of follow-up while worsening in the CABG group, such that at 1 month the between-group difference averaged 8.2 points. The gap narrowed over the next 11 months, and by 1 year the CABG patients had caught up.
Scores on the Seattle Angina Questionnaire and the Rose Dyspnea Scale were significantly better in the PCI group than the CABG arm at 1 month, but at 12 and 36 months the two groups were indistinguishable in these domains.
Dr. Spertus, who is credited with inventing both the Seattle Angina Questionnaire and the Kansas City Cardiomyopathy Questionnaire, said that in the context of EXCEL he puts more stock in the SF-12 and PHQ-8 results than the angina and dyspnea measures.
Jonathan Hill, MD, an interventional cardiologist at King’s College London, said the EXCEL quality-of-life substudy provides a valuable picture of the real-life impact of sternotomy.
“We mustn’t underplay that, the months and even up to a year of your life for recovery from the revascularization procedure, compared with days of recovery time with PCI. Patients want the option of PCI if it’s available. This data really vindicates that decision making,” he said.
“I think we minimize the recovery period from CABG. People talk a lot about outcomes at 3 years and 5 years, but look at this prolonged recovery. I think that’s very, very important,” said Dr. Grines, chair of cardiology at Hofstra University, Hempstead, N.Y.
The updated full 3-year data show a trend, albeit not statistically significant, for higher all-cause mortality in the PCI group, by a margin of 8% versus 5.8% with CABG. When asked about it, Dr. Baron said she and her coinvestigators took a closer look and determined that the cardiovascular death rate was virtually identical in the two groups.
“You have to wonder if this was just a random signal regarding the non-cardiovascular-associated deaths,” she added.
The EXCEL trial was supported by Abbott Vascular. Dr. Baron reported serving as a consultant to Edwards Lifesciences and St. Jude Medical.
AT TCT 2017
Key clinical point:
Major finding: The rate of clinically significant depression 1 year after revascularization of unprotected left main CAD via PCI using an everolimus-eluting stent was 8%, significantly lower than the 12% rate in CABG patients.
Data source: This was a prespecified prospective quality-of-life substudy featuring 3 years of follow-up in 1,788 patients randomized to PCI or CABG.
Disclosures: The EXCEL trial was supported by Abbott Vascular. The presenter reported serving as a consultant to Edwards Lifesciences and St. Jude Medical.
Bilateral ACP shown similar to unilateral in arch replacement study
What may be the largest study comparing unilateral and bilateral antegrade cerebral perfusion during total arch replacement for type A aortic dissection has reported that outcomes between the two approaches are comparable, although the bilateral approach showed some advantages during the operation itself, investigators from China reported in the Journal of Thoracic and Cardiovascular Surgery (2017;154:767-75).
The effectiveness of bilateral antegrade cerebral perfusion (b-ACP) vs. unilateral antegrade cerebral perfusion (u-ACP) has been the focus of extensive debate, lead study author Guang Tong, MD, of the Guangzhou (China) General Hospital, and coauthors said. They compared outcomes in six different metrics, ranging from cardiopulmonary bypass time to length of stay (LOS) in the ICU and hospital, in 203 patients with type A aortic dissection who had total aortic arch replacement with hypothermic circulatory arrest over an 8-year period ending in August 2014; 121 had b-ACP and 82 had u-ACP. “The issue of u-ACP vs. b-ACP has been examined in aortic arch surgery, but few reports have focused on type A aortic dissection,” Dr. Tong and coauthors wrote.
They acknowledged that some surgeons are reluctant to use b-ACP because of its complexity, but their study found no increase in cross-clamp time, cardiopulmonary bypass time, or surgery time in the b-ACP group. They cited another reason surgeons give for avoiding b-ACP: the risk of embolic injury caused by canulating the left common carotid artery in an atheromatous aorta. “In the present study, this risk was avoided by attaching the left common carotid artery to the four-branched prosthetic graft for left hemisphere perfusion,” Dr. Tong and coauthors wrote.
Key outcomes that the researchers found not statistically significant were:
- Overall 30-day mortality (11.6% for b-ACP vs. 20.7% for u-ACP; P = .075).
- Prevalence of postoperative permanent neurologic dysfunction (8.4% vs. 16.9%; P = .091).
- Average ICU LOS (16 ± 17.75 days vs. 17 ± 11.5 days, P =.454).
- Average hospital LOS (26.5 ± 20.6 days vs. 24.8 ± 10.3 days, P = .434).
However, average ventilation time was lower in the b-ACP group (95.5 hours vs. 147 hours; P less than or equal to.001).
Dr. Tong and coauthors used an aggressive approach, as advocated by Dhaval Trivedi, MD, and colleagues (Ann Thorac Surg. 2016;101:896-903), and had a total arch replacement rate of 57.8%. This rate is higher than most published series in the west but comparable to other studies from China, perhaps because of the relatively young age of this study cohort – an average age of 51 years – compared to data sets other studies have used. Dr. Tong and coauthors used a b-ACP strategy that established both cerebral perfusion routes before circulatory arrest.
Rates of the following complications were also not significantly different across the study population: paraplegia (2.8% for b-ACP vs. 3.1% for u-ACP), temporary neurologic dysfunction (4.7% vs. 9.2%), permanent neurologic dysfunction (8.4% vs. 16.9%), renal failure (18% vs. 23.1%), reoperation for bleeding (2.8% vs. 4.6%), and mediastinal infection (3.7% vs. 6.2%).
While b-ACP patients did not have a statistically significant lower incidence of TND, Dr. Tong and coauthors noted the shorter time on ventilation and significantly lower tracheostomy rates for the b-ACP patients, 3.7% vs. 16.9% for the u-ACP group (P = .003). “In our institute, protocols to wean patients from ventilation were normally initiated as soon as consciousness was regained,” Dr. Tong and coauthors wrote.
Among the study limits Dr. Tong and coauthors acknowledged were its retrospective, nonrandomized, single-center nature, and the fact that the surgeries were performed over an 8-year period representing different eras.
The investigators reported having no relevant financial disclosures.
The study by Dr. Tong and coauthors adds to the discussion between the “bilateralists” and “unilateralists,” as Jean Bachet, MD, called the two prevailing camps on cerebral perfusion strategies in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:765-6). And while most clinical reports find outcomes similar between the two approaches, the evidence favors the bilateral approach for total arch replacement.
Citing how the study implied mortality and neurologic morbidity rates almost half those for unilateral perfusion, but not reaching statistical significance, Dr. Bachet said, “The statisticians would say that this is only a trend and no proof, but some trends might be indicative, and significance might only be a matter of number in each arm of the comparison.”
Dr. Bachet raised a question about the unilateral approach – that once the arch is opened it takes a minute or so to insert the small balloon canula into the origin of the left carotid artery or divided vessel and start bilateral perfusion. “A major question arises,” said Dr. Bachet: “Why should we expose our patients to any undue risk just to avoid a simple maneuver, to spare a little time, or for any other fancy and questionable reason?”
Cardiologists have raised that question for more than 20 years. Said Dr. Bachet, “We still wait for the answer.”
Dr. Bachet is a cardiac surgeon in Surgenes, France. He reported having no financial relationships to disclose.
The study by Dr. Tong and coauthors adds to the discussion between the “bilateralists” and “unilateralists,” as Jean Bachet, MD, called the two prevailing camps on cerebral perfusion strategies in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:765-6). And while most clinical reports find outcomes similar between the two approaches, the evidence favors the bilateral approach for total arch replacement.
Citing how the study implied mortality and neurologic morbidity rates almost half those for unilateral perfusion, but not reaching statistical significance, Dr. Bachet said, “The statisticians would say that this is only a trend and no proof, but some trends might be indicative, and significance might only be a matter of number in each arm of the comparison.”
Dr. Bachet raised a question about the unilateral approach – that once the arch is opened it takes a minute or so to insert the small balloon canula into the origin of the left carotid artery or divided vessel and start bilateral perfusion. “A major question arises,” said Dr. Bachet: “Why should we expose our patients to any undue risk just to avoid a simple maneuver, to spare a little time, or for any other fancy and questionable reason?”
Cardiologists have raised that question for more than 20 years. Said Dr. Bachet, “We still wait for the answer.”
Dr. Bachet is a cardiac surgeon in Surgenes, France. He reported having no financial relationships to disclose.
The study by Dr. Tong and coauthors adds to the discussion between the “bilateralists” and “unilateralists,” as Jean Bachet, MD, called the two prevailing camps on cerebral perfusion strategies in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:765-6). And while most clinical reports find outcomes similar between the two approaches, the evidence favors the bilateral approach for total arch replacement.
Citing how the study implied mortality and neurologic morbidity rates almost half those for unilateral perfusion, but not reaching statistical significance, Dr. Bachet said, “The statisticians would say that this is only a trend and no proof, but some trends might be indicative, and significance might only be a matter of number in each arm of the comparison.”
Dr. Bachet raised a question about the unilateral approach – that once the arch is opened it takes a minute or so to insert the small balloon canula into the origin of the left carotid artery or divided vessel and start bilateral perfusion. “A major question arises,” said Dr. Bachet: “Why should we expose our patients to any undue risk just to avoid a simple maneuver, to spare a little time, or for any other fancy and questionable reason?”
Cardiologists have raised that question for more than 20 years. Said Dr. Bachet, “We still wait for the answer.”
Dr. Bachet is a cardiac surgeon in Surgenes, France. He reported having no financial relationships to disclose.
What may be the largest study comparing unilateral and bilateral antegrade cerebral perfusion during total arch replacement for type A aortic dissection has reported that outcomes between the two approaches are comparable, although the bilateral approach showed some advantages during the operation itself, investigators from China reported in the Journal of Thoracic and Cardiovascular Surgery (2017;154:767-75).
The effectiveness of bilateral antegrade cerebral perfusion (b-ACP) vs. unilateral antegrade cerebral perfusion (u-ACP) has been the focus of extensive debate, lead study author Guang Tong, MD, of the Guangzhou (China) General Hospital, and coauthors said. They compared outcomes in six different metrics, ranging from cardiopulmonary bypass time to length of stay (LOS) in the ICU and hospital, in 203 patients with type A aortic dissection who had total aortic arch replacement with hypothermic circulatory arrest over an 8-year period ending in August 2014; 121 had b-ACP and 82 had u-ACP. “The issue of u-ACP vs. b-ACP has been examined in aortic arch surgery, but few reports have focused on type A aortic dissection,” Dr. Tong and coauthors wrote.
They acknowledged that some surgeons are reluctant to use b-ACP because of its complexity, but their study found no increase in cross-clamp time, cardiopulmonary bypass time, or surgery time in the b-ACP group. They cited another reason surgeons give for avoiding b-ACP: the risk of embolic injury caused by canulating the left common carotid artery in an atheromatous aorta. “In the present study, this risk was avoided by attaching the left common carotid artery to the four-branched prosthetic graft for left hemisphere perfusion,” Dr. Tong and coauthors wrote.
Key outcomes that the researchers found not statistically significant were:
- Overall 30-day mortality (11.6% for b-ACP vs. 20.7% for u-ACP; P = .075).
- Prevalence of postoperative permanent neurologic dysfunction (8.4% vs. 16.9%; P = .091).
- Average ICU LOS (16 ± 17.75 days vs. 17 ± 11.5 days, P =.454).
- Average hospital LOS (26.5 ± 20.6 days vs. 24.8 ± 10.3 days, P = .434).
However, average ventilation time was lower in the b-ACP group (95.5 hours vs. 147 hours; P less than or equal to.001).
Dr. Tong and coauthors used an aggressive approach, as advocated by Dhaval Trivedi, MD, and colleagues (Ann Thorac Surg. 2016;101:896-903), and had a total arch replacement rate of 57.8%. This rate is higher than most published series in the west but comparable to other studies from China, perhaps because of the relatively young age of this study cohort – an average age of 51 years – compared to data sets other studies have used. Dr. Tong and coauthors used a b-ACP strategy that established both cerebral perfusion routes before circulatory arrest.
Rates of the following complications were also not significantly different across the study population: paraplegia (2.8% for b-ACP vs. 3.1% for u-ACP), temporary neurologic dysfunction (4.7% vs. 9.2%), permanent neurologic dysfunction (8.4% vs. 16.9%), renal failure (18% vs. 23.1%), reoperation for bleeding (2.8% vs. 4.6%), and mediastinal infection (3.7% vs. 6.2%).
While b-ACP patients did not have a statistically significant lower incidence of TND, Dr. Tong and coauthors noted the shorter time on ventilation and significantly lower tracheostomy rates for the b-ACP patients, 3.7% vs. 16.9% for the u-ACP group (P = .003). “In our institute, protocols to wean patients from ventilation were normally initiated as soon as consciousness was regained,” Dr. Tong and coauthors wrote.
Among the study limits Dr. Tong and coauthors acknowledged were its retrospective, nonrandomized, single-center nature, and the fact that the surgeries were performed over an 8-year period representing different eras.
The investigators reported having no relevant financial disclosures.
What may be the largest study comparing unilateral and bilateral antegrade cerebral perfusion during total arch replacement for type A aortic dissection has reported that outcomes between the two approaches are comparable, although the bilateral approach showed some advantages during the operation itself, investigators from China reported in the Journal of Thoracic and Cardiovascular Surgery (2017;154:767-75).
The effectiveness of bilateral antegrade cerebral perfusion (b-ACP) vs. unilateral antegrade cerebral perfusion (u-ACP) has been the focus of extensive debate, lead study author Guang Tong, MD, of the Guangzhou (China) General Hospital, and coauthors said. They compared outcomes in six different metrics, ranging from cardiopulmonary bypass time to length of stay (LOS) in the ICU and hospital, in 203 patients with type A aortic dissection who had total aortic arch replacement with hypothermic circulatory arrest over an 8-year period ending in August 2014; 121 had b-ACP and 82 had u-ACP. “The issue of u-ACP vs. b-ACP has been examined in aortic arch surgery, but few reports have focused on type A aortic dissection,” Dr. Tong and coauthors wrote.
They acknowledged that some surgeons are reluctant to use b-ACP because of its complexity, but their study found no increase in cross-clamp time, cardiopulmonary bypass time, or surgery time in the b-ACP group. They cited another reason surgeons give for avoiding b-ACP: the risk of embolic injury caused by canulating the left common carotid artery in an atheromatous aorta. “In the present study, this risk was avoided by attaching the left common carotid artery to the four-branched prosthetic graft for left hemisphere perfusion,” Dr. Tong and coauthors wrote.
Key outcomes that the researchers found not statistically significant were:
- Overall 30-day mortality (11.6% for b-ACP vs. 20.7% for u-ACP; P = .075).
- Prevalence of postoperative permanent neurologic dysfunction (8.4% vs. 16.9%; P = .091).
- Average ICU LOS (16 ± 17.75 days vs. 17 ± 11.5 days, P =.454).
- Average hospital LOS (26.5 ± 20.6 days vs. 24.8 ± 10.3 days, P = .434).
However, average ventilation time was lower in the b-ACP group (95.5 hours vs. 147 hours; P less than or equal to.001).
Dr. Tong and coauthors used an aggressive approach, as advocated by Dhaval Trivedi, MD, and colleagues (Ann Thorac Surg. 2016;101:896-903), and had a total arch replacement rate of 57.8%. This rate is higher than most published series in the west but comparable to other studies from China, perhaps because of the relatively young age of this study cohort – an average age of 51 years – compared to data sets other studies have used. Dr. Tong and coauthors used a b-ACP strategy that established both cerebral perfusion routes before circulatory arrest.
Rates of the following complications were also not significantly different across the study population: paraplegia (2.8% for b-ACP vs. 3.1% for u-ACP), temporary neurologic dysfunction (4.7% vs. 9.2%), permanent neurologic dysfunction (8.4% vs. 16.9%), renal failure (18% vs. 23.1%), reoperation for bleeding (2.8% vs. 4.6%), and mediastinal infection (3.7% vs. 6.2%).
While b-ACP patients did not have a statistically significant lower incidence of TND, Dr. Tong and coauthors noted the shorter time on ventilation and significantly lower tracheostomy rates for the b-ACP patients, 3.7% vs. 16.9% for the u-ACP group (P = .003). “In our institute, protocols to wean patients from ventilation were normally initiated as soon as consciousness was regained,” Dr. Tong and coauthors wrote.
Among the study limits Dr. Tong and coauthors acknowledged were its retrospective, nonrandomized, single-center nature, and the fact that the surgeries were performed over an 8-year period representing different eras.
The investigators reported having no relevant financial disclosures.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Clinical outcomes were comparable between groups who underwent unilateral or bilateral antegrade cerebral perfusion in total arch replacement for type A aortic dissection.
Major finding: Overall 30-day mortality was 11.6% in the bilateral ACP group vs. 20.7% for unilateral ACP (P =.075).
Data source: Population of 203 patients who had aortic arch replacement surgery for type A aortic dissection between September 2006 and August 2014.
Disclosures: Dr. Tong and coauthors reported having no relevant financial disclosures.
Restrictive transfusion strategy safe in cardiac surgery
ANAHEIM, CALIF. – Waiting to transfuse heart surgery patients until their hemoglobin drops below 7.5 g/dL is just as safe as transfusing them when their hemoglobin drops below 9.5 g/dL, and it saves a lot of blood, according to the TRICS III randomized, noninferiority trial of nearly 5,000 patients undergoing cardiac surgery with cardiopulmonary bypass.
Cardiac surgeons have been moving to more restrictive transfusion policies following reports of worse postoperative survival when patients are transfused. However, there are concerns about safety and uncertainty over whether it’s the transfusions themselves that are problematic or whether transfused patients do worse because they are sicker to begin with. The Transfusion Requirements in Cardiac Surgery (TRICS) III trial removes some of the doubt: “A restrictive transfusion strategy is as effective and safe as a liberal strategy in patients undergoing cardiac surgery,” said lead investigator C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
Overall, 11.4% in the restrictive-threshold group and 12.5% in the liberal-threshold group met the study’s composite primary outcome of death from any cause, MI, stroke, and new-onset renal failure with dialysis (P less than .001 for noninferiority). There were no statistically significant between-group differences in the individual components of the composite outcome. Mortality was 3% in the restrictive group and 3.6% in the liberal group, a 15% reduction for the restrictive group.
About 52% of the patients in the restrictive arm, compared with 72.6% in the liberal arm, were transfused. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units. The overall cost difference was roughly $3 million, Dr. Mazer said at the American Heart Association scientific sessions.
There were no statistically significant differences in secondary outcomes. Restrictive patients were on mechanical ventilation for a median of 0.38 days and in the ICU for a median of 2.1 days; patients in the liberal arm were ventilated for a median of 0.36 days and in the ICU for a median of 1.9 days. The median hospital stay was 8 days in both groups.
Unexpectedly, patients 75 years and older did better with the restrictive transfusion strategy, with a 30% lower risk of the composite outcome. “Many people think the older you are, the higher your hemoglobin should be, and the more liberal you should be with transfusions. We didn’t find that. [It] challenges current beliefs and may be considered to be hypothesis generating; at a minimum, it highlights that a restrictive transfusion strategy appears to be safe in elderly patients,” Dr. Mazer said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded from the study. The trial was conducted in 19 countries, including China and India, but “the results were remarkably consistent independent of where the sites were,” he said.
Results of the TRICS III trial were published simultaneously with Dr. Mazer’s presentation (N Engl J Med. 2017 Nov 12. doi: 10.1056/NEJMoa1711818).
The trial was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer reported personal fees from Amgen, Boehringer Ingelheim, Octapharma, and Pharmascience, as well as grants and personal fees from Fresenius Kabi.
This is an extremely important study. There have been multiple other trials, and, unfortunately, results have been quite equivocal. It’s incumbent upon us to figure out the best transfusion strategy, especially in cardiac surgery, since it is associated with a large amount of blood utilization. Also, there’ve been projections for a significant lack of blood supply in the future.
While the overall results showed no significant difference in outcomes between the groups, there was a numerical benefit evident in the restrictive group for the composite outcome, as well as all components of the main primary outcome except MI. This is not entirely unexpected, but we are really looking at the short-term effects here. I’m hoping that the longer-term outcomes will be evaluated, because they are extremely important.
Frank Sellke, MD , is chief of cardiothoracic surgery at Brown University in Providence, R.I. He made his comments after the study was presented at the American Heart Association scientific sessions. He was not involved with the work.
This is an extremely important study. There have been multiple other trials, and, unfortunately, results have been quite equivocal. It’s incumbent upon us to figure out the best transfusion strategy, especially in cardiac surgery, since it is associated with a large amount of blood utilization. Also, there’ve been projections for a significant lack of blood supply in the future.
While the overall results showed no significant difference in outcomes between the groups, there was a numerical benefit evident in the restrictive group for the composite outcome, as well as all components of the main primary outcome except MI. This is not entirely unexpected, but we are really looking at the short-term effects here. I’m hoping that the longer-term outcomes will be evaluated, because they are extremely important.
Frank Sellke, MD , is chief of cardiothoracic surgery at Brown University in Providence, R.I. He made his comments after the study was presented at the American Heart Association scientific sessions. He was not involved with the work.
This is an extremely important study. There have been multiple other trials, and, unfortunately, results have been quite equivocal. It’s incumbent upon us to figure out the best transfusion strategy, especially in cardiac surgery, since it is associated with a large amount of blood utilization. Also, there’ve been projections for a significant lack of blood supply in the future.
While the overall results showed no significant difference in outcomes between the groups, there was a numerical benefit evident in the restrictive group for the composite outcome, as well as all components of the main primary outcome except MI. This is not entirely unexpected, but we are really looking at the short-term effects here. I’m hoping that the longer-term outcomes will be evaluated, because they are extremely important.
Frank Sellke, MD , is chief of cardiothoracic surgery at Brown University in Providence, R.I. He made his comments after the study was presented at the American Heart Association scientific sessions. He was not involved with the work.
ANAHEIM, CALIF. – Waiting to transfuse heart surgery patients until their hemoglobin drops below 7.5 g/dL is just as safe as transfusing them when their hemoglobin drops below 9.5 g/dL, and it saves a lot of blood, according to the TRICS III randomized, noninferiority trial of nearly 5,000 patients undergoing cardiac surgery with cardiopulmonary bypass.
Cardiac surgeons have been moving to more restrictive transfusion policies following reports of worse postoperative survival when patients are transfused. However, there are concerns about safety and uncertainty over whether it’s the transfusions themselves that are problematic or whether transfused patients do worse because they are sicker to begin with. The Transfusion Requirements in Cardiac Surgery (TRICS) III trial removes some of the doubt: “A restrictive transfusion strategy is as effective and safe as a liberal strategy in patients undergoing cardiac surgery,” said lead investigator C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
Overall, 11.4% in the restrictive-threshold group and 12.5% in the liberal-threshold group met the study’s composite primary outcome of death from any cause, MI, stroke, and new-onset renal failure with dialysis (P less than .001 for noninferiority). There were no statistically significant between-group differences in the individual components of the composite outcome. Mortality was 3% in the restrictive group and 3.6% in the liberal group, a 15% reduction for the restrictive group.
About 52% of the patients in the restrictive arm, compared with 72.6% in the liberal arm, were transfused. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units. The overall cost difference was roughly $3 million, Dr. Mazer said at the American Heart Association scientific sessions.
There were no statistically significant differences in secondary outcomes. Restrictive patients were on mechanical ventilation for a median of 0.38 days and in the ICU for a median of 2.1 days; patients in the liberal arm were ventilated for a median of 0.36 days and in the ICU for a median of 1.9 days. The median hospital stay was 8 days in both groups.
Unexpectedly, patients 75 years and older did better with the restrictive transfusion strategy, with a 30% lower risk of the composite outcome. “Many people think the older you are, the higher your hemoglobin should be, and the more liberal you should be with transfusions. We didn’t find that. [It] challenges current beliefs and may be considered to be hypothesis generating; at a minimum, it highlights that a restrictive transfusion strategy appears to be safe in elderly patients,” Dr. Mazer said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded from the study. The trial was conducted in 19 countries, including China and India, but “the results were remarkably consistent independent of where the sites were,” he said.
Results of the TRICS III trial were published simultaneously with Dr. Mazer’s presentation (N Engl J Med. 2017 Nov 12. doi: 10.1056/NEJMoa1711818).
The trial was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer reported personal fees from Amgen, Boehringer Ingelheim, Octapharma, and Pharmascience, as well as grants and personal fees from Fresenius Kabi.
ANAHEIM, CALIF. – Waiting to transfuse heart surgery patients until their hemoglobin drops below 7.5 g/dL is just as safe as transfusing them when their hemoglobin drops below 9.5 g/dL, and it saves a lot of blood, according to the TRICS III randomized, noninferiority trial of nearly 5,000 patients undergoing cardiac surgery with cardiopulmonary bypass.
Cardiac surgeons have been moving to more restrictive transfusion policies following reports of worse postoperative survival when patients are transfused. However, there are concerns about safety and uncertainty over whether it’s the transfusions themselves that are problematic or whether transfused patients do worse because they are sicker to begin with. The Transfusion Requirements in Cardiac Surgery (TRICS) III trial removes some of the doubt: “A restrictive transfusion strategy is as effective and safe as a liberal strategy in patients undergoing cardiac surgery,” said lead investigator C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
Overall, 11.4% in the restrictive-threshold group and 12.5% in the liberal-threshold group met the study’s composite primary outcome of death from any cause, MI, stroke, and new-onset renal failure with dialysis (P less than .001 for noninferiority). There were no statistically significant between-group differences in the individual components of the composite outcome. Mortality was 3% in the restrictive group and 3.6% in the liberal group, a 15% reduction for the restrictive group.
About 52% of the patients in the restrictive arm, compared with 72.6% in the liberal arm, were transfused. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units. The overall cost difference was roughly $3 million, Dr. Mazer said at the American Heart Association scientific sessions.
There were no statistically significant differences in secondary outcomes. Restrictive patients were on mechanical ventilation for a median of 0.38 days and in the ICU for a median of 2.1 days; patients in the liberal arm were ventilated for a median of 0.36 days and in the ICU for a median of 1.9 days. The median hospital stay was 8 days in both groups.
Unexpectedly, patients 75 years and older did better with the restrictive transfusion strategy, with a 30% lower risk of the composite outcome. “Many people think the older you are, the higher your hemoglobin should be, and the more liberal you should be with transfusions. We didn’t find that. [It] challenges current beliefs and may be considered to be hypothesis generating; at a minimum, it highlights that a restrictive transfusion strategy appears to be safe in elderly patients,” Dr. Mazer said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded from the study. The trial was conducted in 19 countries, including China and India, but “the results were remarkably consistent independent of where the sites were,” he said.
Results of the TRICS III trial were published simultaneously with Dr. Mazer’s presentation (N Engl J Med. 2017 Nov 12. doi: 10.1056/NEJMoa1711818).
The trial was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer reported personal fees from Amgen, Boehringer Ingelheim, Octapharma, and Pharmascience, as well as grants and personal fees from Fresenius Kabi.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Overall, 11.4% in the restrictive-threshold group, versus 12.5% in the liberal-threshold group, met the study’s composite primary outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis.
Data source: TRICS III, a randomized, noninferiority trial with almost 5,000 participants
Disclosures: TRICS III was funded by the Canadian Institutes of Health Research, among others. The lead investigator reported personal fees from Amgen, Boehringer Ingelheim, Octapharma, and Pharmascience, as well as grants and personal fees from Fresenius Kabi.
Prescribers mostly ignore clopidogrel pharmacogenomic profiling
ANAHEIM, CALIF. – The boxed warning recommending pharmacogenomic testing of patients receiving clopidogrel to identify reduced metabolizers seems to be playing to a largely deaf audience.
Even when handed information on whether each clopidogrel-treated patient was a poor metabolizer of the drug, treating physicians usually did not switch them to a different antiplatelet drug, ticagrelor, that would be fully effective despite the patient’s reduced-metabolizer status. And clinicians who started patients on ticagrelor did not usually switch those with a good clopidogrel-metabolizing profile to the safer drug, clopidogrel, after learning that clopidogrel would be fully effective.
“Routine reporting of pharmacogenomics test results for acute coronary syndrome patients treated with P2Y12-inhibitor therapy had an uncertain yield and little impact on P2Y12-inhibitor switching,” E. Magnus Ohman, MBBS, said at the American Heart Association scientific sessions.
The study’s design gave each participating clinician free rein on whether to prescribe clopidogrel or ticagrelor (Brilinta) initially, and switching between the drugs was possible at any time after the initial prescription. At the trial’s start, 1,704 patients (56%) were on ticagrelor and 1,333 (44%) were on clopidogrel.
Pharmacogenomic testing showed that 34% of all patients were ultrametabolizers and 38% were extensive metabolizers. Patients in either of these categories metabolize enough clopidogrel into the active form to get full benefit from the drug and derive no additional efficacy benefit from switching to another P2Y12 inhibitor, such as ticagrelor or prasugrel (Effient) – drugs unaffected by metabolizer status. Testing also identified 25% of patients as intermediate metabolizers, who carry one loss-of-function allele for the CYP2C19 gene, and 3% were reduced metabolizers, who are homozygous for loss-of-function alleles. Standard practice is not to treat intermediate or reduced metabolizers with clopidogrel because they would not get an adequate antiplatelet effect; instead, these patients are usually treated with ticagrelor or with prasugrel when it’s an option.
After receiving the results regarding the clopidogrel-metabolizing status for each patient, attending physicians switched the drugs prescribed for only 7% of all patients: 9% of patients initially on ticagrelor and 4% of those initially on clopidogrel, reported Dr. Ohman, professor of medicine at Duke University in Durham, N.C. In addition, Dr. Ohman and his associates asked each participating physician who made a switch about his or her reasons for doing so. Of the patients who switched from clopidogrel to ticagrelor, only 23 were switched because of their pharmacogenomic results; this represents fewer than half of those who switched and only 2% of all patients who took clopidogrel. Only one patient changed from ticagrelor to clopidogrel based on pharmacogenomic results, representing 0.06% of all patients on ticagrelor.
“We believed the findings do not support the utility of mandatory testing in this context, as most did not act on the information,” Dr. Ohman said.
A major reason for the inertia, Dr. Gurbel suggested, may be the absence of any compelling data proving whether there’s any effect on clinical outcomes for switching reduced metabolizers off of clopidogrel or switching good metabolizers onto it.
“We have no large-scale, prospective data supporting pharmacogenomic-based personalization” of clopidogrel treatment leading to improved outcomes, but “we need to get over that,” he said. “It’s a challenge to get funding for this.” But “the answer is not to give ticagrelor or prasugrel to everyone because then the bleeding rate is too high.”
The findings Dr. Ohman reported came from the Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome (GEMINI-ACS-1), which had the primary goal of comparing the safety in acute coronary syndrome patients of a reduced dosage of rivaroxaban plus either clopidogrel or ticagrelor with the safety of aspirin plus one of these P2Y12 inhibitors. The primary endpoint was the rate of clinically significant bleeding events during a year of treatment. The study ran at 371 centers in 21 countries and showed similar bleeding rates in both treatment arms (Lancet. 2017 May 6; 389[10081]:1799-808).
The analysis also showed that patients identified as reduced metabolizers were fivefold more likely to be switched than patients identified as ultra metabolizers, and intermediate metabolizes had a 50% higher switching rate than ultra metabolizers. The rates of both ischemic and major bleeding outcomes were roughly similar across the spectrum of metabolizers, but Dr. Ohman cautioned that the trial was not designed to assess this. Dr. Gurbel urged the investigators to report on outcomes analyzed not just by metabolizer status but also by the treatment they received.
The boxed warning that clopidogrel received in 2010 regarding poor metabolizers led to “regulatory guidance” during design of the GEMINI-ACS-1 trial requiring routine pharmacogenomic testing for clopidogrel-metabolizing status, Dr. Ohman explained.
The trial was funded by Janssen and Bayer, the two companies that jointly market rivaroxaban (Xarelto). Dr. Ohman has been a consultant to Bayer and several other companies including AstraZeneca, the company that markets ticagrelor (Brilinta). He has also received research funding from Janssen, as well as Daiichi Sankyo and Gilead Sciences. Dr. Gurbel holds patents on platelet-function testing methods.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
ANAHEIM, CALIF. – The boxed warning recommending pharmacogenomic testing of patients receiving clopidogrel to identify reduced metabolizers seems to be playing to a largely deaf audience.
Even when handed information on whether each clopidogrel-treated patient was a poor metabolizer of the drug, treating physicians usually did not switch them to a different antiplatelet drug, ticagrelor, that would be fully effective despite the patient’s reduced-metabolizer status. And clinicians who started patients on ticagrelor did not usually switch those with a good clopidogrel-metabolizing profile to the safer drug, clopidogrel, after learning that clopidogrel would be fully effective.
“Routine reporting of pharmacogenomics test results for acute coronary syndrome patients treated with P2Y12-inhibitor therapy had an uncertain yield and little impact on P2Y12-inhibitor switching,” E. Magnus Ohman, MBBS, said at the American Heart Association scientific sessions.
The study’s design gave each participating clinician free rein on whether to prescribe clopidogrel or ticagrelor (Brilinta) initially, and switching between the drugs was possible at any time after the initial prescription. At the trial’s start, 1,704 patients (56%) were on ticagrelor and 1,333 (44%) were on clopidogrel.
Pharmacogenomic testing showed that 34% of all patients were ultrametabolizers and 38% were extensive metabolizers. Patients in either of these categories metabolize enough clopidogrel into the active form to get full benefit from the drug and derive no additional efficacy benefit from switching to another P2Y12 inhibitor, such as ticagrelor or prasugrel (Effient) – drugs unaffected by metabolizer status. Testing also identified 25% of patients as intermediate metabolizers, who carry one loss-of-function allele for the CYP2C19 gene, and 3% were reduced metabolizers, who are homozygous for loss-of-function alleles. Standard practice is not to treat intermediate or reduced metabolizers with clopidogrel because they would not get an adequate antiplatelet effect; instead, these patients are usually treated with ticagrelor or with prasugrel when it’s an option.
After receiving the results regarding the clopidogrel-metabolizing status for each patient, attending physicians switched the drugs prescribed for only 7% of all patients: 9% of patients initially on ticagrelor and 4% of those initially on clopidogrel, reported Dr. Ohman, professor of medicine at Duke University in Durham, N.C. In addition, Dr. Ohman and his associates asked each participating physician who made a switch about his or her reasons for doing so. Of the patients who switched from clopidogrel to ticagrelor, only 23 were switched because of their pharmacogenomic results; this represents fewer than half of those who switched and only 2% of all patients who took clopidogrel. Only one patient changed from ticagrelor to clopidogrel based on pharmacogenomic results, representing 0.06% of all patients on ticagrelor.
“We believed the findings do not support the utility of mandatory testing in this context, as most did not act on the information,” Dr. Ohman said.
A major reason for the inertia, Dr. Gurbel suggested, may be the absence of any compelling data proving whether there’s any effect on clinical outcomes for switching reduced metabolizers off of clopidogrel or switching good metabolizers onto it.
“We have no large-scale, prospective data supporting pharmacogenomic-based personalization” of clopidogrel treatment leading to improved outcomes, but “we need to get over that,” he said. “It’s a challenge to get funding for this.” But “the answer is not to give ticagrelor or prasugrel to everyone because then the bleeding rate is too high.”
The findings Dr. Ohman reported came from the Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome (GEMINI-ACS-1), which had the primary goal of comparing the safety in acute coronary syndrome patients of a reduced dosage of rivaroxaban plus either clopidogrel or ticagrelor with the safety of aspirin plus one of these P2Y12 inhibitors. The primary endpoint was the rate of clinically significant bleeding events during a year of treatment. The study ran at 371 centers in 21 countries and showed similar bleeding rates in both treatment arms (Lancet. 2017 May 6; 389[10081]:1799-808).
The analysis also showed that patients identified as reduced metabolizers were fivefold more likely to be switched than patients identified as ultra metabolizers, and intermediate metabolizes had a 50% higher switching rate than ultra metabolizers. The rates of both ischemic and major bleeding outcomes were roughly similar across the spectrum of metabolizers, but Dr. Ohman cautioned that the trial was not designed to assess this. Dr. Gurbel urged the investigators to report on outcomes analyzed not just by metabolizer status but also by the treatment they received.
The boxed warning that clopidogrel received in 2010 regarding poor metabolizers led to “regulatory guidance” during design of the GEMINI-ACS-1 trial requiring routine pharmacogenomic testing for clopidogrel-metabolizing status, Dr. Ohman explained.
The trial was funded by Janssen and Bayer, the two companies that jointly market rivaroxaban (Xarelto). Dr. Ohman has been a consultant to Bayer and several other companies including AstraZeneca, the company that markets ticagrelor (Brilinta). He has also received research funding from Janssen, as well as Daiichi Sankyo and Gilead Sciences. Dr. Gurbel holds patents on platelet-function testing methods.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
ANAHEIM, CALIF. – The boxed warning recommending pharmacogenomic testing of patients receiving clopidogrel to identify reduced metabolizers seems to be playing to a largely deaf audience.
Even when handed information on whether each clopidogrel-treated patient was a poor metabolizer of the drug, treating physicians usually did not switch them to a different antiplatelet drug, ticagrelor, that would be fully effective despite the patient’s reduced-metabolizer status. And clinicians who started patients on ticagrelor did not usually switch those with a good clopidogrel-metabolizing profile to the safer drug, clopidogrel, after learning that clopidogrel would be fully effective.
“Routine reporting of pharmacogenomics test results for acute coronary syndrome patients treated with P2Y12-inhibitor therapy had an uncertain yield and little impact on P2Y12-inhibitor switching,” E. Magnus Ohman, MBBS, said at the American Heart Association scientific sessions.
The study’s design gave each participating clinician free rein on whether to prescribe clopidogrel or ticagrelor (Brilinta) initially, and switching between the drugs was possible at any time after the initial prescription. At the trial’s start, 1,704 patients (56%) were on ticagrelor and 1,333 (44%) were on clopidogrel.
Pharmacogenomic testing showed that 34% of all patients were ultrametabolizers and 38% were extensive metabolizers. Patients in either of these categories metabolize enough clopidogrel into the active form to get full benefit from the drug and derive no additional efficacy benefit from switching to another P2Y12 inhibitor, such as ticagrelor or prasugrel (Effient) – drugs unaffected by metabolizer status. Testing also identified 25% of patients as intermediate metabolizers, who carry one loss-of-function allele for the CYP2C19 gene, and 3% were reduced metabolizers, who are homozygous for loss-of-function alleles. Standard practice is not to treat intermediate or reduced metabolizers with clopidogrel because they would not get an adequate antiplatelet effect; instead, these patients are usually treated with ticagrelor or with prasugrel when it’s an option.
After receiving the results regarding the clopidogrel-metabolizing status for each patient, attending physicians switched the drugs prescribed for only 7% of all patients: 9% of patients initially on ticagrelor and 4% of those initially on clopidogrel, reported Dr. Ohman, professor of medicine at Duke University in Durham, N.C. In addition, Dr. Ohman and his associates asked each participating physician who made a switch about his or her reasons for doing so. Of the patients who switched from clopidogrel to ticagrelor, only 23 were switched because of their pharmacogenomic results; this represents fewer than half of those who switched and only 2% of all patients who took clopidogrel. Only one patient changed from ticagrelor to clopidogrel based on pharmacogenomic results, representing 0.06% of all patients on ticagrelor.
“We believed the findings do not support the utility of mandatory testing in this context, as most did not act on the information,” Dr. Ohman said.
A major reason for the inertia, Dr. Gurbel suggested, may be the absence of any compelling data proving whether there’s any effect on clinical outcomes for switching reduced metabolizers off of clopidogrel or switching good metabolizers onto it.
“We have no large-scale, prospective data supporting pharmacogenomic-based personalization” of clopidogrel treatment leading to improved outcomes, but “we need to get over that,” he said. “It’s a challenge to get funding for this.” But “the answer is not to give ticagrelor or prasugrel to everyone because then the bleeding rate is too high.”
The findings Dr. Ohman reported came from the Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome (GEMINI-ACS-1), which had the primary goal of comparing the safety in acute coronary syndrome patients of a reduced dosage of rivaroxaban plus either clopidogrel or ticagrelor with the safety of aspirin plus one of these P2Y12 inhibitors. The primary endpoint was the rate of clinically significant bleeding events during a year of treatment. The study ran at 371 centers in 21 countries and showed similar bleeding rates in both treatment arms (Lancet. 2017 May 6; 389[10081]:1799-808).
The analysis also showed that patients identified as reduced metabolizers were fivefold more likely to be switched than patients identified as ultra metabolizers, and intermediate metabolizes had a 50% higher switching rate than ultra metabolizers. The rates of both ischemic and major bleeding outcomes were roughly similar across the spectrum of metabolizers, but Dr. Ohman cautioned that the trial was not designed to assess this. Dr. Gurbel urged the investigators to report on outcomes analyzed not just by metabolizer status but also by the treatment they received.
The boxed warning that clopidogrel received in 2010 regarding poor metabolizers led to “regulatory guidance” during design of the GEMINI-ACS-1 trial requiring routine pharmacogenomic testing for clopidogrel-metabolizing status, Dr. Ohman explained.
The trial was funded by Janssen and Bayer, the two companies that jointly market rivaroxaban (Xarelto). Dr. Ohman has been a consultant to Bayer and several other companies including AstraZeneca, the company that markets ticagrelor (Brilinta). He has also received research funding from Janssen, as well as Daiichi Sankyo and Gilead Sciences. Dr. Gurbel holds patents on platelet-function testing methods.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Physicians switched P2Y12 inhibitors for only 2% of patients on clopidogrel and only 0.06% on ticagrelor on the basis of their pharmacogenomic results.
Data source: GEMINI-ACS-1, a multicenter, prospective trial with 3,037 patients.
Disclosures: The GEMINI-ACS-1 trial was funded by Janssen and Bayer, the two companies that jointly market rivaroxaban (Xarelto). Dr. Ohman has been a consultant to Bayer and several other companies, including AstraZeneca, the company that markets ticagrelor (Brilinta). He has also received research funding from Janssen, as well as Daiichi Sankyo and Gilead Sciences. Dr. Gurbel holds patents on platelet-function testing methods.
Heart transplantation: Preop LVAD erases adverse impact of pulmonary hypertension
COLORADO SPRINGS – Reconsideration of the role of pulmonary hypertension in heart transplant outcomes is appropriate in the emerging era of the use of left ventricular assist devices (LVADs) as bridge to transplant, according to Ann C. Gaffey, MD, of the University of Pennsylvania, Philadelphia.
“Pulmonary hypertension secondary to congestive heart failure more than likely can be reversed to the values acceptable for heart transplant by the use of an LVAD. For bridge-to-transplant patients, pretransplant pulmonary hypertension does not affect recipient outcomes post transplantation,” she said at the annual meeting of the Western Thoracic Surgical Association.
Vasodilators are prescribed in an effort to reduce PH; however, 40% of patients with PH are unresponsive to the medications and have therefore been excluded from consideration as potential candidates for a donor heart.
But the growing use of LVADs as a bridge to transplant has changed all that, Dr. Gaffey said. As supporting evidence, she presented a retrospective analysis of the United Network for Organ Sharing database on adult heart transplants from mid-2004 through the end of 2014.
The review turned up 3,951 heart transplant recipients who had been bridged to transplant with an LVAD. Dr. Gaffey and her coinvestigators divided them into three groups: 281 patients without pretransplant PH; 1,454 with moderate PH as defined by 1-3 Wood units; and 592 with severe PH and more than 3 Wood units.
The three groups didn’t differ in terms of age, sex, wait-list time, or the prevalence of diabetes or renal, liver, or cerebrovascular disease. Nor did their donors differ in age, sex, left ventricular function, or allograft ischemic time.
Key in-hospital outcomes were similar between the groups with no, mild, and severe PH.
Moreover, there was no between-group difference in the rate of rejection at 1 year. Five-year survival rates were closely similar in the three groups, in the mid-70s.
Audience member Nahush A. Mokadam, MD, rose to praise Dr. Gaffey’s report.
“This is a great and important study. I think as a group we have been too conservative with pulmonary hypertension, so thank you for shining a good light on it,” said Dr. Mokadam of the University of Washington, Seattle.
Dr. Gaffey reported having no financial conflicts regarding the study, which was conducted free of commercial support.
COLORADO SPRINGS – Reconsideration of the role of pulmonary hypertension in heart transplant outcomes is appropriate in the emerging era of the use of left ventricular assist devices (LVADs) as bridge to transplant, according to Ann C. Gaffey, MD, of the University of Pennsylvania, Philadelphia.
“Pulmonary hypertension secondary to congestive heart failure more than likely can be reversed to the values acceptable for heart transplant by the use of an LVAD. For bridge-to-transplant patients, pretransplant pulmonary hypertension does not affect recipient outcomes post transplantation,” she said at the annual meeting of the Western Thoracic Surgical Association.
Vasodilators are prescribed in an effort to reduce PH; however, 40% of patients with PH are unresponsive to the medications and have therefore been excluded from consideration as potential candidates for a donor heart.
But the growing use of LVADs as a bridge to transplant has changed all that, Dr. Gaffey said. As supporting evidence, she presented a retrospective analysis of the United Network for Organ Sharing database on adult heart transplants from mid-2004 through the end of 2014.
The review turned up 3,951 heart transplant recipients who had been bridged to transplant with an LVAD. Dr. Gaffey and her coinvestigators divided them into three groups: 281 patients without pretransplant PH; 1,454 with moderate PH as defined by 1-3 Wood units; and 592 with severe PH and more than 3 Wood units.
The three groups didn’t differ in terms of age, sex, wait-list time, or the prevalence of diabetes or renal, liver, or cerebrovascular disease. Nor did their donors differ in age, sex, left ventricular function, or allograft ischemic time.
Key in-hospital outcomes were similar between the groups with no, mild, and severe PH.
Moreover, there was no between-group difference in the rate of rejection at 1 year. Five-year survival rates were closely similar in the three groups, in the mid-70s.
Audience member Nahush A. Mokadam, MD, rose to praise Dr. Gaffey’s report.
“This is a great and important study. I think as a group we have been too conservative with pulmonary hypertension, so thank you for shining a good light on it,” said Dr. Mokadam of the University of Washington, Seattle.
Dr. Gaffey reported having no financial conflicts regarding the study, which was conducted free of commercial support.
COLORADO SPRINGS – Reconsideration of the role of pulmonary hypertension in heart transplant outcomes is appropriate in the emerging era of the use of left ventricular assist devices (LVADs) as bridge to transplant, according to Ann C. Gaffey, MD, of the University of Pennsylvania, Philadelphia.
“Pulmonary hypertension secondary to congestive heart failure more than likely can be reversed to the values acceptable for heart transplant by the use of an LVAD. For bridge-to-transplant patients, pretransplant pulmonary hypertension does not affect recipient outcomes post transplantation,” she said at the annual meeting of the Western Thoracic Surgical Association.
Vasodilators are prescribed in an effort to reduce PH; however, 40% of patients with PH are unresponsive to the medications and have therefore been excluded from consideration as potential candidates for a donor heart.
But the growing use of LVADs as a bridge to transplant has changed all that, Dr. Gaffey said. As supporting evidence, she presented a retrospective analysis of the United Network for Organ Sharing database on adult heart transplants from mid-2004 through the end of 2014.
The review turned up 3,951 heart transplant recipients who had been bridged to transplant with an LVAD. Dr. Gaffey and her coinvestigators divided them into three groups: 281 patients without pretransplant PH; 1,454 with moderate PH as defined by 1-3 Wood units; and 592 with severe PH and more than 3 Wood units.
The three groups didn’t differ in terms of age, sex, wait-list time, or the prevalence of diabetes or renal, liver, or cerebrovascular disease. Nor did their donors differ in age, sex, left ventricular function, or allograft ischemic time.
Key in-hospital outcomes were similar between the groups with no, mild, and severe PH.
Moreover, there was no between-group difference in the rate of rejection at 1 year. Five-year survival rates were closely similar in the three groups, in the mid-70s.
Audience member Nahush A. Mokadam, MD, rose to praise Dr. Gaffey’s report.
“This is a great and important study. I think as a group we have been too conservative with pulmonary hypertension, so thank you for shining a good light on it,” said Dr. Mokadam of the University of Washington, Seattle.
Dr. Gaffey reported having no financial conflicts regarding the study, which was conducted free of commercial support.
AT THE WTSA ANNUAL MEETING
Key clinical point:
Major finding: It’s time to reconsider the practice of excluding patients with pulmonary hypertension from consideration for a donor heart.
Data source: A retrospective analysis of the United Network for Organ Sharing database including outcomes out to 5 years on 3,951 heart transplant recipients who had been bridged to transplant with an LVAD, most of whom had moderate or severe pulmonary hypertension before transplant.
Disclosures: This study was conducted free of commercial support. The presenter reported having no relevant financial conflicts of interest.
Keep PCI patients on aspirin for noncardiac surgery
ANAHEIM, CALIF. – For every 1,000 patients with a history of percutaneous coronary intervention undergoing noncardiac surgery, perioperative aspirin would prevent 59 myocardial infarctions but cause 8 major/life-threatening bleeds, according to a substudy of the POISE-2 trial presented at the American Heart Association scientific sessions.
For patients with previous PCI undergoing noncardiac surgery, “I think aspirin will be more likely to benefit them than harm them,” so long as they are not having an operation where bleeding would be devastating.” These include “delicate neurosurgery in which, if you bleed into your spine, you end up paralyzed,” said lead investigator Michelle Graham, MD, an interventional cardiologist and professor of cardiology at the University of Alberta, Edmonton.
The original multisite POISE-2 trial (Perioperative Ischemic Evaluation 2) evaluated the effect of perioperative aspirin for noncardiac surgery. Patients were randomized to receive 200 mg aspirin or placebo within 4 hours of surgery and then 100 mg aspirin or placebo in the early postoperative period. There was no significant effect on the composite rate of death or myocardial infarction, but an increased risk of serious bleeding (N Engl J Med. 2014 Apr 17;370[16]:1494-503).
The new substudy focused on the 470 patients with previous PCIs, because such patients are known to have a higher risk for postop complications. More than half received bare-metal stents and a quarter got drug-eluting stents; in most of the rest, the stent type was not known. The median duration from PCI to noncardiac surgery was 64 months, ranging from 34 to 113 months. Patients with bare-metal stents placed within 6 weeks or drug-eluting stents within a year, were excluded.
Overall, 234 patients were randomized to the aspirin group, and 236 to placebo. Among those who came in on chronic, daily aspirin therapy – as almost all of the PCI subjects did – those who were randomized to perioperative aspirin stayed on daily 100 mg aspirin for a week postop, and then flipped back to whatever dose they were on at home. Likewise, placebo patients resumed their home aspirin after 1 week.
The results were very different from the main trial. At 30 days’ follow-up, just 6% of patients in the aspirin arm reached the primary endpoint of death or MI, versus 11.5% in the placebo group, a statistically significant 50% reduction.
This difference was driven almost entirely by a reduction in MIs. Whereas 5.1% of patients in the aspirin arm had MIs, 11% of the placebo group did, a significant 64% reduction. Meanwhile, the risk of major or life-threatening bleeding was not only similar between groups, but also to the overall trial, noted in 5.6% of aspirin and 4.2% of placebo subjects.
Over 75% of the participants were men, almost 60% were undergoing a major surgery, 30% had diabetes, and many had hypertension. Very few were on direct oral anticoagulants. The two arms were well matched, with a median age of about 68 years.
Simultaneously with Dr. Graham’s presentation, the results were published online (Ann Intern Med. 2017 Nov 14; doi: 10.7326/M17-2341)
The work was funded mostly by the Canadian Institutes of Health Research. Bayer supplied the aspirin. Dr. Graham has no industry disclosures.
ANAHEIM, CALIF. – For every 1,000 patients with a history of percutaneous coronary intervention undergoing noncardiac surgery, perioperative aspirin would prevent 59 myocardial infarctions but cause 8 major/life-threatening bleeds, according to a substudy of the POISE-2 trial presented at the American Heart Association scientific sessions.
For patients with previous PCI undergoing noncardiac surgery, “I think aspirin will be more likely to benefit them than harm them,” so long as they are not having an operation where bleeding would be devastating.” These include “delicate neurosurgery in which, if you bleed into your spine, you end up paralyzed,” said lead investigator Michelle Graham, MD, an interventional cardiologist and professor of cardiology at the University of Alberta, Edmonton.
The original multisite POISE-2 trial (Perioperative Ischemic Evaluation 2) evaluated the effect of perioperative aspirin for noncardiac surgery. Patients were randomized to receive 200 mg aspirin or placebo within 4 hours of surgery and then 100 mg aspirin or placebo in the early postoperative period. There was no significant effect on the composite rate of death or myocardial infarction, but an increased risk of serious bleeding (N Engl J Med. 2014 Apr 17;370[16]:1494-503).
The new substudy focused on the 470 patients with previous PCIs, because such patients are known to have a higher risk for postop complications. More than half received bare-metal stents and a quarter got drug-eluting stents; in most of the rest, the stent type was not known. The median duration from PCI to noncardiac surgery was 64 months, ranging from 34 to 113 months. Patients with bare-metal stents placed within 6 weeks or drug-eluting stents within a year, were excluded.
Overall, 234 patients were randomized to the aspirin group, and 236 to placebo. Among those who came in on chronic, daily aspirin therapy – as almost all of the PCI subjects did – those who were randomized to perioperative aspirin stayed on daily 100 mg aspirin for a week postop, and then flipped back to whatever dose they were on at home. Likewise, placebo patients resumed their home aspirin after 1 week.
The results were very different from the main trial. At 30 days’ follow-up, just 6% of patients in the aspirin arm reached the primary endpoint of death or MI, versus 11.5% in the placebo group, a statistically significant 50% reduction.
This difference was driven almost entirely by a reduction in MIs. Whereas 5.1% of patients in the aspirin arm had MIs, 11% of the placebo group did, a significant 64% reduction. Meanwhile, the risk of major or life-threatening bleeding was not only similar between groups, but also to the overall trial, noted in 5.6% of aspirin and 4.2% of placebo subjects.
Over 75% of the participants were men, almost 60% were undergoing a major surgery, 30% had diabetes, and many had hypertension. Very few were on direct oral anticoagulants. The two arms were well matched, with a median age of about 68 years.
Simultaneously with Dr. Graham’s presentation, the results were published online (Ann Intern Med. 2017 Nov 14; doi: 10.7326/M17-2341)
The work was funded mostly by the Canadian Institutes of Health Research. Bayer supplied the aspirin. Dr. Graham has no industry disclosures.
ANAHEIM, CALIF. – For every 1,000 patients with a history of percutaneous coronary intervention undergoing noncardiac surgery, perioperative aspirin would prevent 59 myocardial infarctions but cause 8 major/life-threatening bleeds, according to a substudy of the POISE-2 trial presented at the American Heart Association scientific sessions.
For patients with previous PCI undergoing noncardiac surgery, “I think aspirin will be more likely to benefit them than harm them,” so long as they are not having an operation where bleeding would be devastating.” These include “delicate neurosurgery in which, if you bleed into your spine, you end up paralyzed,” said lead investigator Michelle Graham, MD, an interventional cardiologist and professor of cardiology at the University of Alberta, Edmonton.
The original multisite POISE-2 trial (Perioperative Ischemic Evaluation 2) evaluated the effect of perioperative aspirin for noncardiac surgery. Patients were randomized to receive 200 mg aspirin or placebo within 4 hours of surgery and then 100 mg aspirin or placebo in the early postoperative period. There was no significant effect on the composite rate of death or myocardial infarction, but an increased risk of serious bleeding (N Engl J Med. 2014 Apr 17;370[16]:1494-503).
The new substudy focused on the 470 patients with previous PCIs, because such patients are known to have a higher risk for postop complications. More than half received bare-metal stents and a quarter got drug-eluting stents; in most of the rest, the stent type was not known. The median duration from PCI to noncardiac surgery was 64 months, ranging from 34 to 113 months. Patients with bare-metal stents placed within 6 weeks or drug-eluting stents within a year, were excluded.
Overall, 234 patients were randomized to the aspirin group, and 236 to placebo. Among those who came in on chronic, daily aspirin therapy – as almost all of the PCI subjects did – those who were randomized to perioperative aspirin stayed on daily 100 mg aspirin for a week postop, and then flipped back to whatever dose they were on at home. Likewise, placebo patients resumed their home aspirin after 1 week.
The results were very different from the main trial. At 30 days’ follow-up, just 6% of patients in the aspirin arm reached the primary endpoint of death or MI, versus 11.5% in the placebo group, a statistically significant 50% reduction.
This difference was driven almost entirely by a reduction in MIs. Whereas 5.1% of patients in the aspirin arm had MIs, 11% of the placebo group did, a significant 64% reduction. Meanwhile, the risk of major or life-threatening bleeding was not only similar between groups, but also to the overall trial, noted in 5.6% of aspirin and 4.2% of placebo subjects.
Over 75% of the participants were men, almost 60% were undergoing a major surgery, 30% had diabetes, and many had hypertension. Very few were on direct oral anticoagulants. The two arms were well matched, with a median age of about 68 years.
Simultaneously with Dr. Graham’s presentation, the results were published online (Ann Intern Med. 2017 Nov 14; doi: 10.7326/M17-2341)
The work was funded mostly by the Canadian Institutes of Health Research. Bayer supplied the aspirin. Dr. Graham has no industry disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: For every 1,000 patients with a history of percutaneous coronary intervention undergoing noncardiac surgery, perioperative aspirin would prevent 59 myocardial infarctions but cause 8 major/life-threatening bleeds.
Data source: POISE-2, a randomized trial of 470 PCI patients.
Disclosures: The work was funded mostly by the Canadian Institutes of Health Research. Bayer supplied the aspirin. The lead investigator has no industry disclosures.