Heart Failure

Thyroid dysfunction was associated with an increased risk of mortality in patients with heart failure due to idiopathic dilated cardiomyopathy (IDCM), according to research reported in the Journal of Clinical Endocrinology and Metabolism.

Lead author Wenyao Wang of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and associates gathered data from 458 consecutive patients with IDCM who were admitted to the National Center of Cardiovascular diseases in Beijing, and then evaluated their risk of mortality based on levels of free T₃ and TSH and the whole thyroid function profile.

Hypothyroidism was the strongest predictor of mortality (hazard ratio, 4.189; 95% confidence interval, 2.118-8.283), followed by low-T₃ syndrome (HR, 3.147; 95% CI, 1.558-6.355) and subclinical hypothyroidism (HR, 2.869; 95% CI, 1.817-4.532); subclinical hyperthyroidism did not have a significant impact on mortality. The most common forms of thyroid dysfunction were subclinical hypothyroidism (n = 41, 9%), followed by subclinical hyperthyroidism (n = 35, 7%), low-T3 syndrome (n = 17, 4%), and overt hypothyroidism (n = 12, 3%).

“Monitoring thyroid function is necessary for patients with IDCM, and further study is warranted to investigate whether reversing low thyroid function can benefit these patients,” the investigators noted.

Read the full article here: (J. Clin. Endocrinol. Metab. 2015 [doi:10.1210/jc.2014-4159]).

The investigators reported that they had no financial disclosures to make.

mbock@frontlinemedcom.com

Thyroid dysfunction was associated with an increased risk of mortality in patients with heart failure due to idiopathic dilated cardiomyopathy (IDCM), according to research reported in the Journal of Clinical Endocrinology and Metabolism.

Lead author Wenyao Wang of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and associates gathered data from 458 consecutive patients with IDCM who were admitted to the National Center of Cardiovascular diseases in Beijing, and then evaluated their risk of mortality based on levels of free T₃ and TSH and the whole thyroid function profile.

Hypothyroidism was the strongest predictor of mortality (hazard ratio, 4.189; 95% confidence interval, 2.118-8.283), followed by low-T₃ syndrome (HR, 3.147; 95% CI, 1.558-6.355) and subclinical hypothyroidism (HR, 2.869; 95% CI, 1.817-4.532); subclinical hyperthyroidism did not have a significant impact on mortality. The most common forms of thyroid dysfunction were subclinical hypothyroidism (n = 41, 9%), followed by subclinical hyperthyroidism (n = 35, 7%), low-T3 syndrome (n = 17, 4%), and overt hypothyroidism (n = 12, 3%).

“Monitoring thyroid function is necessary for patients with IDCM, and further study is warranted to investigate whether reversing low thyroid function can benefit these patients,” the investigators noted.

Read the full article here: (J. Clin. Endocrinol. Metab. 2015 [doi:10.1210/jc.2014-4159]).

The investigators reported that they had no financial disclosures to make.

mbock@frontlinemedcom.com

Thyroid dysfunction was associated with an increased risk of mortality in patients with heart failure due to idiopathic dilated cardiomyopathy (IDCM), according to research reported in the Journal of Clinical Endocrinology and Metabolism.

Lead author Wenyao Wang of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and associates gathered data from 458 consecutive patients with IDCM who were admitted to the National Center of Cardiovascular diseases in Beijing, and then evaluated their risk of mortality based on levels of free T₃ and TSH and the whole thyroid function profile.

Hypothyroidism was the strongest predictor of mortality (hazard ratio, 4.189; 95% confidence interval, 2.118-8.283), followed by low-T₃ syndrome (HR, 3.147; 95% CI, 1.558-6.355) and subclinical hypothyroidism (HR, 2.869; 95% CI, 1.817-4.532); subclinical hyperthyroidism did not have a significant impact on mortality. The most common forms of thyroid dysfunction were subclinical hypothyroidism (n = 41, 9%), followed by subclinical hyperthyroidism (n = 35, 7%), low-T3 syndrome (n = 17, 4%), and overt hypothyroidism (n = 12, 3%).

“Monitoring thyroid function is necessary for patients with IDCM, and further study is warranted to investigate whether reversing low thyroid function can benefit these patients,” the investigators noted.

Read the full article here: (J. Clin. Endocrinol. Metab. 2015 [doi:10.1210/jc.2014-4159]).

The investigators reported that they had no financial disclosures to make.

mbock@frontlinemedcom.com

BOSTON – The ELIXA trial confirms that the GLP-1 receptor agonist lixisenatide neither decreases nor increases the risk of major adverse cardiac events in postacute coronary syndrome patients, and that it improves glucose control, compared with placebo, and provides modest benefits with respect to body weight, blood pressure, progression of albuminuria, and hypoglycemia rates, Dr. Silvio E. Inzucchi said at the annual scientific sessions of the American Diabetes Association.

Particularly encouraging was the lack of any signal for pancreatic injury, thyroid cancer, or heart failure. The latter finding is especially timely given recent concerns raised by DPP-4 inhibitors, said Dr. Inzucchi, who was invited by the ADA to comment on the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important end point, “the answer to this is a resounding yes,” he said, congratulating the investigators, who “have done a fine job of conducting this study, which represents another example of the great collaboration between diabetologists and cardiologists.”

“We all see the same patients and we need to work more and more together to find out the best treatments for our patients,” he said, noting that finding a glucose-lowering agent that has a clearcut cardiovascular benefit represents the “holy grail.”

The neutral finding, as opposed to a positive one, in ELIXA with respect to effects on cardiovascular outcomes is not surprising, said Dr. Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn.

“Hypoglycemia is more tightly linked to micro- than to macrovascular outcomes, so not surprisingly it is much easier to show a benefit on these microvascular complications from controlling blood glucose. Any cardiovascular benefit accrues over many years, outside the time course of most of our randomized clinical trials, and any cardiovascular benefit is likely to be attenuated in those with pre-existing atherosclerosis,” he said.

Although Dr. Inzucchi said that he is skeptical that any of the numerous ongoing cardiovascular outcomes trials (CVOTs) will be able to show such a benefit unless a particular agent shows “some dramatic off-target effect on atherosclerosis,” which is an unlikely outcome since glucose lowering has only a modest effect that is disclosed only after a number of years, he noted. It is “just kind of fun to think that, if one of these CVOTs does turn positive … that drug may potentially be positioned as the favored treatment in addition to metformin. Obviously, it depends on the degree of risk reduction and other effects as well, but only then will we have achieved the holy grail.”

sworcester@frontlinemedcom.com

BOSTON – The ELIXA trial confirms that the GLP-1 receptor agonist lixisenatide neither decreases nor increases the risk of major adverse cardiac events in postacute coronary syndrome patients, and that it improves glucose control, compared with placebo, and provides modest benefits with respect to body weight, blood pressure, progression of albuminuria, and hypoglycemia rates, Dr. Silvio E. Inzucchi said at the annual scientific sessions of the American Diabetes Association.

Particularly encouraging was the lack of any signal for pancreatic injury, thyroid cancer, or heart failure. The latter finding is especially timely given recent concerns raised by DPP-4 inhibitors, said Dr. Inzucchi, who was invited by the ADA to comment on the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important end point, “the answer to this is a resounding yes,” he said, congratulating the investigators, who “have done a fine job of conducting this study, which represents another example of the great collaboration between diabetologists and cardiologists.”

“We all see the same patients and we need to work more and more together to find out the best treatments for our patients,” he said, noting that finding a glucose-lowering agent that has a clearcut cardiovascular benefit represents the “holy grail.”

The neutral finding, as opposed to a positive one, in ELIXA with respect to effects on cardiovascular outcomes is not surprising, said Dr. Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn.

“Hypoglycemia is more tightly linked to micro- than to macrovascular outcomes, so not surprisingly it is much easier to show a benefit on these microvascular complications from controlling blood glucose. Any cardiovascular benefit accrues over many years, outside the time course of most of our randomized clinical trials, and any cardiovascular benefit is likely to be attenuated in those with pre-existing atherosclerosis,” he said.

Although Dr. Inzucchi said that he is skeptical that any of the numerous ongoing cardiovascular outcomes trials (CVOTs) will be able to show such a benefit unless a particular agent shows “some dramatic off-target effect on atherosclerosis,” which is an unlikely outcome since glucose lowering has only a modest effect that is disclosed only after a number of years, he noted. It is “just kind of fun to think that, if one of these CVOTs does turn positive … that drug may potentially be positioned as the favored treatment in addition to metformin. Obviously, it depends on the degree of risk reduction and other effects as well, but only then will we have achieved the holy grail.”

sworcester@frontlinemedcom.com

BOSTON – The ELIXA trial confirms that the GLP-1 receptor agonist lixisenatide neither decreases nor increases the risk of major adverse cardiac events in postacute coronary syndrome patients, and that it improves glucose control, compared with placebo, and provides modest benefits with respect to body weight, blood pressure, progression of albuminuria, and hypoglycemia rates, Dr. Silvio E. Inzucchi said at the annual scientific sessions of the American Diabetes Association.

Particularly encouraging was the lack of any signal for pancreatic injury, thyroid cancer, or heart failure. The latter finding is especially timely given recent concerns raised by DPP-4 inhibitors, said Dr. Inzucchi, who was invited by the ADA to comment on the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important end point, “the answer to this is a resounding yes,” he said, congratulating the investigators, who “have done a fine job of conducting this study, which represents another example of the great collaboration between diabetologists and cardiologists.”

“We all see the same patients and we need to work more and more together to find out the best treatments for our patients,” he said, noting that finding a glucose-lowering agent that has a clearcut cardiovascular benefit represents the “holy grail.”

The neutral finding, as opposed to a positive one, in ELIXA with respect to effects on cardiovascular outcomes is not surprising, said Dr. Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn.

“Hypoglycemia is more tightly linked to micro- than to macrovascular outcomes, so not surprisingly it is much easier to show a benefit on these microvascular complications from controlling blood glucose. Any cardiovascular benefit accrues over many years, outside the time course of most of our randomized clinical trials, and any cardiovascular benefit is likely to be attenuated in those with pre-existing atherosclerosis,” he said.

Although Dr. Inzucchi said that he is skeptical that any of the numerous ongoing cardiovascular outcomes trials (CVOTs) will be able to show such a benefit unless a particular agent shows “some dramatic off-target effect on atherosclerosis,” which is an unlikely outcome since glucose lowering has only a modest effect that is disclosed only after a number of years, he noted. It is “just kind of fun to think that, if one of these CVOTs does turn positive … that drug may potentially be positioned as the favored treatment in addition to metformin. Obviously, it depends on the degree of risk reduction and other effects as well, but only then will we have achieved the holy grail.”

sworcester@frontlinemedcom.com

BOSTON – Findings presented at the annual scientific sessions of the American Diabetes Association showed that one widely used glucose-lowering agent, sitagliptin, was not associated with an increase in major atherosclerotic cardiovascular events or hospitalizations for heart failure, compared with placebo.

Results from TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) were reassuring to clinicians who consider sitagliptin (Januvia), like other dipeptidyl peptidase-4 (DPP-4) inhibitors, to be a well-tolerated, effective drug not associated with weight gain or hypoglycemia in patients with type 2 diabetes.

The TECOS findings, however, did raise questions about whether sitagliptin was different than other DPP-4 inhibitors in people with known cardiovascular disease.

A randomized controlled trial of saxagliptin (Onglyza) found a 27% increased risk of hospitalization for heart failure, compared with placebo.

A trial of alogliptin (Nesina) saw a numerical imbalance in hospitalizations for heart failure that did not reach statistical significance.

Speaking at the conference after the presentation of the TECOS findings, Dr. Allison B. Goldfine, head of the section of clinical, behavioral, and outcomes research at the Joslin Diabetes Center and of Harvard Medical School, both in Boston, who was not an investigator on any of the three trials, suggested several potential reasons that the signal for heart failure hospitalizations was inconsistent across the trials.

Dr. Goldfine pointed to important differences in trial design and duration. Patients in the alogliptin trial had acute coronary syndrome at baseline and hemoglobin A_1c levels of between 6.5% and 11%, and they were followed up a median of 18 months.

Patients in the saxagliptin trial had either established cardiovascular disease or multiple risk factors for vascular disease, HbA_1c of 6.5%-12%, and were followed 2 years. TECOS patients had a history of coronary artery disease, ischemic cerebrovascular disease, or atherosclerotic peripheral arterial disease, and had an HbA_1c between 6.5% and 8%. They were followed for 3 years.

Dr. Goldfine also noted the potential for differences in activity among the individual agents. “There are some different specificities and the potential for on- and off-target effects across these drugs,” she said, though these remain poorly understood.

“Is it a class effect? Maybe not, as there was no hospitalization for heart failure increase in TECOS,” Dr. Goldfine said. “But I want you to be very cautious in using this interpretation. These were not head-to-head studies, and there were differences in the patient illnesses and severities, comorbidities and concomitant therapies, sample sizes, duration of follow up, and a potential for altered attentiveness and therapeutic practices due to these baseline differences.”

Clinicians considering use of the DPP4 inhibitors “need to realize that there’s some uncertainty when evaluating the risk and benefit of any of our drugs,” she noted.

The TECOS findings will not be the last word on DPP-4 inhibitors and the mixed signals on heart failure seen to date, Dr. Goldfine said. “I think a lot of effort will go on in the very near future to try to understand these better to see if there’s an explanation.”

Dr. Goldfine disclosed past research support from Amneal, LifeScan, Nestle, Novo, and Nordisk.

BOSTON – Findings presented at the annual scientific sessions of the American Diabetes Association showed that one widely used glucose-lowering agent, sitagliptin, was not associated with an increase in major atherosclerotic cardiovascular events or hospitalizations for heart failure, compared with placebo.

Results from TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) were reassuring to clinicians who consider sitagliptin (Januvia), like other dipeptidyl peptidase-4 (DPP-4) inhibitors, to be a well-tolerated, effective drug not associated with weight gain or hypoglycemia in patients with type 2 diabetes.

The TECOS findings, however, did raise questions about whether sitagliptin was different than other DPP-4 inhibitors in people with known cardiovascular disease.

A randomized controlled trial of saxagliptin (Onglyza) found a 27% increased risk of hospitalization for heart failure, compared with placebo.

A trial of alogliptin (Nesina) saw a numerical imbalance in hospitalizations for heart failure that did not reach statistical significance.

Speaking at the conference after the presentation of the TECOS findings, Dr. Allison B. Goldfine, head of the section of clinical, behavioral, and outcomes research at the Joslin Diabetes Center and of Harvard Medical School, both in Boston, who was not an investigator on any of the three trials, suggested several potential reasons that the signal for heart failure hospitalizations was inconsistent across the trials.

Dr. Goldfine pointed to important differences in trial design and duration. Patients in the alogliptin trial had acute coronary syndrome at baseline and hemoglobin A_1c levels of between 6.5% and 11%, and they were followed up a median of 18 months.

Patients in the saxagliptin trial had either established cardiovascular disease or multiple risk factors for vascular disease, HbA_1c of 6.5%-12%, and were followed 2 years. TECOS patients had a history of coronary artery disease, ischemic cerebrovascular disease, or atherosclerotic peripheral arterial disease, and had an HbA_1c between 6.5% and 8%. They were followed for 3 years.

Dr. Goldfine also noted the potential for differences in activity among the individual agents. “There are some different specificities and the potential for on- and off-target effects across these drugs,” she said, though these remain poorly understood.

“Is it a class effect? Maybe not, as there was no hospitalization for heart failure increase in TECOS,” Dr. Goldfine said. “But I want you to be very cautious in using this interpretation. These were not head-to-head studies, and there were differences in the patient illnesses and severities, comorbidities and concomitant therapies, sample sizes, duration of follow up, and a potential for altered attentiveness and therapeutic practices due to these baseline differences.”

Clinicians considering use of the DPP4 inhibitors “need to realize that there’s some uncertainty when evaluating the risk and benefit of any of our drugs,” she noted.

The TECOS findings will not be the last word on DPP-4 inhibitors and the mixed signals on heart failure seen to date, Dr. Goldfine said. “I think a lot of effort will go on in the very near future to try to understand these better to see if there’s an explanation.”

Dr. Goldfine disclosed past research support from Amneal, LifeScan, Nestle, Novo, and Nordisk.

BOSTON – Findings presented at the annual scientific sessions of the American Diabetes Association showed that one widely used glucose-lowering agent, sitagliptin, was not associated with an increase in major atherosclerotic cardiovascular events or hospitalizations for heart failure, compared with placebo.

Results from TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) were reassuring to clinicians who consider sitagliptin (Januvia), like other dipeptidyl peptidase-4 (DPP-4) inhibitors, to be a well-tolerated, effective drug not associated with weight gain or hypoglycemia in patients with type 2 diabetes.

The TECOS findings, however, did raise questions about whether sitagliptin was different than other DPP-4 inhibitors in people with known cardiovascular disease.

A randomized controlled trial of saxagliptin (Onglyza) found a 27% increased risk of hospitalization for heart failure, compared with placebo.

A trial of alogliptin (Nesina) saw a numerical imbalance in hospitalizations for heart failure that did not reach statistical significance.

Speaking at the conference after the presentation of the TECOS findings, Dr. Allison B. Goldfine, head of the section of clinical, behavioral, and outcomes research at the Joslin Diabetes Center and of Harvard Medical School, both in Boston, who was not an investigator on any of the three trials, suggested several potential reasons that the signal for heart failure hospitalizations was inconsistent across the trials.

Dr. Goldfine pointed to important differences in trial design and duration. Patients in the alogliptin trial had acute coronary syndrome at baseline and hemoglobin A_1c levels of between 6.5% and 11%, and they were followed up a median of 18 months.

Patients in the saxagliptin trial had either established cardiovascular disease or multiple risk factors for vascular disease, HbA_1c of 6.5%-12%, and were followed 2 years. TECOS patients had a history of coronary artery disease, ischemic cerebrovascular disease, or atherosclerotic peripheral arterial disease, and had an HbA_1c between 6.5% and 8%. They were followed for 3 years.

Dr. Goldfine also noted the potential for differences in activity among the individual agents. “There are some different specificities and the potential for on- and off-target effects across these drugs,” she said, though these remain poorly understood.

“Is it a class effect? Maybe not, as there was no hospitalization for heart failure increase in TECOS,” Dr. Goldfine said. “But I want you to be very cautious in using this interpretation. These were not head-to-head studies, and there were differences in the patient illnesses and severities, comorbidities and concomitant therapies, sample sizes, duration of follow up, and a potential for altered attentiveness and therapeutic practices due to these baseline differences.”

Clinicians considering use of the DPP4 inhibitors “need to realize that there’s some uncertainty when evaluating the risk and benefit of any of our drugs,” she noted.

The TECOS findings will not be the last word on DPP-4 inhibitors and the mixed signals on heart failure seen to date, Dr. Goldfine said. “I think a lot of effort will go on in the very near future to try to understand these better to see if there’s an explanation.”

Dr. Goldfine disclosed past research support from Amneal, LifeScan, Nestle, Novo, and Nordisk.

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

sworcester@frontlinemedcom.com

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

sworcester@frontlinemedcom.com

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

sworcester@frontlinemedcom.com

BOSTON – The glucose-lowering drug sitagliptin, part of a class of drugs whose cardiovascular safety has been cast into doubt based on findings in trials of similar agents, was shown not to increase the risk of heart failure or other adverse cardiovascular outcomes in a large randomized trial.

Results presented June 8 at the annual scientific sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine (doi:10.1056/NEJMoa1501352) revealed “no evidence of harm one way or another” for cardiovascular events or heart failure, Dr. Rury F. Holman, professor of diabetic medicine and diabetes trials unit director at the Oxford (England) Centre for Diabetes, Endocrinology & Metabolism, the study’s corresponding author, said at a press conference.

Though the manufacturer announced the main cardiovascular findings on sitagliptin (Januvia), earlier this year, the details of this trial – driven by concerns about a signal for increased risk of heart failure in two earlier trials of dipeptidyl peptidase 4 (DPP-4) inhibitors – were presented for the first time.

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) enrolled 14,671 patients with type 2 diabetes in combination with cardiovascular disease who were age 50 years or older. Patients were recruited in 38 countries and randomized to add-on therapy with

sitagliptin or placebo in addition to other antihyperglycemic therapies used openly at physician discretion. At mean 3 years’ follow-up, sitagliptin was noninferior to placebo for a combined cardiovascular endpoint comprising first time to CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09, P < .001).

Hospitalizations for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.83-1.20, P = .98), and no significant differences were seen in rates of pancreatitis or pancreatic cancer.

All patients in both the control and intervention arms were treated to similar glucose targets by their physicians. Levels of glycated hemoglobin between the groups were close throughout the study period, with a difference of –0.29 for the sitagliptin arm (95% CI, –0.32 to –0.27). “That’s important because we didn’t want a glucose difference that might have influenced the cardiovascular outcomes one way or another,” Dr. Holman commented.

Dr. Eric D. Peterson, executive director of the Duke Clinical Research Institute as well as professor in the departments of medicine and cardiology and the Fred Cobb, MD, Distinguished Professor of Medicine of Duke University, Durham, N.C., who was a coauthor on the study, commented on its heart failure finding. TECOS had been prompted by unexpected

heart-failure signals seen in two earlier trials of DPP-4 inhibitors, saxagliptin and alogliptin.

“Given the size of our study, and the longer duration of follow-up, as well as the higher risk of our population, we feel that this puts to bed the question – at least with sitagliptin – that there’s any risk for heart failure increases,” Dr. Peterson said.

The investigators were careful to assert that few conclusions could be drawn for the class of drugs as a whole based on the TECOS findings but suggested chance could have played a role in the earlier studies.

The study was funded by sitagliptin’s manufacturer, Merck Sharp & Dohme. Dr. Holman disclosed a financial relationship with the study sponsor. Dr. Peterson disclosed financial relationships with other manufacturers.

BOSTON – The glucose-lowering drug sitagliptin, part of a class of drugs whose cardiovascular safety has been cast into doubt based on findings in trials of similar agents, was shown not to increase the risk of heart failure or other adverse cardiovascular outcomes in a large randomized trial.

Results presented June 8 at the annual scientific sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine (doi:10.1056/NEJMoa1501352) revealed “no evidence of harm one way or another” for cardiovascular events or heart failure, Dr. Rury F. Holman, professor of diabetic medicine and diabetes trials unit director at the Oxford (England) Centre for Diabetes, Endocrinology & Metabolism, the study’s corresponding author, said at a press conference.

Though the manufacturer announced the main cardiovascular findings on sitagliptin (Januvia), earlier this year, the details of this trial – driven by concerns about a signal for increased risk of heart failure in two earlier trials of dipeptidyl peptidase 4 (DPP-4) inhibitors – were presented for the first time.

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) enrolled 14,671 patients with type 2 diabetes in combination with cardiovascular disease who were age 50 years or older. Patients were recruited in 38 countries and randomized to add-on therapy with

sitagliptin or placebo in addition to other antihyperglycemic therapies used openly at physician discretion. At mean 3 years’ follow-up, sitagliptin was noninferior to placebo for a combined cardiovascular endpoint comprising first time to CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09, P < .001).

Hospitalizations for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.83-1.20, P = .98), and no significant differences were seen in rates of pancreatitis or pancreatic cancer.

All patients in both the control and intervention arms were treated to similar glucose targets by their physicians. Levels of glycated hemoglobin between the groups were close throughout the study period, with a difference of –0.29 for the sitagliptin arm (95% CI, –0.32 to –0.27). “That’s important because we didn’t want a glucose difference that might have influenced the cardiovascular outcomes one way or another,” Dr. Holman commented.

Dr. Eric D. Peterson, executive director of the Duke Clinical Research Institute as well as professor in the departments of medicine and cardiology and the Fred Cobb, MD, Distinguished Professor of Medicine of Duke University, Durham, N.C., who was a coauthor on the study, commented on its heart failure finding. TECOS had been prompted by unexpected

heart-failure signals seen in two earlier trials of DPP-4 inhibitors, saxagliptin and alogliptin.

“Given the size of our study, and the longer duration of follow-up, as well as the higher risk of our population, we feel that this puts to bed the question – at least with sitagliptin – that there’s any risk for heart failure increases,” Dr. Peterson said.

The investigators were careful to assert that few conclusions could be drawn for the class of drugs as a whole based on the TECOS findings but suggested chance could have played a role in the earlier studies.

The study was funded by sitagliptin’s manufacturer, Merck Sharp & Dohme. Dr. Holman disclosed a financial relationship with the study sponsor. Dr. Peterson disclosed financial relationships with other manufacturers.

BOSTON – The glucose-lowering drug sitagliptin, part of a class of drugs whose cardiovascular safety has been cast into doubt based on findings in trials of similar agents, was shown not to increase the risk of heart failure or other adverse cardiovascular outcomes in a large randomized trial.

Results presented June 8 at the annual scientific sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine (doi:10.1056/NEJMoa1501352) revealed “no evidence of harm one way or another” for cardiovascular events or heart failure, Dr. Rury F. Holman, professor of diabetic medicine and diabetes trials unit director at the Oxford (England) Centre for Diabetes, Endocrinology & Metabolism, the study’s corresponding author, said at a press conference.

Though the manufacturer announced the main cardiovascular findings on sitagliptin (Januvia), earlier this year, the details of this trial – driven by concerns about a signal for increased risk of heart failure in two earlier trials of dipeptidyl peptidase 4 (DPP-4) inhibitors – were presented for the first time.

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) enrolled 14,671 patients with type 2 diabetes in combination with cardiovascular disease who were age 50 years or older. Patients were recruited in 38 countries and randomized to add-on therapy with

sitagliptin or placebo in addition to other antihyperglycemic therapies used openly at physician discretion. At mean 3 years’ follow-up, sitagliptin was noninferior to placebo for a combined cardiovascular endpoint comprising first time to CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09, P < .001).

Hospitalizations for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.83-1.20, P = .98), and no significant differences were seen in rates of pancreatitis or pancreatic cancer.

All patients in both the control and intervention arms were treated to similar glucose targets by their physicians. Levels of glycated hemoglobin between the groups were close throughout the study period, with a difference of –0.29 for the sitagliptin arm (95% CI, –0.32 to –0.27). “That’s important because we didn’t want a glucose difference that might have influenced the cardiovascular outcomes one way or another,” Dr. Holman commented.

Dr. Eric D. Peterson, executive director of the Duke Clinical Research Institute as well as professor in the departments of medicine and cardiology and the Fred Cobb, MD, Distinguished Professor of Medicine of Duke University, Durham, N.C., who was a coauthor on the study, commented on its heart failure finding. TECOS had been prompted by unexpected

heart-failure signals seen in two earlier trials of DPP-4 inhibitors, saxagliptin and alogliptin.

“Given the size of our study, and the longer duration of follow-up, as well as the higher risk of our population, we feel that this puts to bed the question – at least with sitagliptin – that there’s any risk for heart failure increases,” Dr. Peterson said.

The investigators were careful to assert that few conclusions could be drawn for the class of drugs as a whole based on the TECOS findings but suggested chance could have played a role in the earlier studies.

The study was funded by sitagliptin’s manufacturer, Merck Sharp & Dohme. Dr. Holman disclosed a financial relationship with the study sponsor. Dr. Peterson disclosed financial relationships with other manufacturers.

BOSTON – An implantable cardioverter defibrillator device that can safely undergo magnetic resonance imaging may soon be a commercial reality as two different models from two different manufacturers showed safety and mostly uncompromised efficacy during and after MRI in two separate studies reported at the annual scientific sessions of the Heart Rhythm Society.

The impending availability of two different brands of implantable cardioverter defibrillators (ICDs) that allow patients to safely undergo MRI “will hopefully open a new era when most [ICDs] are designed” to be MRI safe, said Dr. Khaled A. Awad, an electrophysiologist at the University of Alabama at Birmingham, and lead investigator for one of the new studies.

“Within 10 years, all ICDs getting implanted will be MRI compatible,” predicted Dr. Michael R. Gold, chief of cardiology and medical director of the heart and vascular center at the Medical University of South Carolina in Charleston and lead investigator for the second study.

Until now, having an ICD in a patient created a contraindication for using MRI on the patient, a situation that would change once MRI-safe ICDs become routinely available, noted Dr. Gold. MRI-compatible implanted pacemakers have been on the U.S. market since 2011; ICDs able to safely undergo MRI exposure became the next frontier for creating implanted cardiovascular devices that allow MRIs. Both studies used MRI performed with a 1.5-T magnetic field, a strength commonly used in routine practice today.

The ProMRI study reported by Dr. Awad enrolled patients at 39 U.S. centers who at least 5 weeks previously had received an Iforia ICD made by Biotronik along with commercially available leads believed to be MRI safe. The researchers performed MRIs of the heart or thoracic spine on 154 patients, and then ran follow-up examinations on 150 patients 1 month after the MRI, and a second, 3-month follow-up on 92 of the enrolled patients. The study did not include any control patients who received the ICD and did not undergo MRI.

No patient had an adverse event related or possibly related to their ICD either at the time of the MRI or at follow-up, Dr. Awad reported. In addition, no patients had a significant change in their ICD’s ventricular capture threshold, and one patient had a significant change in the ICD’s ventricular sensing. During follow-up, the ICDs of enrolled patients detected a total of 403 ventricular arrhythmias in 39 patients, with all these episodes appropriately detected and treated.

The study reported by Dr. Gold enrolled patients at 42 centers in 13 countries including the United States. The investigators implanted ICDs into 263 patients using commercially available leads, and then 9-12 weeks after placement, they randomized patients at a 2:1 rate to either undergo MRI or receive no MRI and serve as controls. Of the 175 patients randomized to undergo MRI, 156 actually received the examination, a full-body examination, and 147 participated in follow-up to at least 1 month and were part of the safety analysis.

Patient follow-up showed no complications, no episodes of a significant change in ventricular-pacing sensing threshold, and one episode of a significant change in ventricular-sensing amplitude, Dr. Gold reported, showing safety and efficacy outcomes identical to those in the trial of the Biotronik device. During follow-up 34 episodes of ventricular tachycardia or fibrillation occurred in 24 patients in the MRI group, and the implanted ICDs detected and treated all episodes appropriately. Concurrent with Dr. Gold’s report, the results also appeared in an article published online (J. Am. Coll. Cardiol. 2015 [doi:10.1016/j.jacc.2015.04.047]).

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler 

BOSTON – An implantable cardioverter defibrillator device that can safely undergo magnetic resonance imaging may soon be a commercial reality as two different models from two different manufacturers showed safety and mostly uncompromised efficacy during and after MRI in two separate studies reported at the annual scientific sessions of the Heart Rhythm Society.

The impending availability of two different brands of implantable cardioverter defibrillators (ICDs) that allow patients to safely undergo MRI “will hopefully open a new era when most [ICDs] are designed” to be MRI safe, said Dr. Khaled A. Awad, an electrophysiologist at the University of Alabama at Birmingham, and lead investigator for one of the new studies.

“Within 10 years, all ICDs getting implanted will be MRI compatible,” predicted Dr. Michael R. Gold, chief of cardiology and medical director of the heart and vascular center at the Medical University of South Carolina in Charleston and lead investigator for the second study.

Until now, having an ICD in a patient created a contraindication for using MRI on the patient, a situation that would change once MRI-safe ICDs become routinely available, noted Dr. Gold. MRI-compatible implanted pacemakers have been on the U.S. market since 2011; ICDs able to safely undergo MRI exposure became the next frontier for creating implanted cardiovascular devices that allow MRIs. Both studies used MRI performed with a 1.5-T magnetic field, a strength commonly used in routine practice today.

The ProMRI study reported by Dr. Awad enrolled patients at 39 U.S. centers who at least 5 weeks previously had received an Iforia ICD made by Biotronik along with commercially available leads believed to be MRI safe. The researchers performed MRIs of the heart or thoracic spine on 154 patients, and then ran follow-up examinations on 150 patients 1 month after the MRI, and a second, 3-month follow-up on 92 of the enrolled patients. The study did not include any control patients who received the ICD and did not undergo MRI.

No patient had an adverse event related or possibly related to their ICD either at the time of the MRI or at follow-up, Dr. Awad reported. In addition, no patients had a significant change in their ICD’s ventricular capture threshold, and one patient had a significant change in the ICD’s ventricular sensing. During follow-up, the ICDs of enrolled patients detected a total of 403 ventricular arrhythmias in 39 patients, with all these episodes appropriately detected and treated.

The study reported by Dr. Gold enrolled patients at 42 centers in 13 countries including the United States. The investigators implanted ICDs into 263 patients using commercially available leads, and then 9-12 weeks after placement, they randomized patients at a 2:1 rate to either undergo MRI or receive no MRI and serve as controls. Of the 175 patients randomized to undergo MRI, 156 actually received the examination, a full-body examination, and 147 participated in follow-up to at least 1 month and were part of the safety analysis.

Patient follow-up showed no complications, no episodes of a significant change in ventricular-pacing sensing threshold, and one episode of a significant change in ventricular-sensing amplitude, Dr. Gold reported, showing safety and efficacy outcomes identical to those in the trial of the Biotronik device. During follow-up 34 episodes of ventricular tachycardia or fibrillation occurred in 24 patients in the MRI group, and the implanted ICDs detected and treated all episodes appropriately. Concurrent with Dr. Gold’s report, the results also appeared in an article published online (J. Am. Coll. Cardiol. 2015 [doi:10.1016/j.jacc.2015.04.047]).

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler 

BOSTON – An implantable cardioverter defibrillator device that can safely undergo magnetic resonance imaging may soon be a commercial reality as two different models from two different manufacturers showed safety and mostly uncompromised efficacy during and after MRI in two separate studies reported at the annual scientific sessions of the Heart Rhythm Society.

The impending availability of two different brands of implantable cardioverter defibrillators (ICDs) that allow patients to safely undergo MRI “will hopefully open a new era when most [ICDs] are designed” to be MRI safe, said Dr. Khaled A. Awad, an electrophysiologist at the University of Alabama at Birmingham, and lead investigator for one of the new studies.

“Within 10 years, all ICDs getting implanted will be MRI compatible,” predicted Dr. Michael R. Gold, chief of cardiology and medical director of the heart and vascular center at the Medical University of South Carolina in Charleston and lead investigator for the second study.

Until now, having an ICD in a patient created a contraindication for using MRI on the patient, a situation that would change once MRI-safe ICDs become routinely available, noted Dr. Gold. MRI-compatible implanted pacemakers have been on the U.S. market since 2011; ICDs able to safely undergo MRI exposure became the next frontier for creating implanted cardiovascular devices that allow MRIs. Both studies used MRI performed with a 1.5-T magnetic field, a strength commonly used in routine practice today.

The ProMRI study reported by Dr. Awad enrolled patients at 39 U.S. centers who at least 5 weeks previously had received an Iforia ICD made by Biotronik along with commercially available leads believed to be MRI safe. The researchers performed MRIs of the heart or thoracic spine on 154 patients, and then ran follow-up examinations on 150 patients 1 month after the MRI, and a second, 3-month follow-up on 92 of the enrolled patients. The study did not include any control patients who received the ICD and did not undergo MRI.

No patient had an adverse event related or possibly related to their ICD either at the time of the MRI or at follow-up, Dr. Awad reported. In addition, no patients had a significant change in their ICD’s ventricular capture threshold, and one patient had a significant change in the ICD’s ventricular sensing. During follow-up, the ICDs of enrolled patients detected a total of 403 ventricular arrhythmias in 39 patients, with all these episodes appropriately detected and treated.

The study reported by Dr. Gold enrolled patients at 42 centers in 13 countries including the United States. The investigators implanted ICDs into 263 patients using commercially available leads, and then 9-12 weeks after placement, they randomized patients at a 2:1 rate to either undergo MRI or receive no MRI and serve as controls. Of the 175 patients randomized to undergo MRI, 156 actually received the examination, a full-body examination, and 147 participated in follow-up to at least 1 month and were part of the safety analysis.

Patient follow-up showed no complications, no episodes of a significant change in ventricular-pacing sensing threshold, and one episode of a significant change in ventricular-sensing amplitude, Dr. Gold reported, showing safety and efficacy outcomes identical to those in the trial of the Biotronik device. During follow-up 34 episodes of ventricular tachycardia or fibrillation occurred in 24 patients in the MRI group, and the implanted ICDs detected and treated all episodes appropriately. Concurrent with Dr. Gold’s report, the results also appeared in an article published online (J. Am. Coll. Cardiol. 2015 [doi:10.1016/j.jacc.2015.04.047]).

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler 

NEW YORK – What if correcting secondary mitral regurgitation doesn’t improve patients’ lives or helps them live longer? What if results of the COAPT trial of the MitraClip (Abbott Vascular) repair for mitral regurgitation are negative or inconclusive? What if transcatheter mitral valve repair works too well?

The answers to these questions could determine the future landscape of transcatheter mitral valve replacement (TMVR) for mitral regurgitation (MR) and the prosthetics in various stages of clinical and preclinical investigation, Dr. Michael Mack of Baylor University said at the 2015 Mitral Valve Conclave, which was sponsored by the American Association for Thoracic Surgery.

Dr. Mack reviewed the first four transcatheter mitral valve replacement devices approved for early feasibility studies in the United States, noting that “it has become a very crowded field very quickly,” especially when one considers that only between 20 and 50 TMVR procedures have been done worldwide up until now.

For the makers of the devices, it is becoming a potentially perilous field as well. Replacement, Dr. Mack said, does meet a “large clinical unmet need” in that it can completely correct mitral regurgitation better than valve repair.

“But what are the challenges for transcatheter mitral valve replacement and why isn’t this going to be the same as TAVR (transcatheter aortic valve replacement) all over again?” he said. “Unlike aortic stenosis, there is not a single cause of mitral regurgitation. In addition, it has never even been definitively proven that correcting MR helps prolong survival and improve quality of life.”

Another obstacle for TMVR is that delivery of the device into the mitral valve is more complex than doing so in the aortic valve. “The seating and the anchoring of the valve is more complex,” Dr. Mack said. “Based on the profile of the device, left ventricular outflow tract obstruction can be an issue, and perivalvular leak may carry more import here because mitral perivalvular leaks have the potential to cause hemololysis.”

He reviewed the four systems cleared for early feasibility studies.

CardiAQ (CardiAQ Valve Technologies), a porcine pericardial valve, has been implanted in eight patients worldwide and last month received Food and Drug Administration (FDA) approval for early feasibility study in 20 U.S. patients: 10 by a transfemoral approach and 10 by a transapical approach.

Tendyne Bioprosthetic Mitral Valve (Tendyne Holdings), a trileaflet porcine pericardium, also has been implanted in eight patients worldwide and was used for the first time in the United States last month by Dr. Wes Pederson and colleagues at the Minneapolis Heart Institute.

FORTIS (Edwards Lifesciences), a bovine pericardium valve, has been implanted in early feasibility trials in Europe and has been approved for an early feasibility trial of 15 patients in the United States.

Tiara (Neovasc), a D-shaped bovine pericardium valve, received FDA approval last year for the TIARA-I early feasibility trial in the United States (NCT02276547). The trial will enroll up to 30 patients worldwide.

At least five other TMVR devices are in preclinical studies, Dr. Mack said. These emerging devices face “threats and obstacles” as they move through the pipeline – a number of “what ifs,” Dr. Mack said.

“What if you can’t prove that correcting secondary mitral regurgitation makes a difference? What are the repercussions of the COAPT Trial (NCT01626079) of the MitraClip if it is positive and shows that correcting mitral regurgitation does make a difference? Does completely correcting mitral regurgitation then really make a difference? What if transcatheter mitral valve repair works too well?” (COAPT stands for Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). “With the excellent safety profile of MitraClip, it may be hard to justify TMVR,” he said.

Dr. Mack noted that MitraClip for mitral valve repair has “a superb safety profile.” He added, “How do you choose what patients should be treated by a mitral valve replacement vs. a MitraClip by a transfemoral venous approach that enables them to go home the next day?”

The early feasibility trials of TMVR devices may point a way to answers.

Dr. Mack has received research grants from Edwards Lifesciences. He is a principal investigator in the ongoing COAPT Trial, which is sponsored by EVALVE with the collaboration of Abbott Vascular.

NEW YORK – What if correcting secondary mitral regurgitation doesn’t improve patients’ lives or helps them live longer? What if results of the COAPT trial of the MitraClip (Abbott Vascular) repair for mitral regurgitation are negative or inconclusive? What if transcatheter mitral valve repair works too well?

The answers to these questions could determine the future landscape of transcatheter mitral valve replacement (TMVR) for mitral regurgitation (MR) and the prosthetics in various stages of clinical and preclinical investigation, Dr. Michael Mack of Baylor University said at the 2015 Mitral Valve Conclave, which was sponsored by the American Association for Thoracic Surgery.

Dr. Mack reviewed the first four transcatheter mitral valve replacement devices approved for early feasibility studies in the United States, noting that “it has become a very crowded field very quickly,” especially when one considers that only between 20 and 50 TMVR procedures have been done worldwide up until now.

For the makers of the devices, it is becoming a potentially perilous field as well. Replacement, Dr. Mack said, does meet a “large clinical unmet need” in that it can completely correct mitral regurgitation better than valve repair.

“But what are the challenges for transcatheter mitral valve replacement and why isn’t this going to be the same as TAVR (transcatheter aortic valve replacement) all over again?” he said. “Unlike aortic stenosis, there is not a single cause of mitral regurgitation. In addition, it has never even been definitively proven that correcting MR helps prolong survival and improve quality of life.”

Another obstacle for TMVR is that delivery of the device into the mitral valve is more complex than doing so in the aortic valve. “The seating and the anchoring of the valve is more complex,” Dr. Mack said. “Based on the profile of the device, left ventricular outflow tract obstruction can be an issue, and perivalvular leak may carry more import here because mitral perivalvular leaks have the potential to cause hemololysis.”

He reviewed the four systems cleared for early feasibility studies.

CardiAQ (CardiAQ Valve Technologies), a porcine pericardial valve, has been implanted in eight patients worldwide and last month received Food and Drug Administration (FDA) approval for early feasibility study in 20 U.S. patients: 10 by a transfemoral approach and 10 by a transapical approach.

Tendyne Bioprosthetic Mitral Valve (Tendyne Holdings), a trileaflet porcine pericardium, also has been implanted in eight patients worldwide and was used for the first time in the United States last month by Dr. Wes Pederson and colleagues at the Minneapolis Heart Institute.

FORTIS (Edwards Lifesciences), a bovine pericardium valve, has been implanted in early feasibility trials in Europe and has been approved for an early feasibility trial of 15 patients in the United States.

Tiara (Neovasc), a D-shaped bovine pericardium valve, received FDA approval last year for the TIARA-I early feasibility trial in the United States (NCT02276547). The trial will enroll up to 30 patients worldwide.

At least five other TMVR devices are in preclinical studies, Dr. Mack said. These emerging devices face “threats and obstacles” as they move through the pipeline – a number of “what ifs,” Dr. Mack said.

“What if you can’t prove that correcting secondary mitral regurgitation makes a difference? What are the repercussions of the COAPT Trial (NCT01626079) of the MitraClip if it is positive and shows that correcting mitral regurgitation does make a difference? Does completely correcting mitral regurgitation then really make a difference? What if transcatheter mitral valve repair works too well?” (COAPT stands for Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). “With the excellent safety profile of MitraClip, it may be hard to justify TMVR,” he said.

Dr. Mack noted that MitraClip for mitral valve repair has “a superb safety profile.” He added, “How do you choose what patients should be treated by a mitral valve replacement vs. a MitraClip by a transfemoral venous approach that enables them to go home the next day?”

The early feasibility trials of TMVR devices may point a way to answers.

Dr. Mack has received research grants from Edwards Lifesciences. He is a principal investigator in the ongoing COAPT Trial, which is sponsored by EVALVE with the collaboration of Abbott Vascular.

NEW YORK – What if correcting secondary mitral regurgitation doesn’t improve patients’ lives or helps them live longer? What if results of the COAPT trial of the MitraClip (Abbott Vascular) repair for mitral regurgitation are negative or inconclusive? What if transcatheter mitral valve repair works too well?

The answers to these questions could determine the future landscape of transcatheter mitral valve replacement (TMVR) for mitral regurgitation (MR) and the prosthetics in various stages of clinical and preclinical investigation, Dr. Michael Mack of Baylor University said at the 2015 Mitral Valve Conclave, which was sponsored by the American Association for Thoracic Surgery.

Dr. Mack reviewed the first four transcatheter mitral valve replacement devices approved for early feasibility studies in the United States, noting that “it has become a very crowded field very quickly,” especially when one considers that only between 20 and 50 TMVR procedures have been done worldwide up until now.

For the makers of the devices, it is becoming a potentially perilous field as well. Replacement, Dr. Mack said, does meet a “large clinical unmet need” in that it can completely correct mitral regurgitation better than valve repair.

“But what are the challenges for transcatheter mitral valve replacement and why isn’t this going to be the same as TAVR (transcatheter aortic valve replacement) all over again?” he said. “Unlike aortic stenosis, there is not a single cause of mitral regurgitation. In addition, it has never even been definitively proven that correcting MR helps prolong survival and improve quality of life.”

Another obstacle for TMVR is that delivery of the device into the mitral valve is more complex than doing so in the aortic valve. “The seating and the anchoring of the valve is more complex,” Dr. Mack said. “Based on the profile of the device, left ventricular outflow tract obstruction can be an issue, and perivalvular leak may carry more import here because mitral perivalvular leaks have the potential to cause hemololysis.”

He reviewed the four systems cleared for early feasibility studies.

CardiAQ (CardiAQ Valve Technologies), a porcine pericardial valve, has been implanted in eight patients worldwide and last month received Food and Drug Administration (FDA) approval for early feasibility study in 20 U.S. patients: 10 by a transfemoral approach and 10 by a transapical approach.

Tendyne Bioprosthetic Mitral Valve (Tendyne Holdings), a trileaflet porcine pericardium, also has been implanted in eight patients worldwide and was used for the first time in the United States last month by Dr. Wes Pederson and colleagues at the Minneapolis Heart Institute.

FORTIS (Edwards Lifesciences), a bovine pericardium valve, has been implanted in early feasibility trials in Europe and has been approved for an early feasibility trial of 15 patients in the United States.

Tiara (Neovasc), a D-shaped bovine pericardium valve, received FDA approval last year for the TIARA-I early feasibility trial in the United States (NCT02276547). The trial will enroll up to 30 patients worldwide.

At least five other TMVR devices are in preclinical studies, Dr. Mack said. These emerging devices face “threats and obstacles” as they move through the pipeline – a number of “what ifs,” Dr. Mack said.

“What if you can’t prove that correcting secondary mitral regurgitation makes a difference? What are the repercussions of the COAPT Trial (NCT01626079) of the MitraClip if it is positive and shows that correcting mitral regurgitation does make a difference? Does completely correcting mitral regurgitation then really make a difference? What if transcatheter mitral valve repair works too well?” (COAPT stands for Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). “With the excellent safety profile of MitraClip, it may be hard to justify TMVR,” he said.

Dr. Mack noted that MitraClip for mitral valve repair has “a superb safety profile.” He added, “How do you choose what patients should be treated by a mitral valve replacement vs. a MitraClip by a transfemoral venous approach that enables them to go home the next day?”

The early feasibility trials of TMVR devices may point a way to answers.

Dr. Mack has received research grants from Edwards Lifesciences. He is a principal investigator in the ongoing COAPT Trial, which is sponsored by EVALVE with the collaboration of Abbott Vascular.

BOSTON – The problem-plagued St. Jude Riata leads for implantable cardioverter defibrillators, pulled from the U.S. market in 2010, continue to pose problems for the tens of thousands of patients who still have them as clinicians follow these patients out to periods approaching 10 years.

But the risks of lead extraction continue make prophylactic lead removal a poor option for most patients, leaving the alternative of continuing to closely monitor patients for episodes of electrical lead failure, Dr. Ratika Parkash said at the annual scientific sessions of the Heart Rhythm Society.

Mitchel L. Zoler/Frontline Medical News

“Isolated, prophylactic lead revision or extraction is not warranted,” said Dr. Parkash, a cardiac electrophysiologist at Dalhousie University in Halifax, Canada. “We need to take into account a patient’s comorbidities compared with the possibility of cable externalization,” when the conducting cable of the lead moves outside its insulating sheath, one of the main problems with the St. Jude Riata leads, she explained. “I think we need to individualize what we do” based on each patient’s specific situation, but perhaps collecting more data during another 2 years follow-up might shed more light on this issue, she said. Dr. Parkash and her associates followed Riata-lead recipients for an average of 7.5 years to produce the current report.

Although no U.S. patient has received a Riata lead for nearly 5 years, the Food and Drug Administration estimated that at the time St. Jude stopped selling this lead in late 2010 more than 227,000 Riata leads had gone into patients worldwide, including about 79,000 U.S. patients. Last February, St. Jude announced that it had settled 950 lawsuits or claims from U.S. patients who had received Riata leads.

The CREDO (Canadian Registry of Cardiac Implantable Electronic Device Outcomes) prospective registry review reported by Dr. Parkash included data from 2,707 patients who received Riata leads at any of 15 Canadian centers, representing 60% of the 4,538 Canadian residents who had received on of these leads. The patients averaged 63 years of age, 19% were women, 70% had received an 8 French lead and 30% had received a 7F lead, and follow-up data were available for an average of 7.5 years from the time patients received the leads to attach their implantable cardioverter defibrillator (ICD) to their heart.

Mitchel L. Zoler/Frontline Medical News

During follow-up, 378 of the 2,707 patients (14%) required revision of their leads, a rate well above the rates seen collectively for all ICD lead models in data collected in both randomized trials and in the U.S. national registry of ICD implantations maintained by the National Cardiovascular Data Registry (OpenHeart 2015;2: [doi:10.1136/openhrt-2014-000198]). The rate of lead revisions seen with the Riata lead, 14% during 7.5 years follow-up, puts it in the ballpark of the 17% lead-failure rate with 5 year follow-up seen in Canadian patients who received a Sprint Fidelis lead that was marketed by Medtronic.(Circulation 2012:1217-25)

Triggering the 378 Riata revisions were electrical abnormalities, in 42%, lead dislodgement in 18%, cable externalization in 12%, infection in 12%, and several other types of events causing the other revisions.

The rate of electrical failures remained steady throughout follow-up, averaging about 0.8%/ year for both the 8F leads, which the researchers could follow for up to 10 years, and for the 7F leads, which they followed out to as long as 8 years. Cable externalizations occurred in 7% of the 8F leads and in 5% of the 7F leads, a difference that was not statistically significant. Fewer than half the patients, 1,187 (44%) underwent radiographic assessment of cable externalization. About 90% of all the detected cable externalizations in both the 7F and 8F leads did not produce electrical failure.

A multivariate analysis identified two factors independently linked with lead failure: patient age and left ventricular ejection fraction. Every 10 years of additional patient age linked with a 16% reduced rate of lead failure. And every 10% in additional ejection fraction linked with a 26% increased rate of lead failure.

The Canadian experience also documented the risk of undergoing lead revision, which happened for 253 patients and which led to 16 major complications, a 6% rate. Fifteen of the 16 major complications occurred without lead extraction taking place. Also, the major complications occurred at roughly similar rates in patients with 7F or 8F leads.

Dr. Parkash also highlighted that cable externalization often occurs late after implantation, and so additional cases are still possible. “We may just be seeing the cusp of lead failure” in the data collected so far, she suggested.

One concern the new data did not stoke is the risk for lead shorting that produces sudden ICD failure. “I think [shorting] is not as much of a problem as we previously thought,” Dr. Parkash said.

“These data give credence to the strategy of keeping the Riata leads in place, and, if you are concerned about their function, capping them and putting in a new lead,” commented Dr. Fred M. Kusumoto, an electrophysiologist and professor of medicine at the Mayo Clinic, Florida in Jacksonville. In addition, the new data demonstrate that the problem is in both the 7F as well as the 8F leads. “The entire Riata design was not very good,” he said in an interview. But a reassuring result in the Canadian registry was the low rate of shorting, or high-voltage failure of the lead, Dr. Kusumoto said.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON – The problem-plagued St. Jude Riata leads for implantable cardioverter defibrillators, pulled from the U.S. market in 2010, continue to pose problems for the tens of thousands of patients who still have them as clinicians follow these patients out to periods approaching 10 years.

But the risks of lead extraction continue make prophylactic lead removal a poor option for most patients, leaving the alternative of continuing to closely monitor patients for episodes of electrical lead failure, Dr. Ratika Parkash said at the annual scientific sessions of the Heart Rhythm Society.

Mitchel L. Zoler/Frontline Medical News

“Isolated, prophylactic lead revision or extraction is not warranted,” said Dr. Parkash, a cardiac electrophysiologist at Dalhousie University in Halifax, Canada. “We need to take into account a patient’s comorbidities compared with the possibility of cable externalization,” when the conducting cable of the lead moves outside its insulating sheath, one of the main problems with the St. Jude Riata leads, she explained. “I think we need to individualize what we do” based on each patient’s specific situation, but perhaps collecting more data during another 2 years follow-up might shed more light on this issue, she said. Dr. Parkash and her associates followed Riata-lead recipients for an average of 7.5 years to produce the current report.

Although no U.S. patient has received a Riata lead for nearly 5 years, the Food and Drug Administration estimated that at the time St. Jude stopped selling this lead in late 2010 more than 227,000 Riata leads had gone into patients worldwide, including about 79,000 U.S. patients. Last February, St. Jude announced that it had settled 950 lawsuits or claims from U.S. patients who had received Riata leads.

The CREDO (Canadian Registry of Cardiac Implantable Electronic Device Outcomes) prospective registry review reported by Dr. Parkash included data from 2,707 patients who received Riata leads at any of 15 Canadian centers, representing 60% of the 4,538 Canadian residents who had received on of these leads. The patients averaged 63 years of age, 19% were women, 70% had received an 8 French lead and 30% had received a 7F lead, and follow-up data were available for an average of 7.5 years from the time patients received the leads to attach their implantable cardioverter defibrillator (ICD) to their heart.

Mitchel L. Zoler/Frontline Medical News

During follow-up, 378 of the 2,707 patients (14%) required revision of their leads, a rate well above the rates seen collectively for all ICD lead models in data collected in both randomized trials and in the U.S. national registry of ICD implantations maintained by the National Cardiovascular Data Registry (OpenHeart 2015;2: [doi:10.1136/openhrt-2014-000198]). The rate of lead revisions seen with the Riata lead, 14% during 7.5 years follow-up, puts it in the ballpark of the 17% lead-failure rate with 5 year follow-up seen in Canadian patients who received a Sprint Fidelis lead that was marketed by Medtronic.(Circulation 2012:1217-25)

Triggering the 378 Riata revisions were electrical abnormalities, in 42%, lead dislodgement in 18%, cable externalization in 12%, infection in 12%, and several other types of events causing the other revisions.

The rate of electrical failures remained steady throughout follow-up, averaging about 0.8%/ year for both the 8F leads, which the researchers could follow for up to 10 years, and for the 7F leads, which they followed out to as long as 8 years. Cable externalizations occurred in 7% of the 8F leads and in 5% of the 7F leads, a difference that was not statistically significant. Fewer than half the patients, 1,187 (44%) underwent radiographic assessment of cable externalization. About 90% of all the detected cable externalizations in both the 7F and 8F leads did not produce electrical failure.

A multivariate analysis identified two factors independently linked with lead failure: patient age and left ventricular ejection fraction. Every 10 years of additional patient age linked with a 16% reduced rate of lead failure. And every 10% in additional ejection fraction linked with a 26% increased rate of lead failure.

The Canadian experience also documented the risk of undergoing lead revision, which happened for 253 patients and which led to 16 major complications, a 6% rate. Fifteen of the 16 major complications occurred without lead extraction taking place. Also, the major complications occurred at roughly similar rates in patients with 7F or 8F leads.

Dr. Parkash also highlighted that cable externalization often occurs late after implantation, and so additional cases are still possible. “We may just be seeing the cusp of lead failure” in the data collected so far, she suggested.

One concern the new data did not stoke is the risk for lead shorting that produces sudden ICD failure. “I think [shorting] is not as much of a problem as we previously thought,” Dr. Parkash said.

“These data give credence to the strategy of keeping the Riata leads in place, and, if you are concerned about their function, capping them and putting in a new lead,” commented Dr. Fred M. Kusumoto, an electrophysiologist and professor of medicine at the Mayo Clinic, Florida in Jacksonville. In addition, the new data demonstrate that the problem is in both the 7F as well as the 8F leads. “The entire Riata design was not very good,” he said in an interview. But a reassuring result in the Canadian registry was the low rate of shorting, or high-voltage failure of the lead, Dr. Kusumoto said.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON – The problem-plagued St. Jude Riata leads for implantable cardioverter defibrillators, pulled from the U.S. market in 2010, continue to pose problems for the tens of thousands of patients who still have them as clinicians follow these patients out to periods approaching 10 years.

But the risks of lead extraction continue make prophylactic lead removal a poor option for most patients, leaving the alternative of continuing to closely monitor patients for episodes of electrical lead failure, Dr. Ratika Parkash said at the annual scientific sessions of the Heart Rhythm Society.

Mitchel L. Zoler/Frontline Medical News

“Isolated, prophylactic lead revision or extraction is not warranted,” said Dr. Parkash, a cardiac electrophysiologist at Dalhousie University in Halifax, Canada. “We need to take into account a patient’s comorbidities compared with the possibility of cable externalization,” when the conducting cable of the lead moves outside its insulating sheath, one of the main problems with the St. Jude Riata leads, she explained. “I think we need to individualize what we do” based on each patient’s specific situation, but perhaps collecting more data during another 2 years follow-up might shed more light on this issue, she said. Dr. Parkash and her associates followed Riata-lead recipients for an average of 7.5 years to produce the current report.

Although no U.S. patient has received a Riata lead for nearly 5 years, the Food and Drug Administration estimated that at the time St. Jude stopped selling this lead in late 2010 more than 227,000 Riata leads had gone into patients worldwide, including about 79,000 U.S. patients. Last February, St. Jude announced that it had settled 950 lawsuits or claims from U.S. patients who had received Riata leads.

The CREDO (Canadian Registry of Cardiac Implantable Electronic Device Outcomes) prospective registry review reported by Dr. Parkash included data from 2,707 patients who received Riata leads at any of 15 Canadian centers, representing 60% of the 4,538 Canadian residents who had received on of these leads. The patients averaged 63 years of age, 19% were women, 70% had received an 8 French lead and 30% had received a 7F lead, and follow-up data were available for an average of 7.5 years from the time patients received the leads to attach their implantable cardioverter defibrillator (ICD) to their heart.

Mitchel L. Zoler/Frontline Medical News

During follow-up, 378 of the 2,707 patients (14%) required revision of their leads, a rate well above the rates seen collectively for all ICD lead models in data collected in both randomized trials and in the U.S. national registry of ICD implantations maintained by the National Cardiovascular Data Registry (OpenHeart 2015;2: [doi:10.1136/openhrt-2014-000198]). The rate of lead revisions seen with the Riata lead, 14% during 7.5 years follow-up, puts it in the ballpark of the 17% lead-failure rate with 5 year follow-up seen in Canadian patients who received a Sprint Fidelis lead that was marketed by Medtronic.(Circulation 2012:1217-25)

Triggering the 378 Riata revisions were electrical abnormalities, in 42%, lead dislodgement in 18%, cable externalization in 12%, infection in 12%, and several other types of events causing the other revisions.

The rate of electrical failures remained steady throughout follow-up, averaging about 0.8%/ year for both the 8F leads, which the researchers could follow for up to 10 years, and for the 7F leads, which they followed out to as long as 8 years. Cable externalizations occurred in 7% of the 8F leads and in 5% of the 7F leads, a difference that was not statistically significant. Fewer than half the patients, 1,187 (44%) underwent radiographic assessment of cable externalization. About 90% of all the detected cable externalizations in both the 7F and 8F leads did not produce electrical failure.

A multivariate analysis identified two factors independently linked with lead failure: patient age and left ventricular ejection fraction. Every 10 years of additional patient age linked with a 16% reduced rate of lead failure. And every 10% in additional ejection fraction linked with a 26% increased rate of lead failure.

The Canadian experience also documented the risk of undergoing lead revision, which happened for 253 patients and which led to 16 major complications, a 6% rate. Fifteen of the 16 major complications occurred without lead extraction taking place. Also, the major complications occurred at roughly similar rates in patients with 7F or 8F leads.

Dr. Parkash also highlighted that cable externalization often occurs late after implantation, and so additional cases are still possible. “We may just be seeing the cusp of lead failure” in the data collected so far, she suggested.

One concern the new data did not stoke is the risk for lead shorting that produces sudden ICD failure. “I think [shorting] is not as much of a problem as we previously thought,” Dr. Parkash said.

“These data give credence to the strategy of keeping the Riata leads in place, and, if you are concerned about their function, capping them and putting in a new lead,” commented Dr. Fred M. Kusumoto, an electrophysiologist and professor of medicine at the Mayo Clinic, Florida in Jacksonville. In addition, the new data demonstrate that the problem is in both the 7F as well as the 8F leads. “The entire Riata design was not very good,” he said in an interview. But a reassuring result in the Canadian registry was the low rate of shorting, or high-voltage failure of the lead, Dr. Kusumoto said.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON – Remote monitoring of implanted cardiac devices, already known to save lives, also reduced all-cause hospitalizations and cut hospitalization costs substantially in a review of more than 92,000 U.S. patients followed for 5 years.

The analysis showed that for every 100,000 patient-years of remote monitoring of implanted pacemakers, implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices, there were 9,810 fewer all-cause hospitalizations, 119,000 fewer days spent hospitalized, and a savings of more than $370 million, compared with similar patients who did not undergo remote monitoring, Dr. Jonathan P. Piccini, Sr. said at the annual scientific sessions of the Heart Rhythm Society.

While these results are perhaps the first to document the impact of remote monitoring of implanted cardiac devices on health care use and cost, several previously reported study findings showed the positive impact of remote monitoring on clinical outcomes. For example, the IN-TIME (Influence of Home Monitoring on the Clinical Status of Heart Failure Patients With an Impaired Left Ventricular Function) trial randomized 664 patients with either ICDs or CRT devices to remote monitoring plus clinic visits or to monitoring by clinic visits only. After 1 year, patients on remote monitoring had a statistically significant 37% reduction in bad clinical outcomes, compared with the control patients (Lancet 2014;384:583-90). And findings from an observational study recently published by Dr. Piccini and his associates that involved 269,471 Americans with cardiac devices showed that 47% used remote monitoring, and the survival rate among users ran double that of patients with devices who did not undergo remote monitoring (J. Am. Coll. Cardiol. 2015 [doi:10.1016/j.jacc.2015.04.033]).

Despite this evidence for a substantial clinical benefit, remote monitoring has not become routine for U.S. patients with a pacemaker, ICD, or CRT device. During the period April 2008–March 2013 studied by Dr. Piccini and his associates using a health insurance claims database representative of the U.S. adult population, of 92,566 patients with an implanted device, 34,259 (37%) underwent remote monitoring.

“Remote monitoring has been underutilized,” commented Dr. Michael R. Gold, chief of cardiology and medical director of the Heart and Vascular Center at the Medical University of South Carolina in Charleston. One reason that patients don’t undergo remote monitoring today is that many remote monitoring systems require a land line telephone for data collection and transmittal, while many patients now just have a mobile phone, Dr. Gold said. Mobile phone adapters are available but the patient must buy one.

Remote monitoring can dramatically reduce the need for office visits by patients, Dr. Gold said. “Without remote monitoring we see patients with devices every 3 months; with remote monitoring I usually see then once a year,” he said.

Remote monitoring may now start increasing, driven by the compelling evidence of efficacy and cost saving and also by the statement released in mid-May by the an expert consensus panel of the Heart Rhythm Society that remote monitoring ”represents the new standard of care” for patients with cardiovascular implantable electronic devices (Heart Rhythm 2015 [doi.10.1016/j.hrthm.2015.05.008]).

To run their hospitalization analysis, Dr. Piccini and his associates retrospectively reviewed data from 92,566 U.S. patients with an implanted pacemaker, ICD, or CRT device during April 2008–March 2013 collected in the MarketScan database, which includes patients covered by private insurance or Medicare. During the period studied 58,307 (63%) patients were followed by clinic visits only while the others received both clinic visits and remote monitoring.

Most of the patients, 59%, carried a pacemaker, and 29% of the patients in this device subgroup had remote monitoring. In contrast, about half of the other patients had remote monitoring, both the 30% of patients who had an ICD, as well as the 11% with a CRT device.

The rate of all-cause hospitalization during follow-up, the analysis’s primary outcome, was 18% lower in the remote-monitoring patients, a statistically significant difference. In addition, when hospitalized the average hospital length of stay ran a third lower in the remotely monitored patients, a reduction of nearly 3 days in the hospital for each hospitalized patient and a cost savings of about 30% or $3,703 per hospitalized patient. Device type did not seem to matter, Dr. Piccini reported.

The analysis dug further to focus on rates for two common causes of hospitalization in device patients, and found a statistically significant 24% reduction in hospitalization for heart failure, and a significant 22% drop in the rate of stroke hospitalization. Remote monitoring can reduce heart failure hospitalizations in many ways, by keeping tabs on heart rate, arrhythmias, overall activity level, and chest-cavity fluid level measured by changes in myocardial impedance.

The study findings highlight “a major opportunity for quality improvement,” Dr. Piccini concluded. “There is plenty of evidence to motivate physicians, health care systems, and payers” to embrace the new HRS recommendations on remote monitoring. But to be effective, each patient participating in remote monitoring must be educated about the process and be willing to take the steps necessary to make remote monitoring succeed, he added.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON – Remote monitoring of implanted cardiac devices, already known to save lives, also reduced all-cause hospitalizations and cut hospitalization costs substantially in a review of more than 92,000 U.S. patients followed for 5 years.

The analysis showed that for every 100,000 patient-years of remote monitoring of implanted pacemakers, implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices, there were 9,810 fewer all-cause hospitalizations, 119,000 fewer days spent hospitalized, and a savings of more than $370 million, compared with similar patients who did not undergo remote monitoring, Dr. Jonathan P. Piccini, Sr. said at the annual scientific sessions of the Heart Rhythm Society.

While these results are perhaps the first to document the impact of remote monitoring of implanted cardiac devices on health care use and cost, several previously reported study findings showed the positive impact of remote monitoring on clinical outcomes. For example, the IN-TIME (Influence of Home Monitoring on the Clinical Status of Heart Failure Patients With an Impaired Left Ventricular Function) trial randomized 664 patients with either ICDs or CRT devices to remote monitoring plus clinic visits or to monitoring by clinic visits only. After 1 year, patients on remote monitoring had a statistically significant 37% reduction in bad clinical outcomes, compared with the control patients (Lancet 2014;384:583-90). And findings from an observational study recently published by Dr. Piccini and his associates that involved 269,471 Americans with cardiac devices showed that 47% used remote monitoring, and the survival rate among users ran double that of patients with devices who did not undergo remote monitoring (J. Am. Coll. Cardiol. 2015 [doi:10.1016/j.jacc.2015.04.033]).

Despite this evidence for a substantial clinical benefit, remote monitoring has not become routine for U.S. patients with a pacemaker, ICD, or CRT device. During the period April 2008–March 2013 studied by Dr. Piccini and his associates using a health insurance claims database representative of the U.S. adult population, of 92,566 patients with an implanted device, 34,259 (37%) underwent remote monitoring.

“Remote monitoring has been underutilized,” commented Dr. Michael R. Gold, chief of cardiology and medical director of the Heart and Vascular Center at the Medical University of South Carolina in Charleston. One reason that patients don’t undergo remote monitoring today is that many remote monitoring systems require a land line telephone for data collection and transmittal, while many patients now just have a mobile phone, Dr. Gold said. Mobile phone adapters are available but the patient must buy one.

Remote monitoring can dramatically reduce the need for office visits by patients, Dr. Gold said. “Without remote monitoring we see patients with devices every 3 months; with remote monitoring I usually see then once a year,” he said.

Remote monitoring may now start increasing, driven by the compelling evidence of efficacy and cost saving and also by the statement released in mid-May by the an expert consensus panel of the Heart Rhythm Society that remote monitoring ”represents the new standard of care” for patients with cardiovascular implantable electronic devices (Heart Rhythm 2015 [doi.10.1016/j.hrthm.2015.05.008]).

To run their hospitalization analysis, Dr. Piccini and his associates retrospectively reviewed data from 92,566 U.S. patients with an implanted pacemaker, ICD, or CRT device during April 2008–March 2013 collected in the MarketScan database, which includes patients covered by private insurance or Medicare. During the period studied 58,307 (63%) patients were followed by clinic visits only while the others received both clinic visits and remote monitoring.

Most of the patients, 59%, carried a pacemaker, and 29% of the patients in this device subgroup had remote monitoring. In contrast, about half of the other patients had remote monitoring, both the 30% of patients who had an ICD, as well as the 11% with a CRT device.

The rate of all-cause hospitalization during follow-up, the analysis’s primary outcome, was 18% lower in the remote-monitoring patients, a statistically significant difference. In addition, when hospitalized the average hospital length of stay ran a third lower in the remotely monitored patients, a reduction of nearly 3 days in the hospital for each hospitalized patient and a cost savings of about 30% or $3,703 per hospitalized patient. Device type did not seem to matter, Dr. Piccini reported.

The analysis dug further to focus on rates for two common causes of hospitalization in device patients, and found a statistically significant 24% reduction in hospitalization for heart failure, and a significant 22% drop in the rate of stroke hospitalization. Remote monitoring can reduce heart failure hospitalizations in many ways, by keeping tabs on heart rate, arrhythmias, overall activity level, and chest-cavity fluid level measured by changes in myocardial impedance.

The study findings highlight “a major opportunity for quality improvement,” Dr. Piccini concluded. “There is plenty of evidence to motivate physicians, health care systems, and payers” to embrace the new HRS recommendations on remote monitoring. But to be effective, each patient participating in remote monitoring must be educated about the process and be willing to take the steps necessary to make remote monitoring succeed, he added.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON – Remote monitoring of implanted cardiac devices, already known to save lives, also reduced all-cause hospitalizations and cut hospitalization costs substantially in a review of more than 92,000 U.S. patients followed for 5 years.

The analysis showed that for every 100,000 patient-years of remote monitoring of implanted pacemakers, implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices, there were 9,810 fewer all-cause hospitalizations, 119,000 fewer days spent hospitalized, and a savings of more than $370 million, compared with similar patients who did not undergo remote monitoring, Dr. Jonathan P. Piccini, Sr. said at the annual scientific sessions of the Heart Rhythm Society.

While these results are perhaps the first to document the impact of remote monitoring of implanted cardiac devices on health care use and cost, several previously reported study findings showed the positive impact of remote monitoring on clinical outcomes. For example, the IN-TIME (Influence of Home Monitoring on the Clinical Status of Heart Failure Patients With an Impaired Left Ventricular Function) trial randomized 664 patients with either ICDs or CRT devices to remote monitoring plus clinic visits or to monitoring by clinic visits only. After 1 year, patients on remote monitoring had a statistically significant 37% reduction in bad clinical outcomes, compared with the control patients (Lancet 2014;384:583-90). And findings from an observational study recently published by Dr. Piccini and his associates that involved 269,471 Americans with cardiac devices showed that 47% used remote monitoring, and the survival rate among users ran double that of patients with devices who did not undergo remote monitoring (J. Am. Coll. Cardiol. 2015 [doi:10.1016/j.jacc.2015.04.033]).

Despite this evidence for a substantial clinical benefit, remote monitoring has not become routine for U.S. patients with a pacemaker, ICD, or CRT device. During the period April 2008–March 2013 studied by Dr. Piccini and his associates using a health insurance claims database representative of the U.S. adult population, of 92,566 patients with an implanted device, 34,259 (37%) underwent remote monitoring.

“Remote monitoring has been underutilized,” commented Dr. Michael R. Gold, chief of cardiology and medical director of the Heart and Vascular Center at the Medical University of South Carolina in Charleston. One reason that patients don’t undergo remote monitoring today is that many remote monitoring systems require a land line telephone for data collection and transmittal, while many patients now just have a mobile phone, Dr. Gold said. Mobile phone adapters are available but the patient must buy one.

Remote monitoring can dramatically reduce the need for office visits by patients, Dr. Gold said. “Without remote monitoring we see patients with devices every 3 months; with remote monitoring I usually see then once a year,” he said.

Remote monitoring may now start increasing, driven by the compelling evidence of efficacy and cost saving and also by the statement released in mid-May by the an expert consensus panel of the Heart Rhythm Society that remote monitoring ”represents the new standard of care” for patients with cardiovascular implantable electronic devices (Heart Rhythm 2015 [doi.10.1016/j.hrthm.2015.05.008]).

To run their hospitalization analysis, Dr. Piccini and his associates retrospectively reviewed data from 92,566 U.S. patients with an implanted pacemaker, ICD, or CRT device during April 2008–March 2013 collected in the MarketScan database, which includes patients covered by private insurance or Medicare. During the period studied 58,307 (63%) patients were followed by clinic visits only while the others received both clinic visits and remote monitoring.

Most of the patients, 59%, carried a pacemaker, and 29% of the patients in this device subgroup had remote monitoring. In contrast, about half of the other patients had remote monitoring, both the 30% of patients who had an ICD, as well as the 11% with a CRT device.

The rate of all-cause hospitalization during follow-up, the analysis’s primary outcome, was 18% lower in the remote-monitoring patients, a statistically significant difference. In addition, when hospitalized the average hospital length of stay ran a third lower in the remotely monitored patients, a reduction of nearly 3 days in the hospital for each hospitalized patient and a cost savings of about 30% or $3,703 per hospitalized patient. Device type did not seem to matter, Dr. Piccini reported.

The analysis dug further to focus on rates for two common causes of hospitalization in device patients, and found a statistically significant 24% reduction in hospitalization for heart failure, and a significant 22% drop in the rate of stroke hospitalization. Remote monitoring can reduce heart failure hospitalizations in many ways, by keeping tabs on heart rate, arrhythmias, overall activity level, and chest-cavity fluid level measured by changes in myocardial impedance.

The study findings highlight “a major opportunity for quality improvement,” Dr. Piccini concluded. “There is plenty of evidence to motivate physicians, health care systems, and payers” to embrace the new HRS recommendations on remote monitoring. But to be effective, each patient participating in remote monitoring must be educated about the process and be willing to take the steps necessary to make remote monitoring succeed, he added.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler