The Food and Drug Administration has approved calaspargase pegol-mknl (Asparlas) as a component of a multiagent chemotherapy regimen to treat acute lymphoblastic leukemia (ALL) in pediatric and young adult patients aged 1 month to 21 years.

Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses, compared with other available pegaspargase products. The recommended dosage of calaspargase pegol-mknl is 2,500 units/m² given no more frequently than every 21 days.

The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m² every 3 weeks.

Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years.

Study participants received calaspargase pegol-mknl at 2,500 U/m² (n = 118) or pegaspargase at 2,500 U/m² (n = 119) as part of a Dana-Farber Cancer Institute ALL Consortium backbone therapy. The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase. Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.

Common grade 3 or higher adverse events in the calaspargase pegol-mknl and pegaspargase arms included elevated transaminase (52% and 66%, respectively), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%). There was one fatal adverse event among patients on calaspargase pegol-mknl – multiorgan failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.

The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL. The patients received calaspargase pegol-mknl at 2,500 U/m² (n = 43) or 2,100 U/m² (n = 68) or pegaspargase at 2,500 U/m² (n = 52) as a component of an augmented Berlin-Frankfurt-Münster regimen. The patients’ median age was 11 years. The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase. There were 3 induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.

Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information. Calaspargase pegol-mknl is a product of Servier.

[email protected]

The Food and Drug Administration has approved calaspargase pegol-mknl (Asparlas) as a component of a multiagent chemotherapy regimen to treat acute lymphoblastic leukemia (ALL) in pediatric and young adult patients aged 1 month to 21 years.

Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses, compared with other available pegaspargase products. The recommended dosage of calaspargase pegol-mknl is 2,500 units/m² given no more frequently than every 21 days.

The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m² every 3 weeks.

Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years.

Study participants received calaspargase pegol-mknl at 2,500 U/m² (n = 118) or pegaspargase at 2,500 U/m² (n = 119) as part of a Dana-Farber Cancer Institute ALL Consortium backbone therapy. The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase. Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.

Common grade 3 or higher adverse events in the calaspargase pegol-mknl and pegaspargase arms included elevated transaminase (52% and 66%, respectively), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%). There was one fatal adverse event among patients on calaspargase pegol-mknl – multiorgan failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.

The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL. The patients received calaspargase pegol-mknl at 2,500 U/m² (n = 43) or 2,100 U/m² (n = 68) or pegaspargase at 2,500 U/m² (n = 52) as a component of an augmented Berlin-Frankfurt-Münster regimen. The patients’ median age was 11 years. The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase. There were 3 induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.

Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information. Calaspargase pegol-mknl is a product of Servier.

[email protected]

The Food and Drug Administration has approved calaspargase pegol-mknl (Asparlas) as a component of a multiagent chemotherapy regimen to treat acute lymphoblastic leukemia (ALL) in pediatric and young adult patients aged 1 month to 21 years.

Calaspargase pegol-mknl is an asparagine-specific enzyme intended to provide a longer interval between doses, compared with other available pegaspargase products. The recommended dosage of calaspargase pegol-mknl is 2,500 units/m² given no more frequently than every 21 days.

The FDA said it approved calaspargase pegol-mknl because the drug maintained nadir serum asparaginase activity above the level of 0.1 U/mL when given at 2,500 U/m² every 3 weeks.

Calaspargase pegol-mknl was evaluated in Study DFCI 11-001, a trial of 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma. The patients’ median age was 5 years.

Study participants received calaspargase pegol-mknl at 2,500 U/m² (n = 118) or pegaspargase at 2,500 U/m² (n = 119) as part of a Dana-Farber Cancer Institute ALL Consortium backbone therapy. The median duration of exposure was 8 months for both calaspargase pegol-mknl and pegaspargase. Among the patients with B-cell lineage ALL, the complete remission rate was 98% in the calaspargase pegol-mknl arm and 99% in the pegaspargase arm. Estimated overall survival rates were comparable between the arms.

Common grade 3 or higher adverse events in the calaspargase pegol-mknl and pegaspargase arms included elevated transaminase (52% and 66%, respectively), bilirubin increase (20% and 25%), pancreatitis (18% and 24%), and abnormal clotting studies (14% and 21%). There was one fatal adverse event among patients on calaspargase pegol-mknl – multiorgan failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst.

The safety of calaspargase pegol-mknl was also evaluated in Study AALL07P4, a trial of patients with newly diagnosed, high-risk B-precursor ALL. The patients received calaspargase pegol-mknl at 2,500 U/m² (n = 43) or 2,100 U/m² (n = 68) or pegaspargase at 2,500 U/m² (n = 52) as a component of an augmented Berlin-Frankfurt-Münster regimen. The patients’ median age was 11 years. The median duration of exposure was 7 months for both calaspargase pegol-mknl and pegaspargase. There were 3 induction deaths among the 111 patients who received calaspargase pegol-mknl (2.8%) but no induction deaths among the 52 patients treated with pegaspargase.

Additional details on these studies and calaspargase pegol-mknl can be found in the drug’s prescribing information. Calaspargase pegol-mknl is a product of Servier.

[email protected]

LAS VEGAS – While vaginal hysterectomies are becoming less common, a gynecologic surgeon urges colleagues to reconsider the value of the procedure.

Courtesy Cashman Photo

While “younger trainees are seeing fewer vaginal procedures being done and have less confidence to do the procedure,” research suggests that the vaginal approach can offer major benefits, compared with the alternatives, Rosanne M. Kho, MD, of the Cleveland Clinic, said at the Pelvic Anatomy and Gynecologic Surgery Symposium.

Dr. Kho pointed to several studies suggesting a decline in vaginal hysterectomies as laparoscopic and robot procedures become more common. One study compared hysterectomy surgery approaches during 2007-2010 and found a sharp rise in robotic procedures (0.5% to 10%) and a big decrease in abdominal procedures (from 54% to 40%). The rate of laparoscopic procedures grew (from 24% to 30%), while vaginal procedures dipped slightly (22% to 20%) (JAMA. 2013 Feb 20;309[7]:689-98). Another study tracked hysterectomy strategies at Pittsburgh’s Magee-Womens Hospital in almost 14,000 women during 2000-2010. It found that vaginal hysterectomy rates fell from 22% to 17% while laparoscopic rates grew remarkably from 3% to 43%. Open procedures fell dramatically from 75% to 36% (Am J Obstet Gynecol. 2013 Apr. doi: 10.1016/j.ajog.2013.01.022).

These findings are “telling me that surgeons are steering away from the vaginal approach because the laparoscopic and robotic approach are much more appealing,” Dr. Koh said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

Specifically, it appears that surgeons think the vaginal hysterectomy is more “challenging” and “cumbersome,” Dr. Kho said, and they lack inadequate training.

Why should vaginal hysterectomy still be considered? Dr. Kho pointed to two pieces of evidence:

• Expert opinion. A 2017 committee opinion from the American College of Obstetricians and Gynecologists examined routes of hysterectomy in benign disease and declared that, despite the decrease in its use, “evidence supports the opinion that [when feasible] vaginal hysterectomy is associated with better outcomes” than are laparoscopic or abdominal hysterectomy. Also, the decision to perform a salpingo-oophorectomy is not necessarily a contraindication to performing a vaginal hysterectomy, according to the committee opinion (Obstet Gynecol. 2017 Jun;129[6]:e155-e9).The opinion also says, “the vaginal approach is preferred among the minimally invasive approaches. Laparoscopic hysterectomy is a preferable alternative to open abdominal hysterectomy for those patients in whom a vaginal hysterectomy is not indicated or feasible. Although minimally invasive approaches to hysterectomy are the preferred route, open abdominal hysterectomy remains an important surgical option for some patients.”
• Randomized, controlled studies. A 2015 Cochrane Library systematic review examined 47 randomized, controlled trials and found that “vaginal hysterectomy should be performed whenever possible. Where vaginal hysterectomy is not possible, both a laparoscopic approach and abdominal hysterectomy have their pros and cons, and these should be incorporated in the decision-making process” (Cochrane Database Syst Rev. 2015 Aug 12. doi: 10.1002/14651858.CD003677.pub5).

What if a patient has an enlarged uterus? Dr. Kho coauthored a 2017 review that suggested that vaginal hysterectomy may be appropriate in this case. Her report found that in women with large uteri, “vaginal hysterectomy is preferred over laparoscopic and laparoscopic assistance with less operative time and hospital cost. In morbidly obese patients with large uteri, total laparoscopic hysterectomy is superior to vaginal hysterectomy with lesser odds of blood transfusion and lower length of hospital stay” (Clin Obstet Gynecol. 2017 Jun;60[2]:286-95).

What about the removal of fallopian tubes – salpingectomy – during vaginal hysterectomy? Dr. Kho highlighted a 2017 decision analysis that said these procedures are frequently performed for cancer prevention during laparoscopic and open hysterectomies “but [fallopian tubes] are not routinely removed during vaginal hysterectomy because of perceptions of increased morbidity, difficulty, or inadequate surgical training.”

The analysis, however, determined that “salpingectomy should routinely be performed with vaginal hysterectomy because it was the dominant and therefore cost-effective strategy. Complications are minimally increased, but the trade-off with cancer prevention is highly favorable.” (Am J Obstet Gynecol. 2017 Nov;217[5]:603.e1-603.e6).

Dr. Kho reported consulting for AbbVie, Olympus, and Applied Medical.

LAS VEGAS – While vaginal hysterectomies are becoming less common, a gynecologic surgeon urges colleagues to reconsider the value of the procedure.

Courtesy Cashman Photo

While “younger trainees are seeing fewer vaginal procedures being done and have less confidence to do the procedure,” research suggests that the vaginal approach can offer major benefits, compared with the alternatives, Rosanne M. Kho, MD, of the Cleveland Clinic, said at the Pelvic Anatomy and Gynecologic Surgery Symposium.

Dr. Kho pointed to several studies suggesting a decline in vaginal hysterectomies as laparoscopic and robot procedures become more common. One study compared hysterectomy surgery approaches during 2007-2010 and found a sharp rise in robotic procedures (0.5% to 10%) and a big decrease in abdominal procedures (from 54% to 40%). The rate of laparoscopic procedures grew (from 24% to 30%), while vaginal procedures dipped slightly (22% to 20%) (JAMA. 2013 Feb 20;309[7]:689-98). Another study tracked hysterectomy strategies at Pittsburgh’s Magee-Womens Hospital in almost 14,000 women during 2000-2010. It found that vaginal hysterectomy rates fell from 22% to 17% while laparoscopic rates grew remarkably from 3% to 43%. Open procedures fell dramatically from 75% to 36% (Am J Obstet Gynecol. 2013 Apr. doi: 10.1016/j.ajog.2013.01.022).

These findings are “telling me that surgeons are steering away from the vaginal approach because the laparoscopic and robotic approach are much more appealing,” Dr. Koh said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

Specifically, it appears that surgeons think the vaginal hysterectomy is more “challenging” and “cumbersome,” Dr. Kho said, and they lack inadequate training.

Why should vaginal hysterectomy still be considered? Dr. Kho pointed to two pieces of evidence:

• Expert opinion. A 2017 committee opinion from the American College of Obstetricians and Gynecologists examined routes of hysterectomy in benign disease and declared that, despite the decrease in its use, “evidence supports the opinion that [when feasible] vaginal hysterectomy is associated with better outcomes” than are laparoscopic or abdominal hysterectomy. Also, the decision to perform a salpingo-oophorectomy is not necessarily a contraindication to performing a vaginal hysterectomy, according to the committee opinion (Obstet Gynecol. 2017 Jun;129[6]:e155-e9).The opinion also says, “the vaginal approach is preferred among the minimally invasive approaches. Laparoscopic hysterectomy is a preferable alternative to open abdominal hysterectomy for those patients in whom a vaginal hysterectomy is not indicated or feasible. Although minimally invasive approaches to hysterectomy are the preferred route, open abdominal hysterectomy remains an important surgical option for some patients.”
• Randomized, controlled studies. A 2015 Cochrane Library systematic review examined 47 randomized, controlled trials and found that “vaginal hysterectomy should be performed whenever possible. Where vaginal hysterectomy is not possible, both a laparoscopic approach and abdominal hysterectomy have their pros and cons, and these should be incorporated in the decision-making process” (Cochrane Database Syst Rev. 2015 Aug 12. doi: 10.1002/14651858.CD003677.pub5).

What if a patient has an enlarged uterus? Dr. Kho coauthored a 2017 review that suggested that vaginal hysterectomy may be appropriate in this case. Her report found that in women with large uteri, “vaginal hysterectomy is preferred over laparoscopic and laparoscopic assistance with less operative time and hospital cost. In morbidly obese patients with large uteri, total laparoscopic hysterectomy is superior to vaginal hysterectomy with lesser odds of blood transfusion and lower length of hospital stay” (Clin Obstet Gynecol. 2017 Jun;60[2]:286-95).

What about the removal of fallopian tubes – salpingectomy – during vaginal hysterectomy? Dr. Kho highlighted a 2017 decision analysis that said these procedures are frequently performed for cancer prevention during laparoscopic and open hysterectomies “but [fallopian tubes] are not routinely removed during vaginal hysterectomy because of perceptions of increased morbidity, difficulty, or inadequate surgical training.”

The analysis, however, determined that “salpingectomy should routinely be performed with vaginal hysterectomy because it was the dominant and therefore cost-effective strategy. Complications are minimally increased, but the trade-off with cancer prevention is highly favorable.” (Am J Obstet Gynecol. 2017 Nov;217[5]:603.e1-603.e6).

Dr. Kho reported consulting for AbbVie, Olympus, and Applied Medical.

LAS VEGAS – While vaginal hysterectomies are becoming less common, a gynecologic surgeon urges colleagues to reconsider the value of the procedure.

Courtesy Cashman Photo

While “younger trainees are seeing fewer vaginal procedures being done and have less confidence to do the procedure,” research suggests that the vaginal approach can offer major benefits, compared with the alternatives, Rosanne M. Kho, MD, of the Cleveland Clinic, said at the Pelvic Anatomy and Gynecologic Surgery Symposium.

Dr. Kho pointed to several studies suggesting a decline in vaginal hysterectomies as laparoscopic and robot procedures become more common. One study compared hysterectomy surgery approaches during 2007-2010 and found a sharp rise in robotic procedures (0.5% to 10%) and a big decrease in abdominal procedures (from 54% to 40%). The rate of laparoscopic procedures grew (from 24% to 30%), while vaginal procedures dipped slightly (22% to 20%) (JAMA. 2013 Feb 20;309[7]:689-98). Another study tracked hysterectomy strategies at Pittsburgh’s Magee-Womens Hospital in almost 14,000 women during 2000-2010. It found that vaginal hysterectomy rates fell from 22% to 17% while laparoscopic rates grew remarkably from 3% to 43%. Open procedures fell dramatically from 75% to 36% (Am J Obstet Gynecol. 2013 Apr. doi: 10.1016/j.ajog.2013.01.022).

These findings are “telling me that surgeons are steering away from the vaginal approach because the laparoscopic and robotic approach are much more appealing,” Dr. Koh said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

Specifically, it appears that surgeons think the vaginal hysterectomy is more “challenging” and “cumbersome,” Dr. Kho said, and they lack inadequate training.

Why should vaginal hysterectomy still be considered? Dr. Kho pointed to two pieces of evidence:

• Expert opinion. A 2017 committee opinion from the American College of Obstetricians and Gynecologists examined routes of hysterectomy in benign disease and declared that, despite the decrease in its use, “evidence supports the opinion that [when feasible] vaginal hysterectomy is associated with better outcomes” than are laparoscopic or abdominal hysterectomy. Also, the decision to perform a salpingo-oophorectomy is not necessarily a contraindication to performing a vaginal hysterectomy, according to the committee opinion (Obstet Gynecol. 2017 Jun;129[6]:e155-e9).The opinion also says, “the vaginal approach is preferred among the minimally invasive approaches. Laparoscopic hysterectomy is a preferable alternative to open abdominal hysterectomy for those patients in whom a vaginal hysterectomy is not indicated or feasible. Although minimally invasive approaches to hysterectomy are the preferred route, open abdominal hysterectomy remains an important surgical option for some patients.”
• Randomized, controlled studies. A 2015 Cochrane Library systematic review examined 47 randomized, controlled trials and found that “vaginal hysterectomy should be performed whenever possible. Where vaginal hysterectomy is not possible, both a laparoscopic approach and abdominal hysterectomy have their pros and cons, and these should be incorporated in the decision-making process” (Cochrane Database Syst Rev. 2015 Aug 12. doi: 10.1002/14651858.CD003677.pub5).

What if a patient has an enlarged uterus? Dr. Kho coauthored a 2017 review that suggested that vaginal hysterectomy may be appropriate in this case. Her report found that in women with large uteri, “vaginal hysterectomy is preferred over laparoscopic and laparoscopic assistance with less operative time and hospital cost. In morbidly obese patients with large uteri, total laparoscopic hysterectomy is superior to vaginal hysterectomy with lesser odds of blood transfusion and lower length of hospital stay” (Clin Obstet Gynecol. 2017 Jun;60[2]:286-95).

What about the removal of fallopian tubes – salpingectomy – during vaginal hysterectomy? Dr. Kho highlighted a 2017 decision analysis that said these procedures are frequently performed for cancer prevention during laparoscopic and open hysterectomies “but [fallopian tubes] are not routinely removed during vaginal hysterectomy because of perceptions of increased morbidity, difficulty, or inadequate surgical training.”

The analysis, however, determined that “salpingectomy should routinely be performed with vaginal hysterectomy because it was the dominant and therefore cost-effective strategy. Complications are minimally increased, but the trade-off with cancer prevention is highly favorable.” (Am J Obstet Gynecol. 2017 Nov;217[5]:603.e1-603.e6).

Dr. Kho reported consulting for AbbVie, Olympus, and Applied Medical.

A observational, prospective trial is underway to study the use of surgical glue for hernia repair. Cyanoacrylate Fixation for Laparoscopic Repair of Inguinal Hernias, a multicenter registry, is currently enrolling patients for laparoscopic inguinal hernia repair using surgical tissue glue for mesh fixation.

The trial expects to enroll 1,000 patients and to be completed by December 2019. The primary outcome is postoperative pain evaluated by patient self-assessment using a visual analog scale. Secondary outcomes include intraoperative and postoperative complications, analgesic intake, postoperative quality of life, recurrences, and longer-term complications.

Included in the participant group are adult patients of both sexes with primary inguinal hernia. Exclusions include patients with recurrent inguinal hernia, patients previously treated with Lichtenstein technique, those allergic to the components of the tissue glue, and those whose life expectancy is under 1 year. The patients will be followed up to 1 year.

For further information about to the study, go to clinicaltrials.gov (NCT01669837).

[email protected]

A observational, prospective trial is underway to study the use of surgical glue for hernia repair. Cyanoacrylate Fixation for Laparoscopic Repair of Inguinal Hernias, a multicenter registry, is currently enrolling patients for laparoscopic inguinal hernia repair using surgical tissue glue for mesh fixation.

The trial expects to enroll 1,000 patients and to be completed by December 2019. The primary outcome is postoperative pain evaluated by patient self-assessment using a visual analog scale. Secondary outcomes include intraoperative and postoperative complications, analgesic intake, postoperative quality of life, recurrences, and longer-term complications.

Included in the participant group are adult patients of both sexes with primary inguinal hernia. Exclusions include patients with recurrent inguinal hernia, patients previously treated with Lichtenstein technique, those allergic to the components of the tissue glue, and those whose life expectancy is under 1 year. The patients will be followed up to 1 year.

For further information about to the study, go to clinicaltrials.gov (NCT01669837).

[email protected]

A observational, prospective trial is underway to study the use of surgical glue for hernia repair. Cyanoacrylate Fixation for Laparoscopic Repair of Inguinal Hernias, a multicenter registry, is currently enrolling patients for laparoscopic inguinal hernia repair using surgical tissue glue for mesh fixation.

The trial expects to enroll 1,000 patients and to be completed by December 2019. The primary outcome is postoperative pain evaluated by patient self-assessment using a visual analog scale. Secondary outcomes include intraoperative and postoperative complications, analgesic intake, postoperative quality of life, recurrences, and longer-term complications.

Included in the participant group are adult patients of both sexes with primary inguinal hernia. Exclusions include patients with recurrent inguinal hernia, patients previously treated with Lichtenstein technique, those allergic to the components of the tissue glue, and those whose life expectancy is under 1 year. The patients will be followed up to 1 year.

For further information about to the study, go to clinicaltrials.gov (NCT01669837).

[email protected]

The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.

Louise A. Koenig/MDedge News

Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.

The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.

Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.

With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.

“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.

Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.

The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.

SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.

The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.

Louise A. Koenig/MDedge News

Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.

The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.

Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.

With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.

“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.

Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.

The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.

SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.

The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.

Louise A. Koenig/MDedge News

Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.

The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.

Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.

With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.

“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.

Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.

The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.

SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.

Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.

SilverV/thinkstockphotos

The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.

“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.

The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.

That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.

A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–³), and 6.8% of women with no personal cancer history (P less than .001).

Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.

When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).

While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.

“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.

Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
 

SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.

Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.

SilverV/thinkstockphotos

The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.

“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.

The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.

That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.

A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–³), and 6.8% of women with no personal cancer history (P less than .001).

Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.

When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).

While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.

“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.

Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
 

SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.

Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.

SilverV/thinkstockphotos

The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.

“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.

The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.

That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.

A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–³), and 6.8% of women with no personal cancer history (P less than .001).

Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.

When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).

While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.

“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.

Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
 

SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.

The American College of Cardiology, the American Heart Association, and other groups have jointly released an appropriate use criteria (AUC) document regarding the use of imaging modalities in diagnosing nonvalvular (that is, structural) heart disease.

Imaging plays an important role in diagnosing both valvular and nonvalvular heart diseases, so the goal of the document was to help clinicians provide high-quality care by standardizing the decision-making process. To do so, a committee was formed to devise scenarios that reflected situations in real-world practice; these scenarios were considered within categories to prevent the list from being too exhaustive. The scenarios were then reviewed by a rating panel in terms of how appropriate certain modalities were in each situation. The panel members first evaluated the scenarios independently then face to face as a panel before giving their final scores (from 1 to 9) independently.

For example, for the indication of nonsustained ventricular tachycardia, the panelists rated transthoracic echocardiography with or without 3-D and with contrast as needed as a 8, which means it’s an “appropriate test,” whereas they gave CT for the same indication a 3, which means “rarely appropriate.” For sustained ventricular tachycardia or ventricular fibrillation, they gave a 9 and a 6, respectively; this latter score indicates the test “may be appropriate.” These scenarios and the respective scores for any given test are organized into tables, such as initial evaluation or follow-up.

This AUC document “signals a shift from documents evaluating a single modality in various disease states to documents evaluating multiple imaging modalities and focusing on evidence and clinical experience within a given disease category,” the authors wrote. “We believe this approach better reflects clinical decision making in real-world scenarios and offers the diagnostic choices available to the clinician.”

The full document can be viewed in JACC.
 

[email protected]

The American College of Cardiology, the American Heart Association, and other groups have jointly released an appropriate use criteria (AUC) document regarding the use of imaging modalities in diagnosing nonvalvular (that is, structural) heart disease.

Imaging plays an important role in diagnosing both valvular and nonvalvular heart diseases, so the goal of the document was to help clinicians provide high-quality care by standardizing the decision-making process. To do so, a committee was formed to devise scenarios that reflected situations in real-world practice; these scenarios were considered within categories to prevent the list from being too exhaustive. The scenarios were then reviewed by a rating panel in terms of how appropriate certain modalities were in each situation. The panel members first evaluated the scenarios independently then face to face as a panel before giving their final scores (from 1 to 9) independently.

For example, for the indication of nonsustained ventricular tachycardia, the panelists rated transthoracic echocardiography with or without 3-D and with contrast as needed as a 8, which means it’s an “appropriate test,” whereas they gave CT for the same indication a 3, which means “rarely appropriate.” For sustained ventricular tachycardia or ventricular fibrillation, they gave a 9 and a 6, respectively; this latter score indicates the test “may be appropriate.” These scenarios and the respective scores for any given test are organized into tables, such as initial evaluation or follow-up.

This AUC document “signals a shift from documents evaluating a single modality in various disease states to documents evaluating multiple imaging modalities and focusing on evidence and clinical experience within a given disease category,” the authors wrote. “We believe this approach better reflects clinical decision making in real-world scenarios and offers the diagnostic choices available to the clinician.”

The full document can be viewed in JACC.
 

[email protected]

The American College of Cardiology, the American Heart Association, and other groups have jointly released an appropriate use criteria (AUC) document regarding the use of imaging modalities in diagnosing nonvalvular (that is, structural) heart disease.

Imaging plays an important role in diagnosing both valvular and nonvalvular heart diseases, so the goal of the document was to help clinicians provide high-quality care by standardizing the decision-making process. To do so, a committee was formed to devise scenarios that reflected situations in real-world practice; these scenarios were considered within categories to prevent the list from being too exhaustive. The scenarios were then reviewed by a rating panel in terms of how appropriate certain modalities were in each situation. The panel members first evaluated the scenarios independently then face to face as a panel before giving their final scores (from 1 to 9) independently.

For example, for the indication of nonsustained ventricular tachycardia, the panelists rated transthoracic echocardiography with or without 3-D and with contrast as needed as a 8, which means it’s an “appropriate test,” whereas they gave CT for the same indication a 3, which means “rarely appropriate.” For sustained ventricular tachycardia or ventricular fibrillation, they gave a 9 and a 6, respectively; this latter score indicates the test “may be appropriate.” These scenarios and the respective scores for any given test are organized into tables, such as initial evaluation or follow-up.

This AUC document “signals a shift from documents evaluating a single modality in various disease states to documents evaluating multiple imaging modalities and focusing on evidence and clinical experience within a given disease category,” the authors wrote. “We believe this approach better reflects clinical decision making in real-world scenarios and offers the diagnostic choices available to the clinician.”

The full document can be viewed in JACC.
 

[email protected]

Recurrence of inguinal hernia in women was lower after laparoscopic repair, compared with open repair, according to findings published in JAMA Surgery.

Courtesy Wikimedia Commons/Samuel Bendet, US Air Force/Creative Commons License

In a systematic review of 43,870 female patients in 55 studies, the recurrence rate was 1.2% after laparoscopic repair, compared with 2.4% after open repair. The recurrent hernia was a femoral hernia in 40.9% of patients after open repair, compared with no recurrences after laparoscopic repair, reported Line Schmidt of the department of surgery at Herlev (Denmark) Hospital, and coauthors.

Patients were women aged 18 years and older who had repair of a primary unilateral or bilateral inguinal hernia. The review included all retrospective cohort studies, prospective cohort studies, prospective clinical trials, and retrospective cohort studies with 20 or more women with inguinal hernias. PubMed, Embase, and the Cochrane Library databases were searched. The primary outcome was recurrence rate after primary laparoscopic and open repairs, with or without mesh.

The overall recurrence rate among women was 2.6%. The overall crude recurrence rate for studies with low risk of bias was 3.9%, the authors wrote. A femoral hernia was found in 43% of reoperations, though in one study including both open and laparoscopic repairs in women, the rate of detection of incidental femoral hernia was only 2%.

The results “support the recommendation that women with inguinal hernias should undergo laparoscopic repair, unless there are concerns where an open repair might be more clinically appropriate,” the authors wrote. “A substantial number of recurrences after open repair were femoral hernias that may have been overlooked at the primary operation.”

Authors reported receiving personal fees from Bard and Merck. No other disclosures were reported.

SOURCE: Schmidt L et al. JAMA Surg. 2018;153(12):1135-42.

Recurrence of inguinal hernia in women was lower after laparoscopic repair, compared with open repair, according to findings published in JAMA Surgery.

Courtesy Wikimedia Commons/Samuel Bendet, US Air Force/Creative Commons License

In a systematic review of 43,870 female patients in 55 studies, the recurrence rate was 1.2% after laparoscopic repair, compared with 2.4% after open repair. The recurrent hernia was a femoral hernia in 40.9% of patients after open repair, compared with no recurrences after laparoscopic repair, reported Line Schmidt of the department of surgery at Herlev (Denmark) Hospital, and coauthors.

Patients were women aged 18 years and older who had repair of a primary unilateral or bilateral inguinal hernia. The review included all retrospective cohort studies, prospective cohort studies, prospective clinical trials, and retrospective cohort studies with 20 or more women with inguinal hernias. PubMed, Embase, and the Cochrane Library databases were searched. The primary outcome was recurrence rate after primary laparoscopic and open repairs, with or without mesh.

The overall recurrence rate among women was 2.6%. The overall crude recurrence rate for studies with low risk of bias was 3.9%, the authors wrote. A femoral hernia was found in 43% of reoperations, though in one study including both open and laparoscopic repairs in women, the rate of detection of incidental femoral hernia was only 2%.

The results “support the recommendation that women with inguinal hernias should undergo laparoscopic repair, unless there are concerns where an open repair might be more clinically appropriate,” the authors wrote. “A substantial number of recurrences after open repair were femoral hernias that may have been overlooked at the primary operation.”

Authors reported receiving personal fees from Bard and Merck. No other disclosures were reported.

SOURCE: Schmidt L et al. JAMA Surg. 2018;153(12):1135-42.

Recurrence of inguinal hernia in women was lower after laparoscopic repair, compared with open repair, according to findings published in JAMA Surgery.

Courtesy Wikimedia Commons/Samuel Bendet, US Air Force/Creative Commons License

In a systematic review of 43,870 female patients in 55 studies, the recurrence rate was 1.2% after laparoscopic repair, compared with 2.4% after open repair. The recurrent hernia was a femoral hernia in 40.9% of patients after open repair, compared with no recurrences after laparoscopic repair, reported Line Schmidt of the department of surgery at Herlev (Denmark) Hospital, and coauthors.

Patients were women aged 18 years and older who had repair of a primary unilateral or bilateral inguinal hernia. The review included all retrospective cohort studies, prospective cohort studies, prospective clinical trials, and retrospective cohort studies with 20 or more women with inguinal hernias. PubMed, Embase, and the Cochrane Library databases were searched. The primary outcome was recurrence rate after primary laparoscopic and open repairs, with or without mesh.

The overall recurrence rate among women was 2.6%. The overall crude recurrence rate for studies with low risk of bias was 3.9%, the authors wrote. A femoral hernia was found in 43% of reoperations, though in one study including both open and laparoscopic repairs in women, the rate of detection of incidental femoral hernia was only 2%.

The results “support the recommendation that women with inguinal hernias should undergo laparoscopic repair, unless there are concerns where an open repair might be more clinically appropriate,” the authors wrote. “A substantial number of recurrences after open repair were femoral hernias that may have been overlooked at the primary operation.”

Authors reported receiving personal fees from Bard and Merck. No other disclosures were reported.

SOURCE: Schmidt L et al. JAMA Surg. 2018;153(12):1135-42.

The Society of Hospital Medicine is proud to announce the inaugural National Hospitalist Day, to be held on Thursday, March 7, 2019. Occurring the first Thursday in March annually, National Hospitalist Day will serve to celebrate the fastest-growing specialty in modern medicine and hospitalists’ enduring contributions to the evolving health care landscape.

National Hospitalist Day was recently approved by the National Day Calendar and was one of approximately 30 national days to be approved for the year out of an applicant pool of more than 18,000.

“As the only society dedicated to the specialty of hospital medicine, it is appropriate that SHM spearhead a national day to recognize the countless contributions of hospitalists to health care, from clinical, academic, and leadership perspectives and more,” said Larry Wellikson, MD, MHM, chief executive officer of SHM. “We look forward to hospitalists across the nation contributing to the festivities and making this a tradition for years to come.”

In addition to celebrating hospitalists’ contributions to patient care, SHM will also be highlighting the diverse career paths of hospital medicine professionals, from frontline hospitalist physicians, nurse practitioners, and physician assistants to practice administrators, C-suite executives, and academic hospitalists.

Highlights of SHM’s campaign include the following:

• Downloadable customizable posters and assets for hospitals and individuals’ offices to celebrate their hospital medicine team, available on SHM’s website, hospitalmedicine.org.
• A series of spotlights of hospitalists at all stages of their careers in The Hospitalist, SHM’s monthly newsmagazine.
• A social media campaign inviting hospitalists and their employers to share their success stories using the hashtag #HowWeHospitalist, including banner graphics, profile photo overlays, and more.
• A social media contest to determine the most creative ways of celebrating use of the hashtag.
• A Twitter chat for hospitalists to celebrate virtually with their colleagues and peers from around the world.

“Hospitalists innovate, lead, and push the boundaries of clinical care and deserve to be recognized for their transformative contributions to health care,” said Eric E. Howell, MD, MHM, chief operating officer of SHM. “We hope this is the beginning of a long-standing tradition in honoring hospitalists and the noteworthy work they do.”

For more information, visit www.hospitalmedicine.org/hospitalistday.

Mr. Radler is marketing communications manager at the Society of Hospital Medicine.

The Society of Hospital Medicine is proud to announce the inaugural National Hospitalist Day, to be held on Thursday, March 7, 2019. Occurring the first Thursday in March annually, National Hospitalist Day will serve to celebrate the fastest-growing specialty in modern medicine and hospitalists’ enduring contributions to the evolving health care landscape.

National Hospitalist Day was recently approved by the National Day Calendar and was one of approximately 30 national days to be approved for the year out of an applicant pool of more than 18,000.

“As the only society dedicated to the specialty of hospital medicine, it is appropriate that SHM spearhead a national day to recognize the countless contributions of hospitalists to health care, from clinical, academic, and leadership perspectives and more,” said Larry Wellikson, MD, MHM, chief executive officer of SHM. “We look forward to hospitalists across the nation contributing to the festivities and making this a tradition for years to come.”

In addition to celebrating hospitalists’ contributions to patient care, SHM will also be highlighting the diverse career paths of hospital medicine professionals, from frontline hospitalist physicians, nurse practitioners, and physician assistants to practice administrators, C-suite executives, and academic hospitalists.

Highlights of SHM’s campaign include the following:

• Downloadable customizable posters and assets for hospitals and individuals’ offices to celebrate their hospital medicine team, available on SHM’s website, hospitalmedicine.org.
• A series of spotlights of hospitalists at all stages of their careers in The Hospitalist, SHM’s monthly newsmagazine.
• A social media campaign inviting hospitalists and their employers to share their success stories using the hashtag #HowWeHospitalist, including banner graphics, profile photo overlays, and more.
• A social media contest to determine the most creative ways of celebrating use of the hashtag.
• A Twitter chat for hospitalists to celebrate virtually with their colleagues and peers from around the world.

“Hospitalists innovate, lead, and push the boundaries of clinical care and deserve to be recognized for their transformative contributions to health care,” said Eric E. Howell, MD, MHM, chief operating officer of SHM. “We hope this is the beginning of a long-standing tradition in honoring hospitalists and the noteworthy work they do.”

For more information, visit www.hospitalmedicine.org/hospitalistday.

Mr. Radler is marketing communications manager at the Society of Hospital Medicine.

The Society of Hospital Medicine is proud to announce the inaugural National Hospitalist Day, to be held on Thursday, March 7, 2019. Occurring the first Thursday in March annually, National Hospitalist Day will serve to celebrate the fastest-growing specialty in modern medicine and hospitalists’ enduring contributions to the evolving health care landscape.

National Hospitalist Day was recently approved by the National Day Calendar and was one of approximately 30 national days to be approved for the year out of an applicant pool of more than 18,000.

“As the only society dedicated to the specialty of hospital medicine, it is appropriate that SHM spearhead a national day to recognize the countless contributions of hospitalists to health care, from clinical, academic, and leadership perspectives and more,” said Larry Wellikson, MD, MHM, chief executive officer of SHM. “We look forward to hospitalists across the nation contributing to the festivities and making this a tradition for years to come.”

In addition to celebrating hospitalists’ contributions to patient care, SHM will also be highlighting the diverse career paths of hospital medicine professionals, from frontline hospitalist physicians, nurse practitioners, and physician assistants to practice administrators, C-suite executives, and academic hospitalists.

Highlights of SHM’s campaign include the following:

• Downloadable customizable posters and assets for hospitals and individuals’ offices to celebrate their hospital medicine team, available on SHM’s website, hospitalmedicine.org.
• A series of spotlights of hospitalists at all stages of their careers in The Hospitalist, SHM’s monthly newsmagazine.
• A social media campaign inviting hospitalists and their employers to share their success stories using the hashtag #HowWeHospitalist, including banner graphics, profile photo overlays, and more.
• A social media contest to determine the most creative ways of celebrating use of the hashtag.
• A Twitter chat for hospitalists to celebrate virtually with their colleagues and peers from around the world.

“Hospitalists innovate, lead, and push the boundaries of clinical care and deserve to be recognized for their transformative contributions to health care,” said Eric E. Howell, MD, MHM, chief operating officer of SHM. “We hope this is the beginning of a long-standing tradition in honoring hospitalists and the noteworthy work they do.”

For more information, visit www.hospitalmedicine.org/hospitalistday.

Mr. Radler is marketing communications manager at the Society of Hospital Medicine.

Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.

“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.

The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.

Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.

Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.

Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.

At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.

Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.

Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).

“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.

The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.

“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.

“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.

The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.

SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.

Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.

“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.

The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.

Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.

Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.

Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.

At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.

Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.

Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).

“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.

The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.

“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.

“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.

The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.

SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.

Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.

“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.

The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.

Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.

Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.

Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.

At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.

Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.

Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).

“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.

The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.

“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.

“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.

The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.

SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.

CHICAGO – When the first results from a large trial that showed profound and unexpected benefits for preventing heart failure hospitalizations associated with use of the antihyperglycemic sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin came out – a little over 3 years ago – the general reaction from clinicians was some variant of “Could this be real?”

Since then, as results from some five other large, international trials have come out showing both similar benefits from two other drugs in the same SGLT2 inhibitor class, canagliflozin and dapagliflozin, as well as results showing clear cardiovascular disease benefits from three drugs in a second class of antihyperglycemics, the glucagonlike peptide–1 receptor agonists (GLP-1 RAs), the general consensus among cardiologists became: “The cardiovascular and renal benefits are real. How can we now best use these drugs to help patients?”

This change increasingly forces cardiologists, as well as the primary care physicians who often manage patients with type 2 diabetes mellitus, to become more comfortable prescribing these two classes of antihyperglycemic drugs. During a talk at the American Heart Association scientific sessions, Eugene Braunwald, MD, arguably the top thought leader in cardiology, coined a new name for the medical subspecialty that he foresees navigating this overlap between diabetes care and cardiovascular disease prevention: diabetocardiology (although a more euphonic alternative might be cardiodiabetology, while the more comprehensive name could be cardionephrodiabetology).

“I was certainly surprised” by the first report in 2015 from the EMPA-REG OUTCOME trial (N Engl J Med. 2015 Nov 26;373[22]:2117-28), said Dr. Braunwald, who is professor of medicine at Harvard Medical School in Boston. A lot of his colleagues were surprised and said, “It’s just one trial.”

“Now we have three trials,” with the addition of the CANVAS trial for canagliflozin (N Engl J Med. 2017 Aug 17;377[7]:644-57) and the DECLARE-TIMI 58 trial (N Engl J Med. 2018 Nov 10. doi:10.1056/NEJMoa1812389) for dapagliflozin reported at the AHA meeting in November.

“We are in the midst of two pandemics: heart failure and type 2 diabetes. As cardiologists, we have to learn how to deal with this,” said Dr. Braunwald, and the evidence now clearly shows that these drugs can help with that.

Mitchel L. Zoler/MDedge News

As another speaker at the meeting, Javed Butler, MD, a heart failure specialist, observed in a separate talk at the meeting, “Heart failure is one of the most common, if not the most common complication, of patients with diabetes.” This tight link between heart failure and diabetes helps make cardiovascular mortality “the number one cause of death” in patients with diabetes, said Dr. Butler, professor and chairman of medicine at the University of Mississippi in Jackson.

“Thanks to the cardiovascular outcome trials, we now have a much broader and deeper appreciation of heart failure and renal disease as integral components of the cardiovascular-renal spectrum in people with diabetes,” said Subodh Verma, MD, a professor at the University of Toronto and cardiac surgeon at St. Michael’s Hospital in Toronto. Dr. Braunwald spelled out in his talk some of the interrelationships of diabetes, heart failure, and renal dysfunction that together produce a downward-spiraling vicious circle for patients, a pathophysiological process that clinicians can now short-circuit by treatment with a SGLT2 inhibitor.
 

Cardiovascular outcome trials show the way

Mitchel L. Zoler/MDedge News

In the context of antihyperglycemic drugs, the “cardiovascular outcome trials” refers to a series of large trials mandated by the Food and Drug Administration in 2008 to assess the cardiovascular disease effects of new agents coming onto the U.S. market to treat type 2 diabetes mellitus (T2DM). By the time Dr. Verma spoke at the AHA meeting, he could cite reported results from 12 of these trials: 5 different drugs in the GLP-1 RA class, 4 drugs in the dipeptidyl peptidase-4 (DPP-4) inhibitor class, and 3 drugs from the SGLT2 inhibitor class. Dr. Verma summed what the findings have shown.

The four tested DDP-4 inhibitors (alogliptin, linagliptin, saxagliptin, and sitagliptin) consistently showed neutrality for the primary outcome of major adverse cardiovascular disease events (MACE), constituted by cardiovascular disease death, MI, or stroke.

The five tested GLP-1 RAs (albiglutide, exenatide, liraglutide, lixisenatide, and semaglutide) showed a mixed pattern of MACE results that seemed to be linked with the subclass the drug fell into. The two exedin-4–based drugs, exenatide and lixisenatide, each showed a statistically neutral effect for MACE, as well as collectively in a combined analysis. In contrast, three human GLP-1–based drugs, albiglutide, liraglutide, and semaglutide, each showed a consistent, statistically-significant MACE reduction in their respective outcome trials, and collectively they showed a highly significant 18% reduction in MACE, compared with placebo, Dr. Verma said. Further, recent analysis by Dr. Verma that used data from liraglutide treatment in the LEADER trial showed the MACE benefit occurred only among enrolled patients treated with liraglutide who had established atherosclerotic cardiovascular disease (ASCVD). Patients enrolled in the trial with only multiple risk factors (in addition to having T2DM) but without established ASCVD showed no significant benefit from liraglutide treatment for the MACE endpoint, compared with control patients.

Recently a press-release announcement of results from a sixth GLP-1 RA, dulaglutide, in the REWIND trial of MACE outcomes suggested that a drug in this class could have broader effect. The majority, 69%, of the 9,901 patients with T2DM enrolled in REWIND had risk factors but not established ASCVD at enrollment. A Nov. 5, 2018, statement from the company developing this drug, Lilly, reported that the study overall produced a statistically significant reduction in MACE, although it provided no additional details. As the released noted, this made REWIND the first trial to show a MACE benefit from a drug in the GLP-1 RA class in patients without established ASCVD.

The MACE outcome results from the three SGLT2 inhibitor trials showed a similar pattern as liraglutide: In patients with established ASCVD, the drugs individually each produced a MACE reduction, although dapagliflozin just missed having a statistically significant reduction. Collectively, the three drugs showed a statistically significant, 14% relative risk reduction for MACE, compared with control patients. But among patients with multiple risk factors only, but without established ASCVD, included in two of the three trials (CANVAS and DECLARE-TIMI 58), the results showed both individually and collectively a neutral MACE effect.

But unlike the other antihyperglycemic drugs tested in the cardiovascular outcome trials, the SGLT2 inhibitors have shown two additional, highly important secondary outcomes: a consistent reduction in hospitalization for heart failure and a consistent reduction in renal-disease progression.

A meta-analysis of the three SGLT2 inhibitor trials published coincident with the release of the DECLARE-TIMI 58 results showed that, for the outcome of either cardiovascular death or hospitalization for heart failure, the SGLT2 inhibitors collectively showed a significant 29% relative decrease in this incidence among patients with a history of heart failure, and a significant 21% relative decrease among patients without history of heart failure (Lancet. 2018 Nov 10. doi: 10.1016/S0140-6736(18)32590-X). Among the subset of patients with established ASCVD, treatment with a SGLT2 inhibitor across all three trials showed a significant 16% relative risk reduction, and in the subset with multiple risk factors but no established ASCVD, the two SGLT2 inhibitors collectively produced a 16% relative cut in cardiovascular death or heart failure hospitalization with a P value of .06. Finally, the Lancet meta-analysis showed that, for a combined endpoint that reflected renal worsening, the SGLT2 inhibitors showed a significant relative reduction of about 45% in both the subgroup of patients with established ASCVD and in the subgroup of those with just risk factors.

“This is a big step forward for patients with multiple risk factors and diabetes but without ASCVD, that both renal disease and hospitalization for heart failure are sensitive” to the SGLT2 inhibitors, Dr. Verma noted. “We see renal protection and reduction of heart failure hospitalization across both primary and secondary prevention patients, with no need to distinguish them based on ASCVD.” In contrast, he noted, the MACE benefit from the SGLT2 inhibitors seems limited to patients with ASCVD. The day before making this point in a talk during the meeting, Dr. Verma had published the same message in a commentary (Lancet. 2018 Nov 10. doi: 10.1016/S0140-6736(18)32824-1).

Although the “nomenclature of primary versus secondary prevention is appropriate for atherosclerotic outcomes, it is likely to be inappropriate for a person with type 2 diabetes who is at risk of hospitalization for heart failure and renal disease,” Dr. Verma wrote with his associates in the commentary.

What it means for clinicians

The upshot of all of these cardiovascular outcome trial results that came out over the past 3 years has been a new appreciation of how antihyperglycemic drugs can have cardiovascular and renal benefits that transcend their effects on glycemia. The evidence has put the SGLT2 inhibitors and GLP-1 RAs on track to challenge, and potentially displace, metformin as the top drug to prescribe for patients with T2DM.

Clinicians should realize that they should prescribe SGLT2 inhibitors and selected GLP-1 RAs “as early as metformin in patients with established ASCVD,” said Dr. Verma. “For patients with recalcitrant atherosclerotic disease and a history of MI and ischemia, I’d primarily treat with a GLP-1 RA. In a patient with left ventricular dysfunction or evidence of heart failure, I’d use an SGLT2 inhibitor. But it’s not a fight between these two. You could treat a patients with type 2 diabetes with both classes,” although the practicality of this approach is limited by the high cost of these drugs.

The SGLT2 inhibitors “should now be considered as first-line therapy after metformin in most people with type 2 diabetes, irrespective of whether or not they have established atherosclerotic vascular disease, chronic kidney disease, or heart failure,” he and his associates wrote in their recent commentary.

“What I struggle with the most is how we prioritize and individualize secondary-prevention therapies based on risk for ischemia and heart failure. Some therapies [the SGLT2 inhibitors] are predominantly for heart failure prevention, and some [the GLP-1 RAs] are primarily for ischemia. How do we choose when a patient cannot afford to take both? Does a combination of a SGLT2 inhibitor and a GLP-1 RA offer the greatest CVD benefit? We need to test this in a trial. And will metformin be displaced as first-line treatment?” Dr. Verma asked.

Mitchel L. Zoler/MDedge News

“The day will probably come when, for maximal protection, you treat with both classes. But right now we’re forced to choose because of the cost,” said John McMurray, MD, professor of cardiology at the University of Glasgow, in a talk during the meeting.

As to specifically which SGLT2 inhibitor to prescribe, “they all look pretty much the same” in the newly published meta-analysis, Dr. McMurray said, although he noted that safety differences among agents in the class remain possible.

“For patients similar to those studied in the three SGLT2 inhibitor trials, clinicians should use one of these drugs to reduce the risk for incident heart failure, irrespective of their effect on MACE,” said Dr. Butler. Reducing the risk for incident heart failure and of progressive renal dysfunction are two new goals for antihyperglycemic therapy that now overlay the long-standing goals of controlling glycemia and reducing cardiovascular disease risk and the more recent goals of cutting cardiovascular disease mortality and cutting the risk for a MACE event.

A current limitation for practice is that the none of the three drug companies that market the tested SGLT2 inhibitor drugs has sought regulatory approval for an indication of reducing the risk for heart failure hospitalization. Despite that, “these drugs should be used for renal protection and reducing heart failure hospitalizations,” Dr. Butler said. “We need to start thinking about this and not get lost thinking about only their MACE effect because, when you focus on MACE, there is a competition between the SGLT2 inhibitors and the GLP-1 RA. If we think of GLP-1 RAs as drugs to prevent MACE, and SGLT2 inhibitors as drugs that primarily prevent heart failure and renal dysfunction, then there is no competition. Perhaps combined treatment is where we need to go,” he said in an interview.

But the enthusiasm that experts like Dr. Butler, Dr. McMurray, and Dr. Verma have for wider use of both classes of drugs in appropriate patients is not necessarily matched right now among many community physicians. Cardiologist David J. Becker, MD, is an example of the clinicians who appreciate the growing evidence that supports wider use of these antihyperglycemic drugs but remain uneasy about applying this evidence in their practice.

Dr. Becker, associate director of the Preventive and Integrative Heart Health Program of the Temple Heart and Vascular Institute in Philadelphia, writes a column for the Philadelphia Inquirer on medical care. In a December 2018 piece, he said “like most cardiologists, I ‘don’t do diabetes’ – because it’s not my expertise. The new drugs, however, mean I need to learn more” about treating these patients. “The problem: There are so many of these medications that they present a bewildering choice for patients and doctors.”

Dr. Becker cited several barriers he sees for himself and his nonendocrinologist colleagues to prescribe these drugs – and for patients to take them:

• High cost, with prices that run close to $20/day for each medication.
• A thicket of names and choices that “lead to confusion and paralysis,” which has been exacerbated by “advertising wars” among competing drug companies.
• Cardiologists and primary care physicians usually defer to endocrinologists to prescribe these drugs, but most patients with T2DM aren’t seen by endocrinologists. The result: “Few doctors prescribe them.”

The cardiovascular disease benefits of these drugs have not been adequately promoted. Until that changes, “cardiologists like me will not realize their importance,” Dr. Becker concluded.

While christening the new diabetocardiology subspecialty, Dr. Braunwald placed the onus for managing this emerging facet of diabetes largely outside the scope of endocrinology.

“We can’t call in a consultant every time we have a patient with diabetes; it would bankrupt the system,” he said. Training of cardiologists now needs to include several months of treating patients with diabetes, Dr. Braunwald advised, just like 30 or so years ago when cardiologists like himself had to become more familiar with blood clotting to better manage thrombotic disease.

Dr. Braunwald has been a consultant to Cardurion, Myokardia, and Sanofi; an advisor to Endcardia; and has received research funding from AstraZeneca, Daiishi Sankyo, and Novartis. Dr. Butler has been a consultant or advisor to AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi. Dr. Verma has received honoraria and research funding from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck, Novartis, NovoNordisk, Sanofi, and Valeant. Dr. McMurray has received research funding from 12 companies. Dr. Becker had no disclosures.

[email protected]

CHICAGO – When the first results from a large trial that showed profound and unexpected benefits for preventing heart failure hospitalizations associated with use of the antihyperglycemic sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin came out – a little over 3 years ago – the general reaction from clinicians was some variant of “Could this be real?”

Since then, as results from some five other large, international trials have come out showing both similar benefits from two other drugs in the same SGLT2 inhibitor class, canagliflozin and dapagliflozin, as well as results showing clear cardiovascular disease benefits from three drugs in a second class of antihyperglycemics, the glucagonlike peptide–1 receptor agonists (GLP-1 RAs), the general consensus among cardiologists became: “The cardiovascular and renal benefits are real. How can we now best use these drugs to help patients?”

This change increasingly forces cardiologists, as well as the primary care physicians who often manage patients with type 2 diabetes mellitus, to become more comfortable prescribing these two classes of antihyperglycemic drugs. During a talk at the American Heart Association scientific sessions, Eugene Braunwald, MD, arguably the top thought leader in cardiology, coined a new name for the medical subspecialty that he foresees navigating this overlap between diabetes care and cardiovascular disease prevention: diabetocardiology (although a more euphonic alternative might be cardiodiabetology, while the more comprehensive name could be cardionephrodiabetology).

“I was certainly surprised” by the first report in 2015 from the EMPA-REG OUTCOME trial (N Engl J Med. 2015 Nov 26;373[22]:2117-28), said Dr. Braunwald, who is professor of medicine at Harvard Medical School in Boston. A lot of his colleagues were surprised and said, “It’s just one trial.”

“Now we have three trials,” with the addition of the CANVAS trial for canagliflozin (N Engl J Med. 2017 Aug 17;377[7]:644-57) and the DECLARE-TIMI 58 trial (N Engl J Med. 2018 Nov 10. doi:10.1056/NEJMoa1812389) for dapagliflozin reported at the AHA meeting in November.

“We are in the midst of two pandemics: heart failure and type 2 diabetes. As cardiologists, we have to learn how to deal with this,” said Dr. Braunwald, and the evidence now clearly shows that these drugs can help with that.

Mitchel L. Zoler/MDedge News

As another speaker at the meeting, Javed Butler, MD, a heart failure specialist, observed in a separate talk at the meeting, “Heart failure is one of the most common, if not the most common complication, of patients with diabetes.” This tight link between heart failure and diabetes helps make cardiovascular mortality “the number one cause of death” in patients with diabetes, said Dr. Butler, professor and chairman of medicine at the University of Mississippi in Jackson.

“Thanks to the cardiovascular outcome trials, we now have a much broader and deeper appreciation of heart failure and renal disease as integral components of the cardiovascular-renal spectrum in people with diabetes,” said Subodh Verma, MD, a professor at the University of Toronto and cardiac surgeon at St. Michael’s Hospital in Toronto. Dr. Braunwald spelled out in his talk some of the interrelationships of diabetes, heart failure, and renal dysfunction that together produce a downward-spiraling vicious circle for patients, a pathophysiological process that clinicians can now short-circuit by treatment with a SGLT2 inhibitor.
 

Cardiovascular outcome trials show the way

Mitchel L. Zoler/MDedge News

In the context of antihyperglycemic drugs, the “cardiovascular outcome trials” refers to a series of large trials mandated by the Food and Drug Administration in 2008 to assess the cardiovascular disease effects of new agents coming onto the U.S. market to treat type 2 diabetes mellitus (T2DM). By the time Dr. Verma spoke at the AHA meeting, he could cite reported results from 12 of these trials: 5 different drugs in the GLP-1 RA class, 4 drugs in the dipeptidyl peptidase-4 (DPP-4) inhibitor class, and 3 drugs from the SGLT2 inhibitor class. Dr. Verma summed what the findings have shown.

The four tested DDP-4 inhibitors (alogliptin, linagliptin, saxagliptin, and sitagliptin) consistently showed neutrality for the primary outcome of major adverse cardiovascular disease events (MACE), constituted by cardiovascular disease death, MI, or stroke.

The five tested GLP-1 RAs (albiglutide, exenatide, liraglutide, lixisenatide, and semaglutide) showed a mixed pattern of MACE results that seemed to be linked with the subclass the drug fell into. The two exedin-4–based drugs, exenatide and lixisenatide, each showed a statistically neutral effect for MACE, as well as collectively in a combined analysis. In contrast, three human GLP-1–based drugs, albiglutide, liraglutide, and semaglutide, each showed a consistent, statistically-significant MACE reduction in their respective outcome trials, and collectively they showed a highly significant 18% reduction in MACE, compared with placebo, Dr. Verma said. Further, recent analysis by Dr. Verma that used data from liraglutide treatment in the LEADER trial showed the MACE benefit occurred only among enrolled patients treated with liraglutide who had established atherosclerotic cardiovascular disease (ASCVD). Patients enrolled in the trial with only multiple risk factors (in addition to having T2DM) but without established ASCVD showed no significant benefit from liraglutide treatment for the MACE endpoint, compared with control patients.

Recently a press-release announcement of results from a sixth GLP-1 RA, dulaglutide, in the REWIND trial of MACE outcomes suggested that a drug in this class could have broader effect. The majority, 69%, of the 9,901 patients with T2DM enrolled in REWIND had risk factors but not established ASCVD at enrollment. A Nov. 5, 2018, statement from the company developing this drug, Lilly, reported that the study overall produced a statistically significant reduction in MACE, although it provided no additional details. As the released noted, this made REWIND the first trial to show a MACE benefit from a drug in the GLP-1 RA class in patients without established ASCVD.

The MACE outcome results from the three SGLT2 inhibitor trials showed a similar pattern as liraglutide: In patients with established ASCVD, the drugs individually each produced a MACE reduction, although dapagliflozin just missed having a statistically significant reduction. Collectively, the three drugs showed a statistically significant, 14% relative risk reduction for MACE, compared with control patients. But among patients with multiple risk factors only, but without established ASCVD, included in two of the three trials (CANVAS and DECLARE-TIMI 58), the results showed both individually and collectively a neutral MACE effect.

But unlike the other antihyperglycemic drugs tested in the cardiovascular outcome trials, the SGLT2 inhibitors have shown two additional, highly important secondary outcomes: a consistent reduction in hospitalization for heart failure and a consistent reduction in renal-disease progression.

A meta-analysis of the three SGLT2 inhibitor trials published coincident with the release of the DECLARE-TIMI 58 results showed that, for the outcome of either cardiovascular death or hospitalization for heart failure, the SGLT2 inhibitors collectively showed a significant 29% relative decrease in this incidence among patients with a history of heart failure, and a significant 21% relative decrease among patients without history of heart failure (Lancet. 2018 Nov 10. doi: 10.1016/S0140-6736(18)32590-X). Among the subset of patients with established ASCVD, treatment with a SGLT2 inhibitor across all three trials showed a significant 16% relative risk reduction, and in the subset with multiple risk factors but no established ASCVD, the two SGLT2 inhibitors collectively produced a 16% relative cut in cardiovascular death or heart failure hospitalization with a P value of .06. Finally, the Lancet meta-analysis showed that, for a combined endpoint that reflected renal worsening, the SGLT2 inhibitors showed a significant relative reduction of about 45% in both the subgroup of patients with established ASCVD and in the subgroup of those with just risk factors.

“This is a big step forward for patients with multiple risk factors and diabetes but without ASCVD, that both renal disease and hospitalization for heart failure are sensitive” to the SGLT2 inhibitors, Dr. Verma noted. “We see renal protection and reduction of heart failure hospitalization across both primary and secondary prevention patients, with no need to distinguish them based on ASCVD.” In contrast, he noted, the MACE benefit from the SGLT2 inhibitors seems limited to patients with ASCVD. The day before making this point in a talk during the meeting, Dr. Verma had published the same message in a commentary (Lancet. 2018 Nov 10. doi: 10.1016/S0140-6736(18)32824-1).

Although the “nomenclature of primary versus secondary prevention is appropriate for atherosclerotic outcomes, it is likely to be inappropriate for a person with type 2 diabetes who is at risk of hospitalization for heart failure and renal disease,” Dr. Verma wrote with his associates in the commentary.

What it means for clinicians

The upshot of all of these cardiovascular outcome trial results that came out over the past 3 years has been a new appreciation of how antihyperglycemic drugs can have cardiovascular and renal benefits that transcend their effects on glycemia. The evidence has put the SGLT2 inhibitors and GLP-1 RAs on track to challenge, and potentially displace, metformin as the top drug to prescribe for patients with T2DM.

Clinicians should realize that they should prescribe SGLT2 inhibitors and selected GLP-1 RAs “as early as metformin in patients with established ASCVD,” said Dr. Verma. “For patients with recalcitrant atherosclerotic disease and a history of MI and ischemia, I’d primarily treat with a GLP-1 RA. In a patient with left ventricular dysfunction or evidence of heart failure, I’d use an SGLT2 inhibitor. But it’s not a fight between these two. You could treat a patients with type 2 diabetes with both classes,” although the practicality of this approach is limited by the high cost of these drugs.

The SGLT2 inhibitors “should now be considered as first-line therapy after metformin in most people with type 2 diabetes, irrespective of whether or not they have established atherosclerotic vascular disease, chronic kidney disease, or heart failure,” he and his associates wrote in their recent commentary.

“What I struggle with the most is how we prioritize and individualize secondary-prevention therapies based on risk for ischemia and heart failure. Some therapies [the SGLT2 inhibitors] are predominantly for heart failure prevention, and some [the GLP-1 RAs] are primarily for ischemia. How do we choose when a patient cannot afford to take both? Does a combination of a SGLT2 inhibitor and a GLP-1 RA offer the greatest CVD benefit? We need to test this in a trial. And will metformin be displaced as first-line treatment?” Dr. Verma asked.

Mitchel L. Zoler/MDedge News

“The day will probably come when, for maximal protection, you treat with both classes. But right now we’re forced to choose because of the cost,” said John McMurray, MD, professor of cardiology at the University of Glasgow, in a talk during the meeting.

As to specifically which SGLT2 inhibitor to prescribe, “they all look pretty much the same” in the newly published meta-analysis, Dr. McMurray said, although he noted that safety differences among agents in the class remain possible.

“For patients similar to those studied in the three SGLT2 inhibitor trials, clinicians should use one of these drugs to reduce the risk for incident heart failure, irrespective of their effect on MACE,” said Dr. Butler. Reducing the risk for incident heart failure and of progressive renal dysfunction are two new goals for antihyperglycemic therapy that now overlay the long-standing goals of controlling glycemia and reducing cardiovascular disease risk and the more recent goals of cutting cardiovascular disease mortality and cutting the risk for a MACE event.

A current limitation for practice is that the none of the three drug companies that market the tested SGLT2 inhibitor drugs has sought regulatory approval for an indication of reducing the risk for heart failure hospitalization. Despite that, “these drugs should be used for renal protection and reducing heart failure hospitalizations,” Dr. Butler said. “We need to start thinking about this and not get lost thinking about only their MACE effect because, when you focus on MACE, there is a competition between the SGLT2 inhibitors and the GLP-1 RA. If we think of GLP-1 RAs as drugs to prevent MACE, and SGLT2 inhibitors as drugs that primarily prevent heart failure and renal dysfunction, then there is no competition. Perhaps combined treatment is where we need to go,” he said in an interview.

But the enthusiasm that experts like Dr. Butler, Dr. McMurray, and Dr. Verma have for wider use of both classes of drugs in appropriate patients is not necessarily matched right now among many community physicians. Cardiologist David J. Becker, MD, is an example of the clinicians who appreciate the growing evidence that supports wider use of these antihyperglycemic drugs but remain uneasy about applying this evidence in their practice.

Dr. Becker, associate director of the Preventive and Integrative Heart Health Program of the Temple Heart and Vascular Institute in Philadelphia, writes a column for the Philadelphia Inquirer on medical care. In a December 2018 piece, he said “like most cardiologists, I ‘don’t do diabetes’ – because it’s not my expertise. The new drugs, however, mean I need to learn more” about treating these patients. “The problem: There are so many of these medications that they present a bewildering choice for patients and doctors.”

Dr. Becker cited several barriers he sees for himself and his nonendocrinologist colleagues to prescribe these drugs – and for patients to take them:

• High cost, with prices that run close to $20/day for each medication.
• A thicket of names and choices that “lead to confusion and paralysis,” which has been exacerbated by “advertising wars” among competing drug companies.
• Cardiologists and primary care physicians usually defer to endocrinologists to prescribe these drugs, but most patients with T2DM aren’t seen by endocrinologists. The result: “Few doctors prescribe them.”

The cardiovascular disease benefits of these drugs have not been adequately promoted. Until that changes, “cardiologists like me will not realize their importance,” Dr. Becker concluded.

While christening the new diabetocardiology subspecialty, Dr. Braunwald placed the onus for managing this emerging facet of diabetes largely outside the scope of endocrinology.

“We can’t call in a consultant every time we have a patient with diabetes; it would bankrupt the system,” he said. Training of cardiologists now needs to include several months of treating patients with diabetes, Dr. Braunwald advised, just like 30 or so years ago when cardiologists like himself had to become more familiar with blood clotting to better manage thrombotic disease.

Dr. Braunwald has been a consultant to Cardurion, Myokardia, and Sanofi; an advisor to Endcardia; and has received research funding from AstraZeneca, Daiishi Sankyo, and Novartis. Dr. Butler has been a consultant or advisor to AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi. Dr. Verma has received honoraria and research funding from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck, Novartis, NovoNordisk, Sanofi, and Valeant. Dr. McMurray has received research funding from 12 companies. Dr. Becker had no disclosures.

[email protected]

CHICAGO – When the first results from a large trial that showed profound and unexpected benefits for preventing heart failure hospitalizations associated with use of the antihyperglycemic sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin came out – a little over 3 years ago – the general reaction from clinicians was some variant of “Could this be real?”

Since then, as results from some five other large, international trials have come out showing both similar benefits from two other drugs in the same SGLT2 inhibitor class, canagliflozin and dapagliflozin, as well as results showing clear cardiovascular disease benefits from three drugs in a second class of antihyperglycemics, the glucagonlike peptide–1 receptor agonists (GLP-1 RAs), the general consensus among cardiologists became: “The cardiovascular and renal benefits are real. How can we now best use these drugs to help patients?”

This change increasingly forces cardiologists, as well as the primary care physicians who often manage patients with type 2 diabetes mellitus, to become more comfortable prescribing these two classes of antihyperglycemic drugs. During a talk at the American Heart Association scientific sessions, Eugene Braunwald, MD, arguably the top thought leader in cardiology, coined a new name for the medical subspecialty that he foresees navigating this overlap between diabetes care and cardiovascular disease prevention: diabetocardiology (although a more euphonic alternative might be cardiodiabetology, while the more comprehensive name could be cardionephrodiabetology).

“I was certainly surprised” by the first report in 2015 from the EMPA-REG OUTCOME trial (N Engl J Med. 2015 Nov 26;373[22]:2117-28), said Dr. Braunwald, who is professor of medicine at Harvard Medical School in Boston. A lot of his colleagues were surprised and said, “It’s just one trial.”

“Now we have three trials,” with the addition of the CANVAS trial for canagliflozin (N Engl J Med. 2017 Aug 17;377[7]:644-57) and the DECLARE-TIMI 58 trial (N Engl J Med. 2018 Nov 10. doi:10.1056/NEJMoa1812389) for dapagliflozin reported at the AHA meeting in November.

“We are in the midst of two pandemics: heart failure and type 2 diabetes. As cardiologists, we have to learn how to deal with this,” said Dr. Braunwald, and the evidence now clearly shows that these drugs can help with that.

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As another speaker at the meeting, Javed Butler, MD, a heart failure specialist, observed in a separate talk at the meeting, “Heart failure is one of the most common, if not the most common complication, of patients with diabetes.” This tight link between heart failure and diabetes helps make cardiovascular mortality “the number one cause of death” in patients with diabetes, said Dr. Butler, professor and chairman of medicine at the University of Mississippi in Jackson.

“Thanks to the cardiovascular outcome trials, we now have a much broader and deeper appreciation of heart failure and renal disease as integral components of the cardiovascular-renal spectrum in people with diabetes,” said Subodh Verma, MD, a professor at the University of Toronto and cardiac surgeon at St. Michael’s Hospital in Toronto. Dr. Braunwald spelled out in his talk some of the interrelationships of diabetes, heart failure, and renal dysfunction that together produce a downward-spiraling vicious circle for patients, a pathophysiological process that clinicians can now short-circuit by treatment with a SGLT2 inhibitor.
 

Cardiovascular outcome trials show the way

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In the context of antihyperglycemic drugs, the “cardiovascular outcome trials” refers to a series of large trials mandated by the Food and Drug Administration in 2008 to assess the cardiovascular disease effects of new agents coming onto the U.S. market to treat type 2 diabetes mellitus (T2DM). By the time Dr. Verma spoke at the AHA meeting, he could cite reported results from 12 of these trials: 5 different drugs in the GLP-1 RA class, 4 drugs in the dipeptidyl peptidase-4 (DPP-4) inhibitor class, and 3 drugs from the SGLT2 inhibitor class. Dr. Verma summed what the findings have shown.

The four tested DDP-4 inhibitors (alogliptin, linagliptin, saxagliptin, and sitagliptin) consistently showed neutrality for the primary outcome of major adverse cardiovascular disease events (MACE), constituted by cardiovascular disease death, MI, or stroke.

The five tested GLP-1 RAs (albiglutide, exenatide, liraglutide, lixisenatide, and semaglutide) showed a mixed pattern of MACE results that seemed to be linked with the subclass the drug fell into. The two exedin-4–based drugs, exenatide and lixisenatide, each showed a statistically neutral effect for MACE, as well as collectively in a combined analysis. In contrast, three human GLP-1–based drugs, albiglutide, liraglutide, and semaglutide, each showed a consistent, statistically-significant MACE reduction in their respective outcome trials, and collectively they showed a highly significant 18% reduction in MACE, compared with placebo, Dr. Verma said. Further, recent analysis by Dr. Verma that used data from liraglutide treatment in the LEADER trial showed the MACE benefit occurred only among enrolled patients treated with liraglutide who had established atherosclerotic cardiovascular disease (ASCVD). Patients enrolled in the trial with only multiple risk factors (in addition to having T2DM) but without established ASCVD showed no significant benefit from liraglutide treatment for the MACE endpoint, compared with control patients.

Recently a press-release announcement of results from a sixth GLP-1 RA, dulaglutide, in the REWIND trial of MACE outcomes suggested that a drug in this class could have broader effect. The majority, 69%, of the 9,901 patients with T2DM enrolled in REWIND had risk factors but not established ASCVD at enrollment. A Nov. 5, 2018, statement from the company developing this drug, Lilly, reported that the study overall produced a statistically significant reduction in MACE, although it provided no additional details. As the released noted, this made REWIND the first trial to show a MACE benefit from a drug in the GLP-1 RA class in patients without established ASCVD.

The MACE outcome results from the three SGLT2 inhibitor trials showed a similar pattern as liraglutide: In patients with established ASCVD, the drugs individually each produced a MACE reduction, although dapagliflozin just missed having a statistically significant reduction. Collectively, the three drugs showed a statistically significant, 14% relative risk reduction for MACE, compared with control patients. But among patients with multiple risk factors only, but without established ASCVD, included in two of the three trials (CANVAS and DECLARE-TIMI 58), the results showed both individually and collectively a neutral MACE effect.

But unlike the other antihyperglycemic drugs tested in the cardiovascular outcome trials, the SGLT2 inhibitors have shown two additional, highly important secondary outcomes: a consistent reduction in hospitalization for heart failure and a consistent reduction in renal-disease progression.

A meta-analysis of the three SGLT2 inhibitor trials published coincident with the release of the DECLARE-TIMI 58 results showed that, for the outcome of either cardiovascular death or hospitalization for heart failure, the SGLT2 inhibitors collectively showed a significant 29% relative decrease in this incidence among patients with a history of heart failure, and a significant 21% relative decrease among patients without history of heart failure (Lancet. 2018 Nov 10. doi: 10.1016/S0140-6736(18)32590-X). Among the subset of patients with established ASCVD, treatment with a SGLT2 inhibitor across all three trials showed a significant 16% relative risk reduction, and in the subset with multiple risk factors but no established ASCVD, the two SGLT2 inhibitors collectively produced a 16% relative cut in cardiovascular death or heart failure hospitalization with a P value of .06. Finally, the Lancet meta-analysis showed that, for a combined endpoint that reflected renal worsening, the SGLT2 inhibitors showed a significant relative reduction of about 45% in both the subgroup of patients with established ASCVD and in the subgroup of those with just risk factors.

“This is a big step forward for patients with multiple risk factors and diabetes but without ASCVD, that both renal disease and hospitalization for heart failure are sensitive” to the SGLT2 inhibitors, Dr. Verma noted. “We see renal protection and reduction of heart failure hospitalization across both primary and secondary prevention patients, with no need to distinguish them based on ASCVD.” In contrast, he noted, the MACE benefit from the SGLT2 inhibitors seems limited to patients with ASCVD. The day before making this point in a talk during the meeting, Dr. Verma had published the same message in a commentary (Lancet. 2018 Nov 10. doi: 10.1016/S0140-6736(18)32824-1).

Although the “nomenclature of primary versus secondary prevention is appropriate for atherosclerotic outcomes, it is likely to be inappropriate for a person with type 2 diabetes who is at risk of hospitalization for heart failure and renal disease,” Dr. Verma wrote with his associates in the commentary.

What it means for clinicians

The upshot of all of these cardiovascular outcome trial results that came out over the past 3 years has been a new appreciation of how antihyperglycemic drugs can have cardiovascular and renal benefits that transcend their effects on glycemia. The evidence has put the SGLT2 inhibitors and GLP-1 RAs on track to challenge, and potentially displace, metformin as the top drug to prescribe for patients with T2DM.

Clinicians should realize that they should prescribe SGLT2 inhibitors and selected GLP-1 RAs “as early as metformin in patients with established ASCVD,” said Dr. Verma. “For patients with recalcitrant atherosclerotic disease and a history of MI and ischemia, I’d primarily treat with a GLP-1 RA. In a patient with left ventricular dysfunction or evidence of heart failure, I’d use an SGLT2 inhibitor. But it’s not a fight between these two. You could treat a patients with type 2 diabetes with both classes,” although the practicality of this approach is limited by the high cost of these drugs.

The SGLT2 inhibitors “should now be considered as first-line therapy after metformin in most people with type 2 diabetes, irrespective of whether or not they have established atherosclerotic vascular disease, chronic kidney disease, or heart failure,” he and his associates wrote in their recent commentary.

“What I struggle with the most is how we prioritize and individualize secondary-prevention therapies based on risk for ischemia and heart failure. Some therapies [the SGLT2 inhibitors] are predominantly for heart failure prevention, and some [the GLP-1 RAs] are primarily for ischemia. How do we choose when a patient cannot afford to take both? Does a combination of a SGLT2 inhibitor and a GLP-1 RA offer the greatest CVD benefit? We need to test this in a trial. And will metformin be displaced as first-line treatment?” Dr. Verma asked.

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“The day will probably come when, for maximal protection, you treat with both classes. But right now we’re forced to choose because of the cost,” said John McMurray, MD, professor of cardiology at the University of Glasgow, in a talk during the meeting.

As to specifically which SGLT2 inhibitor to prescribe, “they all look pretty much the same” in the newly published meta-analysis, Dr. McMurray said, although he noted that safety differences among agents in the class remain possible.

“For patients similar to those studied in the three SGLT2 inhibitor trials, clinicians should use one of these drugs to reduce the risk for incident heart failure, irrespective of their effect on MACE,” said Dr. Butler. Reducing the risk for incident heart failure and of progressive renal dysfunction are two new goals for antihyperglycemic therapy that now overlay the long-standing goals of controlling glycemia and reducing cardiovascular disease risk and the more recent goals of cutting cardiovascular disease mortality and cutting the risk for a MACE event.

A current limitation for practice is that the none of the three drug companies that market the tested SGLT2 inhibitor drugs has sought regulatory approval for an indication of reducing the risk for heart failure hospitalization. Despite that, “these drugs should be used for renal protection and reducing heart failure hospitalizations,” Dr. Butler said. “We need to start thinking about this and not get lost thinking about only their MACE effect because, when you focus on MACE, there is a competition between the SGLT2 inhibitors and the GLP-1 RA. If we think of GLP-1 RAs as drugs to prevent MACE, and SGLT2 inhibitors as drugs that primarily prevent heart failure and renal dysfunction, then there is no competition. Perhaps combined treatment is where we need to go,” he said in an interview.

But the enthusiasm that experts like Dr. Butler, Dr. McMurray, and Dr. Verma have for wider use of both classes of drugs in appropriate patients is not necessarily matched right now among many community physicians. Cardiologist David J. Becker, MD, is an example of the clinicians who appreciate the growing evidence that supports wider use of these antihyperglycemic drugs but remain uneasy about applying this evidence in their practice.

Dr. Becker, associate director of the Preventive and Integrative Heart Health Program of the Temple Heart and Vascular Institute in Philadelphia, writes a column for the Philadelphia Inquirer on medical care. In a December 2018 piece, he said “like most cardiologists, I ‘don’t do diabetes’ – because it’s not my expertise. The new drugs, however, mean I need to learn more” about treating these patients. “The problem: There are so many of these medications that they present a bewildering choice for patients and doctors.”

Dr. Becker cited several barriers he sees for himself and his nonendocrinologist colleagues to prescribe these drugs – and for patients to take them:

• High cost, with prices that run close to $20/day for each medication.
• A thicket of names and choices that “lead to confusion and paralysis,” which has been exacerbated by “advertising wars” among competing drug companies.
• Cardiologists and primary care physicians usually defer to endocrinologists to prescribe these drugs, but most patients with T2DM aren’t seen by endocrinologists. The result: “Few doctors prescribe them.”

The cardiovascular disease benefits of these drugs have not been adequately promoted. Until that changes, “cardiologists like me will not realize their importance,” Dr. Becker concluded.

While christening the new diabetocardiology subspecialty, Dr. Braunwald placed the onus for managing this emerging facet of diabetes largely outside the scope of endocrinology.

“We can’t call in a consultant every time we have a patient with diabetes; it would bankrupt the system,” he said. Training of cardiologists now needs to include several months of treating patients with diabetes, Dr. Braunwald advised, just like 30 or so years ago when cardiologists like himself had to become more familiar with blood clotting to better manage thrombotic disease.

Dr. Braunwald has been a consultant to Cardurion, Myokardia, and Sanofi; an advisor to Endcardia; and has received research funding from AstraZeneca, Daiishi Sankyo, and Novartis. Dr. Butler has been a consultant or advisor to AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi. Dr. Verma has received honoraria and research funding from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck, Novartis, NovoNordisk, Sanofi, and Valeant. Dr. McMurray has received research funding from 12 companies. Dr. Becker had no disclosures.

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