Richard Mark Kirkner

CHICAGO – A care model that uses hospitalists to comanage vascular surgery patients cut myocardial infarction rates by more than half and reduced hospital stays by about 12%, according to results of a study of the hospitalist comanagement model from Loyola University Chicago, Maywood, Ill., presented at the annual meeting of the Midwestern Vascular Surgery Society.

“Hospitalist comanagement was associated with decreased length of stay without affecting readmission for patients undergoing amputation, embolectomy, and infected graft,” said Kaavya Adam, a third-year medical student at Loyola University Chicago. “In the overall population, there was a reduction in cases of MI, 30-day readmissions, and overall length of stay.”

In 2014, Loyola implemented a program that used 11 hospitalists to rotate through the vascular surgery service. The hospitalists call on any patient who stays more than 24 hours on the non-ICU floors. Adam said hospitalist duties include evaluating patient comorbidities, adjusting medication, talking with family about medical management, seeing patients on the day of surgery, ordering preoperative labs, and meeting with the anesthesiology and vascular surgery teams.

The study compared outcomes in 866 patients admitted during 2007-2013, before the comanagement model was put into place, and 572 admitted during 2014-2017.

Rates of diabetes, hypertension, chronic kidney disease, coronary artery disease, hyperlipidemia, and malnutrition were similar between the groups. However, the pre-comanagement group had significantly higher rates of ischemic pain (27.8% vs. 10.7%), gangrene (21.3% vs. 13.6%) and ulceration (30.6% vs. 21.9%), while the comanaged group had significantly higher rates of claudication (34.3% vs. 13.2%). The statistical analysis accounted for these variations, Adam said.

“We did find significant results for the reduction in the odds of MI at 30 days; there was a 61% reduction,” he said.

The reduction in hospital stay was even more pronounced for patients with complex cases, Adam said. In amputation, the length of stay was reduced by 3.77 days (P = .01); in embolectomy, by 7.35 (P = .004); and in infected graft, by 8.35 (P = .007).

Continuing research will evaluate the cost effectiveness of the hospitalist model and define a comanagement model that is most beneficial, Mr. Adam said. He had no relevant financial disclosures.

SOURCE: Adam K et al. Midwestern Vascular 2019, Abstract 14.

CHICAGO – A care model that uses hospitalists to comanage vascular surgery patients cut myocardial infarction rates by more than half and reduced hospital stays by about 12%, according to results of a study of the hospitalist comanagement model from Loyola University Chicago, Maywood, Ill., presented at the annual meeting of the Midwestern Vascular Surgery Society.

“Hospitalist comanagement was associated with decreased length of stay without affecting readmission for patients undergoing amputation, embolectomy, and infected graft,” said Kaavya Adam, a third-year medical student at Loyola University Chicago. “In the overall population, there was a reduction in cases of MI, 30-day readmissions, and overall length of stay.”

In 2014, Loyola implemented a program that used 11 hospitalists to rotate through the vascular surgery service. The hospitalists call on any patient who stays more than 24 hours on the non-ICU floors. Adam said hospitalist duties include evaluating patient comorbidities, adjusting medication, talking with family about medical management, seeing patients on the day of surgery, ordering preoperative labs, and meeting with the anesthesiology and vascular surgery teams.

The study compared outcomes in 866 patients admitted during 2007-2013, before the comanagement model was put into place, and 572 admitted during 2014-2017.

Rates of diabetes, hypertension, chronic kidney disease, coronary artery disease, hyperlipidemia, and malnutrition were similar between the groups. However, the pre-comanagement group had significantly higher rates of ischemic pain (27.8% vs. 10.7%), gangrene (21.3% vs. 13.6%) and ulceration (30.6% vs. 21.9%), while the comanaged group had significantly higher rates of claudication (34.3% vs. 13.2%). The statistical analysis accounted for these variations, Adam said.

“We did find significant results for the reduction in the odds of MI at 30 days; there was a 61% reduction,” he said.

The reduction in hospital stay was even more pronounced for patients with complex cases, Adam said. In amputation, the length of stay was reduced by 3.77 days (P = .01); in embolectomy, by 7.35 (P = .004); and in infected graft, by 8.35 (P = .007).

Continuing research will evaluate the cost effectiveness of the hospitalist model and define a comanagement model that is most beneficial, Mr. Adam said. He had no relevant financial disclosures.

SOURCE: Adam K et al. Midwestern Vascular 2019, Abstract 14.

CHICAGO – A care model that uses hospitalists to comanage vascular surgery patients cut myocardial infarction rates by more than half and reduced hospital stays by about 12%, according to results of a study of the hospitalist comanagement model from Loyola University Chicago, Maywood, Ill., presented at the annual meeting of the Midwestern Vascular Surgery Society.

“Hospitalist comanagement was associated with decreased length of stay without affecting readmission for patients undergoing amputation, embolectomy, and infected graft,” said Kaavya Adam, a third-year medical student at Loyola University Chicago. “In the overall population, there was a reduction in cases of MI, 30-day readmissions, and overall length of stay.”

In 2014, Loyola implemented a program that used 11 hospitalists to rotate through the vascular surgery service. The hospitalists call on any patient who stays more than 24 hours on the non-ICU floors. Adam said hospitalist duties include evaluating patient comorbidities, adjusting medication, talking with family about medical management, seeing patients on the day of surgery, ordering preoperative labs, and meeting with the anesthesiology and vascular surgery teams.

The study compared outcomes in 866 patients admitted during 2007-2013, before the comanagement model was put into place, and 572 admitted during 2014-2017.

Rates of diabetes, hypertension, chronic kidney disease, coronary artery disease, hyperlipidemia, and malnutrition were similar between the groups. However, the pre-comanagement group had significantly higher rates of ischemic pain (27.8% vs. 10.7%), gangrene (21.3% vs. 13.6%) and ulceration (30.6% vs. 21.9%), while the comanaged group had significantly higher rates of claudication (34.3% vs. 13.2%). The statistical analysis accounted for these variations, Adam said.

“We did find significant results for the reduction in the odds of MI at 30 days; there was a 61% reduction,” he said.

The reduction in hospital stay was even more pronounced for patients with complex cases, Adam said. In amputation, the length of stay was reduced by 3.77 days (P = .01); in embolectomy, by 7.35 (P = .004); and in infected graft, by 8.35 (P = .007).

Continuing research will evaluate the cost effectiveness of the hospitalist model and define a comanagement model that is most beneficial, Mr. Adam said. He had no relevant financial disclosures.

SOURCE: Adam K et al. Midwestern Vascular 2019, Abstract 14.

CHICAGO – Early results of a trial evaluating allogeneic mesenchymal stem cells to target aortic inflammation in patients with small abdominal aortic aneurysms (AAAs) has reported encouraging early results, according to research presented here at the annual meeting of the Midwestern Vascular Surgery Society.

Katherin Leckie, MD, an integrated vascular surgery resident in the vascular surgery division, Indiana University, Indianapolis, reported on early results from the ARREST (Aneurysm Repression With Mesenchymal Stem Cells) trial. Twenty-one patients have been enrolled so far, and early results showed that treatment with mesenchymal stem cells (MSCs) increased levels of a key anti-inflammatory cell type, the Tr1, in proportion to a key proinflammatory cell type, the Th17.

“In AAA, the Tr1:Th17 ratio is decreased,” Dr. Leckie said. AAA serum stimulates MSC secretion of IL-10. Previously, mouse studies have shown MSCs restore the Tr1:Th17 balance and prevent aneurysms, Dr. Leckie noted.

The ARREST trial is evaluating that finding in humans with small AAAs of 35-50 mm in diameter. When the trial is fully enrolled, the 36 patients are to be evenly divided between three treatment groups: placebo; 1 million MSC/kg; and 3 million MSC/kg. The primary endpoint is change in Tr1:Th17 ratio at 14 days. Secondary endpoints are change in AAA inflammation at 2 weeks and change in AAA diameter and volume at 1-5 years.

At 14 days, the high-dose group had already seen a more than 100% change in Tr1:Th17 ratio (P = .03), versus about a 35% change for the low-dose and no change for the placebo groups. At 28 days, the high-dose group’s change increased to greater than 150%, while that of the low-dose group reached around 50%, with no change in the placebo group.

The study also found a possible trend toward changes in AAA diameter among the three groups after 1 year, Dr. Leckie said. In the placebo group, AAA diameter increased 3.5 mm on average. In the low-dose group, AAA diameter increased almost 1.5 mm. However, in the high-dose group, aortic diameter actually decreased about 0.5 mm (P = .189), Dr. Leckie said.

“MSCs have significantly improved the Tr1:Th17 imbalance at 14 days,” Dr. Leckie said. “There’s also a possible trend toward decreased aortic inflammation at 14 days as well as decreased growth of AAA at 12 months.”

Dr. Leckie had no relevant financial relationships to disclose.

CHICAGO – Early results of a trial evaluating allogeneic mesenchymal stem cells to target aortic inflammation in patients with small abdominal aortic aneurysms (AAAs) has reported encouraging early results, according to research presented here at the annual meeting of the Midwestern Vascular Surgery Society.

Katherin Leckie, MD, an integrated vascular surgery resident in the vascular surgery division, Indiana University, Indianapolis, reported on early results from the ARREST (Aneurysm Repression With Mesenchymal Stem Cells) trial. Twenty-one patients have been enrolled so far, and early results showed that treatment with mesenchymal stem cells (MSCs) increased levels of a key anti-inflammatory cell type, the Tr1, in proportion to a key proinflammatory cell type, the Th17.

“In AAA, the Tr1:Th17 ratio is decreased,” Dr. Leckie said. AAA serum stimulates MSC secretion of IL-10. Previously, mouse studies have shown MSCs restore the Tr1:Th17 balance and prevent aneurysms, Dr. Leckie noted.

The ARREST trial is evaluating that finding in humans with small AAAs of 35-50 mm in diameter. When the trial is fully enrolled, the 36 patients are to be evenly divided between three treatment groups: placebo; 1 million MSC/kg; and 3 million MSC/kg. The primary endpoint is change in Tr1:Th17 ratio at 14 days. Secondary endpoints are change in AAA inflammation at 2 weeks and change in AAA diameter and volume at 1-5 years.

At 14 days, the high-dose group had already seen a more than 100% change in Tr1:Th17 ratio (P = .03), versus about a 35% change for the low-dose and no change for the placebo groups. At 28 days, the high-dose group’s change increased to greater than 150%, while that of the low-dose group reached around 50%, with no change in the placebo group.

The study also found a possible trend toward changes in AAA diameter among the three groups after 1 year, Dr. Leckie said. In the placebo group, AAA diameter increased 3.5 mm on average. In the low-dose group, AAA diameter increased almost 1.5 mm. However, in the high-dose group, aortic diameter actually decreased about 0.5 mm (P = .189), Dr. Leckie said.

“MSCs have significantly improved the Tr1:Th17 imbalance at 14 days,” Dr. Leckie said. “There’s also a possible trend toward decreased aortic inflammation at 14 days as well as decreased growth of AAA at 12 months.”

Dr. Leckie had no relevant financial relationships to disclose.

CHICAGO – Early results of a trial evaluating allogeneic mesenchymal stem cells to target aortic inflammation in patients with small abdominal aortic aneurysms (AAAs) has reported encouraging early results, according to research presented here at the annual meeting of the Midwestern Vascular Surgery Society.

Katherin Leckie, MD, an integrated vascular surgery resident in the vascular surgery division, Indiana University, Indianapolis, reported on early results from the ARREST (Aneurysm Repression With Mesenchymal Stem Cells) trial. Twenty-one patients have been enrolled so far, and early results showed that treatment with mesenchymal stem cells (MSCs) increased levels of a key anti-inflammatory cell type, the Tr1, in proportion to a key proinflammatory cell type, the Th17.

“In AAA, the Tr1:Th17 ratio is decreased,” Dr. Leckie said. AAA serum stimulates MSC secretion of IL-10. Previously, mouse studies have shown MSCs restore the Tr1:Th17 balance and prevent aneurysms, Dr. Leckie noted.

The ARREST trial is evaluating that finding in humans with small AAAs of 35-50 mm in diameter. When the trial is fully enrolled, the 36 patients are to be evenly divided between three treatment groups: placebo; 1 million MSC/kg; and 3 million MSC/kg. The primary endpoint is change in Tr1:Th17 ratio at 14 days. Secondary endpoints are change in AAA inflammation at 2 weeks and change in AAA diameter and volume at 1-5 years.

At 14 days, the high-dose group had already seen a more than 100% change in Tr1:Th17 ratio (P = .03), versus about a 35% change for the low-dose and no change for the placebo groups. At 28 days, the high-dose group’s change increased to greater than 150%, while that of the low-dose group reached around 50%, with no change in the placebo group.

The study also found a possible trend toward changes in AAA diameter among the three groups after 1 year, Dr. Leckie said. In the placebo group, AAA diameter increased 3.5 mm on average. In the low-dose group, AAA diameter increased almost 1.5 mm. However, in the high-dose group, aortic diameter actually decreased about 0.5 mm (P = .189), Dr. Leckie said.

“MSCs have significantly improved the Tr1:Th17 imbalance at 14 days,” Dr. Leckie said. “There’s also a possible trend toward decreased aortic inflammation at 14 days as well as decreased growth of AAA at 12 months.”

Dr. Leckie had no relevant financial relationships to disclose.

CHICAGO – Numerous studies have shown conflicting results for endovascular repair in ruptured abdominal aortic aneurysms (AAA), but an analysis of 4,000-plus cases from a national registry has found a 41% reduction in mortality with endovascular repair vs. open repair, according to a presentation at the annual meeting of the Midwestern Vascular Surgery Society.

“EVAR is becoming an increasingly popular strategy for treatment of AAA,” said Samer Alharthi, MD, MPH, of the University of Toledo in Ohio. “As surgeon experience and endovascular technology have improved, a greater percentage of ruptured AAA are being treated by EVAR.”

Dr. Alharthi reported on a retrospective analysis of 4,133 patients who had repair for ruptured AAA in the American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2016. Notably, the number of EVAR repairs continue to increase and peaked in 2015, with 53% of ruptured AAA treated by EVAR.

Over the term of the study, the overall mortality rate was 22.6% for EVAR and 33.2% for open repair (P less than .001), Dr. Alharthi said. “After adjusting for cofounders, there was a 41% reduction in the mortality rate with the EVAR approach,” he said.

The only appreciable significant difference in demographics between the two groups was a higher percentage of smokers with chronic obstructive pulmonary disease having open repair – 942 (49.2%) vs. 701 (36.2%) – and a higher percentage of patients with end-stage renal disease having EVAR, Dr. Alharthi said. Other comorbidities had no statistically significant difference.

“Complications – pneumonia, reintubation, and acute renal failure – were higher in the open than the EVAR group,” he said. For example, rates of acute renal failure were 15.4% and 8.2% (P less than.001), respectively. Rates of myocardial infarction were similar between the two groups: 6.3% and 6% (P = .74), respectively.

Dr. Alharthi had no financial relationships to disclose.

SOURCE: Alharthi S et al. Midwestern Vascular 2019, Abstract 13.

CHICAGO – Numerous studies have shown conflicting results for endovascular repair in ruptured abdominal aortic aneurysms (AAA), but an analysis of 4,000-plus cases from a national registry has found a 41% reduction in mortality with endovascular repair vs. open repair, according to a presentation at the annual meeting of the Midwestern Vascular Surgery Society.

“EVAR is becoming an increasingly popular strategy for treatment of AAA,” said Samer Alharthi, MD, MPH, of the University of Toledo in Ohio. “As surgeon experience and endovascular technology have improved, a greater percentage of ruptured AAA are being treated by EVAR.”

Dr. Alharthi reported on a retrospective analysis of 4,133 patients who had repair for ruptured AAA in the American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2016. Notably, the number of EVAR repairs continue to increase and peaked in 2015, with 53% of ruptured AAA treated by EVAR.

Over the term of the study, the overall mortality rate was 22.6% for EVAR and 33.2% for open repair (P less than .001), Dr. Alharthi said. “After adjusting for cofounders, there was a 41% reduction in the mortality rate with the EVAR approach,” he said.

The only appreciable significant difference in demographics between the two groups was a higher percentage of smokers with chronic obstructive pulmonary disease having open repair – 942 (49.2%) vs. 701 (36.2%) – and a higher percentage of patients with end-stage renal disease having EVAR, Dr. Alharthi said. Other comorbidities had no statistically significant difference.

“Complications – pneumonia, reintubation, and acute renal failure – were higher in the open than the EVAR group,” he said. For example, rates of acute renal failure were 15.4% and 8.2% (P less than.001), respectively. Rates of myocardial infarction were similar between the two groups: 6.3% and 6% (P = .74), respectively.

Dr. Alharthi had no financial relationships to disclose.

SOURCE: Alharthi S et al. Midwestern Vascular 2019, Abstract 13.

CHICAGO – Numerous studies have shown conflicting results for endovascular repair in ruptured abdominal aortic aneurysms (AAA), but an analysis of 4,000-plus cases from a national registry has found a 41% reduction in mortality with endovascular repair vs. open repair, according to a presentation at the annual meeting of the Midwestern Vascular Surgery Society.

“EVAR is becoming an increasingly popular strategy for treatment of AAA,” said Samer Alharthi, MD, MPH, of the University of Toledo in Ohio. “As surgeon experience and endovascular technology have improved, a greater percentage of ruptured AAA are being treated by EVAR.”

Dr. Alharthi reported on a retrospective analysis of 4,133 patients who had repair for ruptured AAA in the American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2016. Notably, the number of EVAR repairs continue to increase and peaked in 2015, with 53% of ruptured AAA treated by EVAR.

Over the term of the study, the overall mortality rate was 22.6% for EVAR and 33.2% for open repair (P less than .001), Dr. Alharthi said. “After adjusting for cofounders, there was a 41% reduction in the mortality rate with the EVAR approach,” he said.

The only appreciable significant difference in demographics between the two groups was a higher percentage of smokers with chronic obstructive pulmonary disease having open repair – 942 (49.2%) vs. 701 (36.2%) – and a higher percentage of patients with end-stage renal disease having EVAR, Dr. Alharthi said. Other comorbidities had no statistically significant difference.

“Complications – pneumonia, reintubation, and acute renal failure – were higher in the open than the EVAR group,” he said. For example, rates of acute renal failure were 15.4% and 8.2% (P less than.001), respectively. Rates of myocardial infarction were similar between the two groups: 6.3% and 6% (P = .74), respectively.

Dr. Alharthi had no financial relationships to disclose.

SOURCE: Alharthi S et al. Midwestern Vascular 2019, Abstract 13.

Genotype-guided selection of oral P2Y ₁₂ inhibitors for patients having percutaneous coronary intervention with stent implantation derives no clinical benefits overall when compared to standard treatment, according to results of the large, randomized POPular Genetics trial, although genotype guidance did result in lower rates of primary minor bleeding.

The study was presented at the annual congress of the European Society of Cardiology Study in Paris and published simultaneously in the New England Journal of Medicine.

CDC/Janice Carr

POPular Genetics (CYP2C19 Genotype-Guided Antiplatelet Therapy in ST-Segment Elevation Myocardial Infarction Patients – Patient Outcome After Primary PCI) randomized 2,488 patients who had PCI to either P2Y₁₂ inhibitor on the basis of early genetic testing for the CYP2C19 gene (1,242 patients) or standard treatment with either ticagrelor or prasugrel (1,246 patients) for 12 months. In the genotype-guided group, patients were assigned to one of two arms depending on results; carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and non-carriers receive clopidogrel. The study was conducted from Jun. 2011 to Apr. 2018.

Net adverse clinical events, which included any-cause death, myocardial infarction, stent thrombosis, stroke or major bleeding based on the Platelet Inhibition and Patient Outcomes (PLATO) criteria at 12 months were similar between both groups: 5.1% in the genotype-guided patients and 5.9% in the standard-treatment group (P less than .001), but rates of PLATO major or minor bleeding were 9.8% and 12.5%, respectively (P = .04).

When secondary outcomes were evaluated, no significant differences emerged between the two groups. Secondary outcomes included combined thrombotic outcomes (death from vascular causes, myocardial infarction, stent thrombosis or stroke; 2.7% for the genotype-guided group vs. 3.3% in the standard-treatment group), and PLATO major bleeding (2.3% in both groups). The difference in the primary bleeding outcomes between the groups was driven by a lower incidence of PLATO minor bleeding in the genotype-guided group, 7.6% vs. 10.5%.

The two takeaways from POPular Genetics, said Daniel M.F. Claassens, MD, and coauthors, are that giving clopidogrel to patients without a CYP2C19 loss-of-function allele did not elevate their risk of combined any-cause death and other adverse cardiac outcomes, including major bleeding, 12 months after PCI; and that giving clopidogrel to the genotype-guided group lowered the risk of minor bleeding.

Dr. Claassens and coauthors noted that since the Netherlands trial was designed in 2011, the development of newer-generation stents has considerably lowered rates of thrombotic events after acute coronary syndromes. “With the lower-than-anticipated incidence of the primary combined outcome in our trial, the prespecified noninferiority margin was wider relative to the incidence than originally expected,” they said. While the primary combined outcome was 21% higher than the incidence in the standard-treatment group at the upper end of the 95% confidence interval, the incidence was 11% higher in the standard-treatment group at the observed upper end of the 95% CI. This “gives stronger support to the conclusion that genotype-guided P2Y₁₂ treatment is noninferior to standard treatment for the occurrence of thrombotic events,” Dr. Claassens and coauthors said.

The study report noted a number of limitations, including that more polymorphisms of the CyP2C19 gene may be linked to increased thrombotic or bleeding risk. “Therefore, our strategy based solely on the CYP2C19 genotype may not be the most useful strategy for some patients,” Dr. Claassens and coauthors said.

POPular Genetics received funding from the Netherlands Organization for Health Research and Development (ZonMw). Dr. Claassens receives grants from ZonMw and non-financial support from Spartan Biosciences.

SOURCE: Claassens DMF, et al. N Engl J. Med. Published online September 3, doi.org/10.1016/S0140-6736(19)31996-8.

Genotype-guided selection of oral P2Y ₁₂ inhibitors for patients having percutaneous coronary intervention with stent implantation derives no clinical benefits overall when compared to standard treatment, according to results of the large, randomized POPular Genetics trial, although genotype guidance did result in lower rates of primary minor bleeding.

The study was presented at the annual congress of the European Society of Cardiology Study in Paris and published simultaneously in the New England Journal of Medicine.

CDC/Janice Carr

POPular Genetics (CYP2C19 Genotype-Guided Antiplatelet Therapy in ST-Segment Elevation Myocardial Infarction Patients – Patient Outcome After Primary PCI) randomized 2,488 patients who had PCI to either P2Y₁₂ inhibitor on the basis of early genetic testing for the CYP2C19 gene (1,242 patients) or standard treatment with either ticagrelor or prasugrel (1,246 patients) for 12 months. In the genotype-guided group, patients were assigned to one of two arms depending on results; carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and non-carriers receive clopidogrel. The study was conducted from Jun. 2011 to Apr. 2018.

Net adverse clinical events, which included any-cause death, myocardial infarction, stent thrombosis, stroke or major bleeding based on the Platelet Inhibition and Patient Outcomes (PLATO) criteria at 12 months were similar between both groups: 5.1% in the genotype-guided patients and 5.9% in the standard-treatment group (P less than .001), but rates of PLATO major or minor bleeding were 9.8% and 12.5%, respectively (P = .04).

When secondary outcomes were evaluated, no significant differences emerged between the two groups. Secondary outcomes included combined thrombotic outcomes (death from vascular causes, myocardial infarction, stent thrombosis or stroke; 2.7% for the genotype-guided group vs. 3.3% in the standard-treatment group), and PLATO major bleeding (2.3% in both groups). The difference in the primary bleeding outcomes between the groups was driven by a lower incidence of PLATO minor bleeding in the genotype-guided group, 7.6% vs. 10.5%.

The two takeaways from POPular Genetics, said Daniel M.F. Claassens, MD, and coauthors, are that giving clopidogrel to patients without a CYP2C19 loss-of-function allele did not elevate their risk of combined any-cause death and other adverse cardiac outcomes, including major bleeding, 12 months after PCI; and that giving clopidogrel to the genotype-guided group lowered the risk of minor bleeding.

Dr. Claassens and coauthors noted that since the Netherlands trial was designed in 2011, the development of newer-generation stents has considerably lowered rates of thrombotic events after acute coronary syndromes. “With the lower-than-anticipated incidence of the primary combined outcome in our trial, the prespecified noninferiority margin was wider relative to the incidence than originally expected,” they said. While the primary combined outcome was 21% higher than the incidence in the standard-treatment group at the upper end of the 95% confidence interval, the incidence was 11% higher in the standard-treatment group at the observed upper end of the 95% CI. This “gives stronger support to the conclusion that genotype-guided P2Y₁₂ treatment is noninferior to standard treatment for the occurrence of thrombotic events,” Dr. Claassens and coauthors said.

The study report noted a number of limitations, including that more polymorphisms of the CyP2C19 gene may be linked to increased thrombotic or bleeding risk. “Therefore, our strategy based solely on the CYP2C19 genotype may not be the most useful strategy for some patients,” Dr. Claassens and coauthors said.

POPular Genetics received funding from the Netherlands Organization for Health Research and Development (ZonMw). Dr. Claassens receives grants from ZonMw and non-financial support from Spartan Biosciences.

SOURCE: Claassens DMF, et al. N Engl J. Med. Published online September 3, doi.org/10.1016/S0140-6736(19)31996-8.

Genotype-guided selection of oral P2Y ₁₂ inhibitors for patients having percutaneous coronary intervention with stent implantation derives no clinical benefits overall when compared to standard treatment, according to results of the large, randomized POPular Genetics trial, although genotype guidance did result in lower rates of primary minor bleeding.

The study was presented at the annual congress of the European Society of Cardiology Study in Paris and published simultaneously in the New England Journal of Medicine.

CDC/Janice Carr

POPular Genetics (CYP2C19 Genotype-Guided Antiplatelet Therapy in ST-Segment Elevation Myocardial Infarction Patients – Patient Outcome After Primary PCI) randomized 2,488 patients who had PCI to either P2Y₁₂ inhibitor on the basis of early genetic testing for the CYP2C19 gene (1,242 patients) or standard treatment with either ticagrelor or prasugrel (1,246 patients) for 12 months. In the genotype-guided group, patients were assigned to one of two arms depending on results; carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and non-carriers receive clopidogrel. The study was conducted from Jun. 2011 to Apr. 2018.

Net adverse clinical events, which included any-cause death, myocardial infarction, stent thrombosis, stroke or major bleeding based on the Platelet Inhibition and Patient Outcomes (PLATO) criteria at 12 months were similar between both groups: 5.1% in the genotype-guided patients and 5.9% in the standard-treatment group (P less than .001), but rates of PLATO major or minor bleeding were 9.8% and 12.5%, respectively (P = .04).

When secondary outcomes were evaluated, no significant differences emerged between the two groups. Secondary outcomes included combined thrombotic outcomes (death from vascular causes, myocardial infarction, stent thrombosis or stroke; 2.7% for the genotype-guided group vs. 3.3% in the standard-treatment group), and PLATO major bleeding (2.3% in both groups). The difference in the primary bleeding outcomes between the groups was driven by a lower incidence of PLATO minor bleeding in the genotype-guided group, 7.6% vs. 10.5%.

The two takeaways from POPular Genetics, said Daniel M.F. Claassens, MD, and coauthors, are that giving clopidogrel to patients without a CYP2C19 loss-of-function allele did not elevate their risk of combined any-cause death and other adverse cardiac outcomes, including major bleeding, 12 months after PCI; and that giving clopidogrel to the genotype-guided group lowered the risk of minor bleeding.

Dr. Claassens and coauthors noted that since the Netherlands trial was designed in 2011, the development of newer-generation stents has considerably lowered rates of thrombotic events after acute coronary syndromes. “With the lower-than-anticipated incidence of the primary combined outcome in our trial, the prespecified noninferiority margin was wider relative to the incidence than originally expected,” they said. While the primary combined outcome was 21% higher than the incidence in the standard-treatment group at the upper end of the 95% confidence interval, the incidence was 11% higher in the standard-treatment group at the observed upper end of the 95% CI. This “gives stronger support to the conclusion that genotype-guided P2Y₁₂ treatment is noninferior to standard treatment for the occurrence of thrombotic events,” Dr. Claassens and coauthors said.

The study report noted a number of limitations, including that more polymorphisms of the CyP2C19 gene may be linked to increased thrombotic or bleeding risk. “Therefore, our strategy based solely on the CYP2C19 genotype may not be the most useful strategy for some patients,” Dr. Claassens and coauthors said.

POPular Genetics received funding from the Netherlands Organization for Health Research and Development (ZonMw). Dr. Claassens receives grants from ZonMw and non-financial support from Spartan Biosciences.

SOURCE: Claassens DMF, et al. N Engl J. Med. Published online September 3, doi.org/10.1016/S0140-6736(19)31996-8.

PARIS –A study of the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan supports updated guidelines that encourage ARNI substitution for traditional therapies in lower-risk heart failure patients, although the study found sacubitril-valsartan does not significantly reduce central aortic stiffness, compared with enalapril therapy, according results reported here at the annual congress of the European Society of Cardiology. The study was published simultaneously in JAMA.

“The study findings may provide insight into mechanisms underlying the effects of sacubitril-valsartan in heart failure and reduced ejection fraction,” lead author Akshay S. Desai, MD, of Brigham and Women’s Hospital, Boston, and co-authors wrote.

The study set out to determine the pathophysiologic mechanisms behind the clinical effects of sacubitril-valsartan, compared with enalapril in patients with heart failure and reduced ejection fraction (HFrEF). The EVALUATE-HF trial evaluated 464 patients age 50 years and older with multiple cardiovascular symptoms, including chronic heart failure with ejection fraction of less than 40%. Aortic characteristic impedance, a measure of central aortic stiffness, was evaluated with two-dimensional echocardiography at screening, then at four, 12 and 24 weeks. The primary endpoint was change in aortic characteristic impedance between the two treatment groups at 12 weeks.

Aortic characteristic impedance at baseline to 12 weeks decreased from 223.8 to 218.9 dyne x s/cm ⁵ in the sacubitril-valsartan treatment group and increased from 213.2 to 214.4 dyne x s/cm ⁵ in the enalapril group. “There was no statistically significant difference between groups in the change from baseline,” the investigators wrote. The between-group difference factored out to -2.2 dyne x s/cm ⁵ , ranging from -17.6 to 13.2 dyne x s/cm ⁵ . This was despite a reduction in brachial systolic blood pressure (6.5 and 1.6 mm Hg) and central systolic blood pressure (4.9 and 2.3 mm Hg), respectively.

The sacubitril-valsartan group showed greater reductions in left ventricular end-diastolic volume index, left ventricular end-systolic volume index, left atrial volume index and mitral E/e ′ ratio. “Although ejection fraction increased modestly by 1.9% in the sacubitril-valsartan group and by 1.3% in the enalapril group, we observed no significant between-group differences in change from baseline to 12 weeks in left ventricular ejection fraction or in other measured parameters,” the investigators wrote. Those other parameters include global longitudinal strain, mitral e ′ velocity or arterial elastance:ventricular elastance ratio. Rates of hypertension, hyperkalemia, and worsening renal function were similar in both groups.

Another secondary outcome was change from baseline in the overall 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ). A post-hoc analysis evaluated patients who achieved a statistically significant 5-points-or-greater change in KCCQ score, finding the score improved by 8.9 points in the sacubitril-valsartan group and 4.3 points in the enalapril group, a difference wider than 8-month results from the PARADIGM-HF trial ( Circ Heart Fail. 2017;10:e003430). “These data suggest that clinical benefits of sacubitril-valsartan compared with enalapril in patients with HFrEF are likely unrelated to changes in central aortic stiffness or pulsatile load, despite favorable effects of neprilysin inhibition on myocardial remodeling and wall stress,” the investigators wrote.

The data support the current guidelines for substituting ARNI for angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers therapy, “even in the face of apparent clinical stability,” Dr. Desai and co-authors said. In an invited commentary, Mark H. Drazner, MD , of Texas Southwestern Medical Center in Dallas, said the EVALUATE-HF trial, along with the observational PROVE-HF trial data also reported at the ESC meeting (JAMA. 2019 Sept 2. doi:10.1001/jama.2019.12821), “strongly suggest” ARNI therapy can promote cardiac reverse remodeling in patients with HFrEF. “As with beta-blockers and ACE inhibitors, it thus appears that the benefits of ARNI therapy on clinical outcomes in patients with HFrEF are mediated, at least in part, by their favorable effects on the adverse cardiac remodeling that characterizes the condition,” Dr. Desai and co-authors wrote.

The EVALUATE-HF trial was sponsored by Novartis. Dr. Desai disclosed financial relationships with Alnylam, AstraZeneca, Novartis, Abbott, Biofourmis, Boehringer Ingelheim, Boston Scientific, DalCor Pharma and Regeneron. Dr. Drazner has no financial relationships to disclose.

SOURCE: Desai AS et al. JAMA. 2019 Sept 2. doi:10.1001/jama.2019.12843.

PARIS –A study of the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan supports updated guidelines that encourage ARNI substitution for traditional therapies in lower-risk heart failure patients, although the study found sacubitril-valsartan does not significantly reduce central aortic stiffness, compared with enalapril therapy, according results reported here at the annual congress of the European Society of Cardiology. The study was published simultaneously in JAMA.

“The study findings may provide insight into mechanisms underlying the effects of sacubitril-valsartan in heart failure and reduced ejection fraction,” lead author Akshay S. Desai, MD, of Brigham and Women’s Hospital, Boston, and co-authors wrote.

The study set out to determine the pathophysiologic mechanisms behind the clinical effects of sacubitril-valsartan, compared with enalapril in patients with heart failure and reduced ejection fraction (HFrEF). The EVALUATE-HF trial evaluated 464 patients age 50 years and older with multiple cardiovascular symptoms, including chronic heart failure with ejection fraction of less than 40%. Aortic characteristic impedance, a measure of central aortic stiffness, was evaluated with two-dimensional echocardiography at screening, then at four, 12 and 24 weeks. The primary endpoint was change in aortic characteristic impedance between the two treatment groups at 12 weeks.

Aortic characteristic impedance at baseline to 12 weeks decreased from 223.8 to 218.9 dyne x s/cm ⁵ in the sacubitril-valsartan treatment group and increased from 213.2 to 214.4 dyne x s/cm ⁵ in the enalapril group. “There was no statistically significant difference between groups in the change from baseline,” the investigators wrote. The between-group difference factored out to -2.2 dyne x s/cm ⁵ , ranging from -17.6 to 13.2 dyne x s/cm ⁵ . This was despite a reduction in brachial systolic blood pressure (6.5 and 1.6 mm Hg) and central systolic blood pressure (4.9 and 2.3 mm Hg), respectively.

The sacubitril-valsartan group showed greater reductions in left ventricular end-diastolic volume index, left ventricular end-systolic volume index, left atrial volume index and mitral E/e ′ ratio. “Although ejection fraction increased modestly by 1.9% in the sacubitril-valsartan group and by 1.3% in the enalapril group, we observed no significant between-group differences in change from baseline to 12 weeks in left ventricular ejection fraction or in other measured parameters,” the investigators wrote. Those other parameters include global longitudinal strain, mitral e ′ velocity or arterial elastance:ventricular elastance ratio. Rates of hypertension, hyperkalemia, and worsening renal function were similar in both groups.

Another secondary outcome was change from baseline in the overall 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ). A post-hoc analysis evaluated patients who achieved a statistically significant 5-points-or-greater change in KCCQ score, finding the score improved by 8.9 points in the sacubitril-valsartan group and 4.3 points in the enalapril group, a difference wider than 8-month results from the PARADIGM-HF trial ( Circ Heart Fail. 2017;10:e003430). “These data suggest that clinical benefits of sacubitril-valsartan compared with enalapril in patients with HFrEF are likely unrelated to changes in central aortic stiffness or pulsatile load, despite favorable effects of neprilysin inhibition on myocardial remodeling and wall stress,” the investigators wrote.

The data support the current guidelines for substituting ARNI for angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers therapy, “even in the face of apparent clinical stability,” Dr. Desai and co-authors said. In an invited commentary, Mark H. Drazner, MD , of Texas Southwestern Medical Center in Dallas, said the EVALUATE-HF trial, along with the observational PROVE-HF trial data also reported at the ESC meeting (JAMA. 2019 Sept 2. doi:10.1001/jama.2019.12821), “strongly suggest” ARNI therapy can promote cardiac reverse remodeling in patients with HFrEF. “As with beta-blockers and ACE inhibitors, it thus appears that the benefits of ARNI therapy on clinical outcomes in patients with HFrEF are mediated, at least in part, by their favorable effects on the adverse cardiac remodeling that characterizes the condition,” Dr. Desai and co-authors wrote.

The EVALUATE-HF trial was sponsored by Novartis. Dr. Desai disclosed financial relationships with Alnylam, AstraZeneca, Novartis, Abbott, Biofourmis, Boehringer Ingelheim, Boston Scientific, DalCor Pharma and Regeneron. Dr. Drazner has no financial relationships to disclose.

SOURCE: Desai AS et al. JAMA. 2019 Sept 2. doi:10.1001/jama.2019.12843.

PARIS –A study of the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan supports updated guidelines that encourage ARNI substitution for traditional therapies in lower-risk heart failure patients, although the study found sacubitril-valsartan does not significantly reduce central aortic stiffness, compared with enalapril therapy, according results reported here at the annual congress of the European Society of Cardiology. The study was published simultaneously in JAMA.

“The study findings may provide insight into mechanisms underlying the effects of sacubitril-valsartan in heart failure and reduced ejection fraction,” lead author Akshay S. Desai, MD, of Brigham and Women’s Hospital, Boston, and co-authors wrote.

The study set out to determine the pathophysiologic mechanisms behind the clinical effects of sacubitril-valsartan, compared with enalapril in patients with heart failure and reduced ejection fraction (HFrEF). The EVALUATE-HF trial evaluated 464 patients age 50 years and older with multiple cardiovascular symptoms, including chronic heart failure with ejection fraction of less than 40%. Aortic characteristic impedance, a measure of central aortic stiffness, was evaluated with two-dimensional echocardiography at screening, then at four, 12 and 24 weeks. The primary endpoint was change in aortic characteristic impedance between the two treatment groups at 12 weeks.

Aortic characteristic impedance at baseline to 12 weeks decreased from 223.8 to 218.9 dyne x s/cm ⁵ in the sacubitril-valsartan treatment group and increased from 213.2 to 214.4 dyne x s/cm ⁵ in the enalapril group. “There was no statistically significant difference between groups in the change from baseline,” the investigators wrote. The between-group difference factored out to -2.2 dyne x s/cm ⁵ , ranging from -17.6 to 13.2 dyne x s/cm ⁵ . This was despite a reduction in brachial systolic blood pressure (6.5 and 1.6 mm Hg) and central systolic blood pressure (4.9 and 2.3 mm Hg), respectively.

The sacubitril-valsartan group showed greater reductions in left ventricular end-diastolic volume index, left ventricular end-systolic volume index, left atrial volume index and mitral E/e ′ ratio. “Although ejection fraction increased modestly by 1.9% in the sacubitril-valsartan group and by 1.3% in the enalapril group, we observed no significant between-group differences in change from baseline to 12 weeks in left ventricular ejection fraction or in other measured parameters,” the investigators wrote. Those other parameters include global longitudinal strain, mitral e ′ velocity or arterial elastance:ventricular elastance ratio. Rates of hypertension, hyperkalemia, and worsening renal function were similar in both groups.

Another secondary outcome was change from baseline in the overall 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ). A post-hoc analysis evaluated patients who achieved a statistically significant 5-points-or-greater change in KCCQ score, finding the score improved by 8.9 points in the sacubitril-valsartan group and 4.3 points in the enalapril group, a difference wider than 8-month results from the PARADIGM-HF trial ( Circ Heart Fail. 2017;10:e003430). “These data suggest that clinical benefits of sacubitril-valsartan compared with enalapril in patients with HFrEF are likely unrelated to changes in central aortic stiffness or pulsatile load, despite favorable effects of neprilysin inhibition on myocardial remodeling and wall stress,” the investigators wrote.

The data support the current guidelines for substituting ARNI for angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers therapy, “even in the face of apparent clinical stability,” Dr. Desai and co-authors said. In an invited commentary, Mark H. Drazner, MD , of Texas Southwestern Medical Center in Dallas, said the EVALUATE-HF trial, along with the observational PROVE-HF trial data also reported at the ESC meeting (JAMA. 2019 Sept 2. doi:10.1001/jama.2019.12821), “strongly suggest” ARNI therapy can promote cardiac reverse remodeling in patients with HFrEF. “As with beta-blockers and ACE inhibitors, it thus appears that the benefits of ARNI therapy on clinical outcomes in patients with HFrEF are mediated, at least in part, by their favorable effects on the adverse cardiac remodeling that characterizes the condition,” Dr. Desai and co-authors wrote.

The EVALUATE-HF trial was sponsored by Novartis. Dr. Desai disclosed financial relationships with Alnylam, AstraZeneca, Novartis, Abbott, Biofourmis, Boehringer Ingelheim, Boston Scientific, DalCor Pharma and Regeneron. Dr. Drazner has no financial relationships to disclose.

SOURCE: Desai AS et al. JAMA. 2019 Sept 2. doi:10.1001/jama.2019.12843.

A novel marker of repolarization may identify patients with cardiomyopathy who would benefit from an implanted cardioverter defibrillator, according to a European research study presented at the annual congress of the European Society of Cardiology and published simultaneously in The Lancet.

High periodic repolarization dynamics were linked to substantial reductions in mortality in a prespecified substudy of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators).

The degree of periodic repolarization dynamics correlated with reductions in mortality in the 1,371 patients, 968 of whom had ICD implantation and 403 of whom were treated conservatively, in the prospective, nonrandomized controlled cohort study conducted at 44 centers in 15 countries within the European Union. At a median follow-up of 2-7 years, the ICD group had a mortality rate of 14%; at a follow-up of 1-2 years, the control group had a mortality rate of 16%, resulting in a 43% overall reduction in mortality for the ICD group.

Low periodic repolarization dynamics were associated with a low reduction in ICD-related death, whereas high periodic repolarization dynamics were linked to substantial reductions in mortality. In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls. Periodic repolarization dynamics also served as reliable predictors of appropriate shocks in patients with ICDs as well as death in controls.

Because of the link between high periodic repolarization dynamics and greater benefits, cardiologists may be able to use the measure as a marker to individualize treatment decisions about the use of ICDs, said Axel Bauer, MD, director of University Hospital for Internal Medicine III, Cardiology and Angiology at Medical University Innsbruck, Austria, and coauthors. “Better patient selection could lead to a reduced number of devices needing to be implanted to save a life.

“Our results should help patients to make decisions about their treatment that take into account individual circumstances and preferences,” the researchers noted.

SOURCE: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.

A novel marker of repolarization may identify patients with cardiomyopathy who would benefit from an implanted cardioverter defibrillator, according to a European research study presented at the annual congress of the European Society of Cardiology and published simultaneously in The Lancet.

High periodic repolarization dynamics were linked to substantial reductions in mortality in a prespecified substudy of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators).

The degree of periodic repolarization dynamics correlated with reductions in mortality in the 1,371 patients, 968 of whom had ICD implantation and 403 of whom were treated conservatively, in the prospective, nonrandomized controlled cohort study conducted at 44 centers in 15 countries within the European Union. At a median follow-up of 2-7 years, the ICD group had a mortality rate of 14%; at a follow-up of 1-2 years, the control group had a mortality rate of 16%, resulting in a 43% overall reduction in mortality for the ICD group.

Low periodic repolarization dynamics were associated with a low reduction in ICD-related death, whereas high periodic repolarization dynamics were linked to substantial reductions in mortality. In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls. Periodic repolarization dynamics also served as reliable predictors of appropriate shocks in patients with ICDs as well as death in controls.

Because of the link between high periodic repolarization dynamics and greater benefits, cardiologists may be able to use the measure as a marker to individualize treatment decisions about the use of ICDs, said Axel Bauer, MD, director of University Hospital for Internal Medicine III, Cardiology and Angiology at Medical University Innsbruck, Austria, and coauthors. “Better patient selection could lead to a reduced number of devices needing to be implanted to save a life.

“Our results should help patients to make decisions about their treatment that take into account individual circumstances and preferences,” the researchers noted.

SOURCE: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.

A novel marker of repolarization may identify patients with cardiomyopathy who would benefit from an implanted cardioverter defibrillator, according to a European research study presented at the annual congress of the European Society of Cardiology and published simultaneously in The Lancet.

High periodic repolarization dynamics were linked to substantial reductions in mortality in a prespecified substudy of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators).

The degree of periodic repolarization dynamics correlated with reductions in mortality in the 1,371 patients, 968 of whom had ICD implantation and 403 of whom were treated conservatively, in the prospective, nonrandomized controlled cohort study conducted at 44 centers in 15 countries within the European Union. At a median follow-up of 2-7 years, the ICD group had a mortality rate of 14%; at a follow-up of 1-2 years, the control group had a mortality rate of 16%, resulting in a 43% overall reduction in mortality for the ICD group.

Low periodic repolarization dynamics were associated with a low reduction in ICD-related death, whereas high periodic repolarization dynamics were linked to substantial reductions in mortality. In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls. Periodic repolarization dynamics also served as reliable predictors of appropriate shocks in patients with ICDs as well as death in controls.

Because of the link between high periodic repolarization dynamics and greater benefits, cardiologists may be able to use the measure as a marker to individualize treatment decisions about the use of ICDs, said Axel Bauer, MD, director of University Hospital for Internal Medicine III, Cardiology and Angiology at Medical University Innsbruck, Austria, and coauthors. “Better patient selection could lead to a reduced number of devices needing to be implanted to save a life.

“Our results should help patients to make decisions about their treatment that take into account individual circumstances and preferences,” the researchers noted.

SOURCE: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.

FORT LAUDERDALE, FLA. — A dedicated, 24-hour, 7-day-a-week sickle cell inpatient observation unit staffed by a multidisciplinary care team significantly reduced inpatient admissions and emergency department visits per patient, according to an analysis of a Philadelphia program.

“These findings confirm the need for an individualized approach to treatment,” Sanaa Rizk, MD, director of the hereditary anemia program at Thomas Jefferson University Hospital, Philadelphia, said at the annual meeting of the Foundation for Sickle Cell Disease Research. “The potential strength of a multidisciplinary approach and personalized interventions toward high-utilizing subpopulations may offer the greatest impact.”

The study evaluated what Dr. Rizk called “the second clinical transformation” in care of sickle cell disease patients, which Thomas Jefferson University implemented in 2015. The comprehensive sickle cell center first opened in 2003, and the first transformation in November 2013 consisted of opening a four-bed sickle cell day unit to treat uncomplicated sickle cell vaso-occlusive crises with personalized pain treatment protocols (including IV fluids and opioids). It was staffed by a nurse practitioner, medical assistant, and two registered nurses from 8 a.m. to 5 p.m.

The second transformation transferred care to the inpatient observation unit on the hospital floor with access to 12 patient beds. A sickle cell nurse practitioner sees patients for same-day appointments, conducts sick visits, performs outreach, and handles follow-up with patients. The rest of the multidisciplinary team includes hospitalists, hematologists, internists, and a social worker who performs weekly inpatient rounds and meets monthly with ED leaders and pharmacists.

With the first transformation, ED visits per patient fell from 3.67 to 2.14 a year (P less than .001), and inpatient admissions per patient fell from 1.33 to 0.63 (P less than .0001), Dr. Rizk reported.

The second transformation reduced those per-patient rates even further, to 0.47 ED visits (P less than .01) and 0.29 inpatient admissions (P less than .001), she said.

“The expansion of the service reduced admissions and ED use significantly,” Dr. Rizk said.

She added that a subanalysis of the high-utilizer subgroup showed a decrease in average total medical charges by approximately $100,000/patient per year.

Dr. Rizk reported having no relevant financial disclosures.

SOURCE: Rizk S et al. FSCDR 2019, Abstract JSCDH-D-19-00049.

FORT LAUDERDALE, FLA. — A dedicated, 24-hour, 7-day-a-week sickle cell inpatient observation unit staffed by a multidisciplinary care team significantly reduced inpatient admissions and emergency department visits per patient, according to an analysis of a Philadelphia program.

“These findings confirm the need for an individualized approach to treatment,” Sanaa Rizk, MD, director of the hereditary anemia program at Thomas Jefferson University Hospital, Philadelphia, said at the annual meeting of the Foundation for Sickle Cell Disease Research. “The potential strength of a multidisciplinary approach and personalized interventions toward high-utilizing subpopulations may offer the greatest impact.”

The study evaluated what Dr. Rizk called “the second clinical transformation” in care of sickle cell disease patients, which Thomas Jefferson University implemented in 2015. The comprehensive sickle cell center first opened in 2003, and the first transformation in November 2013 consisted of opening a four-bed sickle cell day unit to treat uncomplicated sickle cell vaso-occlusive crises with personalized pain treatment protocols (including IV fluids and opioids). It was staffed by a nurse practitioner, medical assistant, and two registered nurses from 8 a.m. to 5 p.m.

The second transformation transferred care to the inpatient observation unit on the hospital floor with access to 12 patient beds. A sickle cell nurse practitioner sees patients for same-day appointments, conducts sick visits, performs outreach, and handles follow-up with patients. The rest of the multidisciplinary team includes hospitalists, hematologists, internists, and a social worker who performs weekly inpatient rounds and meets monthly with ED leaders and pharmacists.

With the first transformation, ED visits per patient fell from 3.67 to 2.14 a year (P less than .001), and inpatient admissions per patient fell from 1.33 to 0.63 (P less than .0001), Dr. Rizk reported.

The second transformation reduced those per-patient rates even further, to 0.47 ED visits (P less than .01) and 0.29 inpatient admissions (P less than .001), she said.

“The expansion of the service reduced admissions and ED use significantly,” Dr. Rizk said.

She added that a subanalysis of the high-utilizer subgroup showed a decrease in average total medical charges by approximately $100,000/patient per year.

Dr. Rizk reported having no relevant financial disclosures.

SOURCE: Rizk S et al. FSCDR 2019, Abstract JSCDH-D-19-00049.

FORT LAUDERDALE, FLA. — A dedicated, 24-hour, 7-day-a-week sickle cell inpatient observation unit staffed by a multidisciplinary care team significantly reduced inpatient admissions and emergency department visits per patient, according to an analysis of a Philadelphia program.

“These findings confirm the need for an individualized approach to treatment,” Sanaa Rizk, MD, director of the hereditary anemia program at Thomas Jefferson University Hospital, Philadelphia, said at the annual meeting of the Foundation for Sickle Cell Disease Research. “The potential strength of a multidisciplinary approach and personalized interventions toward high-utilizing subpopulations may offer the greatest impact.”

The study evaluated what Dr. Rizk called “the second clinical transformation” in care of sickle cell disease patients, which Thomas Jefferson University implemented in 2015. The comprehensive sickle cell center first opened in 2003, and the first transformation in November 2013 consisted of opening a four-bed sickle cell day unit to treat uncomplicated sickle cell vaso-occlusive crises with personalized pain treatment protocols (including IV fluids and opioids). It was staffed by a nurse practitioner, medical assistant, and two registered nurses from 8 a.m. to 5 p.m.

The second transformation transferred care to the inpatient observation unit on the hospital floor with access to 12 patient beds. A sickle cell nurse practitioner sees patients for same-day appointments, conducts sick visits, performs outreach, and handles follow-up with patients. The rest of the multidisciplinary team includes hospitalists, hematologists, internists, and a social worker who performs weekly inpatient rounds and meets monthly with ED leaders and pharmacists.

With the first transformation, ED visits per patient fell from 3.67 to 2.14 a year (P less than .001), and inpatient admissions per patient fell from 1.33 to 0.63 (P less than .0001), Dr. Rizk reported.

The second transformation reduced those per-patient rates even further, to 0.47 ED visits (P less than .01) and 0.29 inpatient admissions (P less than .001), she said.

“The expansion of the service reduced admissions and ED use significantly,” Dr. Rizk said.

She added that a subanalysis of the high-utilizer subgroup showed a decrease in average total medical charges by approximately $100,000/patient per year.

Dr. Rizk reported having no relevant financial disclosures.

SOURCE: Rizk S et al. FSCDR 2019, Abstract JSCDH-D-19-00049.

FORT LAUDERDALE, FLA. — Researchers have developed an assay that can be used in noninvasive prenatal testing (NIPT) of cell-free fetal DNA present in maternal blood to identify sickle cell disease without using paternal DNA, which could provide an alternative to other invasive methods, according to results of a pilot study.

Richard Mark Kirkner/MDedge News

The novel NIPT assay had a sensitivity greater than 98% and a specificity greater than 99% in early-phase analysis, Vivien A. Sheehan, MD, PhD, of Baylor College of Medicine, Houston, reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“Noninvasive prenatal testing is a safe and affordable alternative to chorionic villus sampling or amniocentesis and can be performed earlier in pregnancy,” Dr. Sheehan said. “There is a lot of potential for the growth of this test and its impact not only in this country, but worldwide.”

The NIPT uses cell-free fetal DNA from the pregnant mother’s peripheral blood.

“We know that fetal DNA is present in maternal blood and can comprise about 10% by the 10th week of gestation, and it increases as pregnancy progresses,” Dr. Sheehan said.

Maternal alleles from the baby and mother, as well as paternal alleles from the baby, can be identified in maternal blood. “By analyzing cell-free DNA in maternal blood via next-generation sequencing, we can determine fetal disease status,” she said.

Dr. Sheehan noted some reports have supported the use of NIPT for identifying trisomy and aneuploidy, but NIPT has encountered some challenges in identifying autosomal recessive disorders such as sickle cell disease.

To accomplish this, researchers at Baylor and test developer BillionToOne, developed a novel sequencing-based molecular counting strategy that can help measure the ratio of mutant versus normal alleles, Dr. Sheehan said.

The results obtained to date indicate that the assay reliably detects fetal sickle cell disease status when the fetal fraction is as low as 5%, the same limit as aneuploidy NIPT.

The method uses a commercial DNA extraction kit to isolate and purify cell-free fetal DNA from a single blood draw, then performs sickle cell disease NIPT assays using proprietary reagents, Dr. Sheehan explained. The protocol includes bioinformatic analyses that are used to determine hemoglobin S (HbS) mutation ratio and fetal disease status.

The pilot study had two phases. In the first phase, which has been completed, researchers sought to optimize the beta-globin gene probes using cell-free fetal DNA from compound heterozygote patients with sickle cell disease to establish the expected ratio of HbS mutation.

In the second phase, the researchers validated the test on pregnant women with sickle cell trait or sickle cell disease by performing the assay in maternal samples collected between 10-35 weeks of gestation.

Among the six controls who have sickle cell trait, the NIPT reported no false positives when compared with the state newborn screen results, Dr. Sheehan said. For the one participant with sickle cell anemia, the NIPT and newborn screening concurred on two blood draws, but the NIPT was inconclusive on the first blood draw obtained at 10 weeks’ gestation because of low levels of cell-free fetal DNA.

Overall, the analysis showed an analytical sensitivity greater than 98% and a specificity greater than 99%, even in the absence of paternal DNA, the study found.

BillionToOne developed the test. Dr. Sheehan reported having no financial relationships to disclose.

SOURCE: Sheehan VA et al. FSCDR 2019, Abstract JSCDH-D-19-00048.

FORT LAUDERDALE, FLA. — Researchers have developed an assay that can be used in noninvasive prenatal testing (NIPT) of cell-free fetal DNA present in maternal blood to identify sickle cell disease without using paternal DNA, which could provide an alternative to other invasive methods, according to results of a pilot study.

Richard Mark Kirkner/MDedge News

The novel NIPT assay had a sensitivity greater than 98% and a specificity greater than 99% in early-phase analysis, Vivien A. Sheehan, MD, PhD, of Baylor College of Medicine, Houston, reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“Noninvasive prenatal testing is a safe and affordable alternative to chorionic villus sampling or amniocentesis and can be performed earlier in pregnancy,” Dr. Sheehan said. “There is a lot of potential for the growth of this test and its impact not only in this country, but worldwide.”

The NIPT uses cell-free fetal DNA from the pregnant mother’s peripheral blood.

“We know that fetal DNA is present in maternal blood and can comprise about 10% by the 10th week of gestation, and it increases as pregnancy progresses,” Dr. Sheehan said.

Maternal alleles from the baby and mother, as well as paternal alleles from the baby, can be identified in maternal blood. “By analyzing cell-free DNA in maternal blood via next-generation sequencing, we can determine fetal disease status,” she said.

Dr. Sheehan noted some reports have supported the use of NIPT for identifying trisomy and aneuploidy, but NIPT has encountered some challenges in identifying autosomal recessive disorders such as sickle cell disease.

To accomplish this, researchers at Baylor and test developer BillionToOne, developed a novel sequencing-based molecular counting strategy that can help measure the ratio of mutant versus normal alleles, Dr. Sheehan said.

The results obtained to date indicate that the assay reliably detects fetal sickle cell disease status when the fetal fraction is as low as 5%, the same limit as aneuploidy NIPT.

The method uses a commercial DNA extraction kit to isolate and purify cell-free fetal DNA from a single blood draw, then performs sickle cell disease NIPT assays using proprietary reagents, Dr. Sheehan explained. The protocol includes bioinformatic analyses that are used to determine hemoglobin S (HbS) mutation ratio and fetal disease status.

The pilot study had two phases. In the first phase, which has been completed, researchers sought to optimize the beta-globin gene probes using cell-free fetal DNA from compound heterozygote patients with sickle cell disease to establish the expected ratio of HbS mutation.

In the second phase, the researchers validated the test on pregnant women with sickle cell trait or sickle cell disease by performing the assay in maternal samples collected between 10-35 weeks of gestation.

Among the six controls who have sickle cell trait, the NIPT reported no false positives when compared with the state newborn screen results, Dr. Sheehan said. For the one participant with sickle cell anemia, the NIPT and newborn screening concurred on two blood draws, but the NIPT was inconclusive on the first blood draw obtained at 10 weeks’ gestation because of low levels of cell-free fetal DNA.

Overall, the analysis showed an analytical sensitivity greater than 98% and a specificity greater than 99%, even in the absence of paternal DNA, the study found.

BillionToOne developed the test. Dr. Sheehan reported having no financial relationships to disclose.

SOURCE: Sheehan VA et al. FSCDR 2019, Abstract JSCDH-D-19-00048.

FORT LAUDERDALE, FLA. — Researchers have developed an assay that can be used in noninvasive prenatal testing (NIPT) of cell-free fetal DNA present in maternal blood to identify sickle cell disease without using paternal DNA, which could provide an alternative to other invasive methods, according to results of a pilot study.

Richard Mark Kirkner/MDedge News

The novel NIPT assay had a sensitivity greater than 98% and a specificity greater than 99% in early-phase analysis, Vivien A. Sheehan, MD, PhD, of Baylor College of Medicine, Houston, reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“Noninvasive prenatal testing is a safe and affordable alternative to chorionic villus sampling or amniocentesis and can be performed earlier in pregnancy,” Dr. Sheehan said. “There is a lot of potential for the growth of this test and its impact not only in this country, but worldwide.”

The NIPT uses cell-free fetal DNA from the pregnant mother’s peripheral blood.

“We know that fetal DNA is present in maternal blood and can comprise about 10% by the 10th week of gestation, and it increases as pregnancy progresses,” Dr. Sheehan said.

Maternal alleles from the baby and mother, as well as paternal alleles from the baby, can be identified in maternal blood. “By analyzing cell-free DNA in maternal blood via next-generation sequencing, we can determine fetal disease status,” she said.

Dr. Sheehan noted some reports have supported the use of NIPT for identifying trisomy and aneuploidy, but NIPT has encountered some challenges in identifying autosomal recessive disorders such as sickle cell disease.

To accomplish this, researchers at Baylor and test developer BillionToOne, developed a novel sequencing-based molecular counting strategy that can help measure the ratio of mutant versus normal alleles, Dr. Sheehan said.

The results obtained to date indicate that the assay reliably detects fetal sickle cell disease status when the fetal fraction is as low as 5%, the same limit as aneuploidy NIPT.

The method uses a commercial DNA extraction kit to isolate and purify cell-free fetal DNA from a single blood draw, then performs sickle cell disease NIPT assays using proprietary reagents, Dr. Sheehan explained. The protocol includes bioinformatic analyses that are used to determine hemoglobin S (HbS) mutation ratio and fetal disease status.

The pilot study had two phases. In the first phase, which has been completed, researchers sought to optimize the beta-globin gene probes using cell-free fetal DNA from compound heterozygote patients with sickle cell disease to establish the expected ratio of HbS mutation.

In the second phase, the researchers validated the test on pregnant women with sickle cell trait or sickle cell disease by performing the assay in maternal samples collected between 10-35 weeks of gestation.

Among the six controls who have sickle cell trait, the NIPT reported no false positives when compared with the state newborn screen results, Dr. Sheehan said. For the one participant with sickle cell anemia, the NIPT and newborn screening concurred on two blood draws, but the NIPT was inconclusive on the first blood draw obtained at 10 weeks’ gestation because of low levels of cell-free fetal DNA.

Overall, the analysis showed an analytical sensitivity greater than 98% and a specificity greater than 99%, even in the absence of paternal DNA, the study found.

BillionToOne developed the test. Dr. Sheehan reported having no financial relationships to disclose.

SOURCE: Sheehan VA et al. FSCDR 2019, Abstract JSCDH-D-19-00048.

FORT LAUDERDALE, FLA. – Sickle cell patients who received high-dose crizanlizumab had fewer vaso-occlusive crises (VOCs) than patients on a low-dose regimen a year after stopping the treatment, findings from a real-world follow-up study suggest.

But hospitalization rates and use of other health care resources were similar during and after therapy, regardless of dose, Nirmish Shah, MD, of Duke Health in Durham, N.C., reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“This is our attempt at a real-world study of patients after being in a big study that has good results and what happens to them afterward in regard to VOCs and health care utilization,” Dr. Shah said.

He reported results from the SUCCESSOR trial – a multicenter, retrospective cohort study – that evaluated a subset of 48 adult patients up to a year after they completed the SUSTAIN placebo-controlled phase 2 trial of crizanlizumab, a P-selectin inhibitor designed to control sickle cell pain crises.

In SUSTAIN, researchers evaluated two different dosages of crizanlizumab: 5 mg/kg and 2.5 mg/kg.

In the follow-up study, researchers obtained data from medical records over the study period November 2014 to March 2017. Crizanlizumab was not administered in the 52 weeks following the SUSTAIN trial.

They found that the subset of patients on the high dose of crizanlizumab had annual VOC rates of 2.7, compared with 4.0 among patients on the low dose of the drug. By comparison, VOC rates in SUSTAIN were 1.7 per year for the 5-mg/kg–dose group and 3.2 per year for the 2.5-mg/kg–dose group.

Overall, at least 60% of patients in the follow-up study had at least one hospitalization in the year after SUSTAIN. In the higher-dose group, the rates of hospitalization were similar in both SUSTAIN and SUCCESSOR – 53%. In the lower-dose group, hospitalization rates were 67% and 61% in SUCCESSOR and SUSTAIN, respectively.

“Among the previously treated patients with crizanlizumab, the total number of emergency department visits did seem to be higher in SUCCESSOR,” Dr. Shah said.

The study was limited by its retrospective nature and the fact that full data sets and follow-up were available on only a small number of patients, Dr. Shah said. “It was underpowered for a statistical analysis between groups,” he said. The goal was to determine the drug’s effect after treatment is discontinued, he said.

Dr. Shah reported a financial relationship with Novartis, which is developing crizanlizumab.

SOURCE: Shah N et al. FSCDR 2019, Abstract JSCDH-D-19-00031.

FORT LAUDERDALE, FLA. – Sickle cell patients who received high-dose crizanlizumab had fewer vaso-occlusive crises (VOCs) than patients on a low-dose regimen a year after stopping the treatment, findings from a real-world follow-up study suggest.

But hospitalization rates and use of other health care resources were similar during and after therapy, regardless of dose, Nirmish Shah, MD, of Duke Health in Durham, N.C., reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“This is our attempt at a real-world study of patients after being in a big study that has good results and what happens to them afterward in regard to VOCs and health care utilization,” Dr. Shah said.

He reported results from the SUCCESSOR trial – a multicenter, retrospective cohort study – that evaluated a subset of 48 adult patients up to a year after they completed the SUSTAIN placebo-controlled phase 2 trial of crizanlizumab, a P-selectin inhibitor designed to control sickle cell pain crises.

In SUSTAIN, researchers evaluated two different dosages of crizanlizumab: 5 mg/kg and 2.5 mg/kg.

In the follow-up study, researchers obtained data from medical records over the study period November 2014 to March 2017. Crizanlizumab was not administered in the 52 weeks following the SUSTAIN trial.

They found that the subset of patients on the high dose of crizanlizumab had annual VOC rates of 2.7, compared with 4.0 among patients on the low dose of the drug. By comparison, VOC rates in SUSTAIN were 1.7 per year for the 5-mg/kg–dose group and 3.2 per year for the 2.5-mg/kg–dose group.

Overall, at least 60% of patients in the follow-up study had at least one hospitalization in the year after SUSTAIN. In the higher-dose group, the rates of hospitalization were similar in both SUSTAIN and SUCCESSOR – 53%. In the lower-dose group, hospitalization rates were 67% and 61% in SUCCESSOR and SUSTAIN, respectively.

“Among the previously treated patients with crizanlizumab, the total number of emergency department visits did seem to be higher in SUCCESSOR,” Dr. Shah said.

The study was limited by its retrospective nature and the fact that full data sets and follow-up were available on only a small number of patients, Dr. Shah said. “It was underpowered for a statistical analysis between groups,” he said. The goal was to determine the drug’s effect after treatment is discontinued, he said.

Dr. Shah reported a financial relationship with Novartis, which is developing crizanlizumab.

SOURCE: Shah N et al. FSCDR 2019, Abstract JSCDH-D-19-00031.

FORT LAUDERDALE, FLA. – Sickle cell patients who received high-dose crizanlizumab had fewer vaso-occlusive crises (VOCs) than patients on a low-dose regimen a year after stopping the treatment, findings from a real-world follow-up study suggest.

But hospitalization rates and use of other health care resources were similar during and after therapy, regardless of dose, Nirmish Shah, MD, of Duke Health in Durham, N.C., reported at the annual meeting of the Foundation for Sickle Cell Disease Research.

“This is our attempt at a real-world study of patients after being in a big study that has good results and what happens to them afterward in regard to VOCs and health care utilization,” Dr. Shah said.

He reported results from the SUCCESSOR trial – a multicenter, retrospective cohort study – that evaluated a subset of 48 adult patients up to a year after they completed the SUSTAIN placebo-controlled phase 2 trial of crizanlizumab, a P-selectin inhibitor designed to control sickle cell pain crises.

In SUSTAIN, researchers evaluated two different dosages of crizanlizumab: 5 mg/kg and 2.5 mg/kg.

In the follow-up study, researchers obtained data from medical records over the study period November 2014 to March 2017. Crizanlizumab was not administered in the 52 weeks following the SUSTAIN trial.

They found that the subset of patients on the high dose of crizanlizumab had annual VOC rates of 2.7, compared with 4.0 among patients on the low dose of the drug. By comparison, VOC rates in SUSTAIN were 1.7 per year for the 5-mg/kg–dose group and 3.2 per year for the 2.5-mg/kg–dose group.

Overall, at least 60% of patients in the follow-up study had at least one hospitalization in the year after SUSTAIN. In the higher-dose group, the rates of hospitalization were similar in both SUSTAIN and SUCCESSOR – 53%. In the lower-dose group, hospitalization rates were 67% and 61% in SUCCESSOR and SUSTAIN, respectively.

“Among the previously treated patients with crizanlizumab, the total number of emergency department visits did seem to be higher in SUCCESSOR,” Dr. Shah said.

The study was limited by its retrospective nature and the fact that full data sets and follow-up were available on only a small number of patients, Dr. Shah said. “It was underpowered for a statistical analysis between groups,” he said. The goal was to determine the drug’s effect after treatment is discontinued, he said.

Dr. Shah reported a financial relationship with Novartis, which is developing crizanlizumab.

SOURCE: Shah N et al. FSCDR 2019, Abstract JSCDH-D-19-00031.

FORT LAUDERDALE, Fla. – A study of sickle cell patients at a clinic in the Bronx found that upwards of 75% of them get a prescription for hydroxyurea to improve hemoglobin levels, but that one-third have discontinued use for various reasons, according to results reported at the 13^th annual Foundation for Sickle Cell Disease Research symposium here.

“The results identify variability in reported side effects and reasons for discontinuation, and highlight the importance of clear communication between providers and patients to discuss the benefits and challenges of hydroxyurea,” said Caterina Minniti, MD, professor of clinical medicine and pediatrics at Einstein College of Medicine and director of the Sickle Cell Center for Adults at Montefiore Hospital, Bronx, N.Y. The study analyzed self-reporting surveys completed by 224 adult outpatients in the Montefiore sickle cell clinic, and then verified the data in the electronic medical record, Dr. Minniti said. She noted, “Our population is unique in the Bronx in that we have a high percentage of Hispanic patients.” They comprised 24.1% of the study population.

“We found that 77.2% of the patients have ever been prescribed hydroxyurea,” she said. “That was really great.” Also, 91% of those with severe genotypes of SCD had been prescribed the drug; 68% of them were still taking hydroxyurea at the time of the survey, she said. Among patients with the mild genotype, 42.1% had been prescribed hydroxyurea and half were still on it when they completed their surveys.

When the survey evaluated how long patients had been taking the drug, she said, “That’s where I start to get concerned.” About half – 48.6% – had taken the drug for one to five years, “which is a very short period of time,” Dr. Minniti said. Another 15% were on hydroxyurea for less than a year, 23% for 5 to 10 years and 19% for 10 years or more.

The study drilled down into reasons why patients discontinued the drug. Side effects were cited by 24.6% (n=15). They include fatigue, hair loss, and GI upset. Other reasons include perceived ineffectiveness (16.4%, n=10); physician direction (14.8%, n=9), and reproductive health and ulcer formation (each at 8.2%, n=5).

“Many patients perceive ineffectiveness of hydroxyurea in the short term, but the benefits of hydoxyurea stem from chronic use over the long term,” Dr. Minniti said. She noted that some patients discontinued the drug for legitimate medical indications, “such as pregnancy and breast feeding, but were not restarted afterward.”

Dr. Minniti disclosed relationships with Novartis, Global Blood Therapeutics, Teutona, Bluebird Bio, GBT and Bayer.

SOURCE: Minniti C, et al. Abstract no. JSCDH-D-19-00058. Foundation for Sickle Cell Disease Research Symposium; Fort Lauderdale, Fla.; June 9, 2019.

FORT LAUDERDALE, Fla. – A study of sickle cell patients at a clinic in the Bronx found that upwards of 75% of them get a prescription for hydroxyurea to improve hemoglobin levels, but that one-third have discontinued use for various reasons, according to results reported at the 13^th annual Foundation for Sickle Cell Disease Research symposium here.

“The results identify variability in reported side effects and reasons for discontinuation, and highlight the importance of clear communication between providers and patients to discuss the benefits and challenges of hydroxyurea,” said Caterina Minniti, MD, professor of clinical medicine and pediatrics at Einstein College of Medicine and director of the Sickle Cell Center for Adults at Montefiore Hospital, Bronx, N.Y. The study analyzed self-reporting surveys completed by 224 adult outpatients in the Montefiore sickle cell clinic, and then verified the data in the electronic medical record, Dr. Minniti said. She noted, “Our population is unique in the Bronx in that we have a high percentage of Hispanic patients.” They comprised 24.1% of the study population.

“We found that 77.2% of the patients have ever been prescribed hydroxyurea,” she said. “That was really great.” Also, 91% of those with severe genotypes of SCD had been prescribed the drug; 68% of them were still taking hydroxyurea at the time of the survey, she said. Among patients with the mild genotype, 42.1% had been prescribed hydroxyurea and half were still on it when they completed their surveys.

When the survey evaluated how long patients had been taking the drug, she said, “That’s where I start to get concerned.” About half – 48.6% – had taken the drug for one to five years, “which is a very short period of time,” Dr. Minniti said. Another 15% were on hydroxyurea for less than a year, 23% for 5 to 10 years and 19% for 10 years or more.

The study drilled down into reasons why patients discontinued the drug. Side effects were cited by 24.6% (n=15). They include fatigue, hair loss, and GI upset. Other reasons include perceived ineffectiveness (16.4%, n=10); physician direction (14.8%, n=9), and reproductive health and ulcer formation (each at 8.2%, n=5).

“Many patients perceive ineffectiveness of hydroxyurea in the short term, but the benefits of hydoxyurea stem from chronic use over the long term,” Dr. Minniti said. She noted that some patients discontinued the drug for legitimate medical indications, “such as pregnancy and breast feeding, but were not restarted afterward.”

Dr. Minniti disclosed relationships with Novartis, Global Blood Therapeutics, Teutona, Bluebird Bio, GBT and Bayer.

SOURCE: Minniti C, et al. Abstract no. JSCDH-D-19-00058. Foundation for Sickle Cell Disease Research Symposium; Fort Lauderdale, Fla.; June 9, 2019.

FORT LAUDERDALE, Fla. – A study of sickle cell patients at a clinic in the Bronx found that upwards of 75% of them get a prescription for hydroxyurea to improve hemoglobin levels, but that one-third have discontinued use for various reasons, according to results reported at the 13^th annual Foundation for Sickle Cell Disease Research symposium here.

“The results identify variability in reported side effects and reasons for discontinuation, and highlight the importance of clear communication between providers and patients to discuss the benefits and challenges of hydroxyurea,” said Caterina Minniti, MD, professor of clinical medicine and pediatrics at Einstein College of Medicine and director of the Sickle Cell Center for Adults at Montefiore Hospital, Bronx, N.Y. The study analyzed self-reporting surveys completed by 224 adult outpatients in the Montefiore sickle cell clinic, and then verified the data in the electronic medical record, Dr. Minniti said. She noted, “Our population is unique in the Bronx in that we have a high percentage of Hispanic patients.” They comprised 24.1% of the study population.

“We found that 77.2% of the patients have ever been prescribed hydroxyurea,” she said. “That was really great.” Also, 91% of those with severe genotypes of SCD had been prescribed the drug; 68% of them were still taking hydroxyurea at the time of the survey, she said. Among patients with the mild genotype, 42.1% had been prescribed hydroxyurea and half were still on it when they completed their surveys.

When the survey evaluated how long patients had been taking the drug, she said, “That’s where I start to get concerned.” About half – 48.6% – had taken the drug for one to five years, “which is a very short period of time,” Dr. Minniti said. Another 15% were on hydroxyurea for less than a year, 23% for 5 to 10 years and 19% for 10 years or more.

The study drilled down into reasons why patients discontinued the drug. Side effects were cited by 24.6% (n=15). They include fatigue, hair loss, and GI upset. Other reasons include perceived ineffectiveness (16.4%, n=10); physician direction (14.8%, n=9), and reproductive health and ulcer formation (each at 8.2%, n=5).

“Many patients perceive ineffectiveness of hydroxyurea in the short term, but the benefits of hydoxyurea stem from chronic use over the long term,” Dr. Minniti said. She noted that some patients discontinued the drug for legitimate medical indications, “such as pregnancy and breast feeding, but were not restarted afterward.”

Dr. Minniti disclosed relationships with Novartis, Global Blood Therapeutics, Teutona, Bluebird Bio, GBT and Bayer.

SOURCE: Minniti C, et al. Abstract no. JSCDH-D-19-00058. Foundation for Sickle Cell Disease Research Symposium; Fort Lauderdale, Fla.; June 9, 2019.