Using the immune system to help fight cancer is one of newest and most promising directions in cancer research. While many of the findings so far remain preliminary, a number of new studies are being developed or are already underway. Not surprisingly, federal oncologists and hematologists are leading the way with ground-breaking research. Importantly, a number of trials are recruiting patients at VA facilities. Here are a few of the studies already underway:

Study: Vaccine Therapy in Treating Patients With Newly Diagnosed Advanced Colon Polyps

Sponsor: National Cancer Institute

This randomized phase II clinical trial studies how well MUC1 peptide-poly-ICLC adjuvant vaccine works in treating patients with newly diagnosed advanced colon polyps (adenomatous polyps). Adenomatous polyps are growths in the colon that may develop into colorectal cancer over time. Vaccines made from peptides may help the body build an effective immune response to kill polyp cells. MUC1 peptide-poly-ICLC adjuvant vaccine may also prevent the recurrence of adenomatous polyps and may prevent the development of colorectal cancer.

Federal Study Locations (7 total): Kansas City VAMC

Study: Nivolumab and Ipilimumab With or Without Sargramostim in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

Sponsor: National Cancer Institute

This randomized phase II/III trial studies the side effects and best dose of nivolumab and ipilimumab when given together with or without sargramostim and to see how well these drugs work in treating patients with stage III-IV melanoma that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab and nivolumab, may kill tumor cells by blocking blood flow to the tumor, by stimulating white blood cells to kill the tumor cells, or by attacking specific tumor cells and stop them from growing or kill them. Colony-stimulating factors, such as sargramostim, may increase the production of white blood cells. It is not yet known whether nivolumab and ipilimumab are more effective with or without sargramostim in treating patients with melanoma.

Federal Study Locations (311 total): Little Rock (Arkansas) VAMC

Study: Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma (NCT01169337)

Sponsor: National Cancer Institute

This randomized phase II/III trial studies how well lenalidomide works in treating patients with asymptomatic high-risk asymptomatic (smoldering) multiple myeloma. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether lenalidomide is effective in treating patients with high-risk smoldering multiple myeloma than observation alone.

Federal Study Locations (600 total): Kansas City VAMC, VA New Jersey Health Care System, East Orange

Study: Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia (NCT02143414)

Sponsor: National Cancer Institute

This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in treating older patients with acute lymphoblastic leukemia. Monoclonal antibodies, such as blinatumomab, find cancer cells and help kill them. Drugs used in chemotherapy, such as prednisone, vincristine sulfate, methotrexate, and mercaptopurine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or halting the cells’ ability to spread. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab with combination chemotherapy or dasatinib and prednisone may kill more cancer cells.

Federal Study Locations (180 total): Little Rock (Arkansas) VAMC

Study: Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma (NCT01415752)

Sponsor: Eastern Cooperative Oncology Group

Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.

Federal Study Locations (426 total): Kansas City VAMC, VA New Jersey Health Care System, East Orange

Study: Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma (NCT01856192)

This randomized phase II trial studies how well rituximab and combination chemotherapy with or without lenalidomide work in treating patients with newly diagnosed stage II-IV diffuse large B cell lymphoma. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether rituximab and combination chemotherapy are more effective when given with or without lenalidomide in treating patients with diffuse large B cell lymphoma.

Federal Study Locations (511 total): Little Rock (Arkansas) VAMC

Using the immune system to help fight cancer is one of newest and most promising directions in cancer research. While many of the findings so far remain preliminary, a number of new studies are being developed or are already underway. Not surprisingly, federal oncologists and hematologists are leading the way with ground-breaking research. Importantly, a number of trials are recruiting patients at VA facilities. Here are a few of the studies already underway:

Study: Vaccine Therapy in Treating Patients With Newly Diagnosed Advanced Colon Polyps

Sponsor: National Cancer Institute

This randomized phase II clinical trial studies how well MUC1 peptide-poly-ICLC adjuvant vaccine works in treating patients with newly diagnosed advanced colon polyps (adenomatous polyps). Adenomatous polyps are growths in the colon that may develop into colorectal cancer over time. Vaccines made from peptides may help the body build an effective immune response to kill polyp cells. MUC1 peptide-poly-ICLC adjuvant vaccine may also prevent the recurrence of adenomatous polyps and may prevent the development of colorectal cancer.

Federal Study Locations (7 total): Kansas City VAMC

Study: Nivolumab and Ipilimumab With or Without Sargramostim in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

Sponsor: National Cancer Institute

This randomized phase II/III trial studies the side effects and best dose of nivolumab and ipilimumab when given together with or without sargramostim and to see how well these drugs work in treating patients with stage III-IV melanoma that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab and nivolumab, may kill tumor cells by blocking blood flow to the tumor, by stimulating white blood cells to kill the tumor cells, or by attacking specific tumor cells and stop them from growing or kill them. Colony-stimulating factors, such as sargramostim, may increase the production of white blood cells. It is not yet known whether nivolumab and ipilimumab are more effective with or without sargramostim in treating patients with melanoma.

Federal Study Locations (311 total): Little Rock (Arkansas) VAMC

Study: Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma (NCT01169337)

Sponsor: National Cancer Institute

This randomized phase II/III trial studies how well lenalidomide works in treating patients with asymptomatic high-risk asymptomatic (smoldering) multiple myeloma. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether lenalidomide is effective in treating patients with high-risk smoldering multiple myeloma than observation alone.

Federal Study Locations (600 total): Kansas City VAMC, VA New Jersey Health Care System, East Orange

Study: Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia (NCT02143414)

Sponsor: National Cancer Institute

This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in treating older patients with acute lymphoblastic leukemia. Monoclonal antibodies, such as blinatumomab, find cancer cells and help kill them. Drugs used in chemotherapy, such as prednisone, vincristine sulfate, methotrexate, and mercaptopurine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or halting the cells’ ability to spread. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab with combination chemotherapy or dasatinib and prednisone may kill more cancer cells.

Federal Study Locations (180 total): Little Rock (Arkansas) VAMC

Study: Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma (NCT01415752)

Sponsor: Eastern Cooperative Oncology Group

Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.

Federal Study Locations (426 total): Kansas City VAMC, VA New Jersey Health Care System, East Orange

Study: Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma (NCT01856192)

This randomized phase II trial studies how well rituximab and combination chemotherapy with or without lenalidomide work in treating patients with newly diagnosed stage II-IV diffuse large B cell lymphoma. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether rituximab and combination chemotherapy are more effective when given with or without lenalidomide in treating patients with diffuse large B cell lymphoma.

Federal Study Locations (511 total): Little Rock (Arkansas) VAMC

Using the immune system to help fight cancer is one of newest and most promising directions in cancer research. While many of the findings so far remain preliminary, a number of new studies are being developed or are already underway. Not surprisingly, federal oncologists and hematologists are leading the way with ground-breaking research. Importantly, a number of trials are recruiting patients at VA facilities. Here are a few of the studies already underway:

Study: Vaccine Therapy in Treating Patients With Newly Diagnosed Advanced Colon Polyps

Sponsor: National Cancer Institute

This randomized phase II clinical trial studies how well MUC1 peptide-poly-ICLC adjuvant vaccine works in treating patients with newly diagnosed advanced colon polyps (adenomatous polyps). Adenomatous polyps are growths in the colon that may develop into colorectal cancer over time. Vaccines made from peptides may help the body build an effective immune response to kill polyp cells. MUC1 peptide-poly-ICLC adjuvant vaccine may also prevent the recurrence of adenomatous polyps and may prevent the development of colorectal cancer.

Federal Study Locations (7 total): Kansas City VAMC

Study: Nivolumab and Ipilimumab With or Without Sargramostim in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

Sponsor: National Cancer Institute

This randomized phase II/III trial studies the side effects and best dose of nivolumab and ipilimumab when given together with or without sargramostim and to see how well these drugs work in treating patients with stage III-IV melanoma that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab and nivolumab, may kill tumor cells by blocking blood flow to the tumor, by stimulating white blood cells to kill the tumor cells, or by attacking specific tumor cells and stop them from growing or kill them. Colony-stimulating factors, such as sargramostim, may increase the production of white blood cells. It is not yet known whether nivolumab and ipilimumab are more effective with or without sargramostim in treating patients with melanoma.

Federal Study Locations (311 total): Little Rock (Arkansas) VAMC

Study: Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma (NCT01169337)

Sponsor: National Cancer Institute

This randomized phase II/III trial studies how well lenalidomide works in treating patients with asymptomatic high-risk asymptomatic (smoldering) multiple myeloma. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether lenalidomide is effective in treating patients with high-risk smoldering multiple myeloma than observation alone.

Federal Study Locations (600 total): Kansas City VAMC, VA New Jersey Health Care System, East Orange

Study: Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia (NCT02143414)

Sponsor: National Cancer Institute

This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in treating older patients with acute lymphoblastic leukemia. Monoclonal antibodies, such as blinatumomab, find cancer cells and help kill them. Drugs used in chemotherapy, such as prednisone, vincristine sulfate, methotrexate, and mercaptopurine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or halting the cells’ ability to spread. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab with combination chemotherapy or dasatinib and prednisone may kill more cancer cells.

Federal Study Locations (180 total): Little Rock (Arkansas) VAMC

Study: Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma (NCT01415752)

Sponsor: Eastern Cooperative Oncology Group

Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.

Federal Study Locations (426 total): Kansas City VAMC, VA New Jersey Health Care System, East Orange

Study: Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma (NCT01856192)

This randomized phase II trial studies how well rituximab and combination chemotherapy with or without lenalidomide work in treating patients with newly diagnosed stage II-IV diffuse large B cell lymphoma. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether rituximab and combination chemotherapy are more effective when given with or without lenalidomide in treating patients with diffuse large B cell lymphoma.

Federal Study Locations (511 total): Little Rock (Arkansas) VAMC

Lab mouse

Magnetic resonance imaging (MRI) can effectively detect myelofibrosis (MF) in a mouse model, according to research published in the journal Blood Cancer.

In fact, researchers found that MRI could detect early and late stages of primary MF.

The researchers believe this discovery could potentially change the way MF is diagnosed, as MRI might be used to help physicians decide if or where to biopsy.

Katya Ravid, PhD, of Boston University School of Medicine in Massachusetts, and her colleagues conducted this research, aiming to determine whether T2-weighted MRI could detect bone marrow fibrosis in a mouse model of primary MF.

The team looked specifically at how effectively MRI could detect MF during the pre-fibrotic stage (when mice were less than 16 weeks old), when the mice had early MF (16 to 36 weeks old), and once the mice had overt MF (older than 36 weeks).

The researchers found that MRI could detect MF at the pre-fibrotic stage as well as detecting progressive MF.

The team said they observed a clear, bright signal that allowed them to differentiate mice with MF from healthy control mice.

The researchers proposed that the abundance of large megakaryocytes contributed to the bright signal they observed, since, in T2-weighted MR images, increased water/proton content, as in increased cellularity, yields high MR-signal intensity.

The team said this study provides proof of concept that T2-weighted MRI can detect primary MF in the early and late stages.

Lab mouse

Magnetic resonance imaging (MRI) can effectively detect myelofibrosis (MF) in a mouse model, according to research published in the journal Blood Cancer.

In fact, researchers found that MRI could detect early and late stages of primary MF.

The researchers believe this discovery could potentially change the way MF is diagnosed, as MRI might be used to help physicians decide if or where to biopsy.

Katya Ravid, PhD, of Boston University School of Medicine in Massachusetts, and her colleagues conducted this research, aiming to determine whether T2-weighted MRI could detect bone marrow fibrosis in a mouse model of primary MF.

The team looked specifically at how effectively MRI could detect MF during the pre-fibrotic stage (when mice were less than 16 weeks old), when the mice had early MF (16 to 36 weeks old), and once the mice had overt MF (older than 36 weeks).

The researchers found that MRI could detect MF at the pre-fibrotic stage as well as detecting progressive MF.

The team said they observed a clear, bright signal that allowed them to differentiate mice with MF from healthy control mice.

The researchers proposed that the abundance of large megakaryocytes contributed to the bright signal they observed, since, in T2-weighted MR images, increased water/proton content, as in increased cellularity, yields high MR-signal intensity.

The team said this study provides proof of concept that T2-weighted MRI can detect primary MF in the early and late stages.

Lab mouse

Magnetic resonance imaging (MRI) can effectively detect myelofibrosis (MF) in a mouse model, according to research published in the journal Blood Cancer.

In fact, researchers found that MRI could detect early and late stages of primary MF.

The researchers believe this discovery could potentially change the way MF is diagnosed, as MRI might be used to help physicians decide if or where to biopsy.

Katya Ravid, PhD, of Boston University School of Medicine in Massachusetts, and her colleagues conducted this research, aiming to determine whether T2-weighted MRI could detect bone marrow fibrosis in a mouse model of primary MF.

The team looked specifically at how effectively MRI could detect MF during the pre-fibrotic stage (when mice were less than 16 weeks old), when the mice had early MF (16 to 36 weeks old), and once the mice had overt MF (older than 36 weeks).

The researchers found that MRI could detect MF at the pre-fibrotic stage as well as detecting progressive MF.

The team said they observed a clear, bright signal that allowed them to differentiate mice with MF from healthy control mice.

The researchers proposed that the abundance of large megakaryocytes contributed to the bright signal they observed, since, in T2-weighted MR images, increased water/proton content, as in increased cellularity, yields high MR-signal intensity.

The team said this study provides proof of concept that T2-weighted MRI can detect primary MF in the early and late stages.

Ticagrelor tablets

Photo from AstraZeneca

NEW ORLEANS—Results of the EUCLID trial suggest ticagrelor does not a provide a benefit over clopidogrel in patients with symptomatic peripheral artery disease (PAD).

The incidence of atherothrombotic events was similar in patients who received ticagrelor and those who received clopidogrel.

Likewise, there was no significant difference between the treatment arms with regard to major bleeding.

Manesh R. Patel, MD, of Duke University Medical Center in Durham, North Carolina, presented results from the EUCLID trial at the American Heart Association Scientific Sessions.

Results were also published in NEJM. The trial was supported by AstraZeneca.

EUCLID included 13,885 patients with symptomatic PAD. They had median age of 66, and 72% were male.

The patients were randomized to receive ticagrelor at 90 mg twice daily or clopidogrel at 75 mg once daily.

The study’s primary efficacy endpoint was a composite of adjudicated cardiovascular death, myocardial infarction, and ischemic stroke.

At a median follow-up of 30 months, the primary efficacy endpoint had occurred in 10.8% (751/6930) of patients in the ticagrelor arm and 10.6% (740/6955) in the clopidogrel arm (P=0.65).

When the researchers assessed each of the components of the primary endpoint alone, they found a significant difference between the treatment groups in the incidence of ischemic stroke but not cardiovascular death or myocardial infarction.

Cardiovascular death occurred in 5.2% of patients in the ticagrelor arm and 4.9% of those in the clopidogrel arm (P=0.40). Myocardial infarction occurred in 5% and 4.8%, respectively (P=0.48). And ischemic stroke occurred in 1.9% and 2.4%, respectively (P=0.03).

The study’s primary safety endpoint was major bleeding, which occurred in 1.6% of patients in both treatment arms (P=0.49).

Fatal bleeding occurred in 0.1% of patients in the ticagrelor arm and 0.3% of patients in the clopidogrel arm (P=0.10). And intracranial bleeding occurred in 0.5% of patients in both arms (P=0.82).

However, significantly more patients discontinued ticagrelor due to bleeding—2.4%, compared to 1.6% of patients who discontinued clopidogrel due to bleeding (P<0.001).

Significantly more patients discontinued ticagrelor due to dyspnea as well—4.8% vs 0.8% (P<0.001).

In all, 30.1% of patients in the ticagrelor arm and 25.9% of those in the clopidogrel arm prematurely discontinued treatment. This includes patients who discontinued due to adverse events, meeting the primary efficacy endpoint, and death.

Ticagrelor tablets

Photo from AstraZeneca

NEW ORLEANS—Results of the EUCLID trial suggest ticagrelor does not a provide a benefit over clopidogrel in patients with symptomatic peripheral artery disease (PAD).

The incidence of atherothrombotic events was similar in patients who received ticagrelor and those who received clopidogrel.

Likewise, there was no significant difference between the treatment arms with regard to major bleeding.

Manesh R. Patel, MD, of Duke University Medical Center in Durham, North Carolina, presented results from the EUCLID trial at the American Heart Association Scientific Sessions.

Results were also published in NEJM. The trial was supported by AstraZeneca.

EUCLID included 13,885 patients with symptomatic PAD. They had median age of 66, and 72% were male.

The patients were randomized to receive ticagrelor at 90 mg twice daily or clopidogrel at 75 mg once daily.

The study’s primary efficacy endpoint was a composite of adjudicated cardiovascular death, myocardial infarction, and ischemic stroke.

At a median follow-up of 30 months, the primary efficacy endpoint had occurred in 10.8% (751/6930) of patients in the ticagrelor arm and 10.6% (740/6955) in the clopidogrel arm (P=0.65).

When the researchers assessed each of the components of the primary endpoint alone, they found a significant difference between the treatment groups in the incidence of ischemic stroke but not cardiovascular death or myocardial infarction.

Cardiovascular death occurred in 5.2% of patients in the ticagrelor arm and 4.9% of those in the clopidogrel arm (P=0.40). Myocardial infarction occurred in 5% and 4.8%, respectively (P=0.48). And ischemic stroke occurred in 1.9% and 2.4%, respectively (P=0.03).

The study’s primary safety endpoint was major bleeding, which occurred in 1.6% of patients in both treatment arms (P=0.49).

Fatal bleeding occurred in 0.1% of patients in the ticagrelor arm and 0.3% of patients in the clopidogrel arm (P=0.10). And intracranial bleeding occurred in 0.5% of patients in both arms (P=0.82).

However, significantly more patients discontinued ticagrelor due to bleeding—2.4%, compared to 1.6% of patients who discontinued clopidogrel due to bleeding (P<0.001).

Significantly more patients discontinued ticagrelor due to dyspnea as well—4.8% vs 0.8% (P<0.001).

In all, 30.1% of patients in the ticagrelor arm and 25.9% of those in the clopidogrel arm prematurely discontinued treatment. This includes patients who discontinued due to adverse events, meeting the primary efficacy endpoint, and death.

Ticagrelor tablets

Photo from AstraZeneca

NEW ORLEANS—Results of the EUCLID trial suggest ticagrelor does not a provide a benefit over clopidogrel in patients with symptomatic peripheral artery disease (PAD).

The incidence of atherothrombotic events was similar in patients who received ticagrelor and those who received clopidogrel.

Likewise, there was no significant difference between the treatment arms with regard to major bleeding.

Manesh R. Patel, MD, of Duke University Medical Center in Durham, North Carolina, presented results from the EUCLID trial at the American Heart Association Scientific Sessions.

Results were also published in NEJM. The trial was supported by AstraZeneca.

EUCLID included 13,885 patients with symptomatic PAD. They had median age of 66, and 72% were male.

The patients were randomized to receive ticagrelor at 90 mg twice daily or clopidogrel at 75 mg once daily.

The study’s primary efficacy endpoint was a composite of adjudicated cardiovascular death, myocardial infarction, and ischemic stroke.

At a median follow-up of 30 months, the primary efficacy endpoint had occurred in 10.8% (751/6930) of patients in the ticagrelor arm and 10.6% (740/6955) in the clopidogrel arm (P=0.65).

When the researchers assessed each of the components of the primary endpoint alone, they found a significant difference between the treatment groups in the incidence of ischemic stroke but not cardiovascular death or myocardial infarction.

Cardiovascular death occurred in 5.2% of patients in the ticagrelor arm and 4.9% of those in the clopidogrel arm (P=0.40). Myocardial infarction occurred in 5% and 4.8%, respectively (P=0.48). And ischemic stroke occurred in 1.9% and 2.4%, respectively (P=0.03).

The study’s primary safety endpoint was major bleeding, which occurred in 1.6% of patients in both treatment arms (P=0.49).

Fatal bleeding occurred in 0.1% of patients in the ticagrelor arm and 0.3% of patients in the clopidogrel arm (P=0.10). And intracranial bleeding occurred in 0.5% of patients in both arms (P=0.82).

However, significantly more patients discontinued ticagrelor due to bleeding—2.4%, compared to 1.6% of patients who discontinued clopidogrel due to bleeding (P<0.001).

Significantly more patients discontinued ticagrelor due to dyspnea as well—4.8% vs 0.8% (P<0.001).

In all, 30.1% of patients in the ticagrelor arm and 25.9% of those in the clopidogrel arm prematurely discontinued treatment. This includes patients who discontinued due to adverse events, meeting the primary efficacy endpoint, and death.

Mast cells

The US Food and Drug Administration (FDA) has granted priority review for the new drug application for midostaurin (PKC412) as a treatment for advanced systemic mastocytosis (SM) and newly diagnosed, FLT3-mutated acute myeloid leukemia (AML).

The FDA has also accepted for review the premarket approval application for the midostaurin FLT3 companion diagnostic, which is designed to help identify patients who may have a FLT3 mutation and could potentially benefit from treatment with midostaurin.

Midostaurin is being developed by Novartis. The companion diagnostic is being developed by Novartis and Invivoscribe Technologies, Inc.

About priority review

The FDA grants priority review to applications for therapies that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it. The goal in the standard review process is to take action within 10 months.

About midostaurin

Midostaurin is an oral, multi-targeted kinase inhibitor. The drug was granted breakthrough therapy designation by the FDA earlier this year for newly diagnosed, FLT3-mutated AML.

According to Novartis, the new drug application submission for midostaurin includes data from the largest clinical trials conducted to date in advanced SM and newly diagnosed, FLT3-mutated AML.

Midostaurin in AML

In the phase 3 RATIFY trial, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in adults younger than 60 with FLT3-mutated AML. Results from this trial were presented at the 2015 ASH Annual Meeting.

Patients in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in risk of death compared to the placebo arm (hazard ratio=0.77, P=0.0074).

There was no significant difference in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in midostaurin arm and the placebo arm. Similarly, there was no significant difference in treatment-related deaths between the arms.

Midostaurin in SM

Data from the phase 2 study of midostaurin in patients with advanced SM were published in NEJM in June.

The drug produced a 60% overall response rate, and the median duration of response was 24.1 months.

Fifty-six percent of patients required dose reductions due to toxic effects, but 32% of these patients were able to return to the starting dose of midostaurin.

Access to midostaurin

Since midostaurin remains investigational, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and, in the US, an Expanded Treatment Protocol, to provide access to midostaurin for eligible patients with newly diagnosed AML and advanced SM.

Physicians who want to request midostaurin for eligible patients can contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information.

Mast cells

The US Food and Drug Administration (FDA) has granted priority review for the new drug application for midostaurin (PKC412) as a treatment for advanced systemic mastocytosis (SM) and newly diagnosed, FLT3-mutated acute myeloid leukemia (AML).

The FDA has also accepted for review the premarket approval application for the midostaurin FLT3 companion diagnostic, which is designed to help identify patients who may have a FLT3 mutation and could potentially benefit from treatment with midostaurin.

Midostaurin is being developed by Novartis. The companion diagnostic is being developed by Novartis and Invivoscribe Technologies, Inc.

About priority review

The FDA grants priority review to applications for therapies that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it. The goal in the standard review process is to take action within 10 months.

About midostaurin

Midostaurin is an oral, multi-targeted kinase inhibitor. The drug was granted breakthrough therapy designation by the FDA earlier this year for newly diagnosed, FLT3-mutated AML.

According to Novartis, the new drug application submission for midostaurin includes data from the largest clinical trials conducted to date in advanced SM and newly diagnosed, FLT3-mutated AML.

Midostaurin in AML

In the phase 3 RATIFY trial, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in adults younger than 60 with FLT3-mutated AML. Results from this trial were presented at the 2015 ASH Annual Meeting.

Patients in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in risk of death compared to the placebo arm (hazard ratio=0.77, P=0.0074).

There was no significant difference in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in midostaurin arm and the placebo arm. Similarly, there was no significant difference in treatment-related deaths between the arms.

Midostaurin in SM

Data from the phase 2 study of midostaurin in patients with advanced SM were published in NEJM in June.

The drug produced a 60% overall response rate, and the median duration of response was 24.1 months.

Fifty-six percent of patients required dose reductions due to toxic effects, but 32% of these patients were able to return to the starting dose of midostaurin.

Access to midostaurin

Since midostaurin remains investigational, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and, in the US, an Expanded Treatment Protocol, to provide access to midostaurin for eligible patients with newly diagnosed AML and advanced SM.

Physicians who want to request midostaurin for eligible patients can contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information.

Mast cells

The US Food and Drug Administration (FDA) has granted priority review for the new drug application for midostaurin (PKC412) as a treatment for advanced systemic mastocytosis (SM) and newly diagnosed, FLT3-mutated acute myeloid leukemia (AML).

The FDA has also accepted for review the premarket approval application for the midostaurin FLT3 companion diagnostic, which is designed to help identify patients who may have a FLT3 mutation and could potentially benefit from treatment with midostaurin.

Midostaurin is being developed by Novartis. The companion diagnostic is being developed by Novartis and Invivoscribe Technologies, Inc.

About priority review

The FDA grants priority review to applications for therapies that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it. The goal in the standard review process is to take action within 10 months.

About midostaurin

Midostaurin is an oral, multi-targeted kinase inhibitor. The drug was granted breakthrough therapy designation by the FDA earlier this year for newly diagnosed, FLT3-mutated AML.

According to Novartis, the new drug application submission for midostaurin includes data from the largest clinical trials conducted to date in advanced SM and newly diagnosed, FLT3-mutated AML.

Midostaurin in AML

In the phase 3 RATIFY trial, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in adults younger than 60 with FLT3-mutated AML. Results from this trial were presented at the 2015 ASH Annual Meeting.

Patients in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in risk of death compared to the placebo arm (hazard ratio=0.77, P=0.0074).

There was no significant difference in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in midostaurin arm and the placebo arm. Similarly, there was no significant difference in treatment-related deaths between the arms.

Midostaurin in SM

Data from the phase 2 study of midostaurin in patients with advanced SM were published in NEJM in June.

The drug produced a 60% overall response rate, and the median duration of response was 24.1 months.

Fifty-six percent of patients required dose reductions due to toxic effects, but 32% of these patients were able to return to the starting dose of midostaurin.

Access to midostaurin

Since midostaurin remains investigational, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and, in the US, an Expanded Treatment Protocol, to provide access to midostaurin for eligible patients with newly diagnosed AML and advanced SM.

Physicians who want to request midostaurin for eligible patients can contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information.

AML cells

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has recommended that BP1001 receive orphan designation as a treatment for acute myeloid leukemia (AML).

BP1001 (liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated, antisense drug designed to inhibit protein synthesis of growth factor receptor bound protein 2 (Grb2).

BP1001 is being developed by Bio-Path Holdings, Inc.

According to Bio-Path, inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors.

Research has suggested that Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins.

About orphan designation

The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

Trials of BP1001

Bio-Path has completed a phase 1 trial of BP1001 in patients with relapsed/refractory AML, chronic myeloid leukemia, and myelodysplastic syndromes.

The company has also completed the safety segment of a phase 2 trial in which BP1001 is being investigated in combination with low-dose ara-C to treat AML.

Bio-Path recently released data from these studies.

The phase 1 study included patients who had received an average of 6 prior therapies.

The patients received 8 doses of BP1001 over 4 weeks, escalating to a maximum dose of 90 mg/m². There were no dose-limiting toxicities, and Bio-Path said the drug was well tolerated.

Of the 18 evaluable patients with circulating blasts, 83% responded to BP1001. The average reduction in circulating blasts was 67%.

The phase 2 trial included patients with relapsed/refractory AML. There were 3 evaluable patients in each of 2 dosing cohorts—60 mg/m² and 90 mg/m². Patients received BP1001 twice a week for 4 weeks.

Five of the patients responded—3 with a complete response and 2 with a partial response. There were no adverse events attributed to BP1001, and the maximum-tolerated dose was not reached.

AML cells

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has recommended that BP1001 receive orphan designation as a treatment for acute myeloid leukemia (AML).

BP1001 (liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated, antisense drug designed to inhibit protein synthesis of growth factor receptor bound protein 2 (Grb2).

BP1001 is being developed by Bio-Path Holdings, Inc.

According to Bio-Path, inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors.

Research has suggested that Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins.

About orphan designation

The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

Trials of BP1001

Bio-Path has completed a phase 1 trial of BP1001 in patients with relapsed/refractory AML, chronic myeloid leukemia, and myelodysplastic syndromes.

The company has also completed the safety segment of a phase 2 trial in which BP1001 is being investigated in combination with low-dose ara-C to treat AML.

Bio-Path recently released data from these studies.

The phase 1 study included patients who had received an average of 6 prior therapies.

The patients received 8 doses of BP1001 over 4 weeks, escalating to a maximum dose of 90 mg/m². There were no dose-limiting toxicities, and Bio-Path said the drug was well tolerated.

Of the 18 evaluable patients with circulating blasts, 83% responded to BP1001. The average reduction in circulating blasts was 67%.

The phase 2 trial included patients with relapsed/refractory AML. There were 3 evaluable patients in each of 2 dosing cohorts—60 mg/m² and 90 mg/m². Patients received BP1001 twice a week for 4 weeks.

Five of the patients responded—3 with a complete response and 2 with a partial response. There were no adverse events attributed to BP1001, and the maximum-tolerated dose was not reached.

AML cells

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has recommended that BP1001 receive orphan designation as a treatment for acute myeloid leukemia (AML).

BP1001 (liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated, antisense drug designed to inhibit protein synthesis of growth factor receptor bound protein 2 (Grb2).

BP1001 is being developed by Bio-Path Holdings, Inc.

According to Bio-Path, inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors.

Research has suggested that Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins.

About orphan designation

The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

Trials of BP1001

Bio-Path has completed a phase 1 trial of BP1001 in patients with relapsed/refractory AML, chronic myeloid leukemia, and myelodysplastic syndromes.

The company has also completed the safety segment of a phase 2 trial in which BP1001 is being investigated in combination with low-dose ara-C to treat AML.

Bio-Path recently released data from these studies.

The phase 1 study included patients who had received an average of 6 prior therapies.

The patients received 8 doses of BP1001 over 4 weeks, escalating to a maximum dose of 90 mg/m². There were no dose-limiting toxicities, and Bio-Path said the drug was well tolerated.

Of the 18 evaluable patients with circulating blasts, 83% responded to BP1001. The average reduction in circulating blasts was 67%.

The phase 2 trial included patients with relapsed/refractory AML. There were 3 evaluable patients in each of 2 dosing cohorts—60 mg/m² and 90 mg/m². Patients received BP1001 twice a week for 4 weeks.

Five of the patients responded—3 with a complete response and 2 with a partial response. There were no adverse events attributed to BP1001, and the maximum-tolerated dose was not reached.

Patients may understand that diabetes can lead to eye disease, and they may receive a recommendation for screening for diabetic retinopathy—but that doesn’t mean they’ll get screened. Researchers from Harbor-UCLA Medical Center surveyed 101 patients with diabetes and 44 providers and staffers at a clinic where annual screening rates for diabetic retinopathy were low. They found that 93% of patients understood the potential risk, but only 55% were getting screened.

The study goal, however, wasn’t to measure understanding of risk but to find out what patients considered barriers to screening and whether health care providers (HCPs) understood those barriers. And the researchers found a gap between the 2 groups.

Related: Long-Acting Insulin Analogs: Effects on Diabetic Retinopathy

Patients were mostly low-income Hispanics and African Americans. The survey asked participants to rate any given barrier that would delay or prevent getting screened. Health care providers and staff were asked to rate the importance of addressing the barriers.

Most of the patients (26%) reported at least 1 barrier to screening, most commonly depression (22%) and financial problems (26%); others reported language issues, lack of transportation, and lack of time. 

When surveying HCPs, though, the researchers found “markedly divergent perceptions” between the 2 groups. For instance, only small numbers of patients said transportation, language issues, denial, fear, or cultural beliefs were barriers—yet most HCPs and staff thought those were “very” or “extremely important.”

Related: Diabetic Macular Edema: Is Your Patient Going Blind?

By contrast, the barriers the patients did think were important—financial burdens and depression—were rated as less important than other barriers by the HCPs and staff.

The differences in opinions suggest “a lack of high-quality patient-provider communication,” the researchers say. They suggest that more effective patient education as well as heightened awareness of depression and its impact are key to getting more patients screened.

Patients may understand that diabetes can lead to eye disease, and they may receive a recommendation for screening for diabetic retinopathy—but that doesn’t mean they’ll get screened. Researchers from Harbor-UCLA Medical Center surveyed 101 patients with diabetes and 44 providers and staffers at a clinic where annual screening rates for diabetic retinopathy were low. They found that 93% of patients understood the potential risk, but only 55% were getting screened.

The study goal, however, wasn’t to measure understanding of risk but to find out what patients considered barriers to screening and whether health care providers (HCPs) understood those barriers. And the researchers found a gap between the 2 groups.

Related: Long-Acting Insulin Analogs: Effects on Diabetic Retinopathy

Patients were mostly low-income Hispanics and African Americans. The survey asked participants to rate any given barrier that would delay or prevent getting screened. Health care providers and staff were asked to rate the importance of addressing the barriers.

Most of the patients (26%) reported at least 1 barrier to screening, most commonly depression (22%) and financial problems (26%); others reported language issues, lack of transportation, and lack of time. 

When surveying HCPs, though, the researchers found “markedly divergent perceptions” between the 2 groups. For instance, only small numbers of patients said transportation, language issues, denial, fear, or cultural beliefs were barriers—yet most HCPs and staff thought those were “very” or “extremely important.”

Related: Diabetic Macular Edema: Is Your Patient Going Blind?

By contrast, the barriers the patients did think were important—financial burdens and depression—were rated as less important than other barriers by the HCPs and staff.

The differences in opinions suggest “a lack of high-quality patient-provider communication,” the researchers say. They suggest that more effective patient education as well as heightened awareness of depression and its impact are key to getting more patients screened.

Patients may understand that diabetes can lead to eye disease, and they may receive a recommendation for screening for diabetic retinopathy—but that doesn’t mean they’ll get screened. Researchers from Harbor-UCLA Medical Center surveyed 101 patients with diabetes and 44 providers and staffers at a clinic where annual screening rates for diabetic retinopathy were low. They found that 93% of patients understood the potential risk, but only 55% were getting screened.

The study goal, however, wasn’t to measure understanding of risk but to find out what patients considered barriers to screening and whether health care providers (HCPs) understood those barriers. And the researchers found a gap between the 2 groups.

Related: Long-Acting Insulin Analogs: Effects on Diabetic Retinopathy

Patients were mostly low-income Hispanics and African Americans. The survey asked participants to rate any given barrier that would delay or prevent getting screened. Health care providers and staff were asked to rate the importance of addressing the barriers.

Most of the patients (26%) reported at least 1 barrier to screening, most commonly depression (22%) and financial problems (26%); others reported language issues, lack of transportation, and lack of time. 

When surveying HCPs, though, the researchers found “markedly divergent perceptions” between the 2 groups. For instance, only small numbers of patients said transportation, language issues, denial, fear, or cultural beliefs were barriers—yet most HCPs and staff thought those were “very” or “extremely important.”

Related: Diabetic Macular Edema: Is Your Patient Going Blind?

By contrast, the barriers the patients did think were important—financial burdens and depression—were rated as less important than other barriers by the HCPs and staff.

The differences in opinions suggest “a lack of high-quality patient-provider communication,” the researchers say. They suggest that more effective patient education as well as heightened awareness of depression and its impact are key to getting more patients screened.

The introduction of the 2011 American Academy of Pediatrics practice guidelines on attention-deficit/hyperactivity disorder was associated with a leveling off in the number of diagnoses in preschool children.

“In the preguideline period, the trajectory of ADHD diagnosis increased slightly but significantly across practices,” Alexander G. Fiks, MD, from the Children’s Hospital of Philadelphia, and his coinvestigators wrote. “However, the rate of ADHD diagnosis no longer increased significantly after guideline release.”

Thinglass/Thinkstock

pdnews@frontlinemedcom.com

The introduction of the 2011 American Academy of Pediatrics practice guidelines on attention-deficit/hyperactivity disorder was associated with a leveling off in the number of diagnoses in preschool children.

“In the preguideline period, the trajectory of ADHD diagnosis increased slightly but significantly across practices,” Alexander G. Fiks, MD, from the Children’s Hospital of Philadelphia, and his coinvestigators wrote. “However, the rate of ADHD diagnosis no longer increased significantly after guideline release.”

Thinglass/Thinkstock

pdnews@frontlinemedcom.com

The introduction of the 2011 American Academy of Pediatrics practice guidelines on attention-deficit/hyperactivity disorder was associated with a leveling off in the number of diagnoses in preschool children.

“In the preguideline period, the trajectory of ADHD diagnosis increased slightly but significantly across practices,” Alexander G. Fiks, MD, from the Children’s Hospital of Philadelphia, and his coinvestigators wrote. “However, the rate of ADHD diagnosis no longer increased significantly after guideline release.”

Thinglass/Thinkstock

pdnews@frontlinemedcom.com

A 64-year-old woman presents to your office for a follow-up visit for her hypertension. She is currently managed on lisinopril 20 mg/d and hydrochlorothiazide 25 mg/d without any problems. The patient’s blood pressure (BP) in the office today is 148/84 mm Hg, but her home blood pressure (HBP) readings are much lower (see Table). Should you increase her lisinopril dose today?

Hypertension has been diagnosed on the basis of office readings of BP for almost a century, but the readings can be so inaccurate that they are not useful.² The US Preventive Services Task Force recommends the use of ambulatory BP monitoring (ABPM) to accurately diagnose hypertension in all patients, while The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends ABPM for patients suspected of having white-coat hypertension and any patient with resistant hypertension, but ABPM is not always acceptable to patients.^3-5

 

 

HBP monitoring for long-term follow-up

The European Society of Hypertension practice guideline on HBP monitoring suggests that HBP values < 130/80 mm Hg may be considered normal, while a mean HBP ≥ 135/85 mm Hg is considered elevated.⁹ The guideline recommends HBP monitoring for three to seven days prior to a patient’s follow-up appointment, with two readings taken one to two minutes apart in the morning and evening.⁹ In a busy clinic, averaging all of these home values can be time-consuming.

So how can primary care providers accurately and efficiently streamline the process? This study sought to answer that question.

STUDY SUMMARY

3 of 10 readings = predictive

This multicenter trial compared HBP monitoring to 24-hour ABPM in 286 patients with uncomplicated essential hypertension to determine the optimal percentage of HBP readings needed to diagnose uncontrolled BP (HBP ≥ 135/85 mm Hg). Patients were included if they were diagnosed with uncomplicated hypertension, not pregnant, age 18 or older, and taking three or fewer antihypertensive medications. Patients were excluded if they had a significant abnormal left ventricular mass index (women > 59 g/m²; men > 64 g/m²), coronary artery or renal disease, secondary hypertension, serum creatinine exceeding 1.6 mg/dL, aortic valve stenosis, upper limb obstructive atherosclerosis, or BP > 180/100 mm Hg.

Approximately half of the participants were women (53%). Average BMI was 29.4 kg/m², and the average number of hypertension medications being taken was 2.4. Medication compliance was verified by a study nurse at a clinic visit.

The patients were instructed to take two BP readings (one minute apart) at home three times daily, in the morning (between 6 am and 10 am), at noon, and in the evening (between 6 pm and 10 pm), and to record only the second reading for seven days. Only the morning and evening readings were used for analysis in the study. The 24-hour ABP was measured every 30 minutes during the daytime hours and every 60 minutes overnight.

The primary outcome was to determine the optimal number of systolic HBP readings above goal (135 mm Hg), from the last 10 recordings, that would best predict elevated 24-hour ABP. Secondary outcomes were various cardiovascular markers of target end-organ damage.

The researchers found that if at least three of the last 10 HBP readings were elevated (≥ 135 mm Hg systolic), the patient was likely to have hypertension on 24-hour ABPM (≥ 130 mm Hg). When patients had less than three HBP elevations out of 10 readings, their mean (± standard deviation [SD]) 24-hour ambulatory daytime systolic BP was 132.7 (± 11.1) mm Hg and their mean systolic HBP value was 120.4 (± 9.8) mm Hg. When patients had three or more HBP elevations, their mean 24-hour ambulatory daytime systolic BP was 143.4 (± 11.2) mm Hg and their mean systolic HBP value was 147.4 (± 10.5) mm Hg.

The positive and negative predictive values of three or more HBP elevations were 0.85 and 0.56, respectively, for a 24-hour systolic ABP of ≥ 130 mm Hg. Three elevations or more in HBP, out of the last 10 readings, was also an indicator for target organ disease assessed by aortic stiffness and increased left ventricular mass and decreased function.

The sensitivity and specificity of three or more elevations for mean 24-hour ABP systolic readings ≥ 130 mm Hg were 62% and 80%, respectively, and for 24-hour ABP daytime systolic readings ≥ 135 mm Hg were 65% and 77%, respectively.

WHAT’S NEW

Monitoring home BP can be simplified

The researchers found that HBP monitoring correlates well with ABPM and that their method provides clinicians with a simple way (three of the past 10 measurements ≥ 135 mm Hg systolic) to use HBP readings to make clinical decisions regarding BP management.

CAVEATS

BP goals are hazy, patient education is required

Conflicting information and opinions remain regarding the ideal intensive and standard BP goals in different populations.^10,11 Systolic BP goals in this study (≥ 130 mm Hg for overall 24-hour ABP and ≥ 135 mm Hg for 24-hour ABP daytime readings) are recommended by some experts but are not commonly recognized goals in the United States. This study found good correlation between HBP and ABPM at these goals, and it seems likely that this correlation could be extrapolated for similar BP goals.

Other limitations are that (1) The study focused only on systolic BP goals; (2) patients in the study adhered to precise instructions on BP monitoring; HBP monitoring requires significant patient education on the proper use of the equipment and the monitoring schedule; and (3) while end-organ complication outcomes showed numerical decreases in function, the clinical significance of these reductions for patients is unclear.

CHALLENGES TO IMPLEMENTATION

Cost, sizing of cuffs

The cost of HBP monitors ($40-$60) has decreased significantly over time, but the devices are not always covered by insurance and may be unobtainable for some people.

Additionally, patients should be counseled on how to determine the appropriate cuff size to ensure the accuracy of the measurements. The British Hypertension Society maintains a list of validated BP devices on its website: http://bhsoc.org/bp-monitors/bp-monitors.¹²

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(10):719-722.

A 64-year-old woman presents to your office for a follow-up visit for her hypertension. She is currently managed on lisinopril 20 mg/d and hydrochlorothiazide 25 mg/d without any problems. The patient’s blood pressure (BP) in the office today is 148/84 mm Hg, but her home blood pressure (HBP) readings are much lower (see Table). Should you increase her lisinopril dose today?

Hypertension has been diagnosed on the basis of office readings of BP for almost a century, but the readings can be so inaccurate that they are not useful.² The US Preventive Services Task Force recommends the use of ambulatory BP monitoring (ABPM) to accurately diagnose hypertension in all patients, while The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends ABPM for patients suspected of having white-coat hypertension and any patient with resistant hypertension, but ABPM is not always acceptable to patients.^3-5

 

 

HBP monitoring for long-term follow-up

The European Society of Hypertension practice guideline on HBP monitoring suggests that HBP values < 130/80 mm Hg may be considered normal, while a mean HBP ≥ 135/85 mm Hg is considered elevated.⁹ The guideline recommends HBP monitoring for three to seven days prior to a patient’s follow-up appointment, with two readings taken one to two minutes apart in the morning and evening.⁹ In a busy clinic, averaging all of these home values can be time-consuming.

So how can primary care providers accurately and efficiently streamline the process? This study sought to answer that question.

STUDY SUMMARY

3 of 10 readings = predictive

This multicenter trial compared HBP monitoring to 24-hour ABPM in 286 patients with uncomplicated essential hypertension to determine the optimal percentage of HBP readings needed to diagnose uncontrolled BP (HBP ≥ 135/85 mm Hg). Patients were included if they were diagnosed with uncomplicated hypertension, not pregnant, age 18 or older, and taking three or fewer antihypertensive medications. Patients were excluded if they had a significant abnormal left ventricular mass index (women > 59 g/m²; men > 64 g/m²), coronary artery or renal disease, secondary hypertension, serum creatinine exceeding 1.6 mg/dL, aortic valve stenosis, upper limb obstructive atherosclerosis, or BP > 180/100 mm Hg.

Approximately half of the participants were women (53%). Average BMI was 29.4 kg/m², and the average number of hypertension medications being taken was 2.4. Medication compliance was verified by a study nurse at a clinic visit.

The patients were instructed to take two BP readings (one minute apart) at home three times daily, in the morning (between 6 am and 10 am), at noon, and in the evening (between 6 pm and 10 pm), and to record only the second reading for seven days. Only the morning and evening readings were used for analysis in the study. The 24-hour ABP was measured every 30 minutes during the daytime hours and every 60 minutes overnight.

The primary outcome was to determine the optimal number of systolic HBP readings above goal (135 mm Hg), from the last 10 recordings, that would best predict elevated 24-hour ABP. Secondary outcomes were various cardiovascular markers of target end-organ damage.

The researchers found that if at least three of the last 10 HBP readings were elevated (≥ 135 mm Hg systolic), the patient was likely to have hypertension on 24-hour ABPM (≥ 130 mm Hg). When patients had less than three HBP elevations out of 10 readings, their mean (± standard deviation [SD]) 24-hour ambulatory daytime systolic BP was 132.7 (± 11.1) mm Hg and their mean systolic HBP value was 120.4 (± 9.8) mm Hg. When patients had three or more HBP elevations, their mean 24-hour ambulatory daytime systolic BP was 143.4 (± 11.2) mm Hg and their mean systolic HBP value was 147.4 (± 10.5) mm Hg.

The positive and negative predictive values of three or more HBP elevations were 0.85 and 0.56, respectively, for a 24-hour systolic ABP of ≥ 130 mm Hg. Three elevations or more in HBP, out of the last 10 readings, was also an indicator for target organ disease assessed by aortic stiffness and increased left ventricular mass and decreased function.

The sensitivity and specificity of three or more elevations for mean 24-hour ABP systolic readings ≥ 130 mm Hg were 62% and 80%, respectively, and for 24-hour ABP daytime systolic readings ≥ 135 mm Hg were 65% and 77%, respectively.

WHAT’S NEW

Monitoring home BP can be simplified

The researchers found that HBP monitoring correlates well with ABPM and that their method provides clinicians with a simple way (three of the past 10 measurements ≥ 135 mm Hg systolic) to use HBP readings to make clinical decisions regarding BP management.

CAVEATS

BP goals are hazy, patient education is required

Conflicting information and opinions remain regarding the ideal intensive and standard BP goals in different populations.^10,11 Systolic BP goals in this study (≥ 130 mm Hg for overall 24-hour ABP and ≥ 135 mm Hg for 24-hour ABP daytime readings) are recommended by some experts but are not commonly recognized goals in the United States. This study found good correlation between HBP and ABPM at these goals, and it seems likely that this correlation could be extrapolated for similar BP goals.

Other limitations are that (1) The study focused only on systolic BP goals; (2) patients in the study adhered to precise instructions on BP monitoring; HBP monitoring requires significant patient education on the proper use of the equipment and the monitoring schedule; and (3) while end-organ complication outcomes showed numerical decreases in function, the clinical significance of these reductions for patients is unclear.

CHALLENGES TO IMPLEMENTATION

Cost, sizing of cuffs

The cost of HBP monitors ($40-$60) has decreased significantly over time, but the devices are not always covered by insurance and may be unobtainable for some people.

Additionally, patients should be counseled on how to determine the appropriate cuff size to ensure the accuracy of the measurements. The British Hypertension Society maintains a list of validated BP devices on its website: http://bhsoc.org/bp-monitors/bp-monitors.¹²

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(10):719-722.

A 64-year-old woman presents to your office for a follow-up visit for her hypertension. She is currently managed on lisinopril 20 mg/d and hydrochlorothiazide 25 mg/d without any problems. The patient’s blood pressure (BP) in the office today is 148/84 mm Hg, but her home blood pressure (HBP) readings are much lower (see Table). Should you increase her lisinopril dose today?

Hypertension has been diagnosed on the basis of office readings of BP for almost a century, but the readings can be so inaccurate that they are not useful.² The US Preventive Services Task Force recommends the use of ambulatory BP monitoring (ABPM) to accurately diagnose hypertension in all patients, while The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends ABPM for patients suspected of having white-coat hypertension and any patient with resistant hypertension, but ABPM is not always acceptable to patients.^3-5

 

 

HBP monitoring for long-term follow-up

The European Society of Hypertension practice guideline on HBP monitoring suggests that HBP values < 130/80 mm Hg may be considered normal, while a mean HBP ≥ 135/85 mm Hg is considered elevated.⁹ The guideline recommends HBP monitoring for three to seven days prior to a patient’s follow-up appointment, with two readings taken one to two minutes apart in the morning and evening.⁹ In a busy clinic, averaging all of these home values can be time-consuming.

So how can primary care providers accurately and efficiently streamline the process? This study sought to answer that question.

STUDY SUMMARY

3 of 10 readings = predictive

This multicenter trial compared HBP monitoring to 24-hour ABPM in 286 patients with uncomplicated essential hypertension to determine the optimal percentage of HBP readings needed to diagnose uncontrolled BP (HBP ≥ 135/85 mm Hg). Patients were included if they were diagnosed with uncomplicated hypertension, not pregnant, age 18 or older, and taking three or fewer antihypertensive medications. Patients were excluded if they had a significant abnormal left ventricular mass index (women > 59 g/m²; men > 64 g/m²), coronary artery or renal disease, secondary hypertension, serum creatinine exceeding 1.6 mg/dL, aortic valve stenosis, upper limb obstructive atherosclerosis, or BP > 180/100 mm Hg.

Approximately half of the participants were women (53%). Average BMI was 29.4 kg/m², and the average number of hypertension medications being taken was 2.4. Medication compliance was verified by a study nurse at a clinic visit.

The patients were instructed to take two BP readings (one minute apart) at home three times daily, in the morning (between 6 am and 10 am), at noon, and in the evening (between 6 pm and 10 pm), and to record only the second reading for seven days. Only the morning and evening readings were used for analysis in the study. The 24-hour ABP was measured every 30 minutes during the daytime hours and every 60 minutes overnight.

The primary outcome was to determine the optimal number of systolic HBP readings above goal (135 mm Hg), from the last 10 recordings, that would best predict elevated 24-hour ABP. Secondary outcomes were various cardiovascular markers of target end-organ damage.

The researchers found that if at least three of the last 10 HBP readings were elevated (≥ 135 mm Hg systolic), the patient was likely to have hypertension on 24-hour ABPM (≥ 130 mm Hg). When patients had less than three HBP elevations out of 10 readings, their mean (± standard deviation [SD]) 24-hour ambulatory daytime systolic BP was 132.7 (± 11.1) mm Hg and their mean systolic HBP value was 120.4 (± 9.8) mm Hg. When patients had three or more HBP elevations, their mean 24-hour ambulatory daytime systolic BP was 143.4 (± 11.2) mm Hg and their mean systolic HBP value was 147.4 (± 10.5) mm Hg.

The positive and negative predictive values of three or more HBP elevations were 0.85 and 0.56, respectively, for a 24-hour systolic ABP of ≥ 130 mm Hg. Three elevations or more in HBP, out of the last 10 readings, was also an indicator for target organ disease assessed by aortic stiffness and increased left ventricular mass and decreased function.

The sensitivity and specificity of three or more elevations for mean 24-hour ABP systolic readings ≥ 130 mm Hg were 62% and 80%, respectively, and for 24-hour ABP daytime systolic readings ≥ 135 mm Hg were 65% and 77%, respectively.

WHAT’S NEW

Monitoring home BP can be simplified

The researchers found that HBP monitoring correlates well with ABPM and that their method provides clinicians with a simple way (three of the past 10 measurements ≥ 135 mm Hg systolic) to use HBP readings to make clinical decisions regarding BP management.

CAVEATS

BP goals are hazy, patient education is required

Conflicting information and opinions remain regarding the ideal intensive and standard BP goals in different populations.^10,11 Systolic BP goals in this study (≥ 130 mm Hg for overall 24-hour ABP and ≥ 135 mm Hg for 24-hour ABP daytime readings) are recommended by some experts but are not commonly recognized goals in the United States. This study found good correlation between HBP and ABPM at these goals, and it seems likely that this correlation could be extrapolated for similar BP goals.

Other limitations are that (1) The study focused only on systolic BP goals; (2) patients in the study adhered to precise instructions on BP monitoring; HBP monitoring requires significant patient education on the proper use of the equipment and the monitoring schedule; and (3) while end-organ complication outcomes showed numerical decreases in function, the clinical significance of these reductions for patients is unclear.

CHALLENGES TO IMPLEMENTATION

Cost, sizing of cuffs

The cost of HBP monitors ($40-$60) has decreased significantly over time, but the devices are not always covered by insurance and may be unobtainable for some people.

Additionally, patients should be counseled on how to determine the appropriate cuff size to ensure the accuracy of the measurements. The British Hypertension Society maintains a list of validated BP devices on its website: http://bhsoc.org/bp-monitors/bp-monitors.¹²

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(10):719-722.

On October 14, 2016, the Centers for Medicare and Medicaid Services (CMS) released the final rule pertaining to the Medicare Access and CHIP Reauthorization Act (MACRA). As I write, almost three weeks later, Division of Advocacy and Health Policy staff are generally pleased with the contents of the rule as there were no big “negative” surprises and stakeholder input in response to the proposed rule seems to have been broadly taken to heart by the administration at CMS.

As Fellows prepare for 2017, they should take note of several changes that were made to the original proposed rule. Some key changes are summarized below.

Dr. Bailey is a pediatric surgeon, and Medical Director, Advocacy, for the Division of Advocacy and Health Policy in the ACS offices in Washington, D.C.

On October 14, 2016, the Centers for Medicare and Medicaid Services (CMS) released the final rule pertaining to the Medicare Access and CHIP Reauthorization Act (MACRA). As I write, almost three weeks later, Division of Advocacy and Health Policy staff are generally pleased with the contents of the rule as there were no big “negative” surprises and stakeholder input in response to the proposed rule seems to have been broadly taken to heart by the administration at CMS.

As Fellows prepare for 2017, they should take note of several changes that were made to the original proposed rule. Some key changes are summarized below.

Dr. Bailey is a pediatric surgeon, and Medical Director, Advocacy, for the Division of Advocacy and Health Policy in the ACS offices in Washington, D.C.

On October 14, 2016, the Centers for Medicare and Medicaid Services (CMS) released the final rule pertaining to the Medicare Access and CHIP Reauthorization Act (MACRA). As I write, almost three weeks later, Division of Advocacy and Health Policy staff are generally pleased with the contents of the rule as there were no big “negative” surprises and stakeholder input in response to the proposed rule seems to have been broadly taken to heart by the administration at CMS.

As Fellows prepare for 2017, they should take note of several changes that were made to the original proposed rule. Some key changes are summarized below.

Dr. Bailey is a pediatric surgeon, and Medical Director, Advocacy, for the Division of Advocacy and Health Policy in the ACS offices in Washington, D.C.

In the flood of emails, periodicals, Twitter, Facebook, Doximity, Medscape, and other information that washes over surgeons every day, why should they use their precious time to read ACS Surgery News? That question is foremost in the minds of the editors of this publication as we consider news stories and commentaries for inclusion. Is this an article our readers are going to find informative, pertinent, and stimulating? We want ACS Surgery News to be a querencia: a source of reliable, vetted information that gives surgeons a place of intellectual security along the information highway.

Dr. Deveney is professor of surgery and vice chair of education in the department of surgery, Oregon Health & Science University, Portland. She is the Co-Editor of ACS Surgery News.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

In the flood of emails, periodicals, Twitter, Facebook, Doximity, Medscape, and other information that washes over surgeons every day, why should they use their precious time to read ACS Surgery News? That question is foremost in the minds of the editors of this publication as we consider news stories and commentaries for inclusion. Is this an article our readers are going to find informative, pertinent, and stimulating? We want ACS Surgery News to be a querencia: a source of reliable, vetted information that gives surgeons a place of intellectual security along the information highway.

Dr. Deveney is professor of surgery and vice chair of education in the department of surgery, Oregon Health & Science University, Portland. She is the Co-Editor of ACS Surgery News.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

In the flood of emails, periodicals, Twitter, Facebook, Doximity, Medscape, and other information that washes over surgeons every day, why should they use their precious time to read ACS Surgery News? That question is foremost in the minds of the editors of this publication as we consider news stories and commentaries for inclusion. Is this an article our readers are going to find informative, pertinent, and stimulating? We want ACS Surgery News to be a querencia: a source of reliable, vetted information that gives surgeons a place of intellectual security along the information highway.

Dr. Deveney is professor of surgery and vice chair of education in the department of surgery, Oregon Health & Science University, Portland. She is the Co-Editor of ACS Surgery News.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.