Secondary prevention of cardiovascular disease could significantly reduce cardiac mortality among patients with schizophrenia, yet is underused, a study published Oct. 24 has found.

The retrospective study, which included a Danish nationwide cohort of 105,018 patients with myocardial infarction, including 684 patients with schizophrenia, showed that individuals with schizophrenia who did not receive secondary cardioprotective treatment had a more than eight times higher mortality, compared with people in the general population who did receive treatment (hazard ratio, 8.78; 95% confidence interval, 4.37-17.64), Pirathiv Kugathasan and his associates reported in JAMA Psychiatry.

In contrast, the investigators found, patients with schizophrenia who received cardioprotective treatment had a 97% higher mortality (HR, 1.97; 95% CI, 1.25-310), compared with the treated general population, which was not statistically different from individuals in the general population who did not receive treatment (HR, 2.95; 95% CI, 2.62-3.32) after adjustment for baseline characteristics.

“Given the increased cardiovascular risk among patients with schizophrenia, we believe that the current findings support the use of intensive cardioprotective treatments in patients with schizophrenia,” reported Mr. Kugathasan, a PhD candidate in the department of psychiatry at Aalborg University Hospital in Denmark.

However, 7.8% of patients diagnosed with schizophrenia received no prescriptions for cardioprotective medications after a myocardial infarction, compared with 3.3% of the general population. They were significantly less likely than were individuals from the general population to receive a prescription for antiplatelets (84.9% vs. 91.8%), vitamin K antagonists (15.9% vs. 24.2%), beta-blockers (74.1% vs. 84.9%), ACE inhibitors (70.9% vs. 86.6%), and statins (72.2% vs. 87.3%).

The mortality rates were not significantly different between untreated patients with schizophrenia and untreated participants from the general population.

When the researchers examined the effects of different treatment types, they found that mortality rates were still higher in treated patients with schizophrenia, compared with treated patients from the general population – with the exception of those treated with antiplatelets and statins. For ACE inhibitors, treated patients with schizophrenia had a twofold higher mortality than that of treated patients from the general population, while the mortality was more than twofold higher in the case of vitamin K antagonists.

“Previous studies have found that patients with schizophrenia have increased cardiovascular mortality and a lower prescription rate for cardioprotective treatment compared with the general population,” the authors wrote.

They noted that patients with schizophrenia might have more problems with medication adherence, and pointed to another study showing this in patients with schizophrenia and diabetes. Other studies also showed that patients with schizophrenia were less likely to talk to a cardiologist after a cardiac event.

“Together, we believe that these results could point toward a deficit in establishing an appropriate cardiac treatment plan in patients with schizophrenia that causes failure in initiation and maintenance of cardioprotective treatment,” they wrote. “This hypothesis could explain the results of a generally increased mortality rate among patients with schizophrenia, especially when the results suggest that these patients die of cardiovascular causes that might be treatable.”

They called for patients with schizophrenia to be followed up during treatment, and to increase treatment intensity after cardiac events, “because a diagnosis of schizophrenia may be associated with an increased cardiac risk, which potentially can be countered by secondary preventive cardiac treatment.”

In patients who received triple therapy, the mortality rates were similar for those with schizophrenia and the general population. However, there were much higher mortality rate differences between patients with schizophrenia and the general population for those receiving dual or monotherapy.

Significantly more patients from the general population were readmitted with myocardial infarction and more underwent percutaneous coronary intervention than from the group of patients with schizophrenia.

The prevalence of hypertension was similar between the two populations, but more patients with schizophrenia had diabetes and substance abuse, compared with the general population.

The authors noted that they did not have information on the severity of myocardial infarction or the effect of other lifestyle factors.

“Future research should attempt to assess the degree to which these factors contribute to the increased mortality in patients with schizophrenia,” they wrote.

One author declared grants, speaking fees and advisory roles with the pharmaceutical industry. No other conflicts of interest were declared.

SOURCE: Kugathasan P et al. JAMA Psychiatry 2018. Oct 24. doi: 10.1001/jamapsychiatry.2018.2742.

Secondary prevention of cardiovascular disease could significantly reduce cardiac mortality among patients with schizophrenia, yet is underused, a study published Oct. 24 has found.

The retrospective study, which included a Danish nationwide cohort of 105,018 patients with myocardial infarction, including 684 patients with schizophrenia, showed that individuals with schizophrenia who did not receive secondary cardioprotective treatment had a more than eight times higher mortality, compared with people in the general population who did receive treatment (hazard ratio, 8.78; 95% confidence interval, 4.37-17.64), Pirathiv Kugathasan and his associates reported in JAMA Psychiatry.

In contrast, the investigators found, patients with schizophrenia who received cardioprotective treatment had a 97% higher mortality (HR, 1.97; 95% CI, 1.25-310), compared with the treated general population, which was not statistically different from individuals in the general population who did not receive treatment (HR, 2.95; 95% CI, 2.62-3.32) after adjustment for baseline characteristics.

“Given the increased cardiovascular risk among patients with schizophrenia, we believe that the current findings support the use of intensive cardioprotective treatments in patients with schizophrenia,” reported Mr. Kugathasan, a PhD candidate in the department of psychiatry at Aalborg University Hospital in Denmark.

However, 7.8% of patients diagnosed with schizophrenia received no prescriptions for cardioprotective medications after a myocardial infarction, compared with 3.3% of the general population. They were significantly less likely than were individuals from the general population to receive a prescription for antiplatelets (84.9% vs. 91.8%), vitamin K antagonists (15.9% vs. 24.2%), beta-blockers (74.1% vs. 84.9%), ACE inhibitors (70.9% vs. 86.6%), and statins (72.2% vs. 87.3%).

The mortality rates were not significantly different between untreated patients with schizophrenia and untreated participants from the general population.

When the researchers examined the effects of different treatment types, they found that mortality rates were still higher in treated patients with schizophrenia, compared with treated patients from the general population – with the exception of those treated with antiplatelets and statins. For ACE inhibitors, treated patients with schizophrenia had a twofold higher mortality than that of treated patients from the general population, while the mortality was more than twofold higher in the case of vitamin K antagonists.

“Previous studies have found that patients with schizophrenia have increased cardiovascular mortality and a lower prescription rate for cardioprotective treatment compared with the general population,” the authors wrote.

They noted that patients with schizophrenia might have more problems with medication adherence, and pointed to another study showing this in patients with schizophrenia and diabetes. Other studies also showed that patients with schizophrenia were less likely to talk to a cardiologist after a cardiac event.

“Together, we believe that these results could point toward a deficit in establishing an appropriate cardiac treatment plan in patients with schizophrenia that causes failure in initiation and maintenance of cardioprotective treatment,” they wrote. “This hypothesis could explain the results of a generally increased mortality rate among patients with schizophrenia, especially when the results suggest that these patients die of cardiovascular causes that might be treatable.”

They called for patients with schizophrenia to be followed up during treatment, and to increase treatment intensity after cardiac events, “because a diagnosis of schizophrenia may be associated with an increased cardiac risk, which potentially can be countered by secondary preventive cardiac treatment.”

In patients who received triple therapy, the mortality rates were similar for those with schizophrenia and the general population. However, there were much higher mortality rate differences between patients with schizophrenia and the general population for those receiving dual or monotherapy.

Significantly more patients from the general population were readmitted with myocardial infarction and more underwent percutaneous coronary intervention than from the group of patients with schizophrenia.

The prevalence of hypertension was similar between the two populations, but more patients with schizophrenia had diabetes and substance abuse, compared with the general population.

The authors noted that they did not have information on the severity of myocardial infarction or the effect of other lifestyle factors.

“Future research should attempt to assess the degree to which these factors contribute to the increased mortality in patients with schizophrenia,” they wrote.

One author declared grants, speaking fees and advisory roles with the pharmaceutical industry. No other conflicts of interest were declared.

SOURCE: Kugathasan P et al. JAMA Psychiatry 2018. Oct 24. doi: 10.1001/jamapsychiatry.2018.2742.

Secondary prevention of cardiovascular disease could significantly reduce cardiac mortality among patients with schizophrenia, yet is underused, a study published Oct. 24 has found.

The retrospective study, which included a Danish nationwide cohort of 105,018 patients with myocardial infarction, including 684 patients with schizophrenia, showed that individuals with schizophrenia who did not receive secondary cardioprotective treatment had a more than eight times higher mortality, compared with people in the general population who did receive treatment (hazard ratio, 8.78; 95% confidence interval, 4.37-17.64), Pirathiv Kugathasan and his associates reported in JAMA Psychiatry.

In contrast, the investigators found, patients with schizophrenia who received cardioprotective treatment had a 97% higher mortality (HR, 1.97; 95% CI, 1.25-310), compared with the treated general population, which was not statistically different from individuals in the general population who did not receive treatment (HR, 2.95; 95% CI, 2.62-3.32) after adjustment for baseline characteristics.

“Given the increased cardiovascular risk among patients with schizophrenia, we believe that the current findings support the use of intensive cardioprotective treatments in patients with schizophrenia,” reported Mr. Kugathasan, a PhD candidate in the department of psychiatry at Aalborg University Hospital in Denmark.

However, 7.8% of patients diagnosed with schizophrenia received no prescriptions for cardioprotective medications after a myocardial infarction, compared with 3.3% of the general population. They were significantly less likely than were individuals from the general population to receive a prescription for antiplatelets (84.9% vs. 91.8%), vitamin K antagonists (15.9% vs. 24.2%), beta-blockers (74.1% vs. 84.9%), ACE inhibitors (70.9% vs. 86.6%), and statins (72.2% vs. 87.3%).

The mortality rates were not significantly different between untreated patients with schizophrenia and untreated participants from the general population.

When the researchers examined the effects of different treatment types, they found that mortality rates were still higher in treated patients with schizophrenia, compared with treated patients from the general population – with the exception of those treated with antiplatelets and statins. For ACE inhibitors, treated patients with schizophrenia had a twofold higher mortality than that of treated patients from the general population, while the mortality was more than twofold higher in the case of vitamin K antagonists.

“Previous studies have found that patients with schizophrenia have increased cardiovascular mortality and a lower prescription rate for cardioprotective treatment compared with the general population,” the authors wrote.

They noted that patients with schizophrenia might have more problems with medication adherence, and pointed to another study showing this in patients with schizophrenia and diabetes. Other studies also showed that patients with schizophrenia were less likely to talk to a cardiologist after a cardiac event.

“Together, we believe that these results could point toward a deficit in establishing an appropriate cardiac treatment plan in patients with schizophrenia that causes failure in initiation and maintenance of cardioprotective treatment,” they wrote. “This hypothesis could explain the results of a generally increased mortality rate among patients with schizophrenia, especially when the results suggest that these patients die of cardiovascular causes that might be treatable.”

They called for patients with schizophrenia to be followed up during treatment, and to increase treatment intensity after cardiac events, “because a diagnosis of schizophrenia may be associated with an increased cardiac risk, which potentially can be countered by secondary preventive cardiac treatment.”

In patients who received triple therapy, the mortality rates were similar for those with schizophrenia and the general population. However, there were much higher mortality rate differences between patients with schizophrenia and the general population for those receiving dual or monotherapy.

Significantly more patients from the general population were readmitted with myocardial infarction and more underwent percutaneous coronary intervention than from the group of patients with schizophrenia.

The prevalence of hypertension was similar between the two populations, but more patients with schizophrenia had diabetes and substance abuse, compared with the general population.

The authors noted that they did not have information on the severity of myocardial infarction or the effect of other lifestyle factors.

“Future research should attempt to assess the degree to which these factors contribute to the increased mortality in patients with schizophrenia,” they wrote.

One author declared grants, speaking fees and advisory roles with the pharmaceutical industry. No other conflicts of interest were declared.

SOURCE: Kugathasan P et al. JAMA Psychiatry 2018. Oct 24. doi: 10.1001/jamapsychiatry.2018.2742.

CHICAGO – Rheumatology advocates have been working to get a variety of bills passed in Congress, including efforts on creating exemptions to step therapy or “fail first” insurer policies, increasing osteoporosis screening payment, and raising research dollars for arthritis in the Department of Defense, Dr. Angus Worthing said at the annual meeting of the American College of Rheumatology.

Visits by rheumatologist advocates to receptive members of the House and Senate have been fruitful for these issues, said Dr. Worthing, who is chair of the ACR’s Government Affairs Committee and a practicing rheumatologist in the Washington area.

“There’s a bill in the House [H.R. 2077, Restoring the Patient’s Voice Act], reforming step therapy that would institute appropriate exemptions if a doctor can predict that a drug that’s the first step in a step therapy will cause side effects, will be ineffective, or has already been used by a patient, as well as other appropriate guardrails,” so that the policy can be circumvented and the patient can get the prescription that the doctor ordered, he said.


The ACR is working with coalition partners such as the National Psoriasis Foundation and other patient organizations to get a companion bill to H.R. 2077 introduced in the Senate, Dr. Worthing noted.

The ACR is also working to advance separate bills in the House (H.R. 1898) and Senate (S. 3160) to increase payment levels for dual x-ray absorptiometry scans, which were cut by 60%-70% about 10 years ago.

The two bills have broad bipartisan support in both the House and Senate. “Watch for that to hopefully become law,” Dr. Worthing said.

The ACR has been advocating for the last 4 years to increase research dollars specifically for arthritis and rheumatology at the Department of Defense. After years of trying, rheumatologist advocates were able to get funding for studying trauma-related osteoarthritis and military serology data banks added as an amendment in the most recent appropriations bill. However, it was pulled at the last minute because of a lack of support.

“But with that advancement we’ll be able to go into the next Congress in January and either get it into the bill or hopefully have the amendment voted on next year,” he said.

Dr. Worthing called for those interested in advocating for rheumatology to visit the ACR’s Legislative Action Center.

[email protected]

CHICAGO – Rheumatology advocates have been working to get a variety of bills passed in Congress, including efforts on creating exemptions to step therapy or “fail first” insurer policies, increasing osteoporosis screening payment, and raising research dollars for arthritis in the Department of Defense, Dr. Angus Worthing said at the annual meeting of the American College of Rheumatology.

Visits by rheumatologist advocates to receptive members of the House and Senate have been fruitful for these issues, said Dr. Worthing, who is chair of the ACR’s Government Affairs Committee and a practicing rheumatologist in the Washington area.

“There’s a bill in the House [H.R. 2077, Restoring the Patient’s Voice Act], reforming step therapy that would institute appropriate exemptions if a doctor can predict that a drug that’s the first step in a step therapy will cause side effects, will be ineffective, or has already been used by a patient, as well as other appropriate guardrails,” so that the policy can be circumvented and the patient can get the prescription that the doctor ordered, he said.


The ACR is working with coalition partners such as the National Psoriasis Foundation and other patient organizations to get a companion bill to H.R. 2077 introduced in the Senate, Dr. Worthing noted.

The ACR is also working to advance separate bills in the House (H.R. 1898) and Senate (S. 3160) to increase payment levels for dual x-ray absorptiometry scans, which were cut by 60%-70% about 10 years ago.

The two bills have broad bipartisan support in both the House and Senate. “Watch for that to hopefully become law,” Dr. Worthing said.

The ACR has been advocating for the last 4 years to increase research dollars specifically for arthritis and rheumatology at the Department of Defense. After years of trying, rheumatologist advocates were able to get funding for studying trauma-related osteoarthritis and military serology data banks added as an amendment in the most recent appropriations bill. However, it was pulled at the last minute because of a lack of support.

“But with that advancement we’ll be able to go into the next Congress in January and either get it into the bill or hopefully have the amendment voted on next year,” he said.

Dr. Worthing called for those interested in advocating for rheumatology to visit the ACR’s Legislative Action Center.

[email protected]

CHICAGO – Rheumatology advocates have been working to get a variety of bills passed in Congress, including efforts on creating exemptions to step therapy or “fail first” insurer policies, increasing osteoporosis screening payment, and raising research dollars for arthritis in the Department of Defense, Dr. Angus Worthing said at the annual meeting of the American College of Rheumatology.

Visits by rheumatologist advocates to receptive members of the House and Senate have been fruitful for these issues, said Dr. Worthing, who is chair of the ACR’s Government Affairs Committee and a practicing rheumatologist in the Washington area.

“There’s a bill in the House [H.R. 2077, Restoring the Patient’s Voice Act], reforming step therapy that would institute appropriate exemptions if a doctor can predict that a drug that’s the first step in a step therapy will cause side effects, will be ineffective, or has already been used by a patient, as well as other appropriate guardrails,” so that the policy can be circumvented and the patient can get the prescription that the doctor ordered, he said.


The ACR is working with coalition partners such as the National Psoriasis Foundation and other patient organizations to get a companion bill to H.R. 2077 introduced in the Senate, Dr. Worthing noted.

The ACR is also working to advance separate bills in the House (H.R. 1898) and Senate (S. 3160) to increase payment levels for dual x-ray absorptiometry scans, which were cut by 60%-70% about 10 years ago.

The two bills have broad bipartisan support in both the House and Senate. “Watch for that to hopefully become law,” Dr. Worthing said.

The ACR has been advocating for the last 4 years to increase research dollars specifically for arthritis and rheumatology at the Department of Defense. After years of trying, rheumatologist advocates were able to get funding for studying trauma-related osteoarthritis and military serology data banks added as an amendment in the most recent appropriations bill. However, it was pulled at the last minute because of a lack of support.

“But with that advancement we’ll be able to go into the next Congress in January and either get it into the bill or hopefully have the amendment voted on next year,” he said.

Dr. Worthing called for those interested in advocating for rheumatology to visit the ACR’s Legislative Action Center.

[email protected]

CHICAGO – The long path toward a validated definition of low disease activity in patients with systemic lupus erythematosus may be nearing an end as a definition first proposed more than 5 years ago received validation with data from more than 1,700 patients in a prospective, multicenter study.

Mitchel L. Zoler/MDedge News

The next step is to test this definition in treat-to-target intervention studies, and to apply the definition in other clinical trials as well as in routine clinical practice, Vera Golder, MD, said at the annual meeting of the American College of Rheumatology.

The tested definition has five elements that a patient needs to achieve to be considered in a lupus low disease activity state (LLDAS):

• A systemic lupus erythematosus (SLE) disease activity index (SLEDAI) score of 4 or less with no major organ involvement.

• No new disease activity.

• A physician’s global assessment of the patient of 1 or less on a 0-3 scale.

• Maintenance on a prednisolone dosage of 7.5 mg/day or less.

• Maintenance on a standard immunosuppressive regimen.

The Asia Pacific Lupus Collaboration (APLC) first proposed this definition of LLDAS in 2013 (Ann Rheum Dis. 2013 June;72[Suppl 3]:THU0298), and was the organization behind the latest test of its validity. The APLC based its LLDAS definition on recommendations made by an international working party (Ann Rheum Dis. 2014 June;73[6]:958-67).

The APLC prospectively collected data from 1,735 SLE patients at 13 centers in eight countries during May 2013–December 2016, with a median follow-up of 2.2 years. During that time, 78% of the patients achieved the LLDAS at least once. Two-thirds of the patients had at least one sustained period of LLDAS of at least 3 months, and overall the enrolled patients spent 69% of the time in the LLDAS, reported Dr. Golder, a rheumatologist at Monash University in Melbourne.

The validation analysis she described focused on examining the correlation between the amount of time that patients spent in the defined LLDAS and their subsequent clinical outcomes. The analysis showed that when patients were in the LLDAS their rate of subsequent flare or damage accrual was substantially reduced.

Patients in the LLDAS for at least half the time had a 51% reduced rate of subsequent flare and a 47% reduced rate of subsequent damage accrual, she reported. Patients with a LLDAS of 3-6 months had a 57% reduced rate of damage accrual. As time spent in continuous LLDAS continued to increase the rate of subsequent damage accrual continued to drop until the duration reached more than 9 months, at which point the rate of subsequent damage fell to nearly 90% lower than that of patients without this amount of sustained LLDAS. Patients with LLDAS sustained for more than 9 months and as long as 12 months had an 86% reduction in subsequent damage accrual. Periods of sustained LLDAS that extended longer than a year continued to maintain a nearly 90% reduced rate of damage accrual, Dr. Golder said.

The Asia Pacific Lupus Collaboration has received grants from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and UCB. Dr. Golder had no disclosures.

[email protected]

SOURCE: Golder V et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2786.

CHICAGO – The long path toward a validated definition of low disease activity in patients with systemic lupus erythematosus may be nearing an end as a definition first proposed more than 5 years ago received validation with data from more than 1,700 patients in a prospective, multicenter study.

Mitchel L. Zoler/MDedge News

The next step is to test this definition in treat-to-target intervention studies, and to apply the definition in other clinical trials as well as in routine clinical practice, Vera Golder, MD, said at the annual meeting of the American College of Rheumatology.

The tested definition has five elements that a patient needs to achieve to be considered in a lupus low disease activity state (LLDAS):

• A systemic lupus erythematosus (SLE) disease activity index (SLEDAI) score of 4 or less with no major organ involvement.

• No new disease activity.

• A physician’s global assessment of the patient of 1 or less on a 0-3 scale.

• Maintenance on a prednisolone dosage of 7.5 mg/day or less.

• Maintenance on a standard immunosuppressive regimen.

The Asia Pacific Lupus Collaboration (APLC) first proposed this definition of LLDAS in 2013 (Ann Rheum Dis. 2013 June;72[Suppl 3]:THU0298), and was the organization behind the latest test of its validity. The APLC based its LLDAS definition on recommendations made by an international working party (Ann Rheum Dis. 2014 June;73[6]:958-67).

The APLC prospectively collected data from 1,735 SLE patients at 13 centers in eight countries during May 2013–December 2016, with a median follow-up of 2.2 years. During that time, 78% of the patients achieved the LLDAS at least once. Two-thirds of the patients had at least one sustained period of LLDAS of at least 3 months, and overall the enrolled patients spent 69% of the time in the LLDAS, reported Dr. Golder, a rheumatologist at Monash University in Melbourne.

The validation analysis she described focused on examining the correlation between the amount of time that patients spent in the defined LLDAS and their subsequent clinical outcomes. The analysis showed that when patients were in the LLDAS their rate of subsequent flare or damage accrual was substantially reduced.

Patients in the LLDAS for at least half the time had a 51% reduced rate of subsequent flare and a 47% reduced rate of subsequent damage accrual, she reported. Patients with a LLDAS of 3-6 months had a 57% reduced rate of damage accrual. As time spent in continuous LLDAS continued to increase the rate of subsequent damage accrual continued to drop until the duration reached more than 9 months, at which point the rate of subsequent damage fell to nearly 90% lower than that of patients without this amount of sustained LLDAS. Patients with LLDAS sustained for more than 9 months and as long as 12 months had an 86% reduction in subsequent damage accrual. Periods of sustained LLDAS that extended longer than a year continued to maintain a nearly 90% reduced rate of damage accrual, Dr. Golder said.

The Asia Pacific Lupus Collaboration has received grants from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and UCB. Dr. Golder had no disclosures.

[email protected]

SOURCE: Golder V et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2786.

CHICAGO – The long path toward a validated definition of low disease activity in patients with systemic lupus erythematosus may be nearing an end as a definition first proposed more than 5 years ago received validation with data from more than 1,700 patients in a prospective, multicenter study.

Mitchel L. Zoler/MDedge News

The next step is to test this definition in treat-to-target intervention studies, and to apply the definition in other clinical trials as well as in routine clinical practice, Vera Golder, MD, said at the annual meeting of the American College of Rheumatology.

The tested definition has five elements that a patient needs to achieve to be considered in a lupus low disease activity state (LLDAS):

• A systemic lupus erythematosus (SLE) disease activity index (SLEDAI) score of 4 or less with no major organ involvement.

• No new disease activity.

• A physician’s global assessment of the patient of 1 or less on a 0-3 scale.

• Maintenance on a prednisolone dosage of 7.5 mg/day or less.

• Maintenance on a standard immunosuppressive regimen.

The Asia Pacific Lupus Collaboration (APLC) first proposed this definition of LLDAS in 2013 (Ann Rheum Dis. 2013 June;72[Suppl 3]:THU0298), and was the organization behind the latest test of its validity. The APLC based its LLDAS definition on recommendations made by an international working party (Ann Rheum Dis. 2014 June;73[6]:958-67).

The APLC prospectively collected data from 1,735 SLE patients at 13 centers in eight countries during May 2013–December 2016, with a median follow-up of 2.2 years. During that time, 78% of the patients achieved the LLDAS at least once. Two-thirds of the patients had at least one sustained period of LLDAS of at least 3 months, and overall the enrolled patients spent 69% of the time in the LLDAS, reported Dr. Golder, a rheumatologist at Monash University in Melbourne.

The validation analysis she described focused on examining the correlation between the amount of time that patients spent in the defined LLDAS and their subsequent clinical outcomes. The analysis showed that when patients were in the LLDAS their rate of subsequent flare or damage accrual was substantially reduced.

Patients in the LLDAS for at least half the time had a 51% reduced rate of subsequent flare and a 47% reduced rate of subsequent damage accrual, she reported. Patients with a LLDAS of 3-6 months had a 57% reduced rate of damage accrual. As time spent in continuous LLDAS continued to increase the rate of subsequent damage accrual continued to drop until the duration reached more than 9 months, at which point the rate of subsequent damage fell to nearly 90% lower than that of patients without this amount of sustained LLDAS. Patients with LLDAS sustained for more than 9 months and as long as 12 months had an 86% reduction in subsequent damage accrual. Periods of sustained LLDAS that extended longer than a year continued to maintain a nearly 90% reduced rate of damage accrual, Dr. Golder said.

The Asia Pacific Lupus Collaboration has received grants from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and UCB. Dr. Golder had no disclosures.

[email protected]

SOURCE: Golder V et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2786.

MONTEREY, CALIF. – Julie C. Harper, MD, likes to warn her patients with acne about an unexpected possible side effect of treatment with isotretinoin. “You may become a dermatologist.”

After all, that’s exactly how Dr. Harper herself was inspired to pursue a career in dermatology. As a teenager, she had acne and was treated with isotretinoin three times. The experience was so influential that she went into dermatology with a specific goal of treating acne.

“I love all of it, and in my practice I treat everything,” said Dr. Harper, “but I have a special interest in helping people with acne be as clear as they can be.” Indeed, she helped found the American Acne and Rosacea Society, which she now serves as president.

Dr. Harper, who practices in Birmingham, Ala., spoke about her approach to acne and rosacea in an interview following one of her presentations at the annual Coastal Dermatology Symposium.

DERMATOLOGY NEWS: What drew you to focus on rosacea in addition to acne?

Dr. Harper: Acne and rosacea are often coupled together because both of them affect the face, and they create red bumps on the skin. But they’re very distinct diagnoses, and their pathogenesis is completely different. My interest in treating rosacea was secondary to acne, but I love to treat them both.

DN: Are they both equally challenging to treat?

Dr. Harper: In some ways, rosacea is more challenging to treat.

With acne, we have a pretty good algorithm for how we treat it. We can end with isotretinoin, which for many people is a cure. But we really don’t have that last step in rosacea.

DN: What are you doing differently with rosacea than you might not have done a few years ago?

Dr. Harper: More combination therapy. The trend is more toward a comprehensive combination approach to treat everything we see in rosacea: Hit this as hard as you can. Hit everything you see. Part of that is because we have some newer drugs like the alpha-adrenergic agonists that work differently than anything we’ve had before.

We have a couple of good combination studies. One study examined ivermectin plus brimonidine (J Drugs Dermatol. 2017 Sep 1;16[9]:909-16). Those two worked better together if you did not delay the brimonidine for 4 weeks and only used it with the ivermectin for part of the study.


There are also the newer studies that look at doxycycline plus ivermectin and compare it with ivermectin plus placebo. The combination works better, and it works faster (Adv Ther. 2016;33[9]:1481-1501; unpublished clinical trial data on file with Galderma, NCT03075891).

On top of those treatments, we may need to add laser for background redness, or an oral beta-blocker for flushing if the patient still complains of the symptoms.

DN: What’s most challenging to treat in rosacea?

Dr. Harper: The redness and phymatous changes are the hardest. Once you get phymatous changes, you have to do a physical modality.

Most of us think that if we treat rosacea aggressively up front, maybe we can prevent the phymatous changes. Prevention is key, just like prevention of acne scarring is easier than getting rid of scars once you have it.

Other than phyma, it’s the redness. Even the Food and Drug Administration–approved products we have for redness don’t work for flushing. Patients stand up to give up a presentation and “Oh no, here comes a red face.” That’s the hardest part to manage.

DN: How do beta-blockers fare at treating flushing?

Dr. Harper: They can help, but I don’t know that they can knock it out completely.

And we should remember that there are no FDA-approved beta-blockers to treat this. Most of the data we have are small case reports or case series. We don’t have a lot of data.

DN: Is there anything that’s used too much in rosacea?

Dr. Harper: Probably metronidazole. I understand why it’s used. It’s not a bad drug. But we have better drugs now.

I think we use metronidazole whenever things aren’t covered by insurance. And we use it to do too many things. Don’t try to make metronidazole do everything.

Metronidazole is FDA-approved for papules and pustules. It wasn’t ever intended to help with flushing and background erythema, and you’ll need to use something else with it.

DN: What’s coming down the line for rosacea?

Dr. Harper: We’ve got a couple new antibiotics: a new topical antibiotic and another oral antibiotic.

DN: Let’s talk about acne. Do you think isotretinoin is underused?

Dr. Harper: We should be using more of it. Why do we hold this drug hostage from our patients? In many people, it will cure their acne if they take it for just 5-6 months.

Are we worried about inflammatory bowel disease? The most recent studies say that’s not really an association. Are we worried about depression? We’ve had a meta-analysis that suggests if you take all that data, depression – if anything – gets better in people who take isotretinoin (Am J Gastroenterol. 2014 Apr;109[4]:563-9; J Am Acad Dermatol. 2017 Jun;76[6]:1068-76.e9).

We need to take [the risk with pregnancy] seriously. But we need to be putting more people on the drug and giving them the opportunity to be clear.

 

DN: What should be used less in acne?

Dr. Harper: We should use less antibiotics and more of everything else – more hormonal treatments, more isotretinoin, more topical retinoids.

That doesn’t mean no antibiotics. But instead of doing three repetitive courses of antibiotics, do one. If acne recurs, go to isotretinoin. Go to an alternative.

DN: What about spironolactone in acne?

Dr. Harper: It’s a blood pressure medicine, but it’s got an antiandrogenic qualities. It blocks the androgen receptor so it’s like getting the benefits of the birth control pill without the estrogen. It can be very beneficial for acne in women.

Its use increased from 2004 to 2013, and people are getting the hang of it. But when you compare it with the number of antibiotics prescribed, antibiotics are written a whole lot more (J Am Acad Dermatol. 2017 Sep;77[3],456-63.e4).

DN: Is there anything that is especially helpful in treating men?

Dr. Harper: Part of the way that birth control and spironolactone work is by decreasing sebum, and we don’t have anything like that for men. But potentially, there may be a topical antiandrogen product that decreases sebum.

DN: How do you deal with patients who are in a lot of distress because of acne or rosacea?

Dr. Harper: You listen to them and tell them you hear what they’re saying. “I understand that you want to be clear, and I’ll help you do that.”

Listen to why they’re not doing well and why they’re frustrated with what they’ve used. They might say, “I don’t use what you gave me because I don’t like the way it feels.” Or, “the drug that you prescribed is too expensive.”

If they’re really doing everything you said, and they’re not doing well, in both of those conditions it may be time for isotretinoin.

In acne, I’ve never seen it fail. It doesn’t work as predictably in rosacea, but it does pretty well if you do low-dose, intermittent isotretinoin.

DN: Do you ever try treatments that are unexpected for acne and rosacea?

Dr. Harper: If you use the right combination of what we have, and try to target pathogenesis, I don’t think we have to go off the reservation very often. We can get good results with what we have available.

The Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications. Dr. Harper disclosed speaker/advisor relationships with Allergan, Bayer, BioPharmX, Galderma, La Roche–Posay, and Ortho Pharmaceutical, and has served as an investigator for Bayer.

MONTEREY, CALIF. – Julie C. Harper, MD, likes to warn her patients with acne about an unexpected possible side effect of treatment with isotretinoin. “You may become a dermatologist.”

After all, that’s exactly how Dr. Harper herself was inspired to pursue a career in dermatology. As a teenager, she had acne and was treated with isotretinoin three times. The experience was so influential that she went into dermatology with a specific goal of treating acne.

“I love all of it, and in my practice I treat everything,” said Dr. Harper, “but I have a special interest in helping people with acne be as clear as they can be.” Indeed, she helped found the American Acne and Rosacea Society, which she now serves as president.

Dr. Harper, who practices in Birmingham, Ala., spoke about her approach to acne and rosacea in an interview following one of her presentations at the annual Coastal Dermatology Symposium.

DERMATOLOGY NEWS: What drew you to focus on rosacea in addition to acne?

Dr. Harper: Acne and rosacea are often coupled together because both of them affect the face, and they create red bumps on the skin. But they’re very distinct diagnoses, and their pathogenesis is completely different. My interest in treating rosacea was secondary to acne, but I love to treat them both.

DN: Are they both equally challenging to treat?

Dr. Harper: In some ways, rosacea is more challenging to treat.

With acne, we have a pretty good algorithm for how we treat it. We can end with isotretinoin, which for many people is a cure. But we really don’t have that last step in rosacea.

DN: What are you doing differently with rosacea than you might not have done a few years ago?

Dr. Harper: More combination therapy. The trend is more toward a comprehensive combination approach to treat everything we see in rosacea: Hit this as hard as you can. Hit everything you see. Part of that is because we have some newer drugs like the alpha-adrenergic agonists that work differently than anything we’ve had before.

We have a couple of good combination studies. One study examined ivermectin plus brimonidine (J Drugs Dermatol. 2017 Sep 1;16[9]:909-16). Those two worked better together if you did not delay the brimonidine for 4 weeks and only used it with the ivermectin for part of the study.


There are also the newer studies that look at doxycycline plus ivermectin and compare it with ivermectin plus placebo. The combination works better, and it works faster (Adv Ther. 2016;33[9]:1481-1501; unpublished clinical trial data on file with Galderma, NCT03075891).

On top of those treatments, we may need to add laser for background redness, or an oral beta-blocker for flushing if the patient still complains of the symptoms.

DN: What’s most challenging to treat in rosacea?

Dr. Harper: The redness and phymatous changes are the hardest. Once you get phymatous changes, you have to do a physical modality.

Most of us think that if we treat rosacea aggressively up front, maybe we can prevent the phymatous changes. Prevention is key, just like prevention of acne scarring is easier than getting rid of scars once you have it.

Other than phyma, it’s the redness. Even the Food and Drug Administration–approved products we have for redness don’t work for flushing. Patients stand up to give up a presentation and “Oh no, here comes a red face.” That’s the hardest part to manage.

DN: How do beta-blockers fare at treating flushing?

Dr. Harper: They can help, but I don’t know that they can knock it out completely.

And we should remember that there are no FDA-approved beta-blockers to treat this. Most of the data we have are small case reports or case series. We don’t have a lot of data.

DN: Is there anything that’s used too much in rosacea?

Dr. Harper: Probably metronidazole. I understand why it’s used. It’s not a bad drug. But we have better drugs now.

I think we use metronidazole whenever things aren’t covered by insurance. And we use it to do too many things. Don’t try to make metronidazole do everything.

Metronidazole is FDA-approved for papules and pustules. It wasn’t ever intended to help with flushing and background erythema, and you’ll need to use something else with it.

DN: What’s coming down the line for rosacea?

Dr. Harper: We’ve got a couple new antibiotics: a new topical antibiotic and another oral antibiotic.

DN: Let’s talk about acne. Do you think isotretinoin is underused?

Dr. Harper: We should be using more of it. Why do we hold this drug hostage from our patients? In many people, it will cure their acne if they take it for just 5-6 months.

Are we worried about inflammatory bowel disease? The most recent studies say that’s not really an association. Are we worried about depression? We’ve had a meta-analysis that suggests if you take all that data, depression – if anything – gets better in people who take isotretinoin (Am J Gastroenterol. 2014 Apr;109[4]:563-9; J Am Acad Dermatol. 2017 Jun;76[6]:1068-76.e9).

We need to take [the risk with pregnancy] seriously. But we need to be putting more people on the drug and giving them the opportunity to be clear.

 

DN: What should be used less in acne?

Dr. Harper: We should use less antibiotics and more of everything else – more hormonal treatments, more isotretinoin, more topical retinoids.

That doesn’t mean no antibiotics. But instead of doing three repetitive courses of antibiotics, do one. If acne recurs, go to isotretinoin. Go to an alternative.

DN: What about spironolactone in acne?

Dr. Harper: It’s a blood pressure medicine, but it’s got an antiandrogenic qualities. It blocks the androgen receptor so it’s like getting the benefits of the birth control pill without the estrogen. It can be very beneficial for acne in women.

Its use increased from 2004 to 2013, and people are getting the hang of it. But when you compare it with the number of antibiotics prescribed, antibiotics are written a whole lot more (J Am Acad Dermatol. 2017 Sep;77[3],456-63.e4).

DN: Is there anything that is especially helpful in treating men?

Dr. Harper: Part of the way that birth control and spironolactone work is by decreasing sebum, and we don’t have anything like that for men. But potentially, there may be a topical antiandrogen product that decreases sebum.

DN: How do you deal with patients who are in a lot of distress because of acne or rosacea?

Dr. Harper: You listen to them and tell them you hear what they’re saying. “I understand that you want to be clear, and I’ll help you do that.”

Listen to why they’re not doing well and why they’re frustrated with what they’ve used. They might say, “I don’t use what you gave me because I don’t like the way it feels.” Or, “the drug that you prescribed is too expensive.”

If they’re really doing everything you said, and they’re not doing well, in both of those conditions it may be time for isotretinoin.

In acne, I’ve never seen it fail. It doesn’t work as predictably in rosacea, but it does pretty well if you do low-dose, intermittent isotretinoin.

DN: Do you ever try treatments that are unexpected for acne and rosacea?

Dr. Harper: If you use the right combination of what we have, and try to target pathogenesis, I don’t think we have to go off the reservation very often. We can get good results with what we have available.

The Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications. Dr. Harper disclosed speaker/advisor relationships with Allergan, Bayer, BioPharmX, Galderma, La Roche–Posay, and Ortho Pharmaceutical, and has served as an investigator for Bayer.

MONTEREY, CALIF. – Julie C. Harper, MD, likes to warn her patients with acne about an unexpected possible side effect of treatment with isotretinoin. “You may become a dermatologist.”

After all, that’s exactly how Dr. Harper herself was inspired to pursue a career in dermatology. As a teenager, she had acne and was treated with isotretinoin three times. The experience was so influential that she went into dermatology with a specific goal of treating acne.

“I love all of it, and in my practice I treat everything,” said Dr. Harper, “but I have a special interest in helping people with acne be as clear as they can be.” Indeed, she helped found the American Acne and Rosacea Society, which she now serves as president.

Dr. Harper, who practices in Birmingham, Ala., spoke about her approach to acne and rosacea in an interview following one of her presentations at the annual Coastal Dermatology Symposium.

DERMATOLOGY NEWS: What drew you to focus on rosacea in addition to acne?

Dr. Harper: Acne and rosacea are often coupled together because both of them affect the face, and they create red bumps on the skin. But they’re very distinct diagnoses, and their pathogenesis is completely different. My interest in treating rosacea was secondary to acne, but I love to treat them both.

DN: Are they both equally challenging to treat?

Dr. Harper: In some ways, rosacea is more challenging to treat.

With acne, we have a pretty good algorithm for how we treat it. We can end with isotretinoin, which for many people is a cure. But we really don’t have that last step in rosacea.

DN: What are you doing differently with rosacea than you might not have done a few years ago?

Dr. Harper: More combination therapy. The trend is more toward a comprehensive combination approach to treat everything we see in rosacea: Hit this as hard as you can. Hit everything you see. Part of that is because we have some newer drugs like the alpha-adrenergic agonists that work differently than anything we’ve had before.

We have a couple of good combination studies. One study examined ivermectin plus brimonidine (J Drugs Dermatol. 2017 Sep 1;16[9]:909-16). Those two worked better together if you did not delay the brimonidine for 4 weeks and only used it with the ivermectin for part of the study.


There are also the newer studies that look at doxycycline plus ivermectin and compare it with ivermectin plus placebo. The combination works better, and it works faster (Adv Ther. 2016;33[9]:1481-1501; unpublished clinical trial data on file with Galderma, NCT03075891).

On top of those treatments, we may need to add laser for background redness, or an oral beta-blocker for flushing if the patient still complains of the symptoms.

DN: What’s most challenging to treat in rosacea?

Dr. Harper: The redness and phymatous changes are the hardest. Once you get phymatous changes, you have to do a physical modality.

Most of us think that if we treat rosacea aggressively up front, maybe we can prevent the phymatous changes. Prevention is key, just like prevention of acne scarring is easier than getting rid of scars once you have it.

Other than phyma, it’s the redness. Even the Food and Drug Administration–approved products we have for redness don’t work for flushing. Patients stand up to give up a presentation and “Oh no, here comes a red face.” That’s the hardest part to manage.

DN: How do beta-blockers fare at treating flushing?

Dr. Harper: They can help, but I don’t know that they can knock it out completely.

And we should remember that there are no FDA-approved beta-blockers to treat this. Most of the data we have are small case reports or case series. We don’t have a lot of data.

DN: Is there anything that’s used too much in rosacea?

Dr. Harper: Probably metronidazole. I understand why it’s used. It’s not a bad drug. But we have better drugs now.

I think we use metronidazole whenever things aren’t covered by insurance. And we use it to do too many things. Don’t try to make metronidazole do everything.

Metronidazole is FDA-approved for papules and pustules. It wasn’t ever intended to help with flushing and background erythema, and you’ll need to use something else with it.

DN: What’s coming down the line for rosacea?

Dr. Harper: We’ve got a couple new antibiotics: a new topical antibiotic and another oral antibiotic.

DN: Let’s talk about acne. Do you think isotretinoin is underused?

Dr. Harper: We should be using more of it. Why do we hold this drug hostage from our patients? In many people, it will cure their acne if they take it for just 5-6 months.

Are we worried about inflammatory bowel disease? The most recent studies say that’s not really an association. Are we worried about depression? We’ve had a meta-analysis that suggests if you take all that data, depression – if anything – gets better in people who take isotretinoin (Am J Gastroenterol. 2014 Apr;109[4]:563-9; J Am Acad Dermatol. 2017 Jun;76[6]:1068-76.e9).

We need to take [the risk with pregnancy] seriously. But we need to be putting more people on the drug and giving them the opportunity to be clear.

 

DN: What should be used less in acne?

Dr. Harper: We should use less antibiotics and more of everything else – more hormonal treatments, more isotretinoin, more topical retinoids.

That doesn’t mean no antibiotics. But instead of doing three repetitive courses of antibiotics, do one. If acne recurs, go to isotretinoin. Go to an alternative.

DN: What about spironolactone in acne?

Dr. Harper: It’s a blood pressure medicine, but it’s got an antiandrogenic qualities. It blocks the androgen receptor so it’s like getting the benefits of the birth control pill without the estrogen. It can be very beneficial for acne in women.

Its use increased from 2004 to 2013, and people are getting the hang of it. But when you compare it with the number of antibiotics prescribed, antibiotics are written a whole lot more (J Am Acad Dermatol. 2017 Sep;77[3],456-63.e4).

DN: Is there anything that is especially helpful in treating men?

Dr. Harper: Part of the way that birth control and spironolactone work is by decreasing sebum, and we don’t have anything like that for men. But potentially, there may be a topical antiandrogen product that decreases sebum.

DN: How do you deal with patients who are in a lot of distress because of acne or rosacea?

Dr. Harper: You listen to them and tell them you hear what they’re saying. “I understand that you want to be clear, and I’ll help you do that.”

Listen to why they’re not doing well and why they’re frustrated with what they’ve used. They might say, “I don’t use what you gave me because I don’t like the way it feels.” Or, “the drug that you prescribed is too expensive.”

If they’re really doing everything you said, and they’re not doing well, in both of those conditions it may be time for isotretinoin.

In acne, I’ve never seen it fail. It doesn’t work as predictably in rosacea, but it does pretty well if you do low-dose, intermittent isotretinoin.

DN: Do you ever try treatments that are unexpected for acne and rosacea?

Dr. Harper: If you use the right combination of what we have, and try to target pathogenesis, I don’t think we have to go off the reservation very often. We can get good results with what we have available.

The Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications. Dr. Harper disclosed speaker/advisor relationships with Allergan, Bayer, BioPharmX, Galderma, La Roche–Posay, and Ortho Pharmaceutical, and has served as an investigator for Bayer.

DUBROVNIK, CROATIA – Hematopoietic stem cell transplant (HSCT) can be hit or miss in patients with peripheral T-cell lymphomas (PTCLs), according to one expert.

Jennifer Smith/MDedge News

The success of HSCT varies according to the subtype of PTCL and the type of transplant, Ali Bazarbachi, MD, PhD, of the American University of Beirut, Lebanon, said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL–not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.

On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).

Both auto-HSCT and allogeneic (allo) HSCT are options for patients with nonlocalized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
 

State of PTCL treatment

Patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired, Dr. Bazarbachi said.

He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable – localized ENKTL and anaplastic lymphoma kinase–positive (ALK-positive) ALCL.

Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
 

PTCL-NOS, AITL, and ALCL

For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.

In a study published in 2012, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival – compared with previous results with CHOP – in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma (J Clin Oncol. 2012 Sep 1;30[25]:3093-9; ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924).

Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.

“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients – those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”

Results from the COMPLETE study showed improved survival in patients who received consolidation with auto- or allo-HSCT, compared with patients who did not receive a transplant (Blood. 2017;130:342).

COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.

Allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, Dr. Bazarbachi said.

However, chemosensitive patients who have relapsed should receive auto-HSCT only if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.

He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
 

ATLL

ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative, Dr. Bazarbachi said. It is most effective in patients who have achieved a complete or partial response to induction (Blood. 2012 Aug 23;120[8]:1734-41).

However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.

Also, allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.

Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time, as frontline consolidation, after relapse, or if they have refractory disease.

Auto-HSCT “does not work in this disease,” he said. In a study published in 2014, all four ATLL patients who underwent auto-HSCT “rapidly” died (Bone Marrow Transplant. 2014 Oct;49[10]:1266-8).

ENKTL

Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.

Auto-HSCT has been shown to improve survival in these patients, and it is most effective when patients have achieved a complete response to induction (Biol Blood Marrow Transplant. 2008 Dec;14[12]:1356-64).

Allo-HSCT also is an option for frontline consolidation in patients with nonlocalized ENKTL, nasal type, Dr. Bazarbachi said.

He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should receive auto-HSCT only if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.

Patients with refractory, nonlocalized ENKTL, nasal type, should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.

Dr. Bazarbachi did not declare any conflicts of interest.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.

[email protected]

DUBROVNIK, CROATIA – Hematopoietic stem cell transplant (HSCT) can be hit or miss in patients with peripheral T-cell lymphomas (PTCLs), according to one expert.

Jennifer Smith/MDedge News

The success of HSCT varies according to the subtype of PTCL and the type of transplant, Ali Bazarbachi, MD, PhD, of the American University of Beirut, Lebanon, said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL–not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.

On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).

Both auto-HSCT and allogeneic (allo) HSCT are options for patients with nonlocalized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
 

State of PTCL treatment

Patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired, Dr. Bazarbachi said.

He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable – localized ENKTL and anaplastic lymphoma kinase–positive (ALK-positive) ALCL.

Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
 

PTCL-NOS, AITL, and ALCL

For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.

In a study published in 2012, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival – compared with previous results with CHOP – in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma (J Clin Oncol. 2012 Sep 1;30[25]:3093-9; ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924).

Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.

“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients – those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”

Results from the COMPLETE study showed improved survival in patients who received consolidation with auto- or allo-HSCT, compared with patients who did not receive a transplant (Blood. 2017;130:342).

COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.

Allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, Dr. Bazarbachi said.

However, chemosensitive patients who have relapsed should receive auto-HSCT only if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.

He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
 

ATLL

ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative, Dr. Bazarbachi said. It is most effective in patients who have achieved a complete or partial response to induction (Blood. 2012 Aug 23;120[8]:1734-41).

However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.

Also, allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.

Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time, as frontline consolidation, after relapse, or if they have refractory disease.

Auto-HSCT “does not work in this disease,” he said. In a study published in 2014, all four ATLL patients who underwent auto-HSCT “rapidly” died (Bone Marrow Transplant. 2014 Oct;49[10]:1266-8).

ENKTL

Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.

Auto-HSCT has been shown to improve survival in these patients, and it is most effective when patients have achieved a complete response to induction (Biol Blood Marrow Transplant. 2008 Dec;14[12]:1356-64).

Allo-HSCT also is an option for frontline consolidation in patients with nonlocalized ENKTL, nasal type, Dr. Bazarbachi said.

He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should receive auto-HSCT only if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.

Patients with refractory, nonlocalized ENKTL, nasal type, should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.

Dr. Bazarbachi did not declare any conflicts of interest.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.

[email protected]

DUBROVNIK, CROATIA – Hematopoietic stem cell transplant (HSCT) can be hit or miss in patients with peripheral T-cell lymphomas (PTCLs), according to one expert.

Jennifer Smith/MDedge News

The success of HSCT varies according to the subtype of PTCL and the type of transplant, Ali Bazarbachi, MD, PhD, of the American University of Beirut, Lebanon, said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.

For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL–not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.

On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).

Both auto-HSCT and allogeneic (allo) HSCT are options for patients with nonlocalized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
 

State of PTCL treatment

Patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired, Dr. Bazarbachi said.

He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable – localized ENKTL and anaplastic lymphoma kinase–positive (ALK-positive) ALCL.

Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
 

PTCL-NOS, AITL, and ALCL

For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.

In a study published in 2012, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival – compared with previous results with CHOP – in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma (J Clin Oncol. 2012 Sep 1;30[25]:3093-9; ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924).

Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.

“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients – those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”

Results from the COMPLETE study showed improved survival in patients who received consolidation with auto- or allo-HSCT, compared with patients who did not receive a transplant (Blood. 2017;130:342).

COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.

Allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, Dr. Bazarbachi said.

However, chemosensitive patients who have relapsed should receive auto-HSCT only if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.

He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
 

ATLL

ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative, Dr. Bazarbachi said. It is most effective in patients who have achieved a complete or partial response to induction (Blood. 2012 Aug 23;120[8]:1734-41).

However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.

Also, allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.

Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time, as frontline consolidation, after relapse, or if they have refractory disease.

Auto-HSCT “does not work in this disease,” he said. In a study published in 2014, all four ATLL patients who underwent auto-HSCT “rapidly” died (Bone Marrow Transplant. 2014 Oct;49[10]:1266-8).

ENKTL

Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.

Auto-HSCT has been shown to improve survival in these patients, and it is most effective when patients have achieved a complete response to induction (Biol Blood Marrow Transplant. 2008 Dec;14[12]:1356-64).

Allo-HSCT also is an option for frontline consolidation in patients with nonlocalized ENKTL, nasal type, Dr. Bazarbachi said.

He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should receive auto-HSCT only if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.

Patients with refractory, nonlocalized ENKTL, nasal type, should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.

Dr. Bazarbachi did not declare any conflicts of interest.

The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.

[email protected]

In the largest analysis ever of cardiovascular risk associated with the initiation of nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac was associated with higher risk for adverse cardiovascular outcomes. The study findings were published online September 4 in BMJ.

Those beginning diclofenac had a 50% increased 30-day risk for a composite outcome of major adverse cardiovascular events (MACE), compared with individuals who did not initiate an NSAID or acetaminophen (95% confidence interval for incidence rate ratio, 1.4–1.7).

The risk was still significantly elevated when the study’s first author, Morten Schmidt, MD, PhD, of the Department of Clinical Epidemiology at Aarhus University in Denmark, and his colleagues compared diclofenac initiation with beginning other NSAIDs or acetaminophen. Compared with that associated with ibuprofen or acetaminophen, the MACE risk was elevated 20% in diclofenac initiators (95% CI, 1.1–1.3 for both). Initiating diclofenac was associated with 30% greater risk for MACE, compared with initiating naproxen (95% CI, 1.1–1.5).

Novel Methodology

The researchers used the longstanding and comprehensive Danish health registry system to their advantage in designing a cohort trial that was modeled to resemble a clinical trial. For each month, beginning in 1996 and continuing through 2016, Dr. Schmidt and his collaborators assembled propensity-matched cohorts of individuals to compare each study group. The study design achieved many of the aims of a clinical trial while working within the ethical constraints of studying medications known to elevate cardiovascular risk.

For each 30-day period, the investigators tracked and compared cardiovascular outcomes for each group. Each month, data for a new cohort were collected, beginning a new “clinical trial.” Individuals could be included in more than one month’s worth of “trial” data as long as they continued to meet inclusion criteria.

The completeness of Danish health data meant that the researchers were confident in data about comorbidities, other prescription medications, and outcomes.

Dr. Schmidt and his colleagues performed subgroup and sensitivity analyses to look at the extent to which preexisting risks for cardiovascular disease mediated MACE risk on diclofenac initiation. They found that diclofenac initiators in the highest risk group had as many as 40 excess cardiovascular events per year—about half of them fatal—that were attributable to starting the medication. Although that group had the highest absolute risk, “the relative risks were highest in those with the lowest baseline risk,” said the investigators.

Secondary outcomes for the study included the association between medication use or non-use and each component of the composite primary outcome. These components included first-time occurrences of the nonfatal end points of atrial fibrillation or flutter, ischemic stroke, heart failure, and myocardial infarction. Cardiac death included death from any cardiac cause.

“Supporting use of a combined end point, event rates consistently increased for all individual outcomes” for diclofenac initiators, compared with those who did not start an NSAID, said Dr. Schmidt and his colleagues.

Individuals were excluded if they had known cardiovascular, kidney, liver, or ulcer disease and if they had malignancy or serious mental health diagnoses such as dementia or schizophrenia. Participants, mean age 48 to 56, had to be at least 18 and could not have filled a prescription for an NSAID within the previous 12 months. Men made up 36.6% to 46.3% of the cohorts.

Dr. Schmidt and his collaborators said that in comparison with other NSAIDs, the short half-life of diclofenac means that a supratherapeutic plasma concentration of diclofenac soon after initiation achieves not just cyclooxygenase-2 (COX-2), but also COX-1 inhibition. However, after those high levels fall, patients taking diclofenac spend a substantial period of time with unopposed COX-2 inhibition, a prothrombotic state that also is associated with blood pressure elevation, atherogenesis, and worsening of heart failure.

Diclofenac and ibuprofen entailed similar gastrointestinal bleeding risks, and both medications were associated with a higher risk of bleeding than were ibuprofen, acetaminophen, and no medication.

Public Health Implications

“Comparing diclofenac initiation with no NSAID initiation, the consistency between our results and those of previous meta-analyses of both trial and observational data provides strong evidence to guide clinical decision making,” said Dr. Schmidt and his coauthors.

“Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs,” noted the investigators. “It is time to acknowledge the potential health risk of diclofenac and to reduce its use.”

The study was funded by the Department of Clinical Epidemiology Research Foundation, University of Aarhus, and by the Program for Clinical Research Infrastructure, funded by the Lundbeck Foundation, Novo Nordisk Foundation, and the Danish Research Council. The authors reported that they had no relevant conflicts of interest.

—Kari Oakes

Suggested Reading

Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018;362:k3426.

For expert commentary on this article, please visit our Migraine Resource Center online at https://www.mdedge.com/neurologyreviews/migraineresourcecenter/article/177937/headache-migraine/physician-commentary

In the largest analysis ever of cardiovascular risk associated with the initiation of nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac was associated with higher risk for adverse cardiovascular outcomes. The study findings were published online September 4 in BMJ.

Those beginning diclofenac had a 50% increased 30-day risk for a composite outcome of major adverse cardiovascular events (MACE), compared with individuals who did not initiate an NSAID or acetaminophen (95% confidence interval for incidence rate ratio, 1.4–1.7).

The risk was still significantly elevated when the study’s first author, Morten Schmidt, MD, PhD, of the Department of Clinical Epidemiology at Aarhus University in Denmark, and his colleagues compared diclofenac initiation with beginning other NSAIDs or acetaminophen. Compared with that associated with ibuprofen or acetaminophen, the MACE risk was elevated 20% in diclofenac initiators (95% CI, 1.1–1.3 for both). Initiating diclofenac was associated with 30% greater risk for MACE, compared with initiating naproxen (95% CI, 1.1–1.5).

Novel Methodology

The researchers used the longstanding and comprehensive Danish health registry system to their advantage in designing a cohort trial that was modeled to resemble a clinical trial. For each month, beginning in 1996 and continuing through 2016, Dr. Schmidt and his collaborators assembled propensity-matched cohorts of individuals to compare each study group. The study design achieved many of the aims of a clinical trial while working within the ethical constraints of studying medications known to elevate cardiovascular risk.

For each 30-day period, the investigators tracked and compared cardiovascular outcomes for each group. Each month, data for a new cohort were collected, beginning a new “clinical trial.” Individuals could be included in more than one month’s worth of “trial” data as long as they continued to meet inclusion criteria.

The completeness of Danish health data meant that the researchers were confident in data about comorbidities, other prescription medications, and outcomes.

Dr. Schmidt and his colleagues performed subgroup and sensitivity analyses to look at the extent to which preexisting risks for cardiovascular disease mediated MACE risk on diclofenac initiation. They found that diclofenac initiators in the highest risk group had as many as 40 excess cardiovascular events per year—about half of them fatal—that were attributable to starting the medication. Although that group had the highest absolute risk, “the relative risks were highest in those with the lowest baseline risk,” said the investigators.

Secondary outcomes for the study included the association between medication use or non-use and each component of the composite primary outcome. These components included first-time occurrences of the nonfatal end points of atrial fibrillation or flutter, ischemic stroke, heart failure, and myocardial infarction. Cardiac death included death from any cardiac cause.

“Supporting use of a combined end point, event rates consistently increased for all individual outcomes” for diclofenac initiators, compared with those who did not start an NSAID, said Dr. Schmidt and his colleagues.

Individuals were excluded if they had known cardiovascular, kidney, liver, or ulcer disease and if they had malignancy or serious mental health diagnoses such as dementia or schizophrenia. Participants, mean age 48 to 56, had to be at least 18 and could not have filled a prescription for an NSAID within the previous 12 months. Men made up 36.6% to 46.3% of the cohorts.

Dr. Schmidt and his collaborators said that in comparison with other NSAIDs, the short half-life of diclofenac means that a supratherapeutic plasma concentration of diclofenac soon after initiation achieves not just cyclooxygenase-2 (COX-2), but also COX-1 inhibition. However, after those high levels fall, patients taking diclofenac spend a substantial period of time with unopposed COX-2 inhibition, a prothrombotic state that also is associated with blood pressure elevation, atherogenesis, and worsening of heart failure.

Diclofenac and ibuprofen entailed similar gastrointestinal bleeding risks, and both medications were associated with a higher risk of bleeding than were ibuprofen, acetaminophen, and no medication.

Public Health Implications

“Comparing diclofenac initiation with no NSAID initiation, the consistency between our results and those of previous meta-analyses of both trial and observational data provides strong evidence to guide clinical decision making,” said Dr. Schmidt and his coauthors.

“Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs,” noted the investigators. “It is time to acknowledge the potential health risk of diclofenac and to reduce its use.”

The study was funded by the Department of Clinical Epidemiology Research Foundation, University of Aarhus, and by the Program for Clinical Research Infrastructure, funded by the Lundbeck Foundation, Novo Nordisk Foundation, and the Danish Research Council. The authors reported that they had no relevant conflicts of interest.

—Kari Oakes

Suggested Reading

Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018;362:k3426.

For expert commentary on this article, please visit our Migraine Resource Center online at https://www.mdedge.com/neurologyreviews/migraineresourcecenter/article/177937/headache-migraine/physician-commentary

In the largest analysis ever of cardiovascular risk associated with the initiation of nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac was associated with higher risk for adverse cardiovascular outcomes. The study findings were published online September 4 in BMJ.

Those beginning diclofenac had a 50% increased 30-day risk for a composite outcome of major adverse cardiovascular events (MACE), compared with individuals who did not initiate an NSAID or acetaminophen (95% confidence interval for incidence rate ratio, 1.4–1.7).

The risk was still significantly elevated when the study’s first author, Morten Schmidt, MD, PhD, of the Department of Clinical Epidemiology at Aarhus University in Denmark, and his colleagues compared diclofenac initiation with beginning other NSAIDs or acetaminophen. Compared with that associated with ibuprofen or acetaminophen, the MACE risk was elevated 20% in diclofenac initiators (95% CI, 1.1–1.3 for both). Initiating diclofenac was associated with 30% greater risk for MACE, compared with initiating naproxen (95% CI, 1.1–1.5).

Novel Methodology

The researchers used the longstanding and comprehensive Danish health registry system to their advantage in designing a cohort trial that was modeled to resemble a clinical trial. For each month, beginning in 1996 and continuing through 2016, Dr. Schmidt and his collaborators assembled propensity-matched cohorts of individuals to compare each study group. The study design achieved many of the aims of a clinical trial while working within the ethical constraints of studying medications known to elevate cardiovascular risk.

For each 30-day period, the investigators tracked and compared cardiovascular outcomes for each group. Each month, data for a new cohort were collected, beginning a new “clinical trial.” Individuals could be included in more than one month’s worth of “trial” data as long as they continued to meet inclusion criteria.

The completeness of Danish health data meant that the researchers were confident in data about comorbidities, other prescription medications, and outcomes.

Dr. Schmidt and his colleagues performed subgroup and sensitivity analyses to look at the extent to which preexisting risks for cardiovascular disease mediated MACE risk on diclofenac initiation. They found that diclofenac initiators in the highest risk group had as many as 40 excess cardiovascular events per year—about half of them fatal—that were attributable to starting the medication. Although that group had the highest absolute risk, “the relative risks were highest in those with the lowest baseline risk,” said the investigators.

Secondary outcomes for the study included the association between medication use or non-use and each component of the composite primary outcome. These components included first-time occurrences of the nonfatal end points of atrial fibrillation or flutter, ischemic stroke, heart failure, and myocardial infarction. Cardiac death included death from any cardiac cause.

“Supporting use of a combined end point, event rates consistently increased for all individual outcomes” for diclofenac initiators, compared with those who did not start an NSAID, said Dr. Schmidt and his colleagues.

Individuals were excluded if they had known cardiovascular, kidney, liver, or ulcer disease and if they had malignancy or serious mental health diagnoses such as dementia or schizophrenia. Participants, mean age 48 to 56, had to be at least 18 and could not have filled a prescription for an NSAID within the previous 12 months. Men made up 36.6% to 46.3% of the cohorts.

Dr. Schmidt and his collaborators said that in comparison with other NSAIDs, the short half-life of diclofenac means that a supratherapeutic plasma concentration of diclofenac soon after initiation achieves not just cyclooxygenase-2 (COX-2), but also COX-1 inhibition. However, after those high levels fall, patients taking diclofenac spend a substantial period of time with unopposed COX-2 inhibition, a prothrombotic state that also is associated with blood pressure elevation, atherogenesis, and worsening of heart failure.

Diclofenac and ibuprofen entailed similar gastrointestinal bleeding risks, and both medications were associated with a higher risk of bleeding than were ibuprofen, acetaminophen, and no medication.

Public Health Implications

“Comparing diclofenac initiation with no NSAID initiation, the consistency between our results and those of previous meta-analyses of both trial and observational data provides strong evidence to guide clinical decision making,” said Dr. Schmidt and his coauthors.

“Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs,” noted the investigators. “It is time to acknowledge the potential health risk of diclofenac and to reduce its use.”

The study was funded by the Department of Clinical Epidemiology Research Foundation, University of Aarhus, and by the Program for Clinical Research Infrastructure, funded by the Lundbeck Foundation, Novo Nordisk Foundation, and the Danish Research Council. The authors reported that they had no relevant conflicts of interest.

—Kari Oakes

Suggested Reading

Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018;362:k3426.

For expert commentary on this article, please visit our Migraine Resource Center online at https://www.mdedge.com/neurologyreviews/migraineresourcecenter/article/177937/headache-migraine/physician-commentary

A positive B cell clonality test in a peripheral blood sample predicts imminent onset of rheumatoid arthritis with a high degree of accuracy in at-risk individual Also today, radiation to survival of metastatic cancer, cannabis crimps teen cognitive development, bipolar patients’ relatives face increased cardiovascular risk. Amazon Alexa

Apple Podcasts

Spotify

A positive B cell clonality test in a peripheral blood sample predicts imminent onset of rheumatoid arthritis with a high degree of accuracy in at-risk individual Also today, radiation to survival of metastatic cancer, cannabis crimps teen cognitive development, bipolar patients’ relatives face increased cardiovascular risk. Amazon Alexa

Apple Podcasts

Spotify

A positive B cell clonality test in a peripheral blood sample predicts imminent onset of rheumatoid arthritis with a high degree of accuracy in at-risk individual Also today, radiation to survival of metastatic cancer, cannabis crimps teen cognitive development, bipolar patients’ relatives face increased cardiovascular risk. Amazon Alexa

Apple Podcasts

Spotify

Physicians continue to support advanced alternative payment models despite the fact that operational issues have not improved over the last 4 years and new ones have cropped up, according to a follow-up survey conducted by the RAND Corporation for the American Medical Association.

“All the things we heard in 2014 were still present in 2018. Both the challenges that practices had experienced back in 2014 having to do with data timeliness, data completeness and accuracy, payment model execution, all those challenges persisted,” Mark W. Friedberg, MD, senior physician policy researcher at RAND, said in an interview.

RAND surveyed 31 practices of varying practice size and specialty across six geographic regions, some of which participated in the 2014 survey. Supplemental information was provided by interviews with 32 market observers, 8 health plan leaders, 10 hospital and hospital system leaders, 10 state and local medical society leaders, and 4 chapter leaders with MGMA (formerly the Medical Group Management Association).

“We had thought we would hear that the problem had gotten a little bit better since there has been some investment in trying to tamp down the wide range of measures that are involved in these alternative payment models,” Dr. Friedberg said. “We did not see any evidence of that having any effect on the practices that participated in this study this time around.”

Indeed, concerns reported in 2014 were again reported in 2018, along with a new set of concerns, including the perceived pace of change in alternative payment models (APMs), the complexity of APMs, and physician concerns over two-sided risk models.

“Practices, especially those that participated both times, said in 2014 we had these challenges [of rapid changes in APM models] and since then, things have just gotten a lot faster,” he said, noting that doctors are complaining of models that are going through changes, sometimes without much warning. “They are changing quite rapidly from year to year. If you look at the MACRA QPP [Quality Payment Program] for example, that model changes every year to some extent and those things are hard for them to keep up with.”

Running hand in hand with the change is the complexity of the changes, a result of expanding performance measures and uncertainty with thresholds for penalties and rewards and in some ways has had little impact on improving care.

Dr. Friedberg noted that some practices are hiring people to examine APMs to devise strategic ways to choose and report data for maximum return.

“In a practice, for example, if their quality of care was already very good, what these folks ended up doing was help them choose measures and work the attribution algorithms in a strategic way to either guarantee a bonus or minimize the risk of incurring a penalty,” he said.

He also noted that practices appear to becoming more risk averse.

“We heard a lot more of the following thing, which is that if [practices] were in a two-sided risk model, several of them reported trying and succeeding in some cases offloading the downside risk to partners,” Dr. Friedberg reported. “And what this resulted in was that the practice, even though from the payer’s perspective they are in a two-sided model, the practice was actually in a one-sided model with a partner who is taking all of the downside risk and a portion of the upside risk, leaving a small upside risk proposition that remained for the practice.”

He said the range of partners that were absorbing the downside risk included hospitals, device manufacturers, consulting companies, or private equity firms.

Despite the concerns surrounding APMs, Dr. Friedberg said that “we did not hear practices broadly saying that they just weren’t interested in alternative payment models. In general, practices still remained pretty enthusiastic about these alternative payment models in theory. If they could be made simpler, if the pace of change weren’t quite so fast, that they would have a chance to really do some important care improvements in alternative payment models.”

He noted some of the surveyed practices were able to make investments in care as a direct result of participating in APMs, such as in behavioral health capabilities in primary care, for example, leading to quality of care improvements.

However, these issues could reveal a future unwillingness to participate in APMs, especially two-sided risk models, something at least the Centers for Medicare & Medicaid Services are pushing for as a stated goal of the QPP is to get practices to participate in APMs and take on more risk.

The growing aversion to taking on downside risk could lead practices to simply stay in fee for service and simply take the payment penalty because it is a fixed amount that can be planned for, as opposed to the fluctuations of bonuses and penalties that comes with a rapidly changing APM environment, Dr. Friedberg said.

Going forward, the report makes a number of recommendations to help create an environment that would potentially make APMs more successful, including simplifying the models; creating stable, predictable, and moderately paced pathways to APM participation; making data available in a more timely fashion; minimizing downside risk or helping practices better manage it; and designing APMs that will encourage clinical changes to help improve the effectiveness of care delivered.

[email protected]

Physicians continue to support advanced alternative payment models despite the fact that operational issues have not improved over the last 4 years and new ones have cropped up, according to a follow-up survey conducted by the RAND Corporation for the American Medical Association.

“All the things we heard in 2014 were still present in 2018. Both the challenges that practices had experienced back in 2014 having to do with data timeliness, data completeness and accuracy, payment model execution, all those challenges persisted,” Mark W. Friedberg, MD, senior physician policy researcher at RAND, said in an interview.

RAND surveyed 31 practices of varying practice size and specialty across six geographic regions, some of which participated in the 2014 survey. Supplemental information was provided by interviews with 32 market observers, 8 health plan leaders, 10 hospital and hospital system leaders, 10 state and local medical society leaders, and 4 chapter leaders with MGMA (formerly the Medical Group Management Association).

“We had thought we would hear that the problem had gotten a little bit better since there has been some investment in trying to tamp down the wide range of measures that are involved in these alternative payment models,” Dr. Friedberg said. “We did not see any evidence of that having any effect on the practices that participated in this study this time around.”

Indeed, concerns reported in 2014 were again reported in 2018, along with a new set of concerns, including the perceived pace of change in alternative payment models (APMs), the complexity of APMs, and physician concerns over two-sided risk models.

“Practices, especially those that participated both times, said in 2014 we had these challenges [of rapid changes in APM models] and since then, things have just gotten a lot faster,” he said, noting that doctors are complaining of models that are going through changes, sometimes without much warning. “They are changing quite rapidly from year to year. If you look at the MACRA QPP [Quality Payment Program] for example, that model changes every year to some extent and those things are hard for them to keep up with.”

Running hand in hand with the change is the complexity of the changes, a result of expanding performance measures and uncertainty with thresholds for penalties and rewards and in some ways has had little impact on improving care.

Dr. Friedberg noted that some practices are hiring people to examine APMs to devise strategic ways to choose and report data for maximum return.

“In a practice, for example, if their quality of care was already very good, what these folks ended up doing was help them choose measures and work the attribution algorithms in a strategic way to either guarantee a bonus or minimize the risk of incurring a penalty,” he said.

He also noted that practices appear to becoming more risk averse.

“We heard a lot more of the following thing, which is that if [practices] were in a two-sided risk model, several of them reported trying and succeeding in some cases offloading the downside risk to partners,” Dr. Friedberg reported. “And what this resulted in was that the practice, even though from the payer’s perspective they are in a two-sided model, the practice was actually in a one-sided model with a partner who is taking all of the downside risk and a portion of the upside risk, leaving a small upside risk proposition that remained for the practice.”

He said the range of partners that were absorbing the downside risk included hospitals, device manufacturers, consulting companies, or private equity firms.

Despite the concerns surrounding APMs, Dr. Friedberg said that “we did not hear practices broadly saying that they just weren’t interested in alternative payment models. In general, practices still remained pretty enthusiastic about these alternative payment models in theory. If they could be made simpler, if the pace of change weren’t quite so fast, that they would have a chance to really do some important care improvements in alternative payment models.”

He noted some of the surveyed practices were able to make investments in care as a direct result of participating in APMs, such as in behavioral health capabilities in primary care, for example, leading to quality of care improvements.

However, these issues could reveal a future unwillingness to participate in APMs, especially two-sided risk models, something at least the Centers for Medicare & Medicaid Services are pushing for as a stated goal of the QPP is to get practices to participate in APMs and take on more risk.

The growing aversion to taking on downside risk could lead practices to simply stay in fee for service and simply take the payment penalty because it is a fixed amount that can be planned for, as opposed to the fluctuations of bonuses and penalties that comes with a rapidly changing APM environment, Dr. Friedberg said.

Going forward, the report makes a number of recommendations to help create an environment that would potentially make APMs more successful, including simplifying the models; creating stable, predictable, and moderately paced pathways to APM participation; making data available in a more timely fashion; minimizing downside risk or helping practices better manage it; and designing APMs that will encourage clinical changes to help improve the effectiveness of care delivered.

[email protected]

Physicians continue to support advanced alternative payment models despite the fact that operational issues have not improved over the last 4 years and new ones have cropped up, according to a follow-up survey conducted by the RAND Corporation for the American Medical Association.

“All the things we heard in 2014 were still present in 2018. Both the challenges that practices had experienced back in 2014 having to do with data timeliness, data completeness and accuracy, payment model execution, all those challenges persisted,” Mark W. Friedberg, MD, senior physician policy researcher at RAND, said in an interview.

RAND surveyed 31 practices of varying practice size and specialty across six geographic regions, some of which participated in the 2014 survey. Supplemental information was provided by interviews with 32 market observers, 8 health plan leaders, 10 hospital and hospital system leaders, 10 state and local medical society leaders, and 4 chapter leaders with MGMA (formerly the Medical Group Management Association).

“We had thought we would hear that the problem had gotten a little bit better since there has been some investment in trying to tamp down the wide range of measures that are involved in these alternative payment models,” Dr. Friedberg said. “We did not see any evidence of that having any effect on the practices that participated in this study this time around.”

Indeed, concerns reported in 2014 were again reported in 2018, along with a new set of concerns, including the perceived pace of change in alternative payment models (APMs), the complexity of APMs, and physician concerns over two-sided risk models.

“Practices, especially those that participated both times, said in 2014 we had these challenges [of rapid changes in APM models] and since then, things have just gotten a lot faster,” he said, noting that doctors are complaining of models that are going through changes, sometimes without much warning. “They are changing quite rapidly from year to year. If you look at the MACRA QPP [Quality Payment Program] for example, that model changes every year to some extent and those things are hard for them to keep up with.”

Running hand in hand with the change is the complexity of the changes, a result of expanding performance measures and uncertainty with thresholds for penalties and rewards and in some ways has had little impact on improving care.

Dr. Friedberg noted that some practices are hiring people to examine APMs to devise strategic ways to choose and report data for maximum return.

“In a practice, for example, if their quality of care was already very good, what these folks ended up doing was help them choose measures and work the attribution algorithms in a strategic way to either guarantee a bonus or minimize the risk of incurring a penalty,” he said.

He also noted that practices appear to becoming more risk averse.

“We heard a lot more of the following thing, which is that if [practices] were in a two-sided risk model, several of them reported trying and succeeding in some cases offloading the downside risk to partners,” Dr. Friedberg reported. “And what this resulted in was that the practice, even though from the payer’s perspective they are in a two-sided model, the practice was actually in a one-sided model with a partner who is taking all of the downside risk and a portion of the upside risk, leaving a small upside risk proposition that remained for the practice.”

He said the range of partners that were absorbing the downside risk included hospitals, device manufacturers, consulting companies, or private equity firms.

Despite the concerns surrounding APMs, Dr. Friedberg said that “we did not hear practices broadly saying that they just weren’t interested in alternative payment models. In general, practices still remained pretty enthusiastic about these alternative payment models in theory. If they could be made simpler, if the pace of change weren’t quite so fast, that they would have a chance to really do some important care improvements in alternative payment models.”

He noted some of the surveyed practices were able to make investments in care as a direct result of participating in APMs, such as in behavioral health capabilities in primary care, for example, leading to quality of care improvements.

However, these issues could reveal a future unwillingness to participate in APMs, especially two-sided risk models, something at least the Centers for Medicare & Medicaid Services are pushing for as a stated goal of the QPP is to get practices to participate in APMs and take on more risk.

The growing aversion to taking on downside risk could lead practices to simply stay in fee for service and simply take the payment penalty because it is a fixed amount that can be planned for, as opposed to the fluctuations of bonuses and penalties that comes with a rapidly changing APM environment, Dr. Friedberg said.

Going forward, the report makes a number of recommendations to help create an environment that would potentially make APMs more successful, including simplifying the models; creating stable, predictable, and moderately paced pathways to APM participation; making data available in a more timely fashion; minimizing downside risk or helping practices better manage it; and designing APMs that will encourage clinical changes to help improve the effectiveness of care delivered.

[email protected]

CHICAGO – Lupus nephritis recurrence rates in kidney transplant recipients declined over the past decade, compared with rates seen in earlier studies, according to a review of cases at the University of Tennessee Health Science Center (UTHSC).

Sharon Worcester/MDedge News

The findings are likely related to improvements in posttransplant immunosuppressive regimens, and may have implications for the timing of transplant going forward, Debendra N. Pattanaik, MD, said at the annual meeting of the American College of Rheumatology.

The biopsy-proven recurrence rate in 38 transplant recipients who received standard immunosuppression with prednisone, tacrolimus, and mycophenolate mofetil was 11%, and graft loss or death occurred in 26% at a median follow-up of 1,230 days, said Dr. Pattanaik, a rheumatologist at UTHSC, Memphis.

Patients with recurrence showed a trend for increased risk for graft loss or death, compared with recipients without recurrence (hazard ratio = 3.14), he noted during a press briefing at the meeting.


Lupus nephritis is a severe complication occurring in more than half of all patients with systemic lupus erythematosus (SLE), and despite a great deal of progress over the years, 10%-30% develop end-stage renal disease and require dialysis and/or transplant, he said, noting that studies have shown that transplant recipients do better over time than do those who remain on dialysis.

“So renal transplant is an important modality of treatment for end-stage renal disease from lupus nephritis,” he added.

However, recurrence of lupus nephritis in the graft is a concern, he said.

In previous eras – prior to improvements in immunosuppressive regimens for transplant recipients – studies showed variable rates of lupus nephritis recurrence, with some reporting rates up to 50% depending on the patient populations and protocols, he noted.

The rates in recent years at UTHSC seemed lower than that, so he and his colleagues looked more closely at the outcomes.

Case patients included all those with end-stage renal disease secondary to lupus nephritis who were transplanted between 2006 and 2017 at the center. Medical records of all 38 were reviewed along with information from the United Network for Organ Sharing Network. The mean age of the patients at baseline was 42 years, 89% were women, 89% were African American, and previous time on dialysis was a median of 4 years. Most (80%) received hemodialysis, and nearly one-third (31%) received living donor transplantation, Dr. Pattanaik said.

The main difference in the past decade compared with those previous eras is the use of posttransplant immunosuppressive regimens consisting of tacrolimus and mycophenolate mofetil rather than cyclosporine and azathioprine in addition to prednisone, he explained.

Previous reports showing higher recurrence rates were from studies in which patients received cyclosporine and azathioprine as part of the posttransplant regimen, he said.

“Our next question is whether patients can be transplanted early,” he said, explaining that transplant is often delayed for many months or years until SLE is in remission, but if the new regimens are reducing recurrence risk, early transplant may be feasible.

Dr. Pattanaik reported having no disclosures.

[email protected]

SOURCE: Pattanaik D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 711.

CHICAGO – Lupus nephritis recurrence rates in kidney transplant recipients declined over the past decade, compared with rates seen in earlier studies, according to a review of cases at the University of Tennessee Health Science Center (UTHSC).

Sharon Worcester/MDedge News

The findings are likely related to improvements in posttransplant immunosuppressive regimens, and may have implications for the timing of transplant going forward, Debendra N. Pattanaik, MD, said at the annual meeting of the American College of Rheumatology.

The biopsy-proven recurrence rate in 38 transplant recipients who received standard immunosuppression with prednisone, tacrolimus, and mycophenolate mofetil was 11%, and graft loss or death occurred in 26% at a median follow-up of 1,230 days, said Dr. Pattanaik, a rheumatologist at UTHSC, Memphis.

Patients with recurrence showed a trend for increased risk for graft loss or death, compared with recipients without recurrence (hazard ratio = 3.14), he noted during a press briefing at the meeting.


Lupus nephritis is a severe complication occurring in more than half of all patients with systemic lupus erythematosus (SLE), and despite a great deal of progress over the years, 10%-30% develop end-stage renal disease and require dialysis and/or transplant, he said, noting that studies have shown that transplant recipients do better over time than do those who remain on dialysis.

“So renal transplant is an important modality of treatment for end-stage renal disease from lupus nephritis,” he added.

However, recurrence of lupus nephritis in the graft is a concern, he said.

In previous eras – prior to improvements in immunosuppressive regimens for transplant recipients – studies showed variable rates of lupus nephritis recurrence, with some reporting rates up to 50% depending on the patient populations and protocols, he noted.

The rates in recent years at UTHSC seemed lower than that, so he and his colleagues looked more closely at the outcomes.

Case patients included all those with end-stage renal disease secondary to lupus nephritis who were transplanted between 2006 and 2017 at the center. Medical records of all 38 were reviewed along with information from the United Network for Organ Sharing Network. The mean age of the patients at baseline was 42 years, 89% were women, 89% were African American, and previous time on dialysis was a median of 4 years. Most (80%) received hemodialysis, and nearly one-third (31%) received living donor transplantation, Dr. Pattanaik said.

The main difference in the past decade compared with those previous eras is the use of posttransplant immunosuppressive regimens consisting of tacrolimus and mycophenolate mofetil rather than cyclosporine and azathioprine in addition to prednisone, he explained.

Previous reports showing higher recurrence rates were from studies in which patients received cyclosporine and azathioprine as part of the posttransplant regimen, he said.

“Our next question is whether patients can be transplanted early,” he said, explaining that transplant is often delayed for many months or years until SLE is in remission, but if the new regimens are reducing recurrence risk, early transplant may be feasible.

Dr. Pattanaik reported having no disclosures.

[email protected]

SOURCE: Pattanaik D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 711.

CHICAGO – Lupus nephritis recurrence rates in kidney transplant recipients declined over the past decade, compared with rates seen in earlier studies, according to a review of cases at the University of Tennessee Health Science Center (UTHSC).

Sharon Worcester/MDedge News

The findings are likely related to improvements in posttransplant immunosuppressive regimens, and may have implications for the timing of transplant going forward, Debendra N. Pattanaik, MD, said at the annual meeting of the American College of Rheumatology.

The biopsy-proven recurrence rate in 38 transplant recipients who received standard immunosuppression with prednisone, tacrolimus, and mycophenolate mofetil was 11%, and graft loss or death occurred in 26% at a median follow-up of 1,230 days, said Dr. Pattanaik, a rheumatologist at UTHSC, Memphis.

Patients with recurrence showed a trend for increased risk for graft loss or death, compared with recipients without recurrence (hazard ratio = 3.14), he noted during a press briefing at the meeting.


Lupus nephritis is a severe complication occurring in more than half of all patients with systemic lupus erythematosus (SLE), and despite a great deal of progress over the years, 10%-30% develop end-stage renal disease and require dialysis and/or transplant, he said, noting that studies have shown that transplant recipients do better over time than do those who remain on dialysis.

“So renal transplant is an important modality of treatment for end-stage renal disease from lupus nephritis,” he added.

However, recurrence of lupus nephritis in the graft is a concern, he said.

In previous eras – prior to improvements in immunosuppressive regimens for transplant recipients – studies showed variable rates of lupus nephritis recurrence, with some reporting rates up to 50% depending on the patient populations and protocols, he noted.

The rates in recent years at UTHSC seemed lower than that, so he and his colleagues looked more closely at the outcomes.

Case patients included all those with end-stage renal disease secondary to lupus nephritis who were transplanted between 2006 and 2017 at the center. Medical records of all 38 were reviewed along with information from the United Network for Organ Sharing Network. The mean age of the patients at baseline was 42 years, 89% were women, 89% were African American, and previous time on dialysis was a median of 4 years. Most (80%) received hemodialysis, and nearly one-third (31%) received living donor transplantation, Dr. Pattanaik said.

The main difference in the past decade compared with those previous eras is the use of posttransplant immunosuppressive regimens consisting of tacrolimus and mycophenolate mofetil rather than cyclosporine and azathioprine in addition to prednisone, he explained.

Previous reports showing higher recurrence rates were from studies in which patients received cyclosporine and azathioprine as part of the posttransplant regimen, he said.

“Our next question is whether patients can be transplanted early,” he said, explaining that transplant is often delayed for many months or years until SLE is in remission, but if the new regimens are reducing recurrence risk, early transplant may be feasible.

Dr. Pattanaik reported having no disclosures.

[email protected]

SOURCE: Pattanaik D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 711.

ATLANTA – Acute myocardial infarction is associated with a risk of stroke that extends beyond the 1-month time window currently considered the at-risk period, according to an analysis of Medicare data.

“The results of our study may allow clinicians to more accurately counsel patients regarding their stroke etiology and may allow refinement of stroke etiology classification systems and clinical trial selection criteria,” lead study author Alexander E. Merkler, MD, said in an interview in advance of the annual meeting of the American Neurological Association.

In an effort to better understand the duration of heightened stroke risk after acute myocardial infarction, Dr. Merkler, a neurologist at New York–based Weill Cornell Medicine, and his colleagues conducted a retrospective cohort study using inpatient and outpatient claims during 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries who were at least 66 years old. They used previously validated ICD-9-CM diagnosis codes to ascertain the exposure variable of acute MI and the outcome of ischemic stroke but excluded strokes that occurred during an acute MI hospitalization.


Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or by Sept. 30, 2015. The researchers fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjusting for demographics, stroke risk factors, and Charlson comorbidities. Next, they used the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge, up to week 12. They also conducted a subgroup analysis to evaluate the duration of heightened ischemic stroke risk by MI type: ST-segment elevation MI (STEMI) versus non-STEMI (NSTEMI).

Dr. Merkler and his colleagues drew from data on 1.7 million eligible beneficiaries. Of these, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. After they adjusted for demographics, stroke risk factors, and Charlson comorbidities, the researchers found that the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (HR, 2.7), yet remained elevated during weeks 5-8 (HR, 2.0) and weeks 9-12 (HR, 1.6). It was no longer significantly elevated afterward. The prolonged period of heightened ischemic stroke risk was evident in patients with both STEMI and NSTEMI.

“We were surprised by how long the risk of stroke lasts after MI,” Dr. Merkler said. He acknowledged certain limitations of the analysis, including the fact that patients were all over the age of 65 years. “In addition, we lack granular detail such as severity of MI [and] the extent of stroke work-up,” he said.

Dr. Merkler disclosed that he is supported by a grant from the National Institutes of Health and by the Leon Levy Foundation in Neuroscience. Most of his coauthors are also supported by NIH grants.

[email protected]

Source: Ann Neurol. 2018;84[S22]:S146-7, Abstract M122.

ATLANTA – Acute myocardial infarction is associated with a risk of stroke that extends beyond the 1-month time window currently considered the at-risk period, according to an analysis of Medicare data.

“The results of our study may allow clinicians to more accurately counsel patients regarding their stroke etiology and may allow refinement of stroke etiology classification systems and clinical trial selection criteria,” lead study author Alexander E. Merkler, MD, said in an interview in advance of the annual meeting of the American Neurological Association.

In an effort to better understand the duration of heightened stroke risk after acute myocardial infarction, Dr. Merkler, a neurologist at New York–based Weill Cornell Medicine, and his colleagues conducted a retrospective cohort study using inpatient and outpatient claims during 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries who were at least 66 years old. They used previously validated ICD-9-CM diagnosis codes to ascertain the exposure variable of acute MI and the outcome of ischemic stroke but excluded strokes that occurred during an acute MI hospitalization.


Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or by Sept. 30, 2015. The researchers fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjusting for demographics, stroke risk factors, and Charlson comorbidities. Next, they used the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge, up to week 12. They also conducted a subgroup analysis to evaluate the duration of heightened ischemic stroke risk by MI type: ST-segment elevation MI (STEMI) versus non-STEMI (NSTEMI).

Dr. Merkler and his colleagues drew from data on 1.7 million eligible beneficiaries. Of these, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. After they adjusted for demographics, stroke risk factors, and Charlson comorbidities, the researchers found that the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (HR, 2.7), yet remained elevated during weeks 5-8 (HR, 2.0) and weeks 9-12 (HR, 1.6). It was no longer significantly elevated afterward. The prolonged period of heightened ischemic stroke risk was evident in patients with both STEMI and NSTEMI.

“We were surprised by how long the risk of stroke lasts after MI,” Dr. Merkler said. He acknowledged certain limitations of the analysis, including the fact that patients were all over the age of 65 years. “In addition, we lack granular detail such as severity of MI [and] the extent of stroke work-up,” he said.

Dr. Merkler disclosed that he is supported by a grant from the National Institutes of Health and by the Leon Levy Foundation in Neuroscience. Most of his coauthors are also supported by NIH grants.

[email protected]

Source: Ann Neurol. 2018;84[S22]:S146-7, Abstract M122.

ATLANTA – Acute myocardial infarction is associated with a risk of stroke that extends beyond the 1-month time window currently considered the at-risk period, according to an analysis of Medicare data.

“The results of our study may allow clinicians to more accurately counsel patients regarding their stroke etiology and may allow refinement of stroke etiology classification systems and clinical trial selection criteria,” lead study author Alexander E. Merkler, MD, said in an interview in advance of the annual meeting of the American Neurological Association.

In an effort to better understand the duration of heightened stroke risk after acute myocardial infarction, Dr. Merkler, a neurologist at New York–based Weill Cornell Medicine, and his colleagues conducted a retrospective cohort study using inpatient and outpatient claims during 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries who were at least 66 years old. They used previously validated ICD-9-CM diagnosis codes to ascertain the exposure variable of acute MI and the outcome of ischemic stroke but excluded strokes that occurred during an acute MI hospitalization.


Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or by Sept. 30, 2015. The researchers fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjusting for demographics, stroke risk factors, and Charlson comorbidities. Next, they used the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge, up to week 12. They also conducted a subgroup analysis to evaluate the duration of heightened ischemic stroke risk by MI type: ST-segment elevation MI (STEMI) versus non-STEMI (NSTEMI).

Dr. Merkler and his colleagues drew from data on 1.7 million eligible beneficiaries. Of these, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. After they adjusted for demographics, stroke risk factors, and Charlson comorbidities, the researchers found that the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (HR, 2.7), yet remained elevated during weeks 5-8 (HR, 2.0) and weeks 9-12 (HR, 1.6). It was no longer significantly elevated afterward. The prolonged period of heightened ischemic stroke risk was evident in patients with both STEMI and NSTEMI.

“We were surprised by how long the risk of stroke lasts after MI,” Dr. Merkler said. He acknowledged certain limitations of the analysis, including the fact that patients were all over the age of 65 years. “In addition, we lack granular detail such as severity of MI [and] the extent of stroke work-up,” he said.

Dr. Merkler disclosed that he is supported by a grant from the National Institutes of Health and by the Leon Levy Foundation in Neuroscience. Most of his coauthors are also supported by NIH grants.

[email protected]

Source: Ann Neurol. 2018;84[S22]:S146-7, Abstract M122.