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, a new Danish nationwide cohort study finds.
Among 8,119 patients aged 50 years and older (54.1% male, mean age 78.4), 4.3% had a recurrent stroke within 1 year following discharge for the initial stroke, reported David Gaist, PhD, of Odense University Hospital, Odense, Denmark, and colleagues in JAMA Neurology.
An adjusted analysis found that those who stopped therapy were more than twice as likely to experience another stroke over a mean 2.9 years (13.4% vs 6.8%, adjusted odds ratio [aOR] = 2.13; 95% confidence interval [CI], 1.57-2.89).
The findings highlight the preventive power of OAC therapy, Dr. Gaist said in an interview, and point to the importance of counseling patients about the benefits of the drugs. “Clinicians can provide balanced information on the pros and cons of discontinuing oral anticoagulants as well as lay out plans on when to restart the medication,” he said.
The researchers launched the study “to provide data on how often recurrent ischemic strokes occur in a large, unselected cohort of patients with atrial fibrillation who had a stroke and started or restarted oral anticoagulants, a situation mirroring what we see in our everyday lives as clinicians,” Dr. Gaist said. “We also wanted to see if patients with breakthrough strokes had particular characteristics compared with patients who did not have a recurrent stroke. Finally, we wanted to quantify a very simple cause of breakthrough stroke by answering the following question: How many of these patients had stopped taking their oral anticoagulant?”
A Large, Unselected Patient Cohort
Dr. Gaist and colleagues tracked 8,119 patients with ischemic stroke and atrial fibrillation who started or restarted OAC therapy within 30 days following their discharge between 2014 and 2021. Patients either had atrial fibrillation before their stroke or developed it afterward.
Eighty-one percent of patients had hypertension, 19.7% had diabetes, and 27.3% had ischemic heart disease; 35.3% had never smoked and smoking information was missing for 15.9%. Race/ethnicity information was not provided.
Patients were followed for an average of 2.9 years until 2022, and all were alive at least 30 days after discharge. During that time, 663 patients had a recurrent ischemic stroke (4.3%), of whom 80.4% were on OAC therapy. The percentage who had stroke at 2 years rose to 6.5%.
While the researchers thought the number of strokes was high, Dr. Gaist said, this isn’t a sign that the drugs aren’t working. “Oral anticoagulant use in secondary prevention in atrial fibrillation is guideline-supported as it has been proven to reduce the risk of stroke by roughly two thirds.”
Of study participants at baseline, 37.9% took oral anticoagulants, 23.5% took direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban), and 15.1% took vitamin K antagonists. In a nested case-control analysis of 663 cases (58.7% men, mean age 80.1) matched to 2,652 controls, at admission for ischemic stroke, 80.4% were on OAC therapy, and 8%-11% of patients stopped OAC therapy after their strokes, the researchers reported.
Patients who stopped OAC therapy had more severe strokes than those who didn’t at 7 days (median recurrent ischemic stroke Scandinavian Stroke Scale [SSS] score = 40.0 vs 46.0, respectively; aOR = 2.10; 95% CI, 1.31-3.36). Those who stopped OAC therapy also had higher mortality rates at 7 days (11.2% vs 3.9%, respectively) and 30 days (28.1% vs 10.9%, respectively).
It’s not clear why some patients discontinued OAC therapy. “We looked for evidence of serious bleeding or surgical procedures around the time of anticoagulant discontinuation but found this only to be the case in roughly 10% of these patients,” Dr. Gaist said.
He added that the study probably “underestimates the issue of anticoagulant discontinuation, particularly for DOACs, where a shorter half-life compared with warfarin means that even a short drug-break of a few days puts the patient at increased risk of stroke.”
The authors noted study limitations, including the lack of data on actual medication usage, alcohol usage, stroke etiology, lesion location, and socioeconomic status. And, they wrote, the study population is mostly of European origin.
No Surprises
Steven R. Messe, MD, professor of neurology at the Hospital of the University of Pennsylvania, Philadelphia, who didn’t take part in the study but is familiar with its findings, said in an interview that the study is a “well-done analysis.”
The findings are not surprising, he said. “The overall risk of stroke recurrence was 4.3% at 1 year while the mortality rate was higher at 15.4%. Given that the median CHA2DS2-VASc score was 4 and the average age was 79, the stroke recurrence rate and mortality rate are in line with prior studies.”
In regard to the power of OAC therapy to prevent recurrent strokes, Dr. Messe noted that patients may not be adhering to prescribed regimens. Also, “while DOACs are clearly safer that vitamin K–dependent anticoagulants, the medications are generally not dose adjusted. It is possible that adjusting the dose based on measured anti-Xa levels to insure therapeutic anticoagulant effects may reduce the stroke risk further.”
He added that “most of these patients with prior stroke and atrial fibrillation are vasculopathic and at risk of additional strokes due to other mechanisms such as small vessel or large vessel disease.”
In the big picture, the study “confirms again that anticoagulation should be prescribed to all patients with atrial fibrillation and prior stroke, unless there is a strong bleeding risk contraindication,” Dr. Messe said. These patients are clearly at high risk of stroke recurrence and mortality, and all risk factors should be aggressively managed.”
Researchers are exploring other options, he said. “For example, there are studies of factor XI inhibitors that could be added to a DOAC for additional reductions in ischemic stroke. In addition, in patients undergoing cardiac surgery, the randomized trial LAOS III demonstrated that surgical left atrial occlusion in addition to anticoagulation may provide additional stroke prevention.”
Dr. Gaist disclosed personal fees from Pfizer and Bristol Myers Squibb, and grants from Bayer. Several other authors reported various relationships with industry. Dr. Messe has no disclosures.
, a new Danish nationwide cohort study finds.
Among 8,119 patients aged 50 years and older (54.1% male, mean age 78.4), 4.3% had a recurrent stroke within 1 year following discharge for the initial stroke, reported David Gaist, PhD, of Odense University Hospital, Odense, Denmark, and colleagues in JAMA Neurology.
An adjusted analysis found that those who stopped therapy were more than twice as likely to experience another stroke over a mean 2.9 years (13.4% vs 6.8%, adjusted odds ratio [aOR] = 2.13; 95% confidence interval [CI], 1.57-2.89).
The findings highlight the preventive power of OAC therapy, Dr. Gaist said in an interview, and point to the importance of counseling patients about the benefits of the drugs. “Clinicians can provide balanced information on the pros and cons of discontinuing oral anticoagulants as well as lay out plans on when to restart the medication,” he said.
The researchers launched the study “to provide data on how often recurrent ischemic strokes occur in a large, unselected cohort of patients with atrial fibrillation who had a stroke and started or restarted oral anticoagulants, a situation mirroring what we see in our everyday lives as clinicians,” Dr. Gaist said. “We also wanted to see if patients with breakthrough strokes had particular characteristics compared with patients who did not have a recurrent stroke. Finally, we wanted to quantify a very simple cause of breakthrough stroke by answering the following question: How many of these patients had stopped taking their oral anticoagulant?”
A Large, Unselected Patient Cohort
Dr. Gaist and colleagues tracked 8,119 patients with ischemic stroke and atrial fibrillation who started or restarted OAC therapy within 30 days following their discharge between 2014 and 2021. Patients either had atrial fibrillation before their stroke or developed it afterward.
Eighty-one percent of patients had hypertension, 19.7% had diabetes, and 27.3% had ischemic heart disease; 35.3% had never smoked and smoking information was missing for 15.9%. Race/ethnicity information was not provided.
Patients were followed for an average of 2.9 years until 2022, and all were alive at least 30 days after discharge. During that time, 663 patients had a recurrent ischemic stroke (4.3%), of whom 80.4% were on OAC therapy. The percentage who had stroke at 2 years rose to 6.5%.
While the researchers thought the number of strokes was high, Dr. Gaist said, this isn’t a sign that the drugs aren’t working. “Oral anticoagulant use in secondary prevention in atrial fibrillation is guideline-supported as it has been proven to reduce the risk of stroke by roughly two thirds.”
Of study participants at baseline, 37.9% took oral anticoagulants, 23.5% took direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban), and 15.1% took vitamin K antagonists. In a nested case-control analysis of 663 cases (58.7% men, mean age 80.1) matched to 2,652 controls, at admission for ischemic stroke, 80.4% were on OAC therapy, and 8%-11% of patients stopped OAC therapy after their strokes, the researchers reported.
Patients who stopped OAC therapy had more severe strokes than those who didn’t at 7 days (median recurrent ischemic stroke Scandinavian Stroke Scale [SSS] score = 40.0 vs 46.0, respectively; aOR = 2.10; 95% CI, 1.31-3.36). Those who stopped OAC therapy also had higher mortality rates at 7 days (11.2% vs 3.9%, respectively) and 30 days (28.1% vs 10.9%, respectively).
It’s not clear why some patients discontinued OAC therapy. “We looked for evidence of serious bleeding or surgical procedures around the time of anticoagulant discontinuation but found this only to be the case in roughly 10% of these patients,” Dr. Gaist said.
He added that the study probably “underestimates the issue of anticoagulant discontinuation, particularly for DOACs, where a shorter half-life compared with warfarin means that even a short drug-break of a few days puts the patient at increased risk of stroke.”
The authors noted study limitations, including the lack of data on actual medication usage, alcohol usage, stroke etiology, lesion location, and socioeconomic status. And, they wrote, the study population is mostly of European origin.
No Surprises
Steven R. Messe, MD, professor of neurology at the Hospital of the University of Pennsylvania, Philadelphia, who didn’t take part in the study but is familiar with its findings, said in an interview that the study is a “well-done analysis.”
The findings are not surprising, he said. “The overall risk of stroke recurrence was 4.3% at 1 year while the mortality rate was higher at 15.4%. Given that the median CHA2DS2-VASc score was 4 and the average age was 79, the stroke recurrence rate and mortality rate are in line with prior studies.”
In regard to the power of OAC therapy to prevent recurrent strokes, Dr. Messe noted that patients may not be adhering to prescribed regimens. Also, “while DOACs are clearly safer that vitamin K–dependent anticoagulants, the medications are generally not dose adjusted. It is possible that adjusting the dose based on measured anti-Xa levels to insure therapeutic anticoagulant effects may reduce the stroke risk further.”
He added that “most of these patients with prior stroke and atrial fibrillation are vasculopathic and at risk of additional strokes due to other mechanisms such as small vessel or large vessel disease.”
In the big picture, the study “confirms again that anticoagulation should be prescribed to all patients with atrial fibrillation and prior stroke, unless there is a strong bleeding risk contraindication,” Dr. Messe said. These patients are clearly at high risk of stroke recurrence and mortality, and all risk factors should be aggressively managed.”
Researchers are exploring other options, he said. “For example, there are studies of factor XI inhibitors that could be added to a DOAC for additional reductions in ischemic stroke. In addition, in patients undergoing cardiac surgery, the randomized trial LAOS III demonstrated that surgical left atrial occlusion in addition to anticoagulation may provide additional stroke prevention.”
Dr. Gaist disclosed personal fees from Pfizer and Bristol Myers Squibb, and grants from Bayer. Several other authors reported various relationships with industry. Dr. Messe has no disclosures.
, a new Danish nationwide cohort study finds.
Among 8,119 patients aged 50 years and older (54.1% male, mean age 78.4), 4.3% had a recurrent stroke within 1 year following discharge for the initial stroke, reported David Gaist, PhD, of Odense University Hospital, Odense, Denmark, and colleagues in JAMA Neurology.
An adjusted analysis found that those who stopped therapy were more than twice as likely to experience another stroke over a mean 2.9 years (13.4% vs 6.8%, adjusted odds ratio [aOR] = 2.13; 95% confidence interval [CI], 1.57-2.89).
The findings highlight the preventive power of OAC therapy, Dr. Gaist said in an interview, and point to the importance of counseling patients about the benefits of the drugs. “Clinicians can provide balanced information on the pros and cons of discontinuing oral anticoagulants as well as lay out plans on when to restart the medication,” he said.
The researchers launched the study “to provide data on how often recurrent ischemic strokes occur in a large, unselected cohort of patients with atrial fibrillation who had a stroke and started or restarted oral anticoagulants, a situation mirroring what we see in our everyday lives as clinicians,” Dr. Gaist said. “We also wanted to see if patients with breakthrough strokes had particular characteristics compared with patients who did not have a recurrent stroke. Finally, we wanted to quantify a very simple cause of breakthrough stroke by answering the following question: How many of these patients had stopped taking their oral anticoagulant?”
A Large, Unselected Patient Cohort
Dr. Gaist and colleagues tracked 8,119 patients with ischemic stroke and atrial fibrillation who started or restarted OAC therapy within 30 days following their discharge between 2014 and 2021. Patients either had atrial fibrillation before their stroke or developed it afterward.
Eighty-one percent of patients had hypertension, 19.7% had diabetes, and 27.3% had ischemic heart disease; 35.3% had never smoked and smoking information was missing for 15.9%. Race/ethnicity information was not provided.
Patients were followed for an average of 2.9 years until 2022, and all were alive at least 30 days after discharge. During that time, 663 patients had a recurrent ischemic stroke (4.3%), of whom 80.4% were on OAC therapy. The percentage who had stroke at 2 years rose to 6.5%.
While the researchers thought the number of strokes was high, Dr. Gaist said, this isn’t a sign that the drugs aren’t working. “Oral anticoagulant use in secondary prevention in atrial fibrillation is guideline-supported as it has been proven to reduce the risk of stroke by roughly two thirds.”
Of study participants at baseline, 37.9% took oral anticoagulants, 23.5% took direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban), and 15.1% took vitamin K antagonists. In a nested case-control analysis of 663 cases (58.7% men, mean age 80.1) matched to 2,652 controls, at admission for ischemic stroke, 80.4% were on OAC therapy, and 8%-11% of patients stopped OAC therapy after their strokes, the researchers reported.
Patients who stopped OAC therapy had more severe strokes than those who didn’t at 7 days (median recurrent ischemic stroke Scandinavian Stroke Scale [SSS] score = 40.0 vs 46.0, respectively; aOR = 2.10; 95% CI, 1.31-3.36). Those who stopped OAC therapy also had higher mortality rates at 7 days (11.2% vs 3.9%, respectively) and 30 days (28.1% vs 10.9%, respectively).
It’s not clear why some patients discontinued OAC therapy. “We looked for evidence of serious bleeding or surgical procedures around the time of anticoagulant discontinuation but found this only to be the case in roughly 10% of these patients,” Dr. Gaist said.
He added that the study probably “underestimates the issue of anticoagulant discontinuation, particularly for DOACs, where a shorter half-life compared with warfarin means that even a short drug-break of a few days puts the patient at increased risk of stroke.”
The authors noted study limitations, including the lack of data on actual medication usage, alcohol usage, stroke etiology, lesion location, and socioeconomic status. And, they wrote, the study population is mostly of European origin.
No Surprises
Steven R. Messe, MD, professor of neurology at the Hospital of the University of Pennsylvania, Philadelphia, who didn’t take part in the study but is familiar with its findings, said in an interview that the study is a “well-done analysis.”
The findings are not surprising, he said. “The overall risk of stroke recurrence was 4.3% at 1 year while the mortality rate was higher at 15.4%. Given that the median CHA2DS2-VASc score was 4 and the average age was 79, the stroke recurrence rate and mortality rate are in line with prior studies.”
In regard to the power of OAC therapy to prevent recurrent strokes, Dr. Messe noted that patients may not be adhering to prescribed regimens. Also, “while DOACs are clearly safer that vitamin K–dependent anticoagulants, the medications are generally not dose adjusted. It is possible that adjusting the dose based on measured anti-Xa levels to insure therapeutic anticoagulant effects may reduce the stroke risk further.”
He added that “most of these patients with prior stroke and atrial fibrillation are vasculopathic and at risk of additional strokes due to other mechanisms such as small vessel or large vessel disease.”
In the big picture, the study “confirms again that anticoagulation should be prescribed to all patients with atrial fibrillation and prior stroke, unless there is a strong bleeding risk contraindication,” Dr. Messe said. These patients are clearly at high risk of stroke recurrence and mortality, and all risk factors should be aggressively managed.”
Researchers are exploring other options, he said. “For example, there are studies of factor XI inhibitors that could be added to a DOAC for additional reductions in ischemic stroke. In addition, in patients undergoing cardiac surgery, the randomized trial LAOS III demonstrated that surgical left atrial occlusion in addition to anticoagulation may provide additional stroke prevention.”
Dr. Gaist disclosed personal fees from Pfizer and Bristol Myers Squibb, and grants from Bayer. Several other authors reported various relationships with industry. Dr. Messe has no disclosures.
FROM JAMA NEUROLOGY