Risk Factors for Intracerebral Hemorrhage in Patients with Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA2DS2-VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA2DS2-VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA2DS2-VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468-0.525) and 0.530 (95% CI, 0.500-0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA2DS2-VASc scores. © 2021 Lippincott Williams and Wilkins. All rights reserved

Risk Factors for Intracerebral Hemorrhage in Patients with Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA2DS2-VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA2DS2-VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA2DS2-VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468-0.525) and 0.530 (95% CI, 0.500-0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA2DS2-VASc scores. © 2021 Lippincott Williams and Wilkins. All rights reserved

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study

BACKGROUND: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. METHODS: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. RESULTS: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). CONCLUSIONS: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding. © 2022 American Heart Association, Inc

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study.

In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA <sub>2</sub> DS <sub>2</sub> -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7]). Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade