Background
Natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or ...efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients.
Materials and methods
The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as “lack of efficacy”, “progressive multifocal leukoencephalopathy (PML) risk” or “other”.
Results
Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1 years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy 1682 (32.7% of 5151) vs 221 (4.3%),
p
< 0.001; other reasons were identified for 99 (1.9%) patients. Patients discontinuing treatment were older, had longer disease duration and worse EDSS at the time of NTZ initiation and at last follow-up on NTZ treatment. The JCV index and EDSS at baseline were predictors for stopping therapy (HR 2.94, 95% CI 1.22–4.75;
p
= 0.02; HR 1.36, 95% CI 1.18–5.41;
p
= 0.04).
Conclusions
Roughly 60% of MS patients stayed on NTZ treatment during the observation period. For those patients in whom NTZ discontinuation was required, it was mainly due to PML concerns.
To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis.
Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. ...Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale NIHSS ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale mRS ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death.
Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio OR 1.68, 95% confidence interval CI 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007).
Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.
Guillain-Barré-Syndrome (GBS) can follow COVID-19 vaccination, with clinical and paraclinical features still to be precisely assessed. We describe a cohort of patients who developed GBS after ...vaccination with different types of COVID-19 vaccines.
Patients with post-COVID-19 vaccination GBS, admitted to the six hospitals that cover the whole Liguria Region, Northwestern Italy, from February 1st to October 30th 2021, were included. Clinical, demographic, and paraclinical data were retrospectively collected.
Among the 13 patients with post-COVID-19 vaccination GBS (9 males; mean age, 64 year), 5 were vaccinated with Oxford-AstraZeneca, 7 with Pfizer-BioNTech, and one with Moderna. Mean time between vaccination and GBS onset was 11.5 days. Ten patients developed GBS after the first vaccination dose, 3 after the second dose. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) was the predominant GBS variant, mainly characterized by sensory involvement. Bilateral seventh cranial nerve involvement followed AstraZeneca vaccination in two cases. Three patients presented treatment-related fluctuations, and 4 mild symptoms that delayed treatments and negatively affected prognosis. Prognosis was poor (GBS-disability score, ≥3) in 5/13 patients, with a disability rate of 3/13.
Our findings confirm that most post-COVID-19 vaccination GBS belong to the AIDP subtype, and occur after the first vaccine dose. Treatment-related fluctuations, and diagnosis-delaying, mild symptoms at onset are clinical features that affect prognosis and deserve particular consideration.
•Most of cases of post-COVID-19 vaccination GBS belong to the AIDP subtype.•AstraZeneca-associated bilateral VII cranial nerve involvement is a common manifestation of post-COVID-19 vaccination GBS.•Treatment-related fluctuations in post-COVID-19 vaccination GBS affect prognosis and deserve prompt recognition.
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
DS
-VASc score after the index event (odds ratio OR, 1.2 95% CI, 1.0-1.3 for each point increase;
=0.05) and hypertension (OR, 2.3 95% CI, 1.0-5.1;
=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;
=0.002), history of major bleeding (OR, 6.9 95% CI, 3.4-14.2;
=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 95% CI, 1.4-5.5;
=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.
The "1-3-6-12-day rule" for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings ...that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity.
The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0-7), moderate (8-15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation.
In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)-initiating DOACS within 1, 2, 3, and 4 days, respectively-than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 95% CI, 0.27-0.89), as was ischemic stroke (1.7% versus 3.2%, 0.54 0.27-0.999). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data.
In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.
BACKGROUND AND PURPOSE—Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control ...study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non–vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention.
METHODS—Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment.
RESULTS—Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio OR, 3.18; 95% CI, 1.95–5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63–9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83–3.16), and CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA2DS2-VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33–0.61).
CONCLUSIONS—In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA2DS2-VASc score were associated with increased risk of cerebrovascular events.
Background
The optimal timing to administer non–vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational ...multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention.
Methods and Results
Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2‐VASc score >4 and less reduced renal function. Thirty‐two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke.
Conclusions
In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.
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