Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study.

OBJECTIVES: Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs). METHODS: Out of all of the 5 339 804 Finnish citizens, individuals born 1964-1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes. RESULTS: Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1-1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis. CONCLUSION: Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes.

Prolonged viral pneumonia and high mortality in COVID-19 patients on anti-CD20 monoclonal antibody therapy.

PURPOSE: In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients. METHODS: All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included. Data was retrospectively obtained from electronic patient records. RESULTS: Ninety-eight patients were identified. 44/93 patients (47.3%) were hospitalized due to COVID-19. Patients with demyelinating disorder (n = 20) were youngest (median age 36.5 years, interquartile range 33-45 years), had less comorbidities, and were least likely to be hospitalized (2/20; 10.0%) or die (n = 0). COVID-19 mortality was 13.3% in the whole group, with age and male sex as independent risk factors. Persistent symptoms were documented in 33/94 patients (35.1%) alive by day 30, in 21/89 patients (23.6%) after 60 days, and in 15/85 after 90 days (17.6%), mostly in patients with haematological malignancy or connective tissue disease. Prolonged symptoms after 60 days predisposed to persistent radiological findings (odds ratio 64.0; 95% confidence interval 6.3-711; p < 0.0001) and persistently positive PCR (odds ratio 45.5, 95% confidence interval 4.0-535; p < 0.0001). Several patients displayed rapid response to late antiviral therapy. CONCLUSION: Anti-CD20 monoclonal antibody therapy is associated with high COVID-19 mortality and with a phenotype consistent with prolonged viral pneumonia. Our study provides rationale for retesting of immunocompromised patients with prolonged COVID-19 symptoms and considering antiviral therapy.

Long-term cardiovascular prognosis of patients with type 1 diabetes after myocardial infarction.

BACKGROUND: To explore long-term cardiovascular prognosis after myocardial infarction (MI) among patients with type 1 diabetes. METHODS: Patients with type 1 diabetes surviving 90 days after MI (n = 1508; 60% male, mean age = 62.1 years) or without any type of diabetes (n = 62,785) in Finland during 2005-2018 were retrospectively studied using multiple national registries. The primary outcome of interest was a combined major adverse cardiovascular event (MACE; cardiovascular death, recurrent MI, ischemic stroke, or heart failure hospitalization) studied with a competing risk Fine-Gray analyses. Median follow-up was 3.9 years (maximum 12 years). Differences between groups were balanced by multivariable adjustments and propensity score matching (n = 1401 patient pairs). RESULTS: Cumulative incidence of MACE after MI was higher in patients with type 1 diabetes (67.6%) compared to propensity score-matched patients without diabetes (46.0%) (sub-distribution hazard ratio [sHR]: 1.94; 95% confidence interval [CI]: 1.74-2.17; p < 0.0001). Probabilities of cardiovascular death (sHR 1.81; p < 0.0001), recurrent MI (sHR 1.91; p < 0.0001), ischemic stroke (sHR 1.50; p = 0.0003), and heart failure hospitalization (sHR 1.98; p < 0.0001) were higher in patients with type 1 diabetes. Incidence of MACE was higher in diabetes patients than in controls in subgroups of men and women, patients aged < 60 and ≥ 60 years, revascularized and non-revascularized patients, and patients with and without atrial fibrillation, heart failure, or malignancy. CONCLUSIONS: Patients with type 1 diabetes have notably poorer long-term cardiovascular prognosis after an MI compared to patients without diabetes. These results underline the importance of effective secondary prevention after MI in patients with type 1 diabetes.

Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers.

OBJECTIVES: To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant. METHODS: FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant. RESULTS: Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men. CONCLUSION: Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD.

Patients with rheumatoid arthritis have impaired long-term outcomes after myocardial infarction: a nationwide case-control registry study.

OBJECTIVE: To investigate the long-term outcomes of patients with RA after myocardial infarction (MI). METHODS: All-comer, real-life MI patients with RA (n = 1614, mean age 74 years) were retrospectively compared with propensity score (1:5) matched MI patients without RA (n = 8070) in a multicentre, nationwide, cohort register study in Finland. The impact of RA duration and the usage of corticosteroids and antirheumatic drugs on RA patients' outcomes were also studied. The median follow-up was 7.3 years. RESULTS: RA was associated with an increased 14-year mortality risk after MI compared with patients without RA [80.4% vs 72.3%; hazard ratio (HR) 1.25; CI: 1.16, 1.35; P <0.0001]. Patients with RA were at higher risk of new MI (HR 1.22; CI: 1.09, 1.36; P =0.0001) and revascularization (HR 1.28; CI: 1.10, 1.49; P =0.002) after discharge from index MI. Cumulative stroke rate after MI did not differ between RA and non-RA patients (P =0.322). RA duration and corticosteroid usage before MI, but not use of methotrexate or biologic antirheumatic drugs, were independently associated with higher mortality (P <0.001) and new MI (P =0.009). A higher dosage of corticosteroids prior to MI was independently associated with higher long-term mortality (P =0.002) and methotrexate usage with lower stroke rate (P =0.034). Serological status of RA was not associated with outcomes. CONCLUSION: RA is independently associated with poorer prognosis after MI. RA duration and corticosteroid usage and dosage were independent predictors of mortality after MI in RA. Special attention is needed for improvement of outcomes after MI in this vulnerable population.

Risk of cardiovascular comorbidities before and after the onset of rheumatic diseases.

OBJECTIVES: To elucidate the risk and temporal relationship of cardiovascular (CV) comorbidities in rheumatic diseases. METHODS: Patients in the FinnGen study diagnosed between 2000 and 2014 with seropositive (n = 2368) or seronegative (n = 916) rheumatoid arthritis (RA), ankylosing spondylitis (AS, n = 715), psoriatic arthritis (PsA, n = 923), systemic lupus erythematosus (SLE, n = 190), primary Sjogren's syndrome (pSS, n = 412) or gout (n = 2034) were identified from healthcare registries. Each patient was matched based on age, sex, and birth region with twenty controls without any rheumatic conditions. Overall risk ratios (RR) were calculated by comparing the prevalence of seven CV diseases between patients and controls. Logistic regression models were used for estimating odds ratios (OR) for CV comorbidities before and after the onset of rheumatic diseases. RESULTS: The RR for 'any CVD' varied from 1.14 (95 % confidence interval [CI] 1.02-1.26) in PsA to 2.05 (95 % CI 1.67-2.52) in SLE. Patients with SLE or gout demonstrated over two-fold risks for several CV comorbidities. Among CV comorbidities, venous thromboembolism (VTE) showed the highest effect sizes in several rheumatic diseases. The ORs for CV comorbidities were highest within one year before and/or after the onset of the rheumatic disease. However, in gout the excess risk of CV disease was especially high before gout diagnosis. CONCLUSIONS: The risk of CV comorbidities was elevated in all studied rheumatic diseases, with highest risks observed in SLE and gout. The risk for CV diseases was highest immediately before and/or after rheumatic disease diagnosis, highlighting the increased risk for CV comorbidities across all rheumatic diseases very early on the disease course.

Less revascularization in young women but impaired long-term outcomes in young men after myocardial infarction.

AIMS: Female sex has previously been associated with poorer outcomes after myocardial infarction (MI), although evidence is scarce among young patients. We studied sex differences in cardiovascular outcomes after MI in young patients <55 years old. METHODS AND RESULTS: Consecutive young (18-54 years) all-comer patients with out-of-hospital MI admitted to 20 Finnish hospitals (n = 8934, 17.3% women) in 2004-2014 were studied by synergizing national registries. Differences between the sexes were balanced by inverse probability weighting. The median follow-up period was 9.1 years (max 14.8 years). Young women with MI had more comorbidities at baseline, were revascularized less frequently, and received fewer evidence-based secondary prevention medications (P2Y12 inhibitors, renin-angiotensin signalling pathway inhibitors, statins, and lower statin dosages) after MI than young men. Long-term mortality or the occurrence of major adverse cardiovascular events (MACE; recurrent MI, stroke, or cardiovascular death) did not differ between the sexes in the unadjusted analysis. However, after baseline feature and treatment-difference adjustment, men had poorer outcomes after MI. Adjusted long-term mortality was 21.3% in men vs. 17.2% in women [hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.10-1.53; P = 0.002]. Cumulative MACE rate was 33.9% in men vs. 27.9% in women during follow-up (HR 1.23; 95% CI 1.09-1.39; P = 0.001). Recurrent MI and cardiovascular death occurrences were more frequent among men. Stroke occurrence did not differ between the sexes. CONCLUSIONS: Young women were found to receive less active treatment after MI than young men. Nevertheless, male sex was associated with poorer long-term cardiovascular outcomes after MI in young patients after baseline feature adjustment.

Case Fatality of Patients With Type 1 Diabetes After Myocardial Infarction.

OBJECTIVE: Type 1 diabetes is a risk factor for myocardial infarction (MI). We aimed to evaluate the case fatality in patients with type 1 diabetes after MI. RESEARCH DESIGN AND METHODS: Consecutive patients experiencing MI with type 1 diabetes (n = 1,935; 41% female; mean age 62.5 years) and without diabetes (n = 74,671) admitted to 20 hospitals in Finland from 2005 to 2018 were studied using national registries. The outcome of interest was death within 1 year after MI. Differences between groups were balanced by multivariable adjustments and propensity score matching. RESULTS: Case fatality was higher in patients with type 1 diabetes than in propensity score-matched controls without diabetes at 30 days (12.8% vs. 8.5%) and at 1 year (24.3% vs. 16.8%) after MI (hazard ratio 1.55; 95% CI 1.32-1.81; P < 0.0001). Patients with type 1 diabetes had poorer prognosis in subgroups of men and women and of those with and without ST-elevation MI, with and without revascularization, with and without atrial fibrillation, and with and without heart failure. The relative fatality risk in type 1 diabetes was highest in younger patients. Older age, heart failure, peripheral vascular disease, renal failure, and no revascularization were associated with worse prognosis after MI. The case fatality among patients with type 1 diabetes decreased during the study period, but outcome differences compared with patients without diabetes remained similar. CONCLUSIONS: Patients with type 1 diabetes are at higher risk of death after MI than patients without diabetes. Our findings call for attention to vigorous cardiovascular disease prevention in patients with type 1 diabetes.

Sex Differences in Cardiovascular Outcomes of Older Adults After Myocardial Infarction.

Background Evidence on the impact of sex on prognoses after myocardial infarction (MI) among older adults is limited. We evaluated sex differences in long-term cardiovascular outcomes after MI in older adults. Methods and Results All patients with MI ≥70 years admitted to 20 Finnish hospitals during a 10-year period and discharged alive were studied retrospectively using a combination of national registries (n=31 578, 51% men, mean age 79). The primary outcome was combined major adverse cardiovascular event within 10-year follow-up. Sex differences in baseline features were equalized using inverse probability weighting adjustment. Women were older, with different comorbidity profiles and rarer ST-segment-elevation MI and revascularization, compared with men. Adenosine diphosphate inhibitors, anticoagulation, statins, and high-dose statins were more frequently used by men, and renin-angiotensin-aldosterone inhibitors and beta blockers by women. After balancing these differences by inverse probability weighting, the cumulative 10-year incidence of major adverse cardiovascular events was 67.7% in men, 62.0% in women (hazard ratio [HR], 1.17; CI, 1.13-1.21; P<0.0001). New MI (37.0% in men, 33.1% in women; HR, 1.16; P<0.0001), ischemic stroke (21.1% versus 19.5%; HR, 1.10; P=0.004), and cardiovascular death (56.0% versus 51.1%; HR, 1.18; P<0.0001) were more frequent in men during long-term follow-up after MI. Sex differences in major adverse cardiovascular events were similar in subgroups of revascularized and non-revascularized patients, and in patients 70 to 79 and ≥80 years. Conclusions Older men had higher long-term risk of major adverse cardiovascular events after MI, compared with older women with similar baseline features and evidence-based medications. Our results highlight the importance of accounting for confounding factors when studying sex differences in cardiovascular outcomes.

Long-term outcomes after coronary artery bypass surgery in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the long-term outcomes of coronary artery bypass grafting surgery (CABG) in patients with rheumatoid arthritis (RA). METHODS: Patients with RA (n = 378) were retrospectively compared to patients without RA (n = 7560), all treated with CABG in a multicentre, population-based cohort register study in Finland. The outcomes were studied with propensity score-matching adjustment for baseline features. The median follow-up was 9.7 years. RESULTS: Diagnosis of RA was associated with an increased risk of mortality after CABG compared to patients without RA (HR 1.50; CI 1.28-1.77; p < .0001). In addition, patients with RA were in higher risk of myocardial infarction during the follow-up period (HR 1.61; CI 1.28-2.04; p < .0001). Cumulative rate of repeated revascularization after CABG was 14.4% in RA patients and 12.0% in control patients (p = .060). Duration of RA before CABG (p = .011) and preoperative corticosteroid usage in RA (p = .041) were independently associated with higher mortality after CABG. There were no differences between the study groups in 30-d mortality or in the post-operative usage of cardiovascular medications. CONCLUSIONS: RA is independently associated with worse prognosis in coronary artery disease treated with CABG. Preoperative corticosteroid use and longer RA disease duration are additional risk factors for mortality.Key messagesPatients with rheumatoid arthritis (RA) have impaired long-term outcomes after coronary artery bypass surgery (CABG).Glucocorticoid use before CABG and duration of RA are associated with higher mortality.Special attention should be paid in secondary prevention of cardiovascular disease in RA patients after CABG.

Long-Term Outcomes of Surgical Aortic Valve Replacement in Patients with Rheumatoid Arthritis.

Background: Patients with rheumatoid arthritis (RA) have increased risk of developing cardiovascular disease and events. Little is, however, known about the influence of RA to the outcomes after surgical aortic valve replacement (SAVR). Methods: In a retrospective, nationwide, multicenter cohort study, RA patients (n = 109) were compared to patients without RA (n = 1090) treated with isolated SAVR for aortic valve stenosis. Propensity score-matching adjustment for baseline features was used to study the outcome differences in a median follow-up of 5.6 years. Results: Patients with RA had higher all-cause mortality (HR 1.76; CI 1.21-2.57; p = 0.003), higher incidence of major adverse cardiovascular events (HR 1.63; CI 1.06-2.49; p = 0.025), and they needed more often coronary artery revascularization for coronary artery disease (HR 3.96; CI 1.21-12.90; p = 0.027) in long-term follow-up after SAVR. As well, cardiovascular mortality rate was higher in patients with RA (35.7% vs. 23.4%, p = 0.023). There was no difference in 30-day mortality (2.8% vs. 1.8%, p = 0.518) or in the need for aortic valve reoperations (3.7% vs. 4.0%, p = 0.532). Conclusions: Patients with rheumatoid arthritis had impaired long-term results and increased cardiovascular mortality after SAVR for aortic valve stenosis. Special attention is needed to improve outcomes of aortic valve stenosis patients with RA after SAVR.

Inadequate oral anticoagulation with warfarin in women with cerebrovascular event and history of atrial fibrillation: the FibStroke study.

BACKGROUND: Women with atrial fibrillation (AF) may be treated less actively with oral anticoagulation (OAC) than men. PATIENTS AND METHODS: We assessed sex differences in the implementation of stroke risk stratification with CHADS2 and CHA2DS2-VASc scores and reasons not to use OAC in 1747 AF patients suffering their first cerebrovascular event after the AF diagnosis. RESULTS: Women were older and had more often a high stroke risk (CHADS2/CHA2DS2-VASc ≥2) than men (p < .001). On admission, 46.4% of women and 48.2% of men were on OAC with no sex difference (p = .437). However, of patients without OAC, 74.4% of women and 49.5% of men should have been on OAC based on CHADS2/CHA2DS2-VASc ≥2 (p < .001). Conversely, 34.8% of men and 17.5% of women on OAC had a low or moderate risk (CHADS2/CHA2DS2-VASc 0-1, p < .001). A valid reason to omit OAC was reported in 38.6% of patients and less often in women (p < .001). CONCLUSIONS: OAC was underused in high-risk AF patients, particularly women, but prescribed often in men with low or moderate stroke risk. Reasons for omitting OAC treatment were poorly reported, particularly for women. KEY MESSAGE Women were at higher stroke risk, but were less often treated with oral anticoagulation (OAC). Men were more often on OAC at low or moderate stroke risk. Reasons for omitting guideline based OAC were poorly reported, particularly for women.

Assessing an Electronic Health Record research platform for identification of clinical trial participants.

Electronic health records (EHR) are a potential resource for identification of clinical trial participants. We evaluated how accurately a commercially available EHR Research Platform, InSite, is able to identify potential trial participants from the EHR system of a large tertiary care hospital. Patient counts were compared with results obtained in a conventional manual search performed for a reference study that investigated the associations of atrial fibrillation (AF) and cerebrovascular incidents. The Clinical Data Warehouse (CDW) of Turku University Hospital was used to verify the capabilities of the EHR Research Platform. The EHR query resulted in a larger patient count than the manual query (EHR Research Platform 5859 patients, manual selection 2166 patients). This was due to the different search logic and some exclusion criteria that were not addressable in structured digital format. The EHR Research Platform (5859 patients) and the CDW search (5840 patients) employed the same search logic. The temporal relationship between the two diagnoses could be identified when they were available in structured format and the time difference was longer than a single hospital visit. Searching for patients with the EHR Research Platform can help to identify potential trial participants from a hospital's EHR system by limiting the number of records to be manually reviewed. EHR query tools can best be utilized in trials where the selection criteria are expressed in structured digital format.

The Clinical Impact of Using 18F-FDG-PET/CT in the Diagnosis of Suspected Vasculitis: The Effect of Dose and Timing of Glucocorticoid Treatment.

18F-Fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) with computed tomography (CT) is effective for diagnosing large vessel vasculitis, but its usefulness in accurately diagnosing suspected, unselected vasculitis remains unknown. We evaluated the feasibility of 18F-FDG-PET/CT in real-life cohort of patients with suspicion of vasculitis. The effect of the dose and the timing of glucocorticoid (GC) medication on imaging findings were in special interest. 82 patients with suspected vasculitis were evaluated by whole-body 18F-FDG-PET/CT. GC treatment as prednisolone equivalent doses at the scanning moment and before imaging was evaluated. 38/82 patients were diagnosed with vasculitis. Twenty-one out of 38 patients had increased 18F-FDG accumulation in blood vessel walls indicating vasculitis in various sized vessels. Vasculitis patients with a positive vasculitis finding in 18F-FDG-PET/CT had a significantly shorter duration of GC use (median = 4.0 vs 7.0 days, P=0.034), and they used lower GC dose during the PET scan (median dose = 15.0 mg/day vs 40.0 mg/day, p=0.004) compared to 18F-FDG-PET/CT-negative patients. Vasculitis patients with a positive 18F-FDG-PET/CT result had significantly higher C-reactive protein (CRP) than patients with a negative 18F-FDG-PET/CT finding (mean value = 154.5 vs 90.4 mg/L, p=0.018). We found that 18F-FDG-PET/CT positivity was significantly associated with a lower dose and shorter duration of GC medication and higher CRP level in vasculitis patients. 18F-FDG-PET/CT revealed clinically significant information in over half of the patients and was effective in confirming the final diagnosis.

Distribution of ischemic strokes in patients with atrial fibrillation: The FibStroke Study.

BACKGROUND: We aimed to determine the relative frequency of affected cerebrovascular territories in patients with atrial fibrillation (AF) suffering an ischemic stroke. METHODS: Altogether, 1,976 patients who suffered their first-ever ischemic stroke during 2003-2012 and were diagnosed with AF either before or within 30 days after the event were included in this retrospective multicenter cohort study. Strokes were classified radiographically to be located either within the anterior or the posterior cerebrovascular territory, and the effect of the CHA2DS2-VASc score, oral anticoagulant (OAC) use, and timing of AF diagnosis on lesion localization was determined. RESULTS: The median age of the patients was 78.4 (interquartile range: 71.7-84.2) years, 1,137 (57.5%) of them were women, their mean CHA2DS2-VASc score was 3.5 (95% confidence interval: 3.4-3.5), 656 (33.2%) were receiving OAC drugs, and altogether, 1,450 (73%) had a previous AF diagnosis. The localization of ischemic lesions between the anterior and the posterior cerebrovascular territories was not affected by the timing of AF diagnosis (p = 0.46), use of OACs (p = 0.70), or the CHA2DS2-VASc score (p = 0.10). Within the anterior territory, altogether 774 strokes (53.2%) were located in the left hemisphere and 3 (0.2%) were bilateral. The timing of AF diagnosis (p = 0.84), use of OACs (p = 0.90), or the CHA2DS2-VASc score (p = 0.21) did not affect the location of the ischemic lesion between the hemispheres. CONCLUSIONS: The timing of AF diagnosis, use of OAC drugs, or the CHA2DS2-VASc score did not affect the distribution of ischemic strokes. Anterior territory strokes were slightly more often located within the left hemisphere.

Traumatic and spontaneous intracranial hemorrhage in atrial fibrillation patients on warfarin.

BACKGROUND: Intracranial hemorrhage is the most devastating complication in patients with atrial fibrillation (AF) receiving oral anticoagulation (OAC). It can be either spontaneous or caused by head trauma. We sought to address the prevalence, clinical characteristics, and prognosis of traumatic and spontaneous intracranial hemorrhages in AF patients on OAC. METHODS: Multicenter FibStroke registry of 5,629 patients identified 592 intracranial hemorrhages during warfarin treatment between 2003 and 2012. RESULTS: A large proportion (40%) of intracranial hemorrhages were traumatic. Of these, 64% were subdural hemorrhages (SDHs) and 20% intracerebral hemorrhages (ICHs). With respect to the spontaneous hemorrhages, 25% were SDHs and 67% ICHs. Patients with traumatic hemorrhage were older (81 vs 78 years, p = 0.01) and more often had congestive heart failure (30% vs 16%, p < 0.01) and anemia (7% vs 3%, p = 0.03) compared to patients with spontaneous hemorrhage. Admission international normalized ratio (INR) values (2.7 vs 2.7, p = 0.79), as well as CHA2DS2-VASc (median 4 vs 4, p = 0.08) and HAS-BLED (median 2 vs 2, p = 0.05) scores, were similar between the groups. The 30-day mortality after traumatic hemorrhage was significantly lower than after spontaneous hemorrhage (25% vs 36%, p < 0.01). CONCLUSIONS: A significant proportion of intracranial hemorrhages in anticoagulated AF patients were traumatic. Traumatic hemorrhages were predominantly SDHs and less often fatal when compared to spontaneous hemorrhages, which were mainly ICHs. Admission INR values as well as CHA2DS2-VASc and HAS-BLED scores were similar in patients with spontaneous and traumatic intracranial hemorrhage. CLINICALTRIALSGOV IDENTIFIER: NCT02146040.

How do anticoagulated atrial fibrillation patients who suffer ischemic stroke or spontaneous intracerebral hemorrhage differ?

BACKGROUND: Atrial fibrillation (AF) increases risk of ischemic stroke, and oral anticoagulation (OAC) increases risk of intracerebral hemorrhage (ICH). This study aimed to compare OAC-treated AF patients with an ischemic stroke/transient ischemic attack (TIA) or spontaneous ICH as their first lifetime cerebrovascular event, especially focusing on patients with therapeutic international normalized ratio (INR). HYPOTHESIS: We assumed that in AF patients suffering ischemic stroke/TIA or ICH, patient characteristics could be different in patients with therapeutic INR than in patients with warfarin. METHODS: FibStroke is a multicenter, retrospective registry collating details of AF patients with ischemic stroke/TIA or intracranial hemorrhage in 2003-2012. This substudy included AF patients on OAC with first lifetime ischemic stroke/TIA or spontaneous ICH. RESULTS: A total of 1457 patients with 1290 ischemic strokes/TIAs and 167 ICHs were identified. Of these, 553 (42.9%) strokes/TIAs and 96 (57.5%) ICHs occurred in patients with INR within therapeutic range. During OAC with therapeutic INR, congestive heart failure (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.18-4.58) and hypercholesterolemia (OR: 2.52, 95% CI: 1.51-4.19) were more common in patients with ischemic stroke/TIA, whereas a history of bleeding (OR: 0.30, 95% CI: 0.11-0.82) was less common when compared with patients with ICH. In the whole cohort, renal impairment (OR: 1.86, 95% CI: 1.23-2.80) and mechanical valve prosthesis (OR: 4.41, 95% CI: 1.32-14.7) were overrepresented in patients with stroke/TIA, whereas aspirin use (OR: 0.52, 95% CI: 0.30-0.91) and high INR (OR: 0.40, 95% CI: 0.33-0.48) were overrepresented in patients with ICH. CONCLUSIONS: In anticoagulated AF patients with therapeutic INR and first lifetime cerebrovascular event, congestive heart failure and hypercholesterolemia were associated with ischemic stroke/TIA and history of bleeding with ICH.

Usefulness of the CHA2DS2-VASc and HAS-BLED Scores in Predicting the Risk of Stroke Versus Intracranial Bleeding in Patients With Atrial Fibrillation (from the FibStroke Study).

CHA2DS2-VASc and HAS-BLED scores stratify the risk of thromboembolic and bleeding events respectively in patients with atrial fibrillation. There is only little information on how they differentiate which of the 2 clinically most important complications (ischemic stroke [IS] or an intracranial bleeding [IB]) the patient is more prone to suffer. We evaluated both scores in patients with either of these major complications. The FibStroke Study collected data on all patients with atrial fibrillation with either an IS or an IB event between 2003 and 2012 in 4 Finnish hospital districts. Individual electronic patient records were manually reviewed to collect the study data. To assess the relative risk of IS and IB, an IS/IB-ratio was calculated by dividing the absolute number of ISs with the absolute number of IBs within each score category. A total of 3,816 (82.7%) ISs and 798 (17.3%) IBs were detected in 3,909 patients. In general, ISs occurred more often than IBs in patients on oral anticoagulation in each score category (ratio 1.6 to 5.1). The ratio decreased below 1, however, only with very high HAS-BLED scores (>4). Moreover, 221 ISs and 53 IBs occurred in patients with HAS-BLED > CHA2DS2-VASc, of whom only 19.7% were on anticoagulation. In conclusion, IS was the predominant intracranial event irrespective of CHA2DS2-VASc score, HAS-BLED score ≤4, or use of oral anticoagulation, also in patients with low estimated thromboembolic risk (CHA2DS2-VASc 0 to 1). Furthermore, the HAS-BLED score predicted the excess of IBs over ISs only at very high-risk levels.

Mortality after stroke in patients with paroxysmal and chronic atrial fibrillation - The FibStroke study.

BACKGROUND: Recent studies have reported that patients with paroxysmal atrial fibrillation (AF) have lower risk of thromboembolism and better prognosis than patients with chronic AF. We sought to address the differences in ischaemic events in patients with paroxysmal AF and chronic AF. METHODS: The FibStroke study is a cross-sectional observational multicenter registry that included AF patients with an ischaemic stroke, TIA (transient ischaemic attack) or intracranial bleed during 2003-2012 identified from discharge registries of four Finnish hospitals. Altogether 1448 patients with paroxysmal and 1808 patients with chronic atrial fibrillation suffered a total of 707 TIA-episodes and 2549 ischaemic strokes. RESULTS: Mortality within 30days after the index event was significantly lower in patients with paroxysmal AF than with chronic AF (7.6% vs 16.9%, p<0.01). At the onset of event, 62.8% of the patients with paroxysmal AF were in sinus rhythm, and these patients had better prognosis after the event compared to patients with other rhythm than sinus rhythm (mortality 5.2% vs 15.7%, p<0.01). In the propensity score matched analysis mortality after stroke was significantly lower in patients with paroxysmal AF than in patients with chronic AF (11.6% vs 17.8%, p<0.01), while mortality after TIA was also lower, but did not reach statistical significance (0.4% vs 1.7%, p=0.31). CONCLUSIONS: A significant proportion of strokes in AF patients occur in patients with paroxysmal AF, but they have better prognosis than patients with chronic AF. The prognosis is also significantly better in patients who are in sinus rhythm at the onset of event.

Strokes after cardioversion of atrial fibrillation--The FibStroke study.

BACKGROUND: Cardioversion of atrial fibrillation (AF) is associated with an increased risk for stroke. We identified all cardioversions during the 30 days preceding stroke or transient ischemic attack (TIA) in patients with a previously diagnosed AF, and sought to assess the characteristics of cardioversions leading to stroke or TIA. METHODS: FibStroke is a cross-sectional observational multicenter registry that included AF patients with an ischemic stroke or intracranial bleed identified from a discharge registry of four Finnish hospitals. In total 3677 consecutive AF patients suffered 3252 strokes and 956 TIA episodes during 2003­2012. This pre-specified analysis focused on the 1644 events that occurred to patients with paroxysmal or persistent AF at the time of stroke/TIA. RESULTS: A total of 78 strokes and 22 TIA episodes were preceded by a cardioversion. Post-cardioversion strokes accounted for 6.4% of strokes in patients with paroxysmal/persistent AF. Of the 100 cardioversions leading to an ischemic event, 77 were acute and 23 were elective, 63 events occurred in patients not using anticoagulation, and 5 patients had periprocedural INR < 2. Importantly, 21 patients were in low risk of stroke, i.e. CHA2DS2-VASc score < 2. The median delay from cardioversion to event was 2 days. All nine patients who after an unsuccessful cardioversion developed a stroke had a spontaneous cardioversion prior to stroke. CONCLUSIONS: Every sixteenth stroke of patients with paroxysmal/persistent AF is preceded by a cardioversion. Most post-cardioversion strokes occur in patients not using oral anticoagulation before cardioversion of acute AF.