Mortality in patients with intracerebral hemorrhage associated with antiplatelet agents, oral anticoagulants or no antithrombotic therapy.
Franco Laura,Paciaroni Maurizio,Enrico Maria Lotti,Scoditti Umberto,Guideri Francesca,Chiti Alberto,De Vito Alessandro,Terruso Valeria,Consoli Domenico,Vanni Simone,Giossi Alessia,Manina Giorgia,Nitti Cinzia,Re Roberta,Sacco Simona,Cappelli Roberto,Beyer-Westendorf Jan,Pomero Fulvio,Agnelli Giancarlo,Becattini Cecilia
European journal of internal medicine
The association between preceding treatment with antiplatelet agents (APs), vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) and mortality after intracerebral hemorrhage (ICH) remains unclear. The aim of this multicenter, prospective cohort study was to assess the risk for death after ICH in consecutive patients who were on treatment with APs, VKAs, DOACs, or no antithrombotic agent. The primary outcome was in-hospital death by day 30. ICH volume at admission and volume expansion were centrally assessed. Out of 598 study patients, in-hospital death occurred in 21% of patients who were on treatment with APs, 25% with VKAs, 30% with DOACs, and 13% with no antithrombotics. Crude death rate was higher in patients on antithrombotics as compared to patients receiving no antithrombotic agent. At multivariate analysis, age (HR 1.07; 95% CI 1.04-1.10), previous stroke (HR 1.83; 95% CI 1.14-2.93), GCS ≤8 at admission (HR 6.06; 95% CI 3.16-9.74) and GCS 9-12 (HR 3.38; 95% CI 1.81-6.33) were independent predictors of death. Treatment with APs (HR 1.29; 95% CI 0.61-2.76), VKAs (HR 1.42; 95% CI 0.70-2.88) or DOACs (HR 1.28; 95% CI 0.61-2.73) were not predictors of death in the overall study population, in non-trauma associated ICH as well as when GCS was not included in the model. ICH volume and volume expansion were independent predictors of death. In conclusion, preceding treatment with antithrombotic is associated with the severity of ICH. Age, previous stroke and clinical severity at presentation were independent predictors of in-hospital death in patients with ICH.
10.1016/j.ejim.2019.12.016
Antiplatelet therapy does not increase mortality of surgical treatment for spontaneous intracerebral haemorrhage.
Song Xiaowen,Zhang Qian,Cao Yong,Wang Shuo,Zhao Jizong
Clinical neurology and neurosurgery
OBJECTIVES:This study aimed to find the effect of antiplatelet therapy on hematoma volume, rehaemorrhage rate and prognosis of intracerebral hemorrhage patients after surgery. PATIENTS AND METHODS:101 surgically treated intracerebral hemorrhage subjects were included and analyzed retrospectively. Prior antiplatelet therapy was ascertained from the clinical history, and the patients included were divided into two groups: antiplatelet therapy and no antiplatelet therapy group. The in-hospital and follow-up outcomes were assessed with the Modified Rankin Scale and were compared between the 2 groups after 1:2 propensity score matching. RESULTS:Before the diagnosis of intracerebral hemorrhage, 21.8 % patients were not on antiplatelet therapy. Antiplatelet therapy group had larger hematoma volume (99.32 mL versus 73.75 mL) with no significant difference (P = 0.308). After propensity score matching, 42 patients were obtained. 4(9.5 %) had rehaemorrhage after surgery, and antiplatelet therapy was not related to higher rehaemorrhage rate (P = 0.628). After follow-up, the overall mortality was 29.3 %, and 22 patients (53.7 %) ended up with severe morbidity. In the multivariate regression, plasma fibrinogen was an independent predictor of both in-hospital and follow-up overall mortality (P = 0.044; P = 0.016), and prior antiplatelet therapy was found to predict better follow-up functional outcome independently (P = 0.032). CONCLUSION:Among surgically treated intracerebral hemorrhage patients, prior antiplatelet therapy did not increase hematoma volume, rehaemorrhage rate and mortality, and was related to lower follow-up severe morbidity independently.
10.1016/j.clineuro.2020.105873
Antiplatelet Therapy in Primary Spontaneous and Oral Anticoagulation-Associated Intracerebral Hemorrhage.
Sprügel Maximilian I,Kuramatsu Joji B,Gerner Stefan T,Sembill Jochen A,Beuscher Vanessa D,Hagen Manuel,Roeder Sebastian S,Lücking Hannes,Struffert Tobias,Dörfler Arnd,Schwab Stefan,Huttner Hagen B
Stroke
Background and Purpose- This study determined the influence of concomitant antiplatelet therapy (APT) on hematoma characteristics and outcome in primary spontaneous intracerebral hemorrhage (ICH), vitamin K antagonist (VKA)- and non-VKA oral anticoagulant-associated ICH. Methods- Data of retrospective cohort studies and a prospective single-center study were pooled. Functional outcome, mortality, and radiological characteristics were defined as primary and secondary outcomes. Propensity score matching and logistic regression analyses were performed to determine the association between single or dual APT and hematoma volume. Results- A total of 3580 patients with ICH were screened, of whom 3545 with information on APT were analyzed. Three hundred forty-six (32.4%) patients in primary spontaneous ICH, 260 (11.4%) in VKA-ICH, and 30 (16.0%) in non-VKA oral anticoagulant-associated ICH were on APT, and these patients had more severe comorbidities. After propensity score matching VKA-ICH patients on APT presented with less favorable functional outcome (modified Rankin Scale score, 0-3; APT, 48/202 [23.8%] versus no APT, 187/587 [31.9%]; P=0.030) and higher mortality (APT, 103/202 [51.0%] versus no APT, 237/587 [40.4%]; P=0.009), whereas no significant differences were present in primary spontaneous ICH and non-VKA oral anticoagulant-associated ICH. In VKA-ICH, hematoma volume was significantly larger in patients with APT (21.9 [7.4-61.4] versus 15.7 [5.7-44.5] mL; P=0.005). Multivariable regression analysis revealed an association of APT and larger ICH volumes (odds ratio, 1.80 [1.20-2.70]; P=0.005), which was more pronounced in dual APT and supratherapeutically anticoagulated patients. Conclusions- APT does not affect ICH characteristics and outcome in primary spontaneous ICH patients; however, it is associated with larger ICH volume and worse functional outcome in VKA-ICH, presumably by additive antihemostatic effects. Combination of anticoagulation and APT should, therefore, be diligently evaluated and restricted to the shortest possible time frame.
10.1161/STROKEAHA.118.021614
Restarting antiplatelet therapy after spontaneous intracerebral hemorrhage: Functional outcomes.
Chen Ching-Jen,Ding Dale,Buell Thomas J,Testai Fernando D,Koch Sebastian,Woo Daniel,Worrall Bradford B,
Neurology
OBJECTIVE:To compare the functional outcomes and health-related quality of life metrics of restarting vs not restarting antiplatelet therapy (APT) in patients presenting with intracerebral hemorrhage (ICH) in the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study. METHODS:Adult patients aged 18 years and older who were on APT before ICH and were alive at hospital discharge were included. Patients were dichotomized based on whether or not APT was restarted after hospital discharge. The primary outcome was a modified Rankin Scale score of 0-2 at 90 days. Secondary outcomes were excellent outcome (modified Rankin Scale score 0-1), mortality, Barthel Index, and health status (EuroQol-5 dimensions [EQ-5D] and EQ-5D visual analog scale scores) at 90 days. RESULTS:The APT and no APT cohorts comprised 127 and 732 patients, respectively. Restarting APT was associated with lower rates of good functional outcome (36.5% vs 40.8%; = 0.021) and lower Barthel Index scores at 90 days ( = 0.041). The 2 cohorts were then matched in a 1:1 ratio, and the matched cohorts each comprised 107 patients. No difference in primary outcome was observed between restarting vs not restarting APT (35.5% vs 43.9%; = 0.105). There were also no differences between the secondary outcomes of the 2 cohorts. CONCLUSION:Restarting APT in patients with ICH of mild to moderate severity after acute hospitalization is not associated with worse functional outcomes or health-related quality of life at 90 days. In patients with significant cardiovascular risk factors who experience an ICH, restarting APT remains the decision of the treating practitioner.
10.1212/WNL.0000000000005742
Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.
Thompson B B,Béjot Y,Caso V,Castillo J,Christensen H,Flaherty M L,Foerch C,Ghandehari K,Giroud M,Greenberg S M,Hallevi H,Hemphill J C,Heuschmann P,Juvela S,Kimura K,Myint P K,Nagakane Y,Naritomi H,Passero S,Rodríguez-Yáñez M R,Roquer J,Rosand J,Rost N S,Saloheimo P,Salomaa V,Sivenius J,Sorimachi T,Togha M,Toyoda K,Turaj W,Vemmos K N,Wolfe C D A,Woo D,Smith E E
Neurology
OBJECTIVES:Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. METHODS:The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. RESULTS:We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). CONCLUSIONS:In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.
10.1212/WNL.0b013e3181f735e5
Prior antiplatelet therapy, platelet infusion therapy, and outcome after intracerebral hemorrhage.
Creutzfeldt Claire J,Weinstein Jonathan R,Longstreth W T,Becker Kyra J,McPharlin Thomas O,Tirschwell David L
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:Recent studies examining the effect of prior antiplatelet therapy (APT) on outcome in patients with spontaneous intracerebral hemorrhage (ICH) have shown conflicting results. The effect of platelet infusion therapy (PIT) on outcome in patients with ICH taking APT is unknown. METHODS:We reviewed records of patients with ICH admitted to a single hospital, excluding those with international normalized ratio greater than or equal to 1.5. Baseline characteristics were compared by APT status in all patients and by PIT status in the subgroup of patients on APT. We used multivariate analyses to generate propensity and prognostic scores for exposures (APT and PIT) and outcomes (favorable outcome and hospital death), respectively. We examined the associations between exposures and outcomes and adjusted these for propensity and/or prognostic scores. We then validated our findings with a sensitivity analysis. RESULTS:Of 368 patients identified, 121 (31.3%) were taking APT, mostly aspirin. Patients on APT were older and more likely to have vascular comorbidities than those not. The APT group also had a higher initial Glasgow Coma Scale score at presentation. In analyses adjusted for both propensity and prognostic scores, APT was associated with a higher likelihood of hospital death (odds ratio [OR] 2.4; 95% confidence interval [CI] 1.1-5.6); PIT did not prevent hospital death (OR 1.2; 95% CI 0.3-5.5) or increase favorable outcome (OR 1.4; 95% CI 0.4-5.4). CONCLUSIONS:In patients with ICH, APT is associated with an increased risk of hospital death. In the subgroup of patients on APT, PIT did not prevent death or improve outcome.
10.1016/j.jstrokecerebrovasdis.2008.10.007
Does prior antiplatelet therapy influence hematoma volume and hematoma growth following intracerebral hemorrhage? Results from a prospective study and a meta-analysis.
Camps-Renom P,Alejaldre-Monforte A,Delgado-Mederos R,Martínez-Domeño A,Prats-Sánchez L,Pascual-Goñi E,Martí-Fàbregas J
European journal of neurology
BACKGROUND AND PURPOSE:Large baseline hematoma volume (HV) and hematoma growth (HG) are related to poor outcome in patients with intracerebral hemorrhage (ICH). It remains controversial whether prior antiplatelet therapy (APT) influences baseline HV and HG, and the outcome following ICH. METHODS:We collected clinical and radiological data from a prospective cohort of patients diagnosed with ICH within 24 h of symptom onset. Prior APT was ascertained from the clinical history. In patients for whom a follow-up computed tomography (CT) was available within 72 h, we assessed HG, defined as an increase of ≥33% and/or ≥12.5 mL in the HV. We assessed mortality and functional outcome during follow-up with the Rankin scale. To perform a meta-analysis, we searched for published studies reporting HG according to previous APT and pooled the available data. RESULTS:We included 223 patients (mean age 72.5 ± 13 years). Previous APT was reported in 74 patients (33.2%). The linear regression model showed that prior APT was independently associated with larger baseline HV. HG was detected in 49 of 130 patients (37.7%) and no differences related to prior APT were observed among our cohort. However, after pooling the data of seven studies in the meta-analysis, prior APT showed an increase in HG frequency (odds ratio, 1.85; 95% confidence interval, 1.37-2.5). Patients who received APT presented with worse outcome during follow-up, although this difference was not significant (P = 0.06). CONCLUSIONS:In the current study, prior APT was related to larger baseline HV in patients with ICH. Data from the meta-analysis also showed a higher risk of HG associated with APT.
10.1111/ene.13193
Association Between Previous Use of Antiplatelet Therapy and Intracerebral Hemorrhage Outcomes.
Khan Nadeem I,Siddiqui Fazeel M,Goldstein Joshua N,Cox Margueritte,Xian Ying,Matsouaka Roland A,Heidenreich Paul A,Peterson Eric D,Bhatt Deepak L,Fonarow Gregg C,Schwamm Lee H,Smith Eric E
Stroke
BACKGROUND AND PURPOSE:Although the use of antiplatelet therapy (APT) is associated with the risk of intracerebral hemorrhage (ICH), there are limited data on prestroke APT and outcomes, particularly among patients on combination APT (CAPT). We hypothesized that the previous use of antiplatelet agents is associated with increased mortality in ICH. METHODS:We analyzed data of 82 576 patients with ICH who were not on oral anticoagulant therapy from 1574 Get with the Guidelines-Stroke hospitals between October 2012 and March 2016. Patients were categorized as not on APT, on single-APT (SAPT), and CAPT before hospital presentation with ICH. We described baseline characteristics, comorbidities, hospital characteristics and outcomes, overall and stratified by APT use. RESULTS:Before the diagnosis of ICH, 65.8% patients were not on APT, 29.5% patients were on SAPT, and 4.8% patients were on CAPT. There was an overall modest increased in-hospital mortality in the APT group versus no APT group (24% versus 23%; adjusted odds ratio, 1.05; 95% confidence interval, 1.01-1.10). Although patients on SAPT and CAPT were older and had higher risk profiles in terms of comorbidities, there was no significant difference in the in-hospital mortality among patients on SAPT versus those not on any APT (23% versus 23%; adjusted odds ratio, 1.01; 95% confidence interval, 0.97-1.05). However, in-hospital mortality was higher among those on CAPT versus those not on APT (30% versus 23%; adjusted odds ratio, 1.50; 95% confidence interval, 1.39-1.63). CONCLUSIONS:Our study suggests that among patients with ICH, previous use of CAPT, but not SAPT, was associated with higher risk for in-hospital mortality.
10.1161/STROKEAHA.117.016290
Prior antiplatelet therapy is not associated with larger hematoma volume or hematoma growth in intracerebral hemorrhage.
van Ginneken Verena,Engel Patricia,Fiebach Jochen B,Audebert Heinrich J,Nolte Christian H,Rocco Andrea
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Hematoma volume (HV) and hematoma growth (HG) predict mortality and poor outcome in intracerebral hemorrhage (ICH). While the influence of oral anticoagulation on HV, HG and outcome is well established, the effect of prior antiplatelet therapy (APT) remains uncertain. We retrospectively examined data from all patients with acute, primary ICH, and baseline head CT admitted to our department between January 2005 and February 2014. HV were calculated by ABC/2 method. HG was defined as present if HV increased between baseline and follow-up CT ≥ 30% or ≥ 6 mL. We analyzed the influence of APT on HV, HG, and in-hospital mortality using univariate and multivariate analyses. In addition, we used propensity score matching to assess differences in in-hospital mortality rates. From 668 screened patients, 343 had primary ICH and fulfilled all inclusion criteria. APT was present in 99 patients (29%). Baseline median HV was 16 mL (IQR 6-46). HG occurred in 44 of 160 patients with follow-up CT (28%). In-hospital mortality was 10% (n = 36). APT was associated with older age, a mRS score before admission (pre-mRS) of > 2, and presence of cardiovascular comorbidities. We did not find an association between APT and larger baseline HV (p = 0.32), or HG (OR 0.8, 95% CI 0.4-1.9). After propensity score matching for age, pre-mRS, gender, and cardiovascular comorbidities, APT was not associated with higher in-hospital mortality (OR 1.90, 95% CI 0.85-4.24, p = 0.117). This study did not show a higher risk for larger HV, HG, or in-hospital mortality in primary ICH patients with APT.
10.1007/s10072-018-3255-z
Previous antiplatelet use is associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage.
Yildiz Ozlem Kayim,Arsava Ethem Murat,Akpinar Erhan,Topcuoglu Mehmet Akif
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:Patients with intracerebral hemorrhage (ICH) often report the use of antiplatelet medications, even more commonly than the use of anticoagulants. The effect of antiplatelet drugs on the course of ICH is controversial. In this study, our aim was to determine the effects of previous antiplatelet therapy on admission hematoma volume and hematoma expansion in patients with spontaneous ICH. METHODS:A consecutive series of patients with a diagnosis of ICH who underwent brain computed tomographic (CT) scans within 12 hours of symptom onset and a follow-up CT scan within 72 hours were included in the study. Hematoma volume was calculated by using the ABC/2 method on admission and follow-up images. Univariate and multivariate analyses were performed to determine the independent role of antiplatelet use on baseline hematoma volume and hematoma expansion (defined as an increase in hematoma volume >12.5 mL or 33% of the baseline ICH volume). RESULTS:A total of 153 patients were included in the study. Fifty-two (34%) patients were using antiplatelet drugs at the time of symptom onset. Antiplatelet users tend to have a larger baseline hematoma volume; however, this difference failed to reach statistical significance (P = .17). Antiplatelet therapy was found to be a significant determinant of substantial hematoma expansion, both in univariate and multivariate analyses (P < .01). CONCLUSIONS:Previous antiplatelet use significantly contributes to hematoma expansion in patients with ICH.
10.1016/j.jstrokecerebrovasdis.2011.04.003
Prescribing antiplatelet medicine and subsequent events after intracerebral hemorrhage.
Flynn Robert W V,MacDonald Thomas M,Murray Gordon D,MacWalter Ronald S,Doney Alexander S F
Stroke
BACKGROUND AND PURPOSE:Antiplatelet medicines are commonly perceived as contraindicated after intracerebral hemorrhage (ICH). Many ICH patients have or will have indications for antiplatelet therapy. This observational study describes the level of antiplatelet prescribing and rate of subsequent events after ICH in Tayside, Scotland. METHODS:This study used record-linkage of an existing stroke cohort with antiplatelet prescribing data from 1994 to 2005. Patients were followed-up from discharge after index event. The primary outcome was recurrent ICH. Other outcomes were subsequent ischemic stroke and a composite of ischemic stroke or myocardial infarction. Event rates were calculated as the number of events divided by patient-years of exposure. Univariate hazard ratios associated with antiplatelet exposure were derived from a Cox model using a time-dependent covariate. RESULTS:There were 417 ICH patients who survived to discharge. Of these, 120 patients were prescribed subsequent antiplatelet medicines (28.8%). The median time from discharge to antiplatelet use was 14.8 months (range, 2 days-7.5 years). Among all survivors, there were 14 recurrent ICH (rate, 9.7 per 1000 patient-years; 95% confidence interval [CI], 5.3-16.4), 29 subsequent ischemic strokes (rate, 20.6; 95% CI, 13.8-29.6), and 40 subsequent ischemic strokes or myocardial infarctions (rate, 28.7; 95% CI, 20.5-39.0). Hazard ratios associated with antiplatelet exposure were 1.07 (95% CI, 0.24-4.84) for recurrent ICH, 0.23 (95% CI, 0.03-1.68) for ischemic stroke, and 0.72 (95% CI, 0.25-2.02) for ischemic strokes or myocardial infarction. CONCLUSIONS:Antiplatelet prescribing was common after ICH. Subsequent ischemic strokes or myocardial infarctions were more common than recurrent ICH. Antiplatelet prescribing did not appear to have a clinically significant impact on outcomes measured. Despite being contraindicated, antiplatelet use was not a major hazard for recurrent ICH.
10.1161/STROKEAHA.110.589143
Major bleeding risk and mortality associated with antiplatelet drugs in real-world clinical practice. A prospective cohort study.
Bouget Jacques,Balusson Frédéric,Viglino Damien,Roy Pierre-Marie,Lacut Karine,Pavageau Laure,Oger Emmanuel
PloS one
BACKGROUND:Major bleedings other than gastrointestinal (GI) and intracranial (ICH) and mortality rates associated with antiplatelet drugs in real-world clinical practice are unknown. The objective was to estimate major bleeding risk and mortality among new users of antiplatelet drugs in real-world clinical practice. METHODS AND FINDINGS:A population-based prospective cohort using the French national health data system (SNIIRAM), identified 69,911 adults living within five well-defined geographical areas, who were new users of antiplatelet drugs in 2013-2015 and who had not received any antithrombotics in 2012. Among them, 63,600 started a monotherapy and 6,311 a dual regimen. Clinical data for all adults referred for bleeding was collected from all emergency departments within these areas, and medically validated. Databases were linked using common key variables. The main outcome measure was time to major bleeding (GI, ICH and other bleedings). Secondary outcomes were death, and event-free survival (EFS). Hazard ratios (HR) were derived from adjusted Cox proportional hazard models. We used Inverse Propensity of Treatment Weighting as a stratified sensitivity analysis according to the antiplatelet monotherapy indication: primary prevention without cardiovascular (CV) risk factors, with CV risk factors, and secondary prevention. We observed 250 (0.36%) major haemorrhages, 81 ICH, 106 GI and 63 other types of bleeding. Incidences were twice as high in dual therapy as in monotherapy. Compared to low-dose aspirin (≤ 100 mg daily), high-dose (> 100 up to 325 mg daily) was associated with an increased risk of ICH (HR = 1.80, 95%CI 1.10 to 2.95). EFS was improved by high-dose compared to low-dose aspirin (1.41, 1.04 to 1.90 and 1.32, 1.03 to 1.68) and clopidogrel (1.30, 0.73 to 2.3 and 1.7, 1.24 to 2.34) respectively in primary prevention with and without CV risk factors. CONCLUSION:The incidence of major bleeding and mortality was low. In monotherapy, low-dose aspirin was the safest therapeutic option whatever the indication. TRIAL REGISTRATION:NCT02886533.
10.1371/journal.pone.0237022
Does preexisting antiplatelet treatment influence postthrombolysis intracranial hemorrhage in community-treated ischemic stroke patients? An observational study.
Meurer William J,Kwok Heemun,Skolarus Lesli E,Adelman Eric E,Kade Allison M,Kalbfleisch Jack,Frederiksen Shirley M,Scott Phillip A
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
OBJECTIVES:Intracranial hemorrhage (ICH) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between preexisting antiplatelet use and the safety of intravenous (IV) thrombolysis have been limited by low event rates. The objective of this study was to determine whether preexisting antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders. METHODS:Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004 and 24 other hospitals from 2007 to 2010 as part of a cluster-randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a prespecified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow-up imaging (primary outcome). Symptomatic ICH (sICH) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to postthrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta-analytic techniques. RESULTS:There were 830 patients included, with 47% having documented preexisting antiplatelet treatment. The mean (± standard deviation [SD]) age was 69 (± 15) years, and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use and 19.3% with antiplatelet use (absolute risk difference = 4.2%, 95% confidence interval [CI] = -1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference = 3.1%, 95% CI = -1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio [OR] = 1.1, 95% CI = 0.8 to 1.7) or sICH (OR = 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference = 11.9%, 95% CI = 0.1% to 23.6%). The meta-analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference = 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference = 4%, 95% CI = 2.3% to 5.6%). The meta-analytic adjusted OR of sICH for antiplatelet use was 1.6 (95% CI = 1.1 to 2.4). CONCLUSIONS:The authors did not find that preexisting antiplatelet use was associated with postthrombolysis ICH or sICH in this cohort of community treated patients. Preexisting tobacco use, younger age, and lower severity were associated with lower odds of sICH. The meta-analyses demonstrated small, but statistically significant increases in the absolute risk of radiographic ICH and sICH, along with increased odds of sICH in patients with preexisting antiplatelet use.
10.1111/acem.12077
Prior Antiplatelet Therapy, Excluding Phosphodiesterase Inhibitor Is Associated with Poor Outcome in Patients with Spontaneous Intracerebral Haemorrhage.
Liu Zhuo-Hao,Liu Chi-Hung,Tu Po-Hsun,Yip Ping K,Chen Ching-Chang,Wang Yu-Chi,Chen Nan-Yu,Lin Yu-Sheng
Translational stroke research
There is conflicting results on whether prior antiplatelet therapy (APT) is associated with poor outcome in spontaneous intracerebral haemorrhage (ICH) patients. To determine whether prior APT is associated with spontaneous ICH, and whether there is a difference between the different types of APT, including cyclooxygenase inhibitor (COX-I), adenosine diphosphate receptor inhibitor (ADP-I) and phosphodiesterase inhibitor (PDE-I). A retrospective study of patients with ICH diagnosed between 2001 and 2013 in the National Health Insurance Research Database. Baseline unbalance between APT and non-APT groups was solved by multivariable adjustment (primary analysis) and propensity score matching (sensitivity analysis). Patients with prior APT had a higher rate of in-hospital death (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.09-1.23) compared to non-APT group. Compared to non-APT group, there was a greater rate of in-hospital death with spontaneous ICH with ADP-I (OR, 1.49; 95% CI, 1.24-1.79) and COX-I (OR, 1.17; 95% CI, 1.09-1.25). PDE-I exhibited no difference in in-hospital death with spontaneous ICH (OR, 1.03; 95% CI, 0.91-1.16) compared to non-APT group. Remarkably, the in-hospital mortality rate was significantly higher in the ADP-I group than in the PDE-I group (hazard ratio, 1.45; 95% CI, 1.17-1.80). In this study, ADP-I and COX-1, but not PDE-I, are the most likely contributors to the association of APT with poor outcome with spontaneous ICH patients. These findings suggest that the complexity of the different mechanism of actions of prior APT can alter the outcome in spontaneous ICH.
10.1007/s12975-019-00722-x
Preinjury Antiplatelet Use Does Not Increase the Risk of Progression of Small Intracranial Hemorrhage.
Billings Joshua D,Khan Abid D,McVicker John H,Schroeppel Thomas J
The American surgeon
BACKGROUND:The modified brain injury guidelines (mBIG) provide an algorithm for surgeons to manage some mild traumatic brain injury (TBI) with intracranial hemorrhage (ICH) without neurosurgical consultation or repeat imaging. Currently, antiplatelet use among patients with any ICH classifies a patient at the highest level, mBIG 3. This study assesses the risk of clinical progression among patients taking antiplatelet medications with mild TBI with ICH. METHODS:A retrospective analysis of patients with traumatic ICH over a 5-year period was conducted. Demographics, injury severity, and outcome data were collected for each patient. Patients taking antiplatelet agents were reclassified as if they were not taking these medications. Patients who would have met criteria for a lower classification (mBIG 1 or 2) without antiplatelet agents were designated mBIG 3 Antiplatelet and compared with all other mBIG 1 and 2 patients. RESULTS:736 patients met the inclusion criteria. 158 patients were taking antiplatelet medications and 53 were reclassified as mBIG 3 Antiplatelet. When comparing mBIG 3 Antiplatelet to the 226 patients originally classified as mBIG 1 and 2, mBIG 3 Antiplatelet patients were more likely to undergo repeat head computed tomography (98.1% vs 76.6%; < .001) and neurosurgical consultation (94.2% vs 76.5%; < .001) but had no significant differences in outcomes. No mBIG 3 Antiplatelet patients had a worsening examination or needed operative intervention. DISCUSSION:This data suggests that antiplatelet medication use should not automatically classify a patient as mBIG 3. Adoption of this strategy would better utilize resources and avoid unnecessary costs without sacrificing care.
10.1177/0003134820942174
Antiplatelet drug use preceding the onset of intracerebral hemorrhage is associated with increased mortality.
Lacut Karine,Le Gal Gregoire,Seizeur Romuald,Prat Gwenael,Mottier Dominique,Oger Emmanuel
Fundamental & clinical pharmacology
Recent studies highlight the contribution of antiplatelet therapy to clinical severity and increased mortality of intracerebral hemorrhage (ICH) but results are discrepant. The aim of this report was to evaluate the association between antiplatelet drug use preceding the onset of ICH and the mortality, assessed at regular intervals, among patients with acute ICH. We analyzed data from a randomized study which enrolled consecutive patients with a documented acute ICH to evaluate the efficacy of intermittent pneumatic compression of the legs in venous thrombosis prevention. Clinical characteristics and treatment used before the onset of ICH were checked at the time of inclusion. Mortality was assessed at regular intervals until 3 months after ICH diagnosis. Among 138 patients included in this report, 30 were current users of antiplatelet therapy at the time of ICH; they were significantly older and less frequently heavy drinkers than non-users of antiplatelet drugs. Mortality rates were 20% at 8 days, 40% at 1 month, and 47% at 3 months among antiplatelet drug users compared with 6.5%, 13% and 19% among non-users. The corresponding estimated risks for mortality related to antiplatelet drug use were 3.6 (95% CI 1.1-12), 4.5 (95% CI 1.8-11), and 3.6 (95% CI 1.5-8.6). Adjusted for age, hypertension and alcohol over use, antiplatelet therapy remained significantly associated with an increased mortality rate of acute ICH. Current antiplatelet drug use preceding the onset of ICH is associated with increased short-term ICH mortality, independently of age.
10.1111/j.1472-8206.2007.00488.x
Antithrombotic Treatment Following Intracerebral Hemorrhage in Patients With and Without Atrial Fibrillation.
Pennlert Johanna,Asplund Kjell,Carlberg Bo,Wiklund Per-Gunnar,Wisten Aase,Åsberg Signild,Eriksson Marie
Stroke
BACKGROUND AND PURPOSE:Patients who survive intracerebral hemorrhage (ICH) often have compelling indications for anticoagulant and antiplatelet medication. This nationwide observational study aimed to determine the extent and predictors of antithrombotic treatment after ICH in Sweden. METHODS:Patients with a first-ever ICH in the Swedish Stroke Register (Riksstroke) 2005 to 2012 who survived hospital discharge were included. Riksstroke data were individually linked with other national registers to determine comorbid conditions and dispensed prescriptions of antithrombotic agents. RESULTS:Among the 2777 patients with atrial fibrillation (AF), the proportion with a dispensed prescription of antithrombotic agents was 8.5% (anticoagulants) and 36.6% (antiplatelet agents) within 6 months and 11.1% (anticoagulants) and 43.6% (antiplatelet agents) within 1 year. Among the 11 268 patients without AF, the corresponding figures were 1.6% (anticoagulants) and 13.8% (antiplatelet agents) within 6 months and 2.0% (anticoagulants) and 17.5% (antiplatelet agents) within 1 year. In patients with AF, predictors of anticoagulant treatment were less severe ICH, younger age, previous anticoagulation, valvular disease, and previous ischemic stroke. High CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke [doubled], vascular disease, age, and sex category [female]) scores did not correlate with anticoagulant treatment. There was a positive correlation between high CHA2DS2-VASc and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol) scores (rs=0.590, P<0.001). CONCLUSIONS:In majority of patients who receive antithrombotic agents, treatment is initiated within 6 months of ICH. Still, many patients with compelling indications for antithrombotic treatment are not prescribed antithrombotic agents. Factors other than high risk of embolic stroke by CHA2DS2-VASc in ICH survivors with concurrent AF are used to guide the anticoagulant treatment decision in Swedish clinical practice.
10.1161/STROKEAHA.115.009087
Antithrombotic pretreatment increases very-early mortality in primary intracerebral hemorrhage.
Roquer Jaume,Vivanco Hidalgo Rosa María,Ois Angel,Rodríguez Campello Ana,Cuadrado Godia Elisa,Giralt Steinhauer Eva,Gómez González Alejandra,Soriano-Tarraga Carolina,Jiménez Conde Jordi
Neurology
OBJECTIVE:To analyze the effect of previous antiplatelet (AP) and vitamin K antagonist (VKA) treatments on outcome in patients with primary intracerebral hemorrhage (ICH). METHODS:In this prospective observational study, we analyzed 529 patients according to antithrombotic pretreatment: none, AP, or VKA. Very-early (24-hour) death, 3-month mortality, and functional independence were analyzed. RESULTS:Of 236 (44.6%) pretreated patients, 147 (27.8%) patients were taking AP and 89 (16.8%) VKA. Very-early death was observed in 13.4% and was increased in pretreated patients: 19.0% for AP and 27.0% for VKA treatment, compared to 6.5% in non-pretreated patients, < 0.0001. Three-month mortality was 40.8% overall (49.7% for AP pretreated, 58.4% for VKA pretreated, and 31.1% for non-pretreated patients, < 0.0001). The adjusted odds of very-early and 3-month mortality were 2.55 ( = 0.004) and 1.56 ( = 0.046) for AP-pretreated patients and 4.24 ( < 0.0001) and 2.34 ( = 0.01) for VKA-pretreated patients, respectively, compared with non-pretreated patients. The effect of antithrombotic pretreatment on mortality from 24 hours to 3 months was nonsignificant. At 3-month follow-up, 28.5% of patients remained functionally independent: 22.4% of AP-pretreated, 15.7% of VKA-pretreated, and 35.5% of non-pretreated patients ( < 0.0001). CONCLUSIONS:A high percentage of patients with ICH preventively treated with VKA or AP died during the first 24 hours after admission. Both treatments were predictors of very-early mortality. The final effect of antithrombotics on 3-month mortality remains significant through its strong effect on very-early mortality. Safety concerns about starting chronic antithrombotic treatment should be considered not only when VKA treatment is planned but also for AP treatment.
10.1212/WNL.0000000000003659
Antiplatelet Therapy After Spontaneous Intracerebral Hemorrhage and Functional Outcomes.
Stroke
Background and Purpose- Observational data suggest that antiplatelet therapy after intracerebral hemorrhage (ICH) alleviates thromboembolic risk without increasing the risk of recurrent ICH. Given the paucity of data on the relationship between antiplatelet therapy after ICH and functional outcomes, we aimed to study this association in a multicenter cohort. Methods- We meta-analyzed data from (1) the Massachusetts General Hospital ICH registry (n=1854), (2) the Virtual International Stroke Trials Archive database (n=762), and (3) the Yale stroke registry (n=185). Our exposure was antiplatelet therapy after ICH, which was modeled as a time-varying covariate. Our primary outcomes were all-cause mortality and a composite of major disability or death (modified Rankin Scale score 4-6). We used Cox proportional regression analyses to estimate the hazard ratio of death or poor functional outcome as a function of antiplatelet therapy and random-effects meta-analysis to pool the estimated HRs across studies. Additional analyses stratified by hematoma location (lobar and deep ICH) were performed. Results- We included a total of 2801 ICH patients, of whom 288 (10.3%) were started on antiplatelet medications after ICH. Median times to antiplatelet therapy ranged from 7 to 39 days. Antiplatelet therapy after ICH was not associated with mortality (hazard ratio, 0.85; 95% CI, 0.66-1.09), or death or major disability (hazard ratio, 0.83; 95% CI, 0.59-1.16) compared with patients not started on antiplatelet therapy. Similar results were obtained in additional analyses stratified by hematoma location. Conclusions- Antiplatelet therapy after ICH appeared safe and was not associated with all-cause mortality or functional outcome, regardless of hematoma location. Randomized clinical trials are needed to determine the effects and harms of antiplatelet therapy after ICH.
10.1161/STROKEAHA.119.025972
Antithrombotic Treatment Prior to Intracerebral Hemorrhage: Analysis in the National Acute Stroke Israeli Registry.
Romem Roy,Tanne David,Geva Diklah,Einhorn-Cohen Michal,Shlomo Nir,Bar-Yehuda Sara,Harnof Sagi
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND AND PURPOSE:Intracerebral hemorrhage (ICH) is the most disastrous stroke subtype. Prognosis is considered worse with prior antithrombotic treatment. Our aim was to evaluate the association of prior antithrombotic treatment on the radiological and clinical outcome after ICH in a subgroup of patients included in a national registry. METHODS:Based on the National Acute Stroke Israeli (NASIS) registry during 2004, 2007, 2010, and 2013 (2-month periods), characteristics, volumetric parameters, and prognosis of a subgroup of patients with ICH were analyzed. RESULTS:Among the 634 patients with ICH in the NASIS registry, 310 (49%) were not treated previously with antithrombotic medications, 232 (37%) were treated with an antiplatelet agent, and 92 (14.5%) patients were on oral anticoagulant therapy, of them 30 patients (33%) with an international normalised ratio (INR) value below 2, 33 (36%) patients with an INR value of 2-3, and 29 patients (31%) with an INR value above 3 upon admission. Patients with deep hemorrhage on prior anticoagulants treatment had the highest probability for poor outcome at hospital discharge. Patients with low bleeding volume (0-30 cm), were likely to have admission National Institute of Health Stroke Scale < 10 (62%), while those with higher volumes (30-59 cm and > 60 cm), had only 16.7% and 14.3% chance, respectively. We did not observe a significant difference between prior antithrombotic treatment and functional outcome at discharge, yet prior anticoagulant treatment was associated with higher long-term mortality rates. CONCLUSIONS:Our findings, based on a national registry, support the high mortality and poor outcome of anticoagulant related ICH.
10.1016/j.jstrokecerebrovasdis.2018.07.040
Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH.
Sansing L H,Messe S R,Cucchiara B L,Cohen S N,Lyden P D,Kasner S E,
Neurology
OBJECTIVE:To examine whether antiplatelet medication use at onset of intracerebral hemorrhage (ICH) is associated with hemorrhage growth and outcome after spontaneous ICH using a large, prospectively collected database from a recent clinical trial. METHODS:The Cerebral Hemorrhage and NXY-059 Treatment trial was a randomized, placebo-controlled trial of NXY-059 after spontaneous ICH. We analyzed patients in the placebo arm, and correlated antiplatelet medication use at the time of ICH with initial ICH volumes, ICH growth in the first 72 hours, and modified Rankin Score at 90 days. Patients on oral anticoagulation were excluded. RESULTS:There were 282 patients included in this analysis, including 70 (24.8%) who were taking antiplatelet medications at ICH onset. Use of antiplatelet medications at ICH onset had no association with the volume of ICH at presentation, growth of ICH at 72 hours, initial edema volume, or edema growth. In multivariable analysis, there was no association of use of antiplatelet medications with any hemorrhage expansion (relative risk [RR] 0.85 [upper limit of confidence interval (UCI) 1.03], p = 0.16), hemorrhage expansion greater than 33% (RR 0.77 [UCI 1.18], p = 0.32), or clinical outcome at 90 days (odds ratio 0.67, 95% confidence interval 0.39-1.14, p = 0.14). CONCLUSIONS:Use of antiplatelet medications at intracerebral hemorrhage (ICH) onset is not associated with increased hemorrhage volumes, hemorrhage expansion, or clinical outcome at 90 days. These findings suggest that attempts to reverse antiplatelet medications after ICH may not be warranted.
10.1212/01.wnl.0000342709.31341.88