Antiplatelet治疗(APT)是罗依utinely prescribed in the setting of arterial thrombosis prevention in cardiovascular and cerebrovascular disease. Prior antiplatelet usage is documented in as many as 30%–40% of patients presenting with acute ischemic stroke (AIS),1,2despite the preemptive intention of this medical intervention. For patients with AIS due to large vessel occlusion treated with endovascular thrombectomy (EVT), prior chronic use of antiplatelet medication has previously been identified as a preprocedural risk factor for symptomatic hemorrhagic transformation,3a leading cause of mortality in this patient population.4Conversely, long-standing anti-aggregation therapy may, in principle, predispose patients to enhanced recanalization and microvascular reperfusion. This phenomenon has been demonstrated in the acute setting, in which administration of aggressive APT for emergency carotid stenting during stroke thrombectomy resulted in improved clinical outcomes without increased hemorrhagic risk.5Because evidence regarding the safety of chronic APT usage in the setting of EVT remains limited, this study proposes a population-level analysis of a national registry to evaluate real-world outcomes of patients with AIS on long-term APT treated with EVT.
开云体育世界杯赔率
Data Source
全国住院病人样本(NIS),和发展maintained by the Healthcare Cost and Utilization Project (HCUP), is among the largest publicly accessible inpatient care databases in the United States. Yearly unweighted data approximate 7,000,000 patients, reflecting a 20% stratified sample of all HCUP-participating community hospitals nationally. The large sample size afforded by the NIS allows for substantive inquiry into healthcare utilization, access, charges, quality, and outcomes, as well as reliable reproduction of national estimates annually. Data elements include demographic characteristics, hospital and regional information, diagnoses, procedures, and discharge disposition (more information regarding the NIS and data access can be found at:www.hcup-us.ahrq.gov). Given the public accessibility and de-identified nature of the information in this database, this study did not meet the requirements for IRB approval at Westchester Medical Center. For the same reason, patient consent was neither sought nor required. This paper was composed in accordance with Reporting of Studies Conducted Using Observational Routinely Collected Data (RECORD) guidelines.
Patient Selection and Cohort Development
International Classification of Diseases, Tenth Revision, Clinical Modification(ICD-10-CM) codes were used to identify adult patients with primary admission diagnoses for anterior circulation AIS of the middle cerebral or internal carotid arteries (codes I63.31, I63.41, I63.51, I63.03, I63.13, I63.23) during the period of 2015 (fourth quarter, October through December) to 2019. Relevant procedural codes were used to identify patients treated with EVT (Procedural Coding System [PCS] codes 03CG3ZZ, 03CG3Z7) with or without preceding intravenous thrombolysis (IVT; PCS codes 3E03317, Z92.82). Prior antiplatelet usage at the time of admission was identified with the corresponding billing codes for "Long term (current) use of antithrombotics/antiplatelets" (code Z79.02) and "Long term (current) use of aspirin" (code Z97.82). Demographic characteristics obtained included age and sex. Stroke patients were stratified by severity of presentation according to National Institutes of Health Stroke Scale (NIHSS) score as well as presence of a "severe feature," inclusive of comatose status or necessity for mechanical ventilation. Comorbid conditions included atrial fibrillation, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), hypertension, diabetes mellitus, tobacco smoking, and alcohol use.
Clinical Endpoints
The primary clinical endpoint of this analysis was favorable functional outcome, defined as routine discharge home without services. This discharge disposition has been previously demonstrated to have high concordance with a modified Rankin Scale (mRS) score ≤ 2 assessed at 90 days, representative of minimal to no disability.6,7In-hospital mortality, any intracranial hemorrhage (ICH), and symptomatic ICH (sICH) were evaluated as secondary endpoints. Symptomatic ICH was defined by concomitant coding for intracerebral or subarachnoid bleeds and associated sequelae (ICD-10-CM codes I69.0 and I69.1 are specific to nontraumatic ICHs and are thus distinct from deficits associated with the acute presentation).
Statistical Analysis
All analyses were performed within a complex samples function with appropriate stratum and cluster variables and discharge weights per HCUP guidelines to account for NIS sampling design and to ultimately yield accurate national estimates. Descriptive statistics were performed to measure variation in baseline demographic and clinical characteristics as well as in outcomes between patients with and without prior APT usage. Dichotomous variables were assessed using Pearson’s chi-square test and presented as number and percentage, while median with interquartile range (IQR) was reported for continuous baseline parameters. Statistical significance was evaluated at p < 0.05 for univariable comparisons. A bias assessment was also conducted to measure variation in baseline clinical characteristics and outcomes between hospitalizations with and without a documented baseline NIHSS score using the same statistical tests as above. Multivariable logistic regression analysis was performed to assess the independent association between prior APT usage and clinical outcomes while adjusting for baseline clinical covariates. Statistical significance was determined following a Bonferroni correction for multiple comparisons. All statistical analyses were performed using IBM SPSS software (version 26, IBM Corp.).
Results
This analysis identified 36,560 patients, 8170 (22.3%) of whom were on APT prior to admission. These patients were older and demonstrated a significantly higher burden of comorbid disease (including atrial fibrillation, CHF, hypertension, diabetes mellitus, hyperlipidemia, and tobacco smoking), but did not differ in terms of stroke severity (baseline NIHSS score) on presentation compared with those not on APT (Table 1). On unadjusted analysis, patients with prior APT demonstrated significantly higher rates of favorable outcomes (24.3% vs 21.5%, p < 0.001), lower rates of in-hospital mortality (7.0% vs 10.1%, p < 0.001), and lower rates of any ICH (20.3% vs 24.2%, p < 0.001), but no difference in rates of sICH (Table 2). Following multivariable adjustment for baseline clinical characteristics including age, acute stroke severity, and comorbidity burden, prior APT was associated with favorable outcome (adjusted odds ratio [aOR] 1.21, 95% CI 1.17–1.25, p < 0.001) and a lower likelihood of mortality (aOR 0.73, 95% CI 0.70–0.77, p < 0.001), without an increased likelihood of ICH (any ICH aOR 0.84, 95% CI 0.81–0.87, p < 0.001; sICH aOR 0.92, 95% CI 0.82–1.03, p = 0.131;Table 3).
Comparison of baseline demographic and clinical characteristics of patients with AIS treated with EVT with and without prior APT
| Variable | Total Cohort | Prior APT | No Prior APT | p Value |
|---|---|---|---|---|
| No. of patients (%) | 36,560 | 8170 (22.3) | 28,390 (77.7) | |
| Median age (IQR), yrs | 71 (60–80) | 73 (62–82) | 70 (59–80) | <0.001 |
| Females, n (%) | 18,850 (51.6) | 4110 (50.3) | 14,740 (51.9) | 0.010 |
| Concomitant IVT, n (%) | 17,165 (46.9) | 3810 (46.6) | 13,355 (47.0) | 0.524 |
| Median NIHSS score (IQR) | 16 (11–21) | 15 (9–20) | 16 (11–21) | 0.161 |
| Coma or mechanical ventilation, n (%) | 1430 (3.9) | 230 (2.8) | 1200 (4.2) | <0.001 |
| Atrial fibrillation, n (%) | 16,955 (46.4) | 4205 (51.5) | 12,750 (44.9) | <0.001 |
| CHF, n (%) | 9000 (24.6) | 2130 (26.1) | 6870 (24.2) | 0.001 |
| COPD, n (%) | 5495 (15) | 1190 (14.6) | 4305 (15.2) | 0.184 |
| Hypertension, n (%) | 29,690 (81.2) | 7235 (88.6) | 22,455 (79.1) | <0.001 |
| Diabetes mellitus, n (%) | 9830 (26.9) | 2440 (29.9) | 7390 (26.0) | <0.001 |
| Hyperlipidemia, n (%) | 20,205 (55.3) | 5405 (66.2) | 14,800 (52.1) | <0.001 |
| Tobacco smoking, n (%) | 12,870 (35.2) | 3450 (42.2) | 9420 (33.2) | <0.001 |
| Alcohol usage, n (%) | 1980 (5.4) | 415 (5.1) | 1565 (5.5) | 0.128 |
Boldface type indicates statistical significance.
Comparison of clinical endpoints of patients with AIS treated with EVT with and without prior APT
| Variable | Total Cohort (%) | Prior APT (%) | No Prior APT (%) | p Value |
|---|---|---|---|---|
| No. of patients | 36,560 | 8170 (22.3) | 28,390 (77.7) | |
| Favorable outcome | 8080 (22.1) | 1985 (24.3) | 6095 (21.5) | <0.001 |
| In-hospital mortality | 3435 (9.4) | 570 (7.0) | 2865 (10.1) | <0.001 |
| sICH | 670 (1.8) | 145 (1.8) | 525 (1.8) | 0.660 |
| Any ICH | 8525 (23.3) | 1655 (20.3) | 6870 (24.2) | <0.001 |
Dichotomous variables assessed using Pearson’s chi-square test. Boldface type indicates statistical significance.
Adjusted analysis: association of prior APT with study endpoints
| Clinical Endpoint | aOR (95% CI) | p Value |
|---|---|---|
| Favorable outcome | 1.21 (1.17–1.25) | <0.001 |
| In-hospital mortality | 0.73 (0.70–0.77) | <0.001 |
| sICH | 0.92 (0.82–1.03) | 0.131 |
| Any ICH | 0.84 (0.81–0.87) | <0.001 |
临床端点效应大小的恰当的礼物ed as aORs with 95% CIs following multivariable logistic regression analysis. Covariates chosen for adjustment included age, sex, concomitant IVT, NIHSS score, presence of severe feature (coma or mechanical ventilation), atrial fibrillation, CHF, COPD, hypertension, diabetes mellitus, hyperlipidemia, tobacco smoking, and alcohol usage. Boldface type indicates statistical significance following Bonferroni correction for multiple comparisons.
研究包含66820人住院criteria, 36,560 (54.7%) had a documented baseline NIHSS score. Consequently, 30,260 hospitalizations (45.3%) were excluded from the analysis. In comparison to hospitalizations without a documented baseline NIHSS score, those with a documented score did not differ in terms of age, proportion of female sex, presence of severe feature (coma or mechanical ventilation), atrial fibrillation, and rates of any ICH or sICH, but had significantly higher rates of APT usage (22.3% vs 18.8%), concomitant IVT (46.9% vs 45.6%), hypertension (81.2% vs 79.7%), hyperlipidemia (55.3% vs 53.1%), tobacco smoking (35.2% vs 32.2%), alcohol use (5.4% vs 4.8%), and favorable outcome (22.1% vs 18.3%), and lower rates of CHF (24.6% vs 27.8%), COPD (15.0% vs 16.2%), diabetes mellitus (26.9% vs 28.4%), and in-hospital mortality (9.4% vs 13.2%; all p < 0.001).
Discussion
This study identified approximately 36,500 AIS hospitalizations in the United States and demonstrated that prior APT use (documented for 22% of the cohort) in the setting of EVT treatment was associated with favorable outcomes and decreased likelihood of mortality, without a concomitant increased risk of hemorrhagic transformation. To the best of our knowledge, this clinical question has not been previously addressed using population-level data on such a scale, and evidence in general remains limited. Because in many circumstances (especially with aspirin) the platelets are irreversibly inhibited for the duration of their lifespan, these findings may be helpful when deciding to initiate APT shortly after EVT.
A post hoc evaluation of the Multicentre Randomised Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR CLEAN) registry identified a 30% chronic use of APT among 3154 EVT patients, but failed to show associations between APT and favorable outcomes, mortality, or sICH, and thus was unable to exclude a substantial beneficial or detrimental effect of prior APT usage in the setting of endovascular therapy.8Similarly, an analysis of 3000 patients in a prospective multicenter French registry found no association between prior APT use and favorable functional outcome at 3 months, sICH, or 90-day mortality.9Among observational studies with smaller sample sizes, a 2022 retrospective study of preadmission antithrombotic use in a cohort of 234 EVT-treated patients in New York City demonstrated no association of APT with extent of reperfusion, postprocedure Alberta Stroke Program Early CT Score (ASPECTS), hemorrhagic conversion, hospital length of stay, discharge NIHSS score, or discharge mRS score, but did report an association with worse outcomes at 3 months (mRS scores 3–6).10Finally, an increased adjusted risk of dependence at 90 days and of sICH was demonstrated in patients with chronic APT use in a single-center retrospective analysis of approximately 200 patients in France.11Collectively, the existing evidence remains heterogeneous and inconclusive regarding the efficacy and safety of preexisting APT in AIS treated with EVT, although observational studies with larger sample sizes appear to demonstrate equipoise in clinical outcomes and propensity for sICH. A potential explanation for lower unadjusted and adjusted rates of ICH in the APT treatment group is that patients on APT may have had smaller strokes and lesser stroke burden, conferring lower likelihood of hemorrhagic transformation.
Limitations of the Study
Although the results of the present study demonstrate a favorable safety profile for APT in the setting of EVT, this analysis was limited to short-term outcomes and does not account for disability or mortality at 30 or 90 days or long-term follow-up of any kind. Although discharge disposition to home has been validated as a reliable proxy for mRS scores at 90 days,6,7it is not a functional outcome per se and must be evaluated accordingly because patients with disability may ultimately be discharged home. Other limitations of this study include a retrospective methodology that is unable to assess causation or a definitive safety profile, an absence of important baseline clinical covariates including comprehensive radiographic information as well as time of presentation, and extent of recanalization following acute reperfusion therapy (including Thrombolysis in Cerebral Infarction [TICI] score), among other parameters. Importantly, patients were not randomized into APT and non-APT groups, potentially resulting in residual confounding even after multivariable analysis accounting for stroke severity and comorbidity burden. Moreover, a bias assessment demonstrated discrepancies in baseline characteristics and outcomes between cohorts with and without documented baseline NIHSS score. In addition, several parameters pertinent to APT therapy were not available in this registry, including the specific type of APT therapy and associated dosage, discontinuation and reinstatement of the APT regimen during hospitalization, APT administration in the perioperative phase, and functionality testing to determine resistance to treatment with APT.
Conclusions
Using registry-based data, a retrospective evaluation of patients with AIS treated with EVT demonstrated an association of prior APT usage with favorable outcomes, without an increased risk of hemorrhagic transformation. Randomized clinical trials are warranted for further investigation.
Disclosures
Dr. Rostanski reported personal fees as an expert witness outside the submitted work.
Author Contributions
Conception and design: Al-Mufti, Dicpinigaitis, Gagliardi, Kaur, Bowers. Acquisition of data: Al-Mufti, Dicpinigaitis. Analysis and interpretation of data: Al-Mufti, Dicpinigaitis, Chowdhury, Gagliardi, Soliman, Nolan, Willey, Medicherla, Chong. Drafting the article: Al-Mufti, Dicpinigaitis, Chowdhury, Gagliardi, Soliman, Mahmoud, Nolan, Kaur. Critically revising the article: Al-Mufti, Dicpinigaitis, Chowdhury, Gagliardi, Mahmoud, Nolan, Clare, Willey, Rostanski, Medicherla, Chong, Gandhi. Reviewed submitted version of manuscript: Al-Mufti, Dicpinigaitis, Chowdhury, Gagliardi, Mahmoud, Nolan, Willey, Medicherla, Patel, Chong. Statistical analysis: Dicpinigaitis. Administrative/technical/material support: Nolan.
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