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1.
Medicine (Baltimore) ; 99(9): e19247, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32118730

RESUMEN

RATIONALE: The capsular warning syndrome (CWS) is a rare and special type of transient ischemic attacks (TIAs) syndrome. The pathophysiology of CWS is very complicate, and intracranial atherosclerotic stenosis (ICAS) is rare cause. Moreover, the effective and standard therapy has not yet been established. PATIENT CONCERNS: A 47-year-old man experienced repeated and exacerbated TIAs of right hemiparesis and dysarthria. Fourteen hours after the first episode of TIAs, he developed more severe right hemiparesis and dysarthria, the National Institute of Health Stroke Scale (NIHSS) score was 12 points, and did not recover in a long time. DIAGNOSIS: The computed tomography (CT) angiography displayed high stenosis in the M1 segment of the left middle cerebral artery. The patient was diagnosed as CWS with ICAS. INTERVENTIONS: Loading dose of clopidogrel and aspirin were started but were ineffective, then we used recombinant tissue plasminogen (r-tPA) for thrombolysis therapy after repeat CT scan that showed small acute infarcts in the right putamen and no bleeding. OUTCOMES: The patient was successfully treated by r-tPA intravenous thrombolysis after loading dose of dual-anti-platelet. He recovered rapidly, and the NIHSS score was 0 point, modified Rankin Scale score was 0 point, and Barthel Index score was 100 points at 3-month follow-up. LESSONS: r-tPA combined with loading dose of dual antiplatelet appears safe and effective in carefully selected CWS patients with ICAS. The collection of similar cases and further randomized controlled trial research would be desirable.


Asunto(s)
Fibrinolíticos/uso terapéutico , Arteriosclerosis Intracraneal/tratamiento farmacológico , Ataque Isquémico Transitorio/tratamiento farmacológico , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Clopidogrel/administración & dosificación , Clopidogrel/uso terapéutico , Angiografía por Tomografía Computarizada , Diagnóstico Diferencial , Fibrinolíticos/administración & dosificación , Humanos , Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis Intracraneal/diagnóstico por imagen , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/diagnóstico por imagen , Síndrome , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Tomografía Computarizada por Rayos X
2.
N Engl J Med ; 382(1): 9, 2020 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-31738483

RESUMEN

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).


Asunto(s)
Anticolesterolemiantes/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangre , Ezetimiba/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Adulto , Anciano , Anticolesterolemiantes/efectos adversos , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Enfermedades Cardiovasculares/mortalidad , Quimioterapia Combinada , Femenino , Humanos , Análisis de Intención de Tratar , Ataque Isquémico Transitorio/complicaciones , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/sangre
3.
Medicina (B Aires) ; 79(4): 315-321, 2019.
Artículo en Español | MEDLINE | ID: mdl-31487255

RESUMEN

One of the main pillars of acute ischemic stroke management is antiplatelet therapy. Different treatment schemes have been compared, suggesting that the combination of multiple antiplatelet drugs is associated with a reduced risk of stroke recurrence. However, it has also been associated with an increased risk of bleeding complications which, in the long term, surpass the mentioned benefits. However, considering that most stroke recurrences occur i n the short term, a time limited double antiplatelet scheme could result in significant benefits to patients with acute ischemic stroke. On this basis, we conducted a rapid systematic review of the literature in order to evaluate the effects of a short-term double antiplatelet therapy both on stroke recurrence and complications. All trials comparing double versus single antiplatelet therapy in patients with acute ischemic stroke were included. Results showed that double therapy reduces recurrence risk but probably marginally increases major bleeding complications. We suggest double antiplatelet therapy for the initial management of patients with minor (Score NIH < or equal to 3 or transient isquemic attack -TIA) acute ischemic stroke.


Asunto(s)
Aspirina/administración & dosificación , Benzodiazepinas/administración & dosificación , Clopidogrel/administración & dosificación , Ataque Isquémico Transitorio/tratamiento farmacológico , Ataque Isquémico Transitorio/prevención & control , Inhibidores de Agregación Plaquetaria/administración & dosificación , Poliaminas/administración & dosificación , Quimioterapia Combinada , Humanos , Recurrencia , Prevención Secundaria
4.
Stud Health Technol Inform ; 262: 110-113, 2019 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-31349278

RESUMEN

A 'Rapid Recommendation' has been produced by the GRADE group, in collaboration with MAGIC and BMJ, in response to an RCT showing Dual Anti-Platelet Therapy (DAPT) is superior to Aspirin alone for patients who had suffered acute high risk transient ischaemic attack or minor ischaemic stroke. The interactive MAGIC decision aid that accompanies each Rapid Recommendation is the main route to their clinical implementation. It can facilitate preference-sensitive person-centred care, but only if a Multi-Criteria Decision Analysis-based decision support tool is added. A demonstration version of such an add-on to the MAGIC aid, divested of recommendations, is available online. Exploring the results of different preference inputs into the tool raises questions about the strong recommendation for DAPT.


Asunto(s)
Isquemia Encefálica , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Isquemia Encefálica/tratamiento farmacológico , Clopidogrel , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Atención Dirigida al Paciente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico
5.
Stroke ; 50(7): 1812-1818, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31177983

RESUMEN

Background and Purpose- We assessed the efficacy and safety of antiplatelet agents after noncardioembolic stroke or transient ischemic attack and examined how these vary according to patients' demographic and clinical characteristics. Methods- We did a network meta-analysis (NMA) of data from 6 randomized trials of the effects of commonly prescribed antiplatelet agents in the long-term (≥3 months) secondary prevention of noncardioembolic stroke or transient ischemic attack. Individual patient data from 43 112 patients were pooled and reanalyzed. Main outcomes were serious vascular events (nonfatal stroke, nonfatal myocardial infarction, or vascular death), major bleeding, and net clinical benefit (serious vascular event or major bleeding). Subgroup analyses were done according to age, sex, ethnicity, hypertension, qualifying diagnosis, type of vessel involved (large versus small vessel disease), and time from qualifying event to randomization. Results- Aspirin/dipyridamole combination (RRNMA-adj, 0.83; 95% CI, 0.74-0.94) significantly reduced the risk of vascular events compared with aspirin, as did clopidogrel (RRNMA-adj, 0.88; 95% CI, 0.78-0.98), and aspirin/clopidogrel combination (RRNMA-adj, 0.83; 95% CI, 0.71-0.96). Clopidogrel caused significantly less major bleeding and intracranial hemorrhage than aspirin, aspirin/dipyridamole combination, and aspirin/clopidogrel combination. Aspirin/clopidogrel combination caused significantly more major bleeding than aspirin, aspirin/dipyridamole combination, and clopidogrel. Net clinical benefit was similar for clopidogrel and aspirin/dipyridamole combination (RRNMA-adj, 0.99; 95% CI, 0.93-1.05). Subgroup analyses showed no heterogeneity of treatment effectiveness across prespecified subgroups. The excess risk of major bleeding associated with aspirin/clopidogrel combination compared with clopidogrel alone was higher in patients aged <65 years than it was in patients ≥65 years (RRNMA-adj, 3.9 versus 1.7). Conclusions- Results favor clopidogrel and aspirin/dipyridamole combination for long-term secondary prevention after noncardioembolic stroke or transient ischemic attack, regardless of patient characteristics. Aspirin/clopidogrel combination was associated with a significantly higher risk of major bleeding compared with other antiplatelet regimens.


Asunto(s)
Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Aspirina/efectos adversos , Aspirina/uso terapéutico , Trastornos Cerebrovasculares/etiología , Trastornos Cerebrovasculares/prevención & control , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Dipiridamol/efectos adversos , Dipiridamol/uso terapéutico , Quimioterapia Combinada , Femenino , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Riesgo , Prevención Secundaria , Accidente Cerebrovascular/complicaciones , Ticlopidina/uso terapéutico , Resultado del Tratamiento
6.
Stroke ; 50(7): 1859-1868, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31177985

RESUMEN

Background and Purpose- Early erythrolysis in the hematoma contributes to brain injury after intracerebral hemorrhage (ICH). This study investigated the effects of N-acetylheparin, a complement inhibitor, and aurin tricarboxylic acid, a membrane attack complex inhibitor, on early erythrolysis, brain iron deposition, and brain injury in aged rats. Methods- There were 3 parts in the study. First, aged (18 months old) male Fischer 344 rats had an ICH. The time course of erythrolysis in the hematoma was determined by T2* weighted magnetic resonance imaging, and the expression of CD163 was examined. Second, aged rats had an ICH with N-acetylheparin or vehicle. Rats were euthanized at days 1, 3, and 28 after magnetic resonance imaging (T2-, T2*-weighted, and T2* array) and behavioral tests. Brains were used for immunohistochemistry. Third, aged rats had an ICH with avaurin tricarboxylic acid or vehicle. The rats had magnetic resonance imaging and behavioral tests and were euthanized at day 3. Brains were used for immunohistochemistry. Results- Early erythrolysis occurred within the clot in aged F344 rats. There were increased numbers of CD163-positive cells after ICH. Almost all perihematomal CD163-positive cells were microglia/macrophages, while positive neurons were found more distant from the hematoma. Coinjection of N-acetylheparin attenuated erythrolysis, iron accumulation, CD163 expression, microglia activation, brain swelling, and neuronal death in the acute phase, as well as reducing brain atrophy and neurological deficits in the chronic phase. Coinjection of aurin tricarboxylic acid also reduced erythrolysis and ICH-induced brain injury. Conclusions- Inhibiting complement activation resulted in less erythrolysis and brain injury after ICH.


Asunto(s)
Ácido Aurintricarboxílico/uso terapéutico , Lesiones Encefálicas/sangre , Lesiones Encefálicas/tratamiento farmacológico , Inactivadores del Complemento/uso terapéutico , Hemólisis , Heparina/análogos & derivados , Hemorragias Intracraneales/sangre , Hemorragias Intracraneales/tratamiento farmacológico , Ataque Isquémico Transitorio/tratamiento farmacológico , Envejecimiento , Animales , Antígenos CD/biosíntesis , Antígenos de Diferenciación Mielomonocítica/biosíntesis , Edema Encefálico/prevención & control , Eritrocitos , Heparina/uso terapéutico , Activación de Macrófagos , Masculino , Microglía , Ratas , Ratas Endogámicas F344 , Receptores de Superficie Celular/biosíntesis
7.
BMJ ; 365: l2211, 2019 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-31171523

RESUMEN

OBJECTIVE: To test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis. DESIGN: Open label, blinded endpoint, randomised controlled phase II trial. SETTING: Prospective studies conducted at 26 centres in China, August 2015 to March 2017. PARTICIPANTS: 675 patients with acute minor stroke or transient ischaemic attack. INTERVENTION: Ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset. MAIN OUTCOME MEASURES: Primary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year. RESULTS: At 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P<0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42). CONCLUSION: Patients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations. TRIAL REGISTRATION: Clinicaltrials.gov NCT02506140.


Asunto(s)
Aspirina/uso terapéutico , Clopidogrel/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Ticagrelor/uso terapéutico , Adulto , Anciano , Plaquetas/efectos de los fármacos , China , Quimioterapia Combinada , Femenino , Humanos , Ataque Isquémico Transitorio/fisiopatología , Masculino , Persona de Mediana Edad , Activación Plaquetaria/fisiología , Estudios Prospectivos , Accidente Cerebrovascular/fisiopatología , Resultado del Tratamiento
8.
Am J Cardiol ; 124(4): 627-635, 2019 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-31248591

RESUMEN

The patient's profile drawing the greatest benefit from dual antiplatelet therapy (DAPT) after a noncardioembolic, ischemic cerebrovascular event is not well characterized. Aim of this metaregression analysis was to compare DAPT versus single antiplatelet therapy (SAPT) in patients with stroke or transient ischemic attack (TIA). We searched randomized trials evaluating clinical outcome with aspirin plus a P2Y12 inhibitor versus SAPT in patients with noncardioembolic stroke or TIA. Primary end point was the incidence of recurrent stroke; safety outcome measure was major bleeding. Eleven trials were included in the analysis, enrolling 24,175 patients treated with DAPT (aspirin plus clopidogrel, n = 12,074) or SAPT (n = 12,101) after a stroke or TIA event. In the DAPT group the rates of recurrent stroke were lower (7.1% vs 8.8% with SAPT; odds ratios [OR] 0.74, 95% confidence interval 0.62 to 0.88; p = 0.0007) and the incidence of major bleeding was twofold higher (OR 2.01, 1.35 to 3.01; p = 0.0006). Metaregression indicated a positive correlation between prevention of recurrent stroke by DAPT and baseline stroke severity (p = 0.019), baseline risk profile (p = 0.0001), or prevalence of carotid atherosclerosis (p = 0.040). DAPT was more effective when initiated ≤7 days (OR 0.67, 0.58 to 0.77; p < 0.00001) and used for ≤3 months (OR 0.66, 0.58 to 0.76; p < 0.00001) after the event. In conclusion, in patients with stroke or TIA, the highest benefit of DAPT was observed in patients with higher baseline risk profile, greater stroke severity, or concomitant carotid disease, and when DAPT was initiated early and given for ≤3 months.


Asunto(s)
Ataque Isquémico Transitorio/tratamiento farmacológico , Selección de Paciente , Accidente Cerebrovascular/tratamiento farmacológico , Fibrinolíticos , Humanos , Ataque Isquémico Transitorio/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/prevención & control , Trombectomía
9.
Cochrane Database Syst Rev ; 6: CD012815, 2019 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-31242320

RESUMEN

BACKGROUND: Currently, with stroke burden increasing, there is a need to explore therapeutic options that ameliorate the acute insult. There is substantial evidence of a neuroprotective effect of marine-derived n-3 polyunsaturated fatty acids (PUFAs) in experimental stroke, leading to a better functional outcome. OBJECTIVES: To assess the effects of administration of marine-derived n-3 PUFAs on functional outcomes and dependence in people with stroke.Our secondary outcomes were vascular-related death, recurrent events, incidence of other type of stroke, adverse events, quality of life, and mood. SEARCH METHODS: We searched the Cochrane Stroke Group trials register (6 August 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, January 2019), MEDLINE Ovid (from 1948 to 6 August 2018), Embase Ovid (from 1980 to 6 August 2018), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; from 1982 to 6 August 2018), Science Citation Index Expanded ‒ Web of Science (SCI-EXPANDED), Conference Proceedings Citation Index-Science - Web of Science (CPCI-S), and BIOSIS Citation Index. We also searched ongoing trial registers, reference lists, relevant systematic reviews, and used the Science Citation Index Reference Search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing marine-derived n-3 PUFAs to placebo or open control (no placebo) in people with a history of stroke or transient ischaemic attack (TIA), or both. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion, extracted data, assessed risk of bias, and used the GRADE approach to assess the quality of the body of evidence. We contacted study authors for clarification and additional information on stroke/TIA participants. We conducted random-effects meta-analysis or narrative synthesis, as appropriate. The primary outcome was efficacy (functional outcome) assessed using a validated scale e.g. Glasgow Outcome Scale Extended (GOSE) dichotomised into poor or good clinical outcome, Barthel Index (higher score is better; scale from 0 to 100) or Rivermead Mobility Index (higher score is better; scale from 0 to 15). MAIN RESULTS: We included 29 RCTs; nine of them provided outcome data (3339 participants). Only one study included participants in the acute phase of stroke (haemorrhagic). Doses of marine-derived n-3 PUFAs ranged from 400 mg/day to 3300 mg/day. Risk of bias was generally low or unclear in most trials, with a higher risk of bias in smaller studies. We assessed results separately for short (up to three months) and longer (more than three months) follow-up studies.Short follow-up (up to three months)Functional outcome was reported in only one pilot study as poor clinical outcome assessed with GOSE (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.36 to 1.68; 40 participants; very low quality evidence). Mood (assessed with GHQ-30, lower score better), was reported by only one study and favoured control (mean difference (MD) 1.41, 95% CI 0.07 to 2.75; 102 participants; low-quality evidence).We found no evidence of an effect of the intervention for the remainder of the secondary outcomes: vascular-related death (two studies, not pooled due to differences in population, RR 0.33, 95% CI 0.01 to 8.00, and RR 0.33, 95% CI 0.01 to 7.72; 142 participants; low-quality evidence); recurrent events (RR 0.41, 95% CI 0.02 to 8.84; 18 participants; very low quality evidence); incidence of other type of stroke (two studies, not pooled due to different type of index stroke, RR 6.11, 95% CI 0.33 to 111.71, and RR 0.63, 95% CI 0.25 to 1.58; 58 participants; very low quality evidence); and quality of life (physical component mean difference (MD) -2.31, 95% CI -4.81 to 0.19, and mental component MD -2.16, 95% CI -5.91 to 1.59; one study; 102 participants; low-quality evidence).Adverse events were reported by two studies (57 participants; very low quality evidence), one trial reporting extracranial haemorrhage (RR 0.25, 95% CI 0.04 to 1.73) and the other one reporting bleeding complications (RR 0.32, 95% CI 0.01 to 7.35).Longer follow-up (more than three months)One small trial assessed functional outcome with both Barthel Index (MD 7.09, 95% CI -5.16 to 19.34) for activities of daily living, and Rivermead Mobility Index (MD 1.30, 95% CI -1.31 to 3.91) for mobility (52 participants; very low quality evidence). We carried out meta-analysis for vascular-related death (RR 1.02, 95% CI 0.78 to 1.35; five studies; 2237 participants; low-quality evidence) and fatal recurrent events (RR 0.69, 95% CI 0.31 to 1.55; three studies; 1819 participants; low-quality evidence).We found no evidence of an effect of the intervention for mood (MD 1.00, 95% CI -2.07 to 4.07; one study; 14 participants; low-quality evidence). Incidence of other type of stroke and quality of life were not reported.Adverse events (all combined) were reported by only one study (RR 0.94, 95% CI 0.56 to 1.58; 1455 participants; low-quality evidence). AUTHORS' CONCLUSIONS: We are very uncertain of the effect of marine-derived n-3 PUFAs therapy on functional outcomes and dependence after stroke as there is insufficient high-quality evidence. More well-designed RCTs are needed, specifically in acute stroke, to determine the efficacy and safety of the intervention.Studies assessing functionality might consider starting the intervention as early as possible after the event, as well as using standardised clinically-relevant measures for functional outcomes, such as the modified Rankin Scale. Optimal doses remain to be determined; delivery forms (type of lipid carriers) and mode of administration (ingestion or injection) also need further consideration.


Asunto(s)
Ácidos Grasos Omega-3/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Afecto , Anciano , Hemorragia Cerebral , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Escala de Consecuencias de Glasgow , Humanos , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/psicología , Masculino , Persona de Mediana Edad , Fármacos Neuroprotectores/administración & dosificación , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/psicología , Hemorragia Subaracnoidea
10.
Neuroscience ; 411: 86-104, 2019 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-31129202

RESUMEN

Calcium overload has been reported to trigger neuronal death following stroke. Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside with various neuroprotective activities, has displayed therapeutic efficacy against permanent ischemic stroke. The present study examined the protective potential of PF11 in rats subjected to 2-h transient middle cerebral artery occlusion (tMCAO) and in cultured primary cortical neuron (PCN) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R). Single intravenous administration of PF11 (12 mg/kg) significantly reduced infarct volume, brain edema, neurological deficit and cortex neuron loss at 24 h after reperfusion. Immunoblotting and immunofluorescence demonstrated that PF11 inhibited the over activation of µ-Calpain and the reduction of calcium calmodulin kinase II-α, reduced the degradation of sarcoplasmic/endoplasmic reticulum ATPase-2 and alleviated endoplasmic reticulum stress (ERS) in tMCAO rats. What's more, rats treated with PF11 (12 mg/kg) intravenously immediately after reperfusion, and then intraperitoneally every 24 h for 14 days exhibited lessened cortex neuron loss, reduced mortality and improved performances of rotarod, grip strength and gait patterns at 1, 4, 7, and 14 days after tMCAO. Furthermore, in vitro investigations showed PF11 increased cell viability, reduced neurites decline, restored ATP level and decreased calcium content in cultured PCN under OGD/R. Moreover, PF11 alleviated ERS, reversed the diminished levels of NMDA-2B subunit, postsynaptic density protein 95 and neuronal nitric oxide synthase both in vivo and in vitro. Our study indicates that PF11 produced neuroprotection and improved long-term outcomes while repressing calcium overload in model of transient focal ischemia, suggesting that PF11 might be a considerable candidate for stroke treatment.


Asunto(s)
Encéfalo/efectos de los fármacos , Calcio/metabolismo , Ginsenósidos/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Animales , Encéfalo/metabolismo , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/metabolismo , Muerte Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Ginsenósidos/farmacología , Ataque Isquémico Transitorio/metabolismo , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Ratas
11.
J Thromb Thrombolysis ; 48(3): 528-531, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31041653

RESUMEN

Current guidelines recommend caution in prescribing concomitant use of direct-acting oral anticoagulants (DOACs) and antiepileptic drugs due to drug-drug interactions leading to potential risk of DOACs subtherapeutic concentration and treatment failure. Herein we report a significant interaction between carbamazepine (CZP) and apixaban, causing subtherapeutic concentration of the drug in a patient with atrial fibrillation who had a transient ischemic attack (TIA) episode. Another anti-Xa DOAC, edoxaban, administered to the patient after TIA occurrence did not show significant interaction with CZP. In addition to confirm that cautions should be used when antiepileptic and DOACs are concomitantly prescribed, the present case also demonstrates that, in the management of certain subsets of patients who need anticoagulant treatment, measurement of DOAC plasma concentration can help guide a personalized management and avoid adverse clinical outcomes.


Asunto(s)
Carbamazepina/farmacología , Inhibidores del Factor Xa/farmacología , Medicina de Precisión/métodos , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Carbamazepina/uso terapéutico , Interacciones Farmacológicas , Monitoreo de Drogas , Inhibidores del Factor Xa/uso terapéutico , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Piridonas/farmacología , Piridonas/uso terapéutico , Tiazoles/farmacología , Tiazoles/uso terapéutico
12.
Scand Cardiovasc J ; 53(4): 169-175, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31112048

RESUMEN

Objectives. Stroke is a common condition after a transient ischemic attack (TIA) or minor ischemic stroke (IS). Adding clopidogrel to aspirin may yield more beneficial outcomes than aspirin mono-therapy; meanwhile, the risk of bleeding in the acute phase remains poorly understood. Therefore, there is increasing emphasis on the risks and benefits of clopidogrel with aspirin compared with aspirin mono-therapy in an effort to treat TIA/IS. Design. We searched several electronic databases, including PubMed, Cochrane, and Embase, to identify eligible randomized controlled trials (RCTs) based on the index words comparing dual-antiplatelet therapy to aspirin mono-therapy for secondary stroke prevention updated to December, 2018. Results. A total of 11 RCTs met our inclusion criteria. The pooled analysis showed that clopidogrel plus aspirin was associated with a trend toward a reduction in recurrent IS (RR = 0.72, 95%CI = 0.65-0.81, p < .001), but not the recurrent stroke rate (RR = 0.81, 95% CI = 0.63-1.03, p = .09) than aspirin mono-therapy. There were differences in bleeding episodes (RR = 1.81, 95%CI = 1.65-1.99, p < .001), moderate-severe major bleeding (RR = 1.64, 95% CI = 1.24-2.16, p = .0005), or mild bleeding (RR = 2.25, 95%CI = 1.54-3.31, p < .001) between the study groups. Meanwhile, no benefit of reducing the risk of intracranial hemorrhage with dual-antiplatelet therapy was found in TIA/IS patients (RR = 1.44, 95% CI = 0.95-2.19, p = .09). Conclusions. The addition of clopidogrel to aspirin for patients with TIA or IS appeared to significantly reduce the risk of IS recurrence with a possible increase in the risk of bleeding compared with aspirin alone.


Asunto(s)
Aspirina/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Clopidogrel/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Aspirina/efectos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Clopidogrel/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/epidemiología , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Resultado del Tratamiento
13.
Neuroscience ; 410: 128-139, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31095985

RESUMEN

Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) arose as one of the candidates for cerebral ischemia treatment but its effects on TIA-like condition remain unknown. Seeking an animal model applicable for investigation of molecular alterations in mild ischemic conditions such as TIA, 15-min bilateral common carotid artery occlusion with 24-h reperfusion was performed to induce ischemia/ reperfusion (I/R) injury in adult male Wistar rats. Additionally, effects of 4-h post-operative DHEA treatment (20 mg/kg) were investigated in physiological and I/R conditions in hippocampus (HIP) and prefrontal cortex (PFC). The study revealed absence of sensorimotor deficits, cerebral infarcts and neurodegeneration along with preserved HIP and PFC overall neuronal morphology and unaltered malondialdehyde and reduced glutathione level following I/R and/or DHEA treatment. I/R induced nitric oxide burst in HIP and PFC was accompanied with increased neuronal nitric oxide synthase protein level exclusively in HIP. DHEA had no effects in physiological conditions, while increase of Bax/Bcl2 ratio and dissipation of mitochondrial membrane potential in treated I/R group suggested DHEA-mediated exacerbation of post-ischemic changes that might lead to pro-apoptotic events in HIP. Interestingly, DHEA restored I/R-induced NO to the control level in PFC. Obtained results indicated that I/R may serve as an appropriate model for investigation of molecular changes and treatment outcome following mild ischemic conditions such as TIA.


Asunto(s)
Enfermedades de las Arterias Carótidas/metabolismo , Arteria Carótida Común/metabolismo , Deshidroepiandrosterona/administración & dosificación , Mediadores de Inflamación/metabolismo , Ataque Isquémico Transitorio/metabolismo , Adyuvantes Inmunológicos/administración & dosificación , Animales , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Común/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Ataque Isquémico Transitorio/tratamiento farmacológico , Ataque Isquémico Transitorio/patología , Masculino , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Ratas , Ratas Wistar , Resultado del Tratamiento
14.
Acta Neurol Scand ; 140(2): 107-115, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31017305

RESUMEN

OBJECTIVES: The clinical benefits of use of secondary preventive pharmacotherapy in ischemic stroke/TIA have been previously demonstrated. A potential target for facilitating the use of recommended medications is primary care physicians. Therefore, we carried out an audit and feedback intervention aimed at primary care centers. The aim was to improve the use of secondary preventive stroke medications and diagnosis recording in ischemic stroke/TIA. MATERIALS AND METHODS: The intervention consisted of structured, healthcare database-derived quality reports on secondary preventive medication use and diagnosis recording, sent in 2015 to half of the primary care centers in Stockholm County, with information specific to each primary care center. Medication dispensation (primary outcome) for statins, antihypertensives, antiplatelets, and anticoagulants, as well as diagnosis recording (secondary outcome), was compared between intervention centers and control centers in the 18 months following the intervention. Outcome data were derived from the healthcare databases of Stockholm County (VAL). RESULTS: Dispensation of medications to the 12 766 patients analyzed in the study was high. Over 77% of patients used antihypertensives and antithrombotics, and 65%-68% used statins. After the intervention, no differences in medication dispensation were seen between the intervention and control centers, even after adjusting for potential confounders. CONCLUSIONS: A simple audit and feedback intervention directed toward physicians in primary care did not improve medication dispensation to ischemic stroke/TIA patients 18 months later. Any future audit and feedback intervention aimed at improving adherence to guidelines for secondary prevention in primary care should consider multiple and continuous reminders, the graphical appeal, and widening the recipients to include patients.


Asunto(s)
Ataque Isquémico Transitorio/tratamiento farmacológico , Prevención Secundaria/normas , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Ataque Isquémico Transitorio/prevención & control , Masculino , Auditoría Médica , Prevención Secundaria/métodos , Accidente Cerebrovascular/prevención & control
15.
BMC Med ; 17(1): 67, 2019 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-30914063

RESUMEN

BACKGROUND: Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the use of statins in secondary prevention for patients with ischemic stroke by comparing benefits and harms of various statins. METHODS: We searched for randomized controlled trials (RCTs) assessing statins in patients with ischemic stroke or transient ischemic attack (TIA) in MEDLINE, EMBASE, and CENTRAL up to July 2017. Two authors extracted data and appraised risks of bias. We performed pairwise meta-analyses and trial sequential analyses (TSA) to compare statins versus placebo/no statin, and network meta-analyses using frequentist random-effects models to compare statins through indirect evidence. We used GRADE to rate the overall certainty of evidence. Primary outcomes were all-cause mortality and all strokes. Secondary outcomes were different types of strokes, cardiovascular events, and adverse events. RESULTS: We identified nine trials (10,741 patients). No head-to-head RCTs were found. The median follow-up period was 2.5 years. Statins did not seem to modify all stroke and all-cause mortality outcomes; they were associated with a decreased risk of ischemic stroke (odds ratio, OR, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, ARD, - 1.6% [95% CI, - 2.6 to - 0.6%]), ischemic stroke or TIA (OR, 0.75 [95% CI, 0.64 to 0.87]; ARD, - 4.2% [95% CI, - 6.2 to - 2.1%]), and cardiovascular event (OR, 0.75 [95% CI, 0.69 to 0.83]; ARD, - 5.4% [95% CI, - 6.8 to - 3.6%]), and did not seem to modify rhabdomyolysis, myalgia, or rise in creatine kinase. In the comparison of different statins, moderate- to high-quality evidence indicated that differences between pharmaceutical products seemed modest, with high doses (e.g., atorvastatin 80 mg/day and simvastatin 40 mg/day) associated with the greatest benefits. TSA excluded random error as a cause of the findings for ischemic stroke and cardiovascular event outcomes. Evidence for increased risk of hemorrhagic stroke was sensitive to the exclusion of the SPARCL trial. CONCLUSIONS: Evidence strongly suggests that statins are associated with a reduction in the absolute risk of ischemic strokes and cardiovascular events. Differences in effects among statins were modest, signaling potential therapeutic equivalence. TRIAL REGISTRATION: PROSPERO CRD42018079112.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Metaanálisis en Red , Prevención Secundaria , Accidente Cerebrovascular/prevención & control
16.
Stroke ; 50(4): 947-953, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30852971

RESUMEN

Background and Purpose- The role of aspirin plus clopidogrel (A+C) therapy compared with aspirin monotherapy in patients presenting with acute ischemic stroke (IS) or transient ischemic attack remains uncertain. We conducted this study to determine the optimal period of efficacy and safety of A+C compared with aspirin monotherapy. Methods- Ten randomized controlled trials (15 434 patients) were selected using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) (inception June 2018) comparing A+C with aspirin monotherapy in patients with transient ischemic attack or IS. The primary efficacy outcome was recurrent IS, and the primary safety outcome was major bleeding. The secondary outcomes were major adverse cardiovascular events (composite of stroke, myocardial infarction, and cardiovascular mortality) and all-cause mortality. We stratified analysis based on the short- (≤1 month), intermediate- (≤3 month), and long-term (>3 month) A+C therapy. Effects were estimated as relative risk (RR) with 95% CI. Results- A+C significantly reduced the risk of recurrent IS at short-term (RR, 0.53; 95% CI, 0.37-0.78) and intermediate-term (RR, 0.72; 95% CI, 0.58-0.90) durations. Similarly, major adverse cardiovascular event was significantly reduced by short-term (RR, 0.68; 95% CI, 0.60-0.78) and intermediate-term (RR, 0.76; 95% CI, 0.61-0.94) A+C therapy. However, long-term A+C did not yield beneficial effect in terms of recurrent IS (RR, 0.81; 95% CI, 0.63-1.04) and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.71-1.07). Intermediate-term (RR, 2.58; 95% CI, 1.19-5.60) and long-term (RR, 1.87; 95% CI, 1.36-2.56) A+C regimens significantly increased the risk of major bleeding as opposed to short-term A+C (RR, 1.82; 95% CI, 0.91-3.62). Excessive all-cause mortality was limited to long-term A+C (RR, 1.45; 95% CI, 1.10-1.93). Conclusions- Short-term A+C is more effective and equally safe in comparison to aspirin alone in patients with acute IS or transient ischemic attack.


Asunto(s)
Aspirina/administración & dosificación , Isquemia Encefálica/tratamiento farmacológico , Clopidogrel/administración & dosificación , Ataque Isquémico Transitorio/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Aspirina/uso terapéutico , Isquemia Encefálica/prevención & control , Clopidogrel/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Humanos , Ataque Isquémico Transitorio/prevención & control , Prevención Secundaria , Accidente Cerebrovascular/prevención & control
18.
Int J Stroke ; 14(3): 220-222, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30722755

RESUMEN

Stroke symptoms can be unsettling, even when symptoms resolve, but focusing on stroke prevention can be empowering provided that effective interventions for appropriate patient populations are available. Current options include interventions for symptomatic carotid artery stenosis, anticoagulation for atrial fibrillation, high-dose statins, new oral anticoagulants, new developments in atrial fibrillation detection, and new therapeutics are in development. For antiplatelet therapy, aspirin monotherapy is effective but dual antiplatelet therapy with the combination of aspirin and clopidogrel increases hemorrhage risks over the long term that outweigh potential benefits. In the short term though, both the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trials have shown a benefit of short-term dual-antiplatelet therapy, though the increased major hemorrhage risk seen in POINT could justify applying dual-antiplatelet therapy to just the first 21 days. Furthermore, since clopidogrel is a prodrug that must be metabolized to have antiplatelet activity, it is not surprising that the treatment effect in CHANCE was limited to patients who were not carriers of loss-of-function alleles for clopidogrel metabolism. Ticagrelor, an antiplatelet agent which failed to meet its primary endpoint as monotherapy compared to aspirin in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial, is currently being tested as combination therapy with aspirin compared to aspirin alone in Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES). These developments along with improvements to the infrastructure to perform rapid evaluations and to apply intensive secondary stroke prevention interventions hold continued promise for the future.


Asunto(s)
Aspirina/uso terapéutico , Fibrinolíticos/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Ticagrelor/uso terapéutico , Ticlopidina/uso terapéutico , Clopidogrel/uso terapéutico , Quimioterapia Combinada , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria , Resultado del Tratamiento
19.
Zhonghua Yi Xue Za Zhi ; 99(5): 349-353, 2019 Jan 29.
Artículo en Chino | MEDLINE | ID: mdl-30772975

RESUMEN

Objective: To assess outcome, safety and possible mechanism of loading dose clopidogrel in patients with transient ischemic attack (TIA) and minor stroke. Methods: We reviewed patients with confirmed TIA and minor stroke admitted between July 2016 and December 2017 into the First Affiliated Hospital of Soochow University. Loss-of-function allele carriers of CYP2C19 were included and randomly divided into loading dose group (first dose of 300 mg clopidogrel) and standard dose group (first dose of 75 mg clopidogrel), 100 mg aspirin was gave at the same time, followed by aspirin 100 mg/d plus clopidogrel 75 mg/d maintaining for 20 days. Platelet aggregation (maximum aggregation ratio, MAR) induced by Adenosine diphosphate (ADP) was examined before and 3 days after administration. The National Institutes of Health Stroke Scale (NIHSS) score method was employed to assess the NIHSS scores before and after treatment in each group of patients; the modified Rankin Scale (mRS) was used to assess the 3-month functional outcome. Results: There was no significant difference in baseline data between the two groups (P>0.05).The proportion of early neurological function improvement in the two groups was 75.0% and 54.8%, and the difference was statistically significant (χ(2)=4.498, P=0.034). The 3-month prognosis was 79.5% and 61.3%, and the difference was statistically significant (χ(2)=4.000, P=0.045). Adverse events: 1 case in the loading dose group, 1 case in the standard dose group, the difference was not statistically significant (2.3% vs 1.6%, χ(2)=0.061, P=0.806). After 3 days of antiplatelet therapy, the MAR of the loading dose group decreased (11%±8%), and the MAR of the standard dose group decreased (9%±4%), the difference was statistically significant (P=0.013).In the loading dose group, there were 32 (72.7%)CYP2C19*2 carriers and 42 (95.5%)CYP2C19*2+*3 carriers; early neurological function improvement in 33 cases, accounting for 93.8% and 76.2%, respectively, and the difference was statistically significant (χ(2)=4.122, P=0.042). There were 35 patients with good prognosis in 3 months, accounting for 96.9% and 81.0%, respectively. The difference was statistically significant (χ(2)=4.310, P=0.038); MAR of CYP2C19*2 carrier was decreased (15%±5%), and MAR of CYP2C19*2+*3 carrier was decreased (12%±8%). The difference was statistically significant (P=0.039). Conclusions: Loading dose clopidogrel can improve the clinical prognosis of minor stroke/TIA without increasing the risk of bleeding. Loading dose clopidogrel may improve the prognosis of minor stroke/TIA by decreasing MAR of CYP2C19*2 carriers.


Asunto(s)
Clopidogrel/uso terapéutico , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Aspirina , Quimioterapia Combinada , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria , Accidente Cerebrovascular/tratamiento farmacológico , Ticlopidina , Resultado del Tratamiento
20.
JAMA Neurol ; 76(5): 552-560, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30742211

RESUMEN

Importance: Genetic variants of ABCB1 may affect intestinal absorption of clopidogrel bisulfate. However, it is unclear whether ABCB1 polymorphisms are associated with clopidogrel efficacy for minor ischemic stroke or transient ischemic attack (TIA). Objectives: To investigate the association between ABCB1 polymorphisms and clopidogrel efficacy for minor stroke or TIA. Design, Setting, and Participants: In this prespecified secondary analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) randomized clinical trial, 3010 patients with minor stroke or TIA at 73 sites in China with experience in conducting genetic studies were included from October 1, 2009, to July 30, 2012. The analysis was conducted on March 20, 2018. Four single-nucleotide polymorphisms (ABCB1 -154T>C [rs4148727], ABCB1 3435C>T [rs1045642], CYP2C19*2 [681G>A, rs4244285], and CYP2C19*3 [636G>A, rs4986893]) were genotyped among 2836 patients treated with clopidogrel plus aspirin (n = 1414) or aspirin alone (n = 1422). The association of ABCB1 genetic variants (-154 TC/CC and 3435 CT/TT) with clopidogrel efficacy was evaluated in the context of CYP2C19 status, another gene associated with clopidogrel efficacy. Interventions: Patients in the CHANCE trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. Main Outcomes and Measures: Primary efficacy outcome was stroke recurrence after 3 months. The safety outcome was any bleeding risk after 3 months. Results: Among 2836 patients, the median age was 61.8 years (interquartile range, 54.4-71.1 years) and 1887 patients (66.5%) were male. A total of 2146 (75.7%) patients were carriers of ABCB1 -154 TC/CC (570 [20.1%]) or 3435 CT/TT (1851 [65.3%]) genotype. Clopidogrel plus aspirin treatment was associated with reduced risk of new stroke in patients with ABCB1 -154 TT and 3435 CC genotype (hazard ratio [HR], 0.43; 95% CI, 0.26-0.71) but not in those with ABCB1 -154 TC/CC or 3435 CT/TT genotype (HR, 0.78; 95% CI, 0.60-1.03) compared with aspirin (P = .04 for interaction). A combined association of ABCB1 and CYP2C19 polymorphisms with new stroke was observed. The risk of bleeding for clopidogrel plus aspirin treatment was not associated with the ABCB1 genotypes (2.3% and 1.3% vs 1.9% and 2.2%; P = .25 for interaction in patients with or without ABCB1 -154 TC/CC or 3435 CT/TT genotype). Conclusions and Relevance: The ABCB1 polymorphism was associated with the reduced efficacy of clopidogrel plus aspirin treatment compared with aspirin among patients with minor ischemic stroke or TIA. Genetic polymorphism of ABCB1 should be considered when prescribing clopidogrel for these patients. Trial Registration: ClinicalTrials.gov identifier: NCT00979589.


Asunto(s)
Clopidogrel/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Anciano , Aspirina/uso terapéutico , Citocromo P-450 CYP2C19/genética , Quimioterapia Combinada , Femenino , Humanos , Ataque Isquémico Transitorio/epidemiología , Masculino , Persona de Mediana Edad , Variantes Farmacogenómicas , Polimorfismo de Nucleótido Simple , Recurrencia , Prevención Secundaria , Accidente Cerebrovascular/epidemiología , Resultado del Tratamiento
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