Fragestellung: Der Einsatz von Flow-divertern (FD) bei der akuten Subarachnoidalblutung (SAB) ist durch die notwendige Thrombozytenaggregationshemmung nur eingeschrankt moglich. Bei Aneurysmen im ...vertebrobasilaren Stromgebiet ist zudem das Risiko eines Verschlusses perforierender Aste gross. Entsprechend wenige Daten gibt es zur Behandlung rupturierter Aneurysmen im vertebrobasilaren Stromgebiet mit FD. Ergebnisse: Bei Aufnahme hatten 6 Patienten eine Fisher IV und 1 Patient eine Fisher III Blutung. Es handelte sich um 2 fusiforme und 5 sakkulare Aneurysmen der BA (n = 3), PICA (n = 2), SCA und VA (je n = 1). Fur Beispiele s. Abb. 1a und c. Die Patienten wurden mittels Implantation eines Pipeline-Stents am Aufnahmetag (n = 2) bzw. nach 1 (n = 3) und 2 (n = 2) Tagen behandelt. Alle Patienten erhielten ASS, Clopidogrel und eine kurzzeitige Vollheparinisierung. Kein Patient entwickelte einen Perforator-Infarkt. Im klinischen Verlauf verstarben 4 Patienten (Folge von Vasospasmen (n = 3), Nachblutung 2 Monate nach Entlassung (n = 1, s. Abb. 1d)). Von den uberlebenden Patienten zeigten 2 einen gunstigen klinischen Verlauf (mRS < 2, s. Abb. 1b).
Fragestellung: Der Einsatz von Flow-divertern (FD) bei der akuten Subarachnoidalblutung (SAB) ist durch die notwendige Thrombozytenaggregationshemmung nur eingeschrankt moglich. Bei Aneurysmen im ...vertebrobasilaren Stromgebiet ist zudem das Risiko eines Verschlusses perforierender Aste gross. Entsprechend wenige Daten gibt es zur Behandlung rupturierter Aneurysmen im vertebrobasilaren Stromgebiet mit FD. Methoden: In dieser retrospektiven Studie wurden 7 Patienten (2010-2014) mit rupturierten Aneurysmen im vertebrobasilaren Stromgebiet, die mit FD behandelt wurden, im Detail hinsichtlich Bildgebungsbefunden, klinischem Verlauf sowie langfristigem Outcome untersucht. Ergebnisse: Bei Aufnahme hatten 6 Patienten eine Fisher IV und 1 Patient eine Fisher III Blutung. Es handelte sich um 2 fusiforme und 5 sakkulare Aneurysmen der BA (n = 3), PICA (n = 2), SCA und VA (je n = 1). Fur Beispiele s. Abb. 1a und c. Die Patienten wurden mittels Implantation eines Pipeline-Stents am Aufnahmetag (n = 2) bzw. nach 1 (n = 3) und 2 (n = 2) Tagen behandelt. Alle Patienten erhielten ASS, Clopidogrel und eine kurzzeitige Vollheparinisierung. Kein Patient entwickelte einen Perforator-Infarkt. Im klinischen Verlauf verstarben 4 Patienten (Folge von Vasospasmen (n = 3), Nachblutung 2 Monate nach Entlassung (n = 1, s. Abb. 1d)). Von den uberlebenden Patienten zeigten 2 einen gunstigen klinischen Verlauf (mRS < 2, s. Abb. 1b). Schlussfolgerungen: In Einzelfallen kann die Behandlung rupturierter Aneurysmen im vertebrobasilaren Stromgebiet mit FD erwogen werden. Das Risiko einer akuten Nachblutung und von Perforator-Infarkten besteht, scheint jedoch niedriger zu sein, als allgemein befurchtet.
AbstractObjectiveTo evaluate the efficacy and safety of standard term (12 months) or long term (>12 months) dual antiplatelet therapy (DAPT) versus short term (<6 months) DAPT after percutaneous ...coronary intervention (PCI) with drug-eluting stent (DES).DesignSystematic review and network meta-analysis.Data sourcesRelevant studies published between June 1983 and April 2018 from Medline, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister.eu.Review methodsRandomised controlled trials comparing two of the three durations of DAPT (short term, standard term, and long term) after PCI with DES were included. The primary study outcomes were cardiac or non-cardiac death, all cause mortality, myocardial infarction, stent thrombosis, and all bleeding events.Results17 studies (n=46 864) were included. Compared with short term DAPT, network meta-analysis showed that long term DAPT resulted in higher rates of major bleeding (odds ratio 1.78, 95% confidence interval 1.27 to 2.49) and non-cardiac death (1.63, 1.03 to 2.59); standard term DAPT was associated with higher rates of any bleeding (1.39, 1.01 to 1.92). No noticeable difference was observed in other primary endpoints. The sensitivity analysis revealed that the risks of non-cardiac death and bleeding were further increased for ≥18 months of DAPT compared with short term or standard term DAPT. In the subgroup analysis, long term DAPT led to higher all cause mortality than short term DAPT in patients implanted with newer-generation DES (1.99, 1.04 to 3.81); short term DAPT presented similar efficacy and safety to standard term DAPT with acute coronary syndrome (ACS) presentation and newer-generation DES placement. The heterogeneity of pooled trials was low, providing more confidence in the interpretation of results.ConclusionsIn patients with all clinical presentations, compared with short term DAPT (clopidogrel), long term DAPT led to higher rates of major bleeding and non-cardiac death, and standard term DAPT was associated with an increased risk of any bleeding. For patients with ACS, short term DAPT presented similar efficacy and safety with standard term DAPT. For patients implanted with newer-generation DES, long term DAPT resulted in more all cause mortality than short term DAPT. Although the optimal duration of DAPT should take personal ischaemic and bleeding risks into account, this study suggested short term DAPT could be considered for most patients after PCI with DES, combining evidence from both direct and indirect comparisons.Systematic review registrationPROSPERO CRD42018099519.
IMPORTANCE: Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. OBJECTIVE: To test the ...hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. INTERVENTIONS: Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. RESULTS: Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, −1.34% 95% CI, −2.57% to −0.11%; hazard ratio HR, 0.64 95% CI, 0.42-0.98), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, −0.55% 95% CI, −1.62% to 0.52%; HR, 0.79 95% CI, 0.49-1.29), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, −1.13% 95% CI, −1.84% to −0.42%; HR, 0.26 95% CI, 0.11-0.64; P = .004 for superiority). CONCLUSIONS AND RELEVANCE: Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02619760
In patients undergoing transcatheter aortic-valve implantation, aspirin alone was associated with fewer bleeding events than aspirin plus clopidogrel administered for 3 months and was noninferior to ...the combination therapy with respect to thrombotic events.
In a trial comparing the addition of clopidogrel with no clopidogrel in patients receiving anticoagulation, the incidence of any bleeding and of non–procedure-related bleeding was lower in the ...monotherapy group. Composite cardiovascular outcomes were noninferior for the monotherapy group but were superior only for a composite that included bleeding.
Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in older patients ...are scarce. We aimed to investigate the safety and efficacy of clopidogrel compared with ticagrelor or prasugrel in older patients with non-ST-elevation acute coronary syndrome (NSTE-ACS).
We did the open-label, randomised controlled POPular AGE trial in 12 sites (ten hospitals and two university hospitals) in the Netherlands. Patients aged 70 years or older with NSTE-ACS were enrolled and randomly assigned in a 1:1 ratio using an internet-based randomisation procedure with block sizes of six to receive a loading dose of clopidogrel 300 mg or 600 mg, or ticagrelor 180 mg or prasugrel 60 mg, and then a maintenance dose for the duration of 12 months (clopidogrel 75 mg once daily, ticagrelor 90 mg twice daily, or prasugrel 10 mg once daily) on top of standard care. Patient and treating physicians were aware of the allocated treatment strategy, but the outcome assessors were masked to treatment allocation. Primary bleeding outcome consisted of PLATelet inhibition and patient Outcomes (PLATO; major or minor bleeding superiority hypothesis). Co-primary net clinical benefit outcome consisted of all-cause death, myocardial infarction, stroke, PLATO major and minor bleeding (non-inferiority hypothesis, margin of 2%). Follow-up duration was 12 months. Analyses were done on intention-to-treat basis. This trial is registered with the Netherlands Trial Register (NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT (2013–001403–37).
Between June 10, 2013, and Oct 17, 2018, 1002 patients were randomly assigned to clopidogrel (n=500) or ticagrelor or prasugrel (n=502). Because 475 (95%) patients received ticagrelor in the ticagrelor or prasugrel group, we will refer to this group as the ticagrelor group. Premature discontinuation of the study drug occurred in 238 (47%) of 502 ticagrelor group patients randomly assigned to ticagrelor, and in 112 (22%) of 500 patients randomly assigned to clopidogrel. Primary bleeding outcome was significantly lower in the clopidogrel group (88 18% of 500 patients) than in the ticagrelor group (118 24% of 502; hazard ratio 0·71, 95% CI 0·54 to 0·94; p=0·02 for superiority). Co-primary net clinical benefit outcome was non-inferior for the use of clopidogrel (139 28%) versus ticagrelor (161 32%; absolute risk difference −4%, 95% CI −10·0 to 1·4; p=0·03 for non-inferiority). The most important reasons for discontinuation were occurrence of bleeding (n=38), dyspnoea (n=40), and the need for treatment with oral anticoagulation (n=35).
In patients aged 70 years or older presenting with NSTE-ACS, clopidogrel is a favourable alternative to ticagrelor, because it leads to fewer bleeding events without an increase in the combined endpoint of all-cause death, myocardial infarction, stroke, and bleeding. Clopidogrel could be an alternative P2Y12 inhibitor especially for elderly patients with a higher bleeding risk.
ZonMw.
IMPORTANCE: Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. OBJECTIVE: To investigate whether dual ...antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale NIHSS score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. INTERVENTIONS: Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. MAIN OUTCOMES AND MEASURES: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to −4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. RESULTS: Among 760 eligible randomized patients (median IQR age, 64 57-71 years; 223 31.0% women; median IQR NIHSS score, 2 1-3), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% 95% CI, −1.5% to 6.2%; crude relative risk, 1.38 95% CI, 0.81-2.32). The unadjusted lower limit of the 1-sided 97.5% CI was −1.5%, which is larger than the −4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. CONCLUSIONS AND RELEVANCE: Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03661411
In a trial in China, patients with a minor stroke or transient ischemic attack with
CYP2C19
loss-of-function alleles as determined by point-of-care testing had modestly fewer second strokes with ...ticagrelor than with clopidogrel but also had more total bleeding events.
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