ImportanceThe optimal treatment of intermediate-high–risk pulmonary embolism (PE) remains unknown.ObjectiveTo assess the effect of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures of right ventricle (RV) to left ventricle (LV) ratio in acute intermediate-high–risk PE.Design, Setting, and ParticipantsThe Catheter-Directed Thrombolysis vs Anticoagulation in Patients with Acute Intermediate-High–Risk Pulmonary Embolism (CANARY) trial was an open-label, randomized clinical trial of patients with intermediate-high–risk PE, conducted in 2 large cardiovascular centers in Tehran, Iran, between December 22, 2018, through February 2, 2020.InterventionsPatients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy.Main Outcomes and MeasuresThe proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory, was the primary outcome. The proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and the 3-month all-cause mortality were among secondary outcomes. Major bleeding (Bleeding Academic Research Consortium type 3 or 5) was the main safety outcome. A clinical events committee, masked to the treatment assignment, adjudicated clinical outcomes.ResultsThe study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 patients (mean [SD] age, 58.4 [2.5] years; 27 women [29%]), of whom 85 patients completed the 3-month echocardiographic follow-up. Overall, 2 of 46 patients (4.3%) in the cCDT group and 5 of 39 patients (12.8%) in the anticoagulation monotherapy group met the primary outcome (odds ratio [OR], 0.31; 95% CI, 0.06-1.69; P = .24). The median (IQR) 3-month RV/LV ratio was significantly lower with cCDT (0.7 [0.6-0.7]) than with anticoagulation (0.8 [0.7-0.9); P = .01). An RV/LV ratio greater than 0.9 at 72 hours after randomization was observed in fewer patients treated with cCDT (13 of 48 [27.0%]) than anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P = .01). Fewer patients assigned to cCDT experienced a 3-month composite of death or RV/LV greater than 0.9 (2 of 48 [4.3%] vs 8 of 46 [17.3%]; OR, 0.20; 95% CI, 0.04-1.03; P = .048). One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group.Conclusions and RelevanceThis prematurely terminated randomized clinical trial of patients with intermediate-high–risk PE was hypothesis-generating for improvement in some efficacy outcomes and acceptable rate of major bleeding for cCDT compared with anticoagulation monotherapy and provided support for a definitive clinical outcomes trial.Trial RegistrationClinicalTrials.gov Identifier: NCT05172115
Although aspirin and clopidogrel seem to be quite enough during low risk percutaneous coronary intervention (PCI), the combination may need some reinforcement in complex situations such as primary PCI. By modifying the route and also the duration of administration, glycoprotein IIb/IIIa inhibitors might be a viable option. The aim of this study is to compare the benefits and disadvantages of three different methods of administration of eptifibatide in primary PCI population. Primary PCI candidates were randomized in three groups on which three different methods of administration of eptifibitide were tested: intravenous bolus injection followed by 12-h infusion (IV-IV), intracoronary bolus injection followed by intravenous infusion (IC-IV) and, only intracoronary bolus injection (IC). 99 patients were included in the present study. There was no significant difference among the three groups regarding all cause in hospital and one month mortality (p value = 0.99), re-myocardial infarction (p value = 0.89), post-PCI TIMI flow grade 3 (p value = 0.97), ST segment resolution (p value = 0.77) and peak troponin levels (p value = 0.82). The comparison of vascular access and major bleeding complications were not possible due to low events rate. By modifying the route of administration of eptifibitide, the clinical effect might be preserved without increasing the short-term mortality and procedural failure.
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