A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study.

OBJECTIVES: The aim of this study was to evaluate the safety and effectiveness of percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, California) in a prospective trial of patients with acute intermediate-risk pulmonary embolism (PE). BACKGROUND: Catheter-directed thrombolysis has been shown to improve right ventricular (RV) function in patients with PE. However, catheter-directed thrombolysis increases bleeding risk and many patients with PE have relative and absolute contraindications to thrombolysis. METHODS: Patients with symptomatic, computed tomography-documented PE and RV/left ventricular (LV) ratios ≥0.9 were eligible for enrollment. The primary effectiveness endpoint was core laboratory-assessed change in RV/LV ratio. The primary safety endpoint comprised device-related death, major bleeding, treatment-related clinical deterioration, pulmonary vascular injury, or cardiac injury within 48 h of thrombectomy. RESULTS: From April 2016 to October 2017, 106 patients were treated with the FlowTriever System at 18 U.S. sites. Two patients (1.9%) received adjunctive thrombolytics and were analyzed separately. Mean procedural time was 94 min; mean intensive care unit stay was 1.5 days. Forty-three patients (41.3%) did not require any intensive care unit stay. At 48 h post-procedure, average RV/LV ratio reduction was 0.38 (25.1%; p < 0.0001). Four patients (3.8%) experienced 6 major adverse events, with 1 patient (1.0%) experiencing major bleeding. One patient (1.0%) died, of undiagnosed breast cancer, through 30-day follow-up. CONCLUSIONS: Percutaneous mechanical thrombectomy with the FlowTriever System appears safe and effective in patients with acute intermediate-risk PE, with significant improvement in RV/LV ratio and minimal major bleeding. Potential advantages include immediate thrombus removal, absence of thrombolytic complications, and reduced need for post-procedural critical care.

Efficacy and safety of clopidogrel pretreatment before percutaneous coronary intervention with and without glycoprotein IIb/IIIa inhibitor use.

BACKGROUND: Clopidogrel pretreatment before percutaneous coronary intervention (PCI) has been shown to reduce the risk of death and ischemic complications after PCI. However, the need for clopidogrel pretreatment is debated in patients receiving a glycoprotein IIb/IIIa inhibitor (GPI). METHODS: We performed a collaborative meta-analysis of the results of 3 randomized trials of clopidogrel pretreatment: PCI-CURE, CREDO, and PCI-CLARITY. Patients were stratified based on GPI use at the time of PCI (a postrandomization subgroup analysis). Odds ratios (ORs) and 95% CIs for the effect of clopidogrel pretreatment versus placebo pretreatment on the incidence of cardiovascular death, myocardial infarction (MI), or stroke for up to 30 days after PCI were calculated for each trial within each GPI stratum and were combined using a random effects model. RESULTS: Six thousand three hundred twenty-five patients were included, 32.4% of whom received a GPI. There was a consistent benefit of clopidogrel pretreatment in reducing the incidence of cardiovascular death, MI, or stroke after PCI both in patients who did not receive a GPI (OR 0.72, 95% CI 0.53-0.98, P = .03) and in those who did (OR 0.69, 95% CI 0.47-1.00, P = .05). There was no evidence of heterogeneity in the benefit of clopidogrel pretreatment between GPI use strata (P = .85 for heterogeneity). Clopidogrel pretreatment was not associated with a significant excess of TIMI major or minor bleeding, either in those who did not receive a GPI (OR 1.20, 95% CI 0.76-1.92) or in those who did (OR 1.22, 95% CI 0.71-2.09) (P = .97 for heterogeneity). CONCLUSION: Clopidogrel pretreatment before PCI is beneficial and safe regardless of whether a GPI is used at the time of PCI.

Oral antiplatelet therapy for percutaneous coronary revascularization.

Great strides in interventional pharmacotherapy have been made over the past few decades, virtually all focused on optimizing peri-PCI antithrombotic therapy in order to reduce thrombotic complications. Our understanding of the role of platelets and of antiplatelet therapies in this process continues to evolve. Today, dual or even triple antiplatelet therapy has become standard of care at the time of PCI followed by dual therapy long-term in the majority of patients. However, currently available oral regimens are hampered by limitations including the need to initiate treatment at least a few hours before the procedure to achieve maximum benefit and the safety issues surrounding irreversible platelet inhibition in the uncommon, but not rare situations when a patient requires surgical revascularization. These limitations have led to the suboptimal "real-world" utilization of these proven agents and have fostered the development of a wide variety of alternative platelet inhibitors with theoretical, but still unproven clinical benefits. There are ample clinical data that strongly support the use of aspirin and clopidogrel in virtually all patients undergoing a PCI today. This review will highlight these data as well as emphasize the gaps in our understanding. (c) 2007 Wiley-Liss, Inc.

Clopidogrel in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention.

Clopidogrel has become a mainstay in the management of acute coronary syndrome patients over the past decade, as well as an essential component of percutaneous coronary intervention (PCI) pharmacotherapy. Until recently, no prospective study has evaluated the effectiveness of clopidogrel in the setting of an ST-segment elevation myocardial infarction (STEMI). The majority of patients presenting with STEMI receive thrombolytic therapy (aspirin, heparin and a fibrinolytic agent) although many do not achieve or maintain adequate reperfusion of the infarct-related artery. The CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy) study and the PCI-CLARITY substudy were designed to address whether a beneficial effect of clopidogrel, including a loading dose, would be attained among STEMI patients who were being treated with thrombolytic therapy and undergoing coronary angiography during the index hospitalisation. A total of 3491 patients who presented within 12 h after the onset of STEMI were randomly assigned to receive clopidogrel (300-mg loading dose followed by 75 mg daily) or placebo. Patients were scheduled to undergo coronary angiography after 48 h, and those who underwent PCI during the index hospitalisation formed the basis of PCI-CLARITY. This PCI cohort was followed for the combined end point of cardiovascular death, recurrent myocardial infarction and stroke for 30 days.