With current advances in medical treatment and effective public health prevention strategies, there has been a dramatic increase in the average life expectancy in an aging population that has increased comorbidites, such as heart and cerebrovascular diseases. It is now estimated that over 30% of the adult population uses aspirin for primary or secondary prevention of cardiovascular disease. Nearly half receive clopidogrel to either prevent arterial thrombosis in the form of myocardial infarctions and cerebrovascular accidents, or to prevent in-stent thrombosis following placement of drug-eluting coronary stents.1 Clopidogrel and its newer counterpart, prasugrel, exhibit exclusive antiplatelet activity by irreversibly binding to the P2Y12 adenosine diphosphate receptor. This inhibits platelet activation and aggregation for the lifespan of the platelet, an effect lasting 5 to 7 days.2
With the rising incidence of lung cancer, bronchoscopists are increasingly faced with the dilemma regarding the safety of certain procedures in patients receiving antiplatelet therapy. The British Thoracic Society guidelines recommend holding clopidogrel or prasugrel for 5 to 7 days before a transbronchial or endobronchial biopsy.3 The American College of Chest Physicians and American Heart Association, however, warn that early discontinuation of antiplatelet therapy, even for a short time, poses a high risk for life-threatening stent thrombosis in patients with drug-eluting stent placement of <12 months.4,5
The few studies that have focused on the safety of thoracic procedures on patients receiving antiplatelet therapy are conflicting. On one hand, studies have shown an increased rate of bleeding with transbronchial biopsy, with one study reporting the risk of significant bleeding as high as 100% on aspirin and clopidogrel and 89% on clopiodgrel alone.6 Conversely, thoracic surgeries such as lobectomies, video-assisted wedge resections, and mediastonoscopies have been deemed safe to perform on patients receiving antiplatelet therapy with no perioperative bleeding, as reported by a prospective study of 33 patients who received clopidogrel up to and including the day of surgery.7
Endobronchial ultrasound-guided tranbronchial needle aspiration (EBUS-TBNA) has generally been deemed to have a low risk for bleeding. Nevertheless, there is a paucity of robust data on the safety of EBUS-TBNA in patients receiving antiplatelet therapy. The majority of the data are derived from case series or retrospective reviews. Stather and colleagues first described the safety of EBUS-TBNA in a retrospective single-center review of 12 cases of EBUS-TBNA performed on patients receiving clopidogrel, 7 (66.7%) of whom were also on aspirin. This was performed under moderate sedation, with no endotracheal intubation, using either a 22- or 21-G needle. There was no significant bleeding observed in any case at the time of bronchoscopy nor at the 4-week follow-up.8 In another single-site retrospective review of 395 patients who underwent EBUS-TBNA or esophageal ultrasound fine-needle aspiration, 37 subjects were on clopidogrel at the time of the procedure. Nodal sampling was performed, using a 22-G needle without Doppler guidance, without significant bleeding.9 A more recent retrospective chart review of 409 cases of EBUS-TBNA included 103 patients on aspirin, 13 on clopidogrel, and 23 on dual antiplatelet therapy. In this study, there was a trend toward an increased bleeding rate in patients on antiplatelet therapy. In total, 8.7% of patients on dual antiplatelet therapy and 7.7% on clopidogrel had bleeding events, compared with a rate of only 2.9% for patients not on antiplatelet therapy.10 The lack of statistical significance in this study may be attributed to its small sample size.
In the current issue of The Journal of Bronchology and Interventional Pulmonology, Webb et al11 present their experience performing EBUS-TBNA on patients on both aspirin and clopidogrel. In this multicenter prospective study, the authors included all subjects presenting with mediastinal or hilar lymphadenopathy requiring sampling for staging and/or diagnosis. Patients were excluded from the study, if the medication could be held for 5 to 7 days before the procedure, as determined by the primary prescriber. A total of 40 patients with a mean age of 69 were included in the study. The majority of these patients (77%) were receiving clopidgrel for coronary artery disease with recent drug-eluting stent placement. In total, 40 EBUS procedures were performed under total intravenous anesthesia by interventional pulmonary faculty or fellows. A total of 92 lymph nodes were aspirated, with the most common stations for biopsy being 7 (27%) and 4R (26%). Three passes were initially made with a 22-G needle. An additional 3 passes were then made with a 21-G needle if no bleeding occurred. The authors defined a bleeding event as significant if an intervention such as balloon tamponade or if the use of cold saline or topical sympathomimetics was required to achieve hemostasis. Patient follow-up included a phone call placed 24 hours postprocedure, as well as a follow-up visit within 1 to 2 weeks of the bronchoscopy. There were no significant bleeding events reported at the time of all 40 bronchoscopies performed using either a 22- or 21-G needle. In addition, no postprocedure bleeding complications were reported during follow-up visits.
To date, this study represents the largest prospective multicenter study designed to evaluate the safety of EBUS-TBNA in patients receiving dual antiplatelet therapy. However, it does have several important limitations including its small sample size and lack of generalizability to less experienced operators without interventional pulmonology training.
The study by Webb et al11 adds to the emerging data on EBUS-TBNA safety, reassuring us that, in the hands of expert bronchoscopists, this procedure can indeed be performed safely on patients receiving antiplatelet therapy. Although there is a collective lack of bleeding complications in all studies performed to date, we should still interpret these results with caution. We continue to advocate for the cessation of antiplatelet therapy whenever possible, as, if bleeding were to occur, it may be significant. In circumstances where the increased risk of thrombosis is believed to outweigh the perceived risk of bleeding, we recommend that the following procedure be performed in the hands of an expert bronchoscopist, capable of managing a potentially massively bleeding airway: the use of total intravenous anesthesia and endotracheal intubation; the use of rapid onsite analysis to minimize the number of passes needed for diagnosis and/or staging; and the use of color Doppler to look for blood vessels if there is concern for indeterminate structures on ultrasound image. Perhaps the most important aspect to consider is adequate preparedness for excessive bleeding by ensuring that a fogarty balloon, bronchial blocker, epinephrine, and/or APC are readily available.
Lastly, with recent advances in antiplatelet reversibility—is there a role for intravenous bridging of antiplatelet therapy, by either using rapidly reversible glycoprotein inhibitors such as epifibatide or tirofiban, or P2Y12 inhibitors such as cangrelor? Further studies that combine larger sample sizes and platelet reversibility need to be explored to provide definitive recommendations on the safety of EBUS-TBNA in patients on antiplatelet therapy.
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