Safety of perioperative low dose aspirin therapy in major lung resection

Aspirin is widely used for the primary and secondary prevention of cardiovascular disease. Gu et al. estimated the prevalence of preventive aspirin use in the US adult population from the National Health and Nutrition Examination Survey, 2011–2012, and about one-third of the US adults aged more than 40 years used aspirin for preventive purposes (1). Some population-based studies reported that among patients diagnosed with lung cancer, 15.3% in Korea and 26% in Sweden were aspirin users (2,3). Accordingly, thoracic surgeons are frequently confronted with patients taking aspirin and need to decide whether to continue or discontinue aspirin in the perioperative period.

Perioperative aspirin could increase the risk of a bleeding complication. However, the discontinuation of aspirin could increase the risk of thromboembolic complication due to aspirin withdrawal syndrome and increased coagulability caused by a systemic reaction to surgery (4).

In 2014, the result of the Perioperative Ischemic Evaluation 2 (POISE-2) trial was published (5). This was the largest randomized trial on the use of aspirin in the perioperative period. In the trial, 10,010 patients who were scheduled for noncardiac surgery and were at risk for vascular complications were assigned to receive aspirin or placebo. The study showed that there was no difference in death or non-fatal myocardial infarction between the groups. Major bleeding was more common in the aspirin group than in the placebo group. This study suggests that perioperative aspirin might be harmful. However, patients who received a bare-metal coronary stent less than 6 weeks before surgery or a drug-eluting coronary stent less than 1 year before surgery were excluded from this study. These patients are at greater risk of perioperative myocardial infarction and are most likely to benefit from aspirin therapy. Moreover, in a subgroup analysis of the POISE-2 trial, perioperative aspirin reduced the risk for death or non-fatal myocardial infarction in patients who had undergone a prior percutaneous coronary intervention (PCI) (6).

Stamenovic et al. evaluated the perioperative use of aspirin in patients undergoing major lung resections (7). Before this study, there had been only a few retrospective studies with relatively small numbers of patients in the field of thoracic surgery (8,9). Among a total of 486 patients, 329 did not use aspirin (group ASA-0), while 157 did (group ASA-1), in the perioperative period. Two hundred and seventy-three patients (56.2%) underwent video assisted thoracoscopic surgery (VATS) and 213 (43.8%) underwent thoracotomies. There was no difference in the surgical approach (VATS vs. thoracotomy) and type of surgical resection between the groups. In terms of postoperative outcomes, there was no difference in intraoperative bleeding, blood loss, blood transfusion, thoracotomy conversion from VATS, cardiovascular complications, and death between the groups. Although there was a trend towards a higher rate of postoperative complications in the ASA-1 group, this might have been related to more comorbidities and older age. Thoracotomy was associated with more blood loss than VATS (P<0.001). Pneumonectomy was associated with more blood loss than lobectomy or segmentectomy (P<0.001). This study showed that perioperative aspirin does not increase the risk of bleeding complication in thoracic surgery, even in thoracotomy and pneumonectomies.

There are two points to be considered. First, there is no mention about for whom to continue or discontinue aspirin therapy in the manuscript. Group ASA-0 may have included those who were not taking aspirin and those who discontinued the aspirin therapy in the perioperative period. The patients who discontinued aspirin therapy may have had lower cardiovascular risks or higher bleeding risks, such as patients with expected pleural adhesion and those who underwent more extensive surgery. Continuing aspirin therapy in the perioperative period may have a greater benefit for patients with a higher cardiovascular risk, such as patients who have undergone a recent PCI. However, the routine use of aspirin may be harmful. Aspirin increased the risk of major postoperative bleeding in the POISE-2 trial (5). It seems to be more difficult to control bleeding from the chest wall secondary to the takedown of adhesion with antiplatelet therapy (9,10). For now, we still have no solid evidence about for whom to continue or discontinue aspirin therapy in thoracic surgery.

Second, the patients who were taking antiplatelet agents other than aspirin were excluded. Previously, we reported increased postoperative bleeding in patients who had undergone dual antiplatelet therapy (aspirin + clopidogrel) compared with other antiplatelet therapies in thoracoscopic surgery for lung cancer (P=0.005) (9). Clopidogrel or dual antiplatelet therapy is a more potent antiplatelet therapy than low-dose aspirin (11) and we still do not have sufficient data about these effects of perioperative antiplatelet therapy other than aspirin on the operative outcomes.

In conclusion, aspirin therapy can be used in major resection surgery without an increase in bleeding complications in patients with a higher cardiovascular risk. Surgeons need to decide whether to continue or discontinue the antiplatelet therapy, considering the cardiovascular risk and the risk of bleeding.

Acknowledgments

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

References

1. Gu Q, Dillon CF, Eberhardt MS, et al. Preventive Aspirin and Other Antiplatelet Medication Use Among U.S. Adults Aged ≥ 40 Years: Data from the National Health and Nutrition Examination Survey, 2011-2012. Public Health Rep 2015;130:643-54. [Crossref] [PubMed]
2. Jonsson F, Yin L, Lundholm C, et al. Low-dose aspirin use and cancer characteristics: a population-based cohort study. Br J Cancer 2013;109:1921-5. [Crossref] [PubMed]
3. Ye S, Lee M, Lee D, et al. Association of Long-term Use of Low-Dose Aspirin as Chemoprevention With Risk of Lung Cancer. JAMA Netw Open 2019;2:e190185. [Crossref] [PubMed]
4. Chassot PG, Delabays A, Spahn DR. Perioperative antiplatelet therapy: the case for continuing therapy in patients at risk of myocardial infarction. Br J Anaesth 2007;99:316-28. [Crossref] [PubMed]
5. Devereaux PJ, Mrkobrada M, Sessler DI, et al. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014;370:1494-503. [Crossref] [PubMed]
6. Graham MM, Sessler DI, Parlow JL, et al. Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery. Ann Intern Med 2018;168:237-44. [Crossref] [PubMed]
7. Stamenovic D, Schneider T, Messerschmidt A. Aspirin for patients undergoing major lung resections: hazardous or harmless? Interact Cardiovasc Thorac Surg 2019;28:535-41. [Crossref] [PubMed]
8. Kanzaki R, Inoue M, Minami M, et al. Feasibility of aspirin continuation during the perioperative period for pulmonary resection in lung cancer patients: a retrospective study at a single institute in Japan. Surg Today 2014;44:2243-8. [Crossref] [PubMed]
9. Yu WS, Jung HS, Lee JG, et al. Safety of thoracoscopic surgery for lung cancer without interruption of anti-platelet agents. J Thorac Dis 2015;7:2024-32. [PubMed]
10. Cerfolio RJ, Minnich DJ, Bryant AS. General thoracic surgery is safe in patients taking clopidogrel (Plavix). J Thorac Cardiovasc Surg 2010;140:970-6. [Crossref] [PubMed]
11. Columbo JA, Lambour AJ, Sundling RA, et al. A Meta-analysis of the Impact of Aspirin, Clopidogrel, and Dual Antiplatelet Therapy on Bleeding Complications in Noncardiac Surgery. Ann Surg 2018;267:1-10. [Crossref] [PubMed]