5-aspirin  

News Author: Megan Brooks
CME Author: Désirée Lie, MD, MSEd

CLINICAL CONTEXT

According to the current study by Gerstein and colleagues, more than 50 million adults in the United States take aspirin regularly for primary and secondary prevention of cardiovascular disease. The cessation of aspirin can cause a platelet rebound phenomenon and prothrombotic state leading to major adverse cardiovascular events. Despite the risks of aspirin withdrawal, exacerbated during the perioperative period, standard practice has been to stop aspirin before elective surgery for fear of excessive bleeding, but evidence suggests that this practice should be abandoned.

This study is a literature review of the cardiovascular risks of discontinuing vs maintaining aspirin therapy and the bleeding risks associated with perioperative aspirin use.

STUDY SYNOPSIS AND PERSPECTIVE

The practice of empirically interrupting chronic aspirin therapy before surgery "should be abandoned," according to the authors of a contemporary literature review.

They say the evidence they found in a PubMed and Medline literature search "strongly supports" continued perioperative use of aspirin in patients taking it for secondary prevention of coronary artery disease, cerebrovascular disease, and peripheral vascular disease.

"Routine discontinuation of aspirin seven to 10 days preoperatively is not only unjustified but likely significantly compounds patients' thromboembolic risk because of the described aspirin withdrawal syndrome that occurs contemporaneously during this time interval," said Dr. Neal Stuart Gerstein from University of New Mexico in Albuquerque and colleagues.

"For an at-risk patient, the hypercoagulable state engendered by the surgical procedure compounded by the aspirin withdrawal syndrome creates an ideal scenario for a major cardiac or vascular thromboembolic complication," they write in Annals of Surgery for May.

But Dr. P.J. Devereaux from Ontario, Canada, who was not involved in the review, told Reuters Health it would be "premature to have physicians believe stopping ASA prior to surgery is clearly the wrong approach to patient management. The authors may be right but the evidence to support their position is very weak." Dr. Devereaux is with the Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Perioperative Medicine and Surgical Research Unit in Hamilton.

More than 50 million adults in the U.S. take aspirin daily for primary and secondary prevention of cardiovascular disease. Whether it's best to stop or continue aspirin before having surgery is an unsettled issue at the moment. Stopping aspirin can cause a platelet rebound phenomenon and prothrombotic state leading to major adverse cardiac events, Dr. Gerstein and colleagues note in their report. But despite the risks of aspirin withdrawal, which are exacerbated during the preoperative period, it's become standard practice to halt aspirin therapy before elective surgery for fear of excessive bleeding.

Based on their literature review, Dr. Gerstein and colleagues conclude that surgical procedures that involve particular anatomic locations, including middle ear, posterior chamber of the eye, intracranial, intramedullary spine and possibly transurethral prostatectomy (TURP) confer the highest risk of complicating hemorrhage while on aspirin therapy.

Aside from these types of procedures, they say, "the thromboembolic risks of aspirin cessation in the at-risk patient often outweigh the minor bleeding risks in the vast majority of operative procedures."

The authors do emphasize, however, that nearly all of the available data they reviewed are observational and retrospective. There remains an "urgent need for prospective randomized trials to evaluate the optimal management strategy of perioperative aspirin therapy," they say.

The POISE-2 trial, which Dr. Devereaux is involved in, promises to shed light on this issue. POISE-2 is a 10,000-patient randomized controlled trial that is evaluating the impact of perioperative ASA in patients undergoing noncardiac surgery.

"In this trial," Dr. Deveraux told Reuters Health, "half the patients are taking chronic ASA and they have to stop it at least three days before surgery, and then they are randomized to restart low-dose ASA or placebo just prior to surgery and they continue it until day eight after surgery when they resume their normal ASA. The other half of the patients in POISE-2 are patients who do not take chronic ASA and they are randomized to start low-dose ASA or placebo just prior to surgery and they take the study drug daily until day 31 after surgery."

"Over 20 countries are participating in this trial, and we have already randomized over 3,700 patients, and we are on track to complete recruitment in the summer of 2013. The independent data safety and monitoring committee evaluated unblinded data after the first 2500 patients completed their first 30 day follow-up and this committee was unanimous in their recommendation to continue the trial. Half of these patients were patients taking chronic ASA," Dr. Devereaux noted.

Dr. Devereaux was also involved in a randomized controlled trial led by Dr. Jean Mantz from Beaujon University Hospital, Clichy, France that was published in August 2011 in the British Journal of Anesthesia. That trial assessed the impact of preoperative maintenance or interruption of chronic aspirin therapy on thrombotic and bleeding events after elective non-cardiac surgery. In this study, Dr. Devereaux told Reuters Health, there was no increase in cardiovascular events in patients who had aspirin held preoperatively.

Ann Surg. 2012;255:811-819.

STUDY HIGHLIGHTS

 

  • According to guidelines from the American Heart Association/American College of Cardiology and the American College of Chest Physicians, aspirin therapy should be started and continued uninterrupted indefinitely unless absolutely contraindicated in virtually all patients with established coronary artery disease.
  • A meta-analysis demonstrated an approximately 25% reduction in death from any vascular cause, myocardial infarction, and stroke with antiplatelet therapy in patients with preexisting cardiovascular events.
  • However, the risk-vs-benefit ratio for primary prevention is less clear than for secondary prevention.
  • In a meta-analysis of primary prevention, aspirin reduced the incidence of vascular events (12% proportional reduction or 0.07% per year absolute reduction, = .0001), mainly for nonfatal myocardial infarction (23% proportional reduction, P < .0001).
  • The net benefit of aspirin in primary prevention is most pronounced in high-risk patients.
  • The 2009 US Preventive Services Task Force recommends aspirin for primary prevention for women 55 to 79 years old when the benefit of reduction in ischemic stroke outweighs the risk of bleeding, and aspirin therapy for men 45 to 79 years old when the benefit from a reduction in myocardial infarction outweighs the risk of increased bleeding.
  • A 2010 position statement by the American Diabetes Association, American Heart Association, and the American College of Cardiology Foundation recommends aspirin for people with diabetes who are at increased cardiac risk (10-year risk for a cardiac event of 10%).
  • Overall, aspirin in primary prevention does not seem to affect cardiovascular mortality (except in high-risk diabetic patients), and its benefit in preventing adverse cardiovascular events is proportional to the degree of underlying risk.
  • On withdrawal of aspirin therapy, the restoration of platelet function is variable.
  • After a single dose, new platelet production begins to recover by approximately 10% per day, and it may take up to 10 days for full restoration of a platelet supply.
  • A robust body of literature substantiates an increased risk for cardiovascular events during the acute aspirin withdrawal period.
  • However, it is still common practice for surgeons or other clinicians to counsel their patients to stop aspirin therapy 7 to 10 days before surgery.
  • Available literature suggests that stopping aspirin confers a risk for increased rates of significant perioperative ischemic events in patients undergoing noncardiac surgery.
  • A patient history of a remote myocardial infarction is independently associated with a serious and severe perioperative cardiac event (odds ratio, 2.2; 95% confidence interval, 1.4 - 3.5).
  • A perioperative myocardial infarction has an in-hospital mortality rate of approximately 17% to 21%.
  • Thus, the discontinuation of aspirin in a population with known coronary artery disease or atherosclerotic disease increases the chance of an ischemic event in the perioperative period.
  • In 1 study, recent withdrawers of oral antiplatelet therapy had a 2-fold increase in rates of death vs prior users and nonusers of aspirin therapy.
  • The average interval between stopping therapy and a cardiac event was 11.9 days, consistent with the expected interval for platelet rebound.
  • Cessation of oral antiplatelet drugs was found to be an independent predictor of both death and major ischemic events.
  • A recent systematic review of 50,279 patients receiving aspirin therapy for primary and secondary prevention reported that the risk for an adverse cardiac event with discontinuation of aspirin was 1.82 (95% confidence interval, 1.52 - 2.18; P < .00001).
  • Surgical procedures that involve particular anatomic sites (middle ear, posterior chamber of the eye, intracranial, intramedullary spine, and possibly TURP) confer the highest risk for a complicating hemorrhage during receipt of aspirin therapy.
  • For these procedures, aspirin discontinuation should be considered.
  • For other procedures in which an increase in surgical blood loss results in no change in transfusion requirements or increase in major morbidity or mortality risks, aspirin should not be discontinued.
  • The authors recommended that discussion about the safety of aspirin continuation vs aspirin cessation should differ on the basis of the level of cardiac risk for the patient and the specific type of surgical procedure.
  • Overall most patients, especially those taking aspirin for secondary cardiovascular prevention, should continue taking aspirin throughout the perioperative period.

 

CLINICAL IMPLICATIONS

 

  • Aspirin is associated with greater benefit for secondary vs primary prevention of cardiovascular disease, and benefits are greater for patients at higher risk for cardiac disease.
  • Most patients taking aspirin for secondary cardiovascular prevention should continue taking aspirin throughout the perioperative period, except for those undergoing surgery involving the middle ear, posterior chamber of the eye, intracranial, intramedullary spine, and possibly TURP.

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