ANTIPLATELET THERAPY AND RISK OF INFECTION?

May 1, 2009 (Baltimore, Maryland) — Another potential problem of using dual antiplatelet therapy in patients due to have surgery has emerged in a new study showing that patients taking both aspirin plus clopidogrel preoperatively had an increased risk of infection after coronary artery bypass surgery [1].

The study, published in the April 27, 2009 issue of the Archives of Internal Medicine, was conducted by a team led by Dr Elena Blasco-Colmenares (Johns Hopkins University School of Medicine, Baltimore, MD). They conclude: "Our study suggests that there may be significant infectious risks due to uninterrupted preoperative use of dual antiplatelet therapy in coronary artery bypass surgery and potentially in other patient populations that are at high risk for infection."

Senior author Dr Nauder Faraday (Johns Hopkins) commented to heartwire : "This association has never been reported before, to my knowledge. We hypothesized that because of laboratory evidence showing that platelets play a role in immunity, it would be possible that inhibiting platelet function would increase the risk of infection in vulnerable populations. So we looked for a possible relationship between dual platelet therapy and infection in CABG patients, and we did indeed find such an association."

Not Due to Transfusions

Faraday said they did what they could to take account of confounding factors, but there is still the possibility that there could be residual confounders not measured, which is why more studies are required to confirm their finding. He noted that the most obvious confounder is bleeding and transfusion. Patients on dual antiplatelet therapy will bleed more and so will be in the OR longer and need more transfusions, which is a well-recognized risk for infection. But they still found a strong association after this was controlled for.

"This is just one study. It requires confirmation. And while other observational studies like ours would be useful, the best thing would be data from randomized trials. There have been many trials done of clopidogrel plus aspirin vs aspirin alone. It would be interesting to look at infection outcomes in the follow-up in these studies, particularly in those patients who ended up going on to CABG," Faraday noted.

Confusion Over Antiplatelet Therapy and Surgery

He pointed out that this idea of a possible increase in infection risk with dual antiplatelet therapy adds to the uncertainty about when to stop such therapy before surgery. "There is a lot of confusion about this already. Surgeons want to stop antiplatelet therapy several days before the operation to reduce bleeding risk, but if a patient has recently had a stent, cardiologists warn that prematurely stopping dual antiplatelet therapy might promote MI. So what do we do? Do we delay surgery for one year, or do we continue with the antiplatelet agents through the perioperative period? We really have no idea. Right now it is up to individual practitioners' discretion. There are no hard data, and the guidelines are confusing. We really need a randomized trial to look at this, and this trial could look at infection risk as well as bleeding risk."

If platelets do play an important role in immunity, the risk of infection would be sustained for as long as patients were on dual antiplatelet therapy, Faraday believes. "We looked for this in CABG patients because we thought we might be able to capture the risk over a short time period in this high-risk group, but it could also have a smaller immune-suppressing effect with long-term treatment in nonsurgery patients," he added.

For the current retrospective cohort study, the researchers collected data from their cardiac-surgery database on 1677 patients who had undergone CABG at Johns Hopkins Hospital, and they looked specifically for reports of infection that they say would be recorded for such patients.

They found that the cumulative incidence of infection at 30 days was 23.1% in patients receiving both aspirin plus clopidogrel preoperatively vs 16.1% in those who were receiving aspirin alone (HR 1.51; 95% CI 1.09–2.08). The risk of infection remained higher among patients who were receiving dual antiplatelet therapy after adjustment for demographic, socioeconomic, preoperative, and intraoperative risk factors and propensity score.

Transfusion rates were also higher among patients who were receiving dual antiplatelet therapy than among patients who were receiving aspirin monotherapy, but transfusion played a modest role in mediating the risk of infection. Mortality rates at 30 days were 5.2% in patients receiving both aspirin and clopidogrel vs 3.1% in patients on aspirin alone, but this was not significant (adjusted HR 1.44; 95% CI, 0.70–2.99).

In the paper, the researchers write: "In addition to their well-known function in primary hemostasis, platelets also participate in innate and adaptive immunity through a variety of mechanisms that depend on platelet activation." They add: "By inhibiting platelet activation, all antiplatelet agents have the theoretical potential to diminish these activation-dependent platelet immune functions. Our data are the first (to our knowledge) to suggest that pharmacologic suppression of platelet function is associated with clinical infection in a human population. Additional work is needed to confirm these observations and to determine the impact of antiplatelet therapy on host immunity in the clinical setting."