Durham, NC - Contrary to ACC/AHA guidelines, the overwhelming majority of non-ST-elevation ACS patients treated with acute clopidogrel do not have their surgery delayed for the recommended five-day interval after stopping the drug, new data from the CRUSADE registry show [1].

While failure to delay surgery is associated with increased blood-transfusion requirements, this must be weighed against the potential clinical and economic impacts of such delays, the authors say. The study, published in the July 18, 2006 issue of the Journal of the American College of Cardiology, was conducted by a group led by Dr Rajendra Mehta (Duke Clinical Research Institute, Durham, NC).

In an interview with heartwire, Mehta noted that although patients taken to surgery within five days of stopping clopidogrel did show an increased risk of bleeding, this was not as high as previously reported and did not translate into an increase in adverse events or mortality. "Physicians seem to be selecting patients appropriately for CABG, and surgeons do not appear to be frightened of operating on patients before the five-day clopidogrel-free period is over," he commented.

Mehta pointed out that it tended to be the lower-risk patients who were taken to surgery within five days of stopping clopidogrel and that surgeons have strategies to deal with the increased bleeding risk. "The ones who waited more than five days tended to be higher-risk patients, and it is likely that surgeons want to wait for these patients to become more stable and to minimize the bleeding risk in this group particularly," he said. "Our data suggest that sometimes practicing commonsense medicine rather than following guidelines is not necessarily associated with bad outcomes and can be more cost-effective," he added.

In the paper, Mehta et al explain that in the CURE trial, the acute administration of clopidogrel to patients with non-ST-elevation ACS reduced the risk for death, MI, or stroke by 20%. But because of an increased risk of bleeding with clopidogrel in patients requiring CABG, it is recommended that clopidogrel be discontinued at least five days before CABG surgery. To investigate whether or not this was actually occurring in clinical practice, Mehta et al analyzed data from 2858 ACS patients undergoing CABG at 264 US hospitals participating in the CRUSADE initiative.

Results showed that within 24 hours of admission, 852 patients (30%) received clopidogrel. In contrast to national guidelines, 87% of these patients underwent CABG within five days of clopidogrel treatment. These patients had a significant increase in blood transfusions. If CABG was delayed for more than five days, acute clopidogrel therapy was not associated with higher transfusion rates. However, the patients who underwent CABG within five days of clopidogrel did not show increased rates of death or MI and had significantly shorter hospital stays than those waiting for more than five days.

Mehta et al say that this is the first study to provide insight into patterns of clopidogrel use and outcomes in the setting of CABG performed on patients with non-ST-elevation ACS. They point out that while it may be suspected that those patients undergoing early CABG before clopidogrel had worn off completely would be at higher risk, the data show that, in fact, this was not the case, and that it appeared that that surgery was electively performed sooner than is recommended after the discontinuation of clopidogrel in the vast majority of patients.

They note that although clopidogrel use within five days of CABG was associated with an increase in transfusions, this increase was smaller than those seen in previous case series, which they say may just reflect a more stable estimate of risks based on a much larger case sample or may be due to increased experience with perioperative management of patients treated with clopidogrel.

Noting that the CURE trial suggested very early benefits with the use of clopidogrel, they conclude, "The benefits of delaying CABG surgery for more than five days after the administration of clopidogrel must be weighed against the potential risk of events while waiting as well as the economic consequences of extended hospital length of stay."