More Bleeding, Not Mortality Seen with Late Clopidogrel Stoppage Before Surgery

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For patients on clopidogrel who require abdominal surgery, there appears to be no difference in major morbidity or mortality regardless of whether the antiplatelet agent is withdrawn within 7 days of the procedure or earlier, according to a study in the March 2011 issue of Archives of Surgery. However, clopidogrel use within 7 days of surgery was associated with more postoperative bleeding and need for transfusion.

Researchers led by Celia M. Divino, MD, of Mount Sinai School of Medicine (New York, NY), reviewed the medical records of 104 patients who underwent a variety of abdominal surgeries and evaluated the outcomes stratified by the timing of clopidogrel cessation: less than 7 days (n = 43) vs. ≥ 7 days (n = 61) prior to surgery.

No Difference in Bleeding-Associated Major Morbidity, Mortality

There were 6 postoperative deaths (6%) and 21 patients (20%) had postoperative bleeding requiring intervention; 19 were managed by transfusion (1-3 units of packed red blood cells), and 2 necessitated reoperation. ICU admission was required in 27 patients (26%).

Overall, more patients who stopped clopidogrel less than 7 days prior to surgery died, required ICU admission, and had significantly higher rates of postoperative bleeding requiring transfusion compared with patients who stopped the antiplatelet earlier (table 1).

Table 1. Outcomes by Timing of Clopidogrel Cessation

However, there were no significant differences between the groups for postoperative bleeding resulting in reoperation or mortality, hospital length of stay, need for reoperation, or bleeding requiring intervention.

Most of the postoperative morbidity and mortality occurred in patients who underwent colorectal resection, which emerged as an independent risk factor for postoperative bleeding (OR 6.3; 95% CI 1.6-23.9). Further assessment of the colorectal group by timing of clopidogrel cessation demonstrated a trend toward increased ICU stay (48% vs. 23%; P = 0.09) and mortality (16% vs. 3%; P = 0.16) for those in whom clopidogrel was last used within 7 days preoperatively.

In the overall cohort, among patients who stopped clopidogrel less than 7 days prior to surgery, 70% underwent elective operations vs. 97% of those who stopped the therapy ≥ 7 days before surgery. While elective patients in the former group had a trend toward increased risk of postoperative bleeding requiring transfusion than did elective patients in the latter group (23% vs. 14%; P = 0.25), no significant difference in ICU admission or mortality was seen.

“[W]hile clopidogrel use within 7 days of operation is an independent risk factor for increased postoperative bleeding, these complications are predominantly not life threatening and are amenable to supportive care with transfusion,” the authors write.

They conclude that “semi-emergency and emergency operative interventions should not be delayed based on recent clopidogrel usage.” However, colorectal resection may be an exception, they add.

Devil Lies in the Details

In an editorial accompanying the study, Richard J. Bold, MD, of the University of California Davis Cancer Center (Sacramento, CA), comments that studies such as this are “the only source of data to guide surgeons in choices of operative management” since for ethical reasons there will never be a randomized trial to determine the optimal timing of clopidogrel cessation in elective abdominal surgery.

According to Dr. Bold, the data demonstrate that the timing of clopidogrel cessation has little effect in most elective abdominal operations if perioperative transfusion is considered an acceptable trade-off for a 7-day delay.

However, he notes, “The devil lies in the details—the consequences of blood product transfusion (which are not insignificant) must be acceptable to both the surgeon and the patient in the decision-making process of the timing of operative intervention.”

Underpowered to Demonstrate Mortality Difference

According to Robert A. Guyton, MD, of the Emory University School of Medicine (Atlanta, GA), the results would be more convincing if more patients were included.

“The numbers are so small that it’s difficult to make much out of the absence of a mortality difference,” he said in a telephone interview with TCTMD. “To find a true difference, you need a couple thousand patients in each group. If you have enough people bleeding, sooner or later you are going to see a mortality difference. The absence of a difference never proves there is no difference when a study is underpowered.”

Dr. Guyton added that the higher risk seen in the colorectal surgery group is a “signal” that further study needs to be done.

“In some sense it is just a marker of a more difficult operation,” he said. “But looking at that group separately [by clopidogrel cessation status] is probably not a bad idea.”

Study Details

Three-fourths (75%) of patients who stopped clopidogrel ≥ 7 days before surgery received coronary stents compared with 56% of those who stopped within 7 days of surgery (P = 0.04).

Abdominal surgeries included hemicolectomy, subtotal colectomy, ileocolic resection, lysis of adhesions/small-bowel resection, adrenalectomy, paraesophageal hernia repair, liver resection or revision, gastrojejunostomy, sleeve gastrectomy, Nissen fundoplication, and retroperitoneal mass resection.

Sources:

1. Chernoguz A, Telem DA, Chu E, et al. Cessation of clopidogrel before major abdominal procedures. Arch Surg. 2011;146:334-339.
2. Bold RJ. Is timing really everything in patients receiving antiplatelet therapy [invited critique]? Arch Surg. 2011;146:339.

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