TARGET-CABG Published: Waiting Period to CABG Flexible Per Platelet Function Test

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Using platelet function testing to determine the optimal time for coronary artery bypass graft (CABG) surgery can shorten the waiting time before bypass in clopidogrel-treated patients without increasing bleeding risk over what is seen in patients naive to the drug, according to a prospective study published online March 6, 2012, ahead of print in Circulation: Cardiovascular Interventions.

American College of Cardiology/American Heart Association guidelines currently recommend clopidogrel cessation 5 days prior to planned CABG.

For the single-center TARGET-CABG (Time bAsed stRateGy to rEduce clopidogrel associaTed bleeding during CABG) study, Paul A. Gurbel, MD, of the Sinai Hospital of Baltimore (Baltimore, MD), and colleagues looked at 109 clopidogrel-treated patients requiring first-time, nonemergent CABG between September 2008 and January 2011. Patients were evaluated using thromboelastography (TEG) to determine when they could safely undergo surgery. Results of the TEG Platelet Mapping Assay, which measures the tensile strength of the platelet-fibrin clot stimulated by adenosine diphosphate (ADP), were used to assign waiting periods for CABG based on the following test thresholds:

• < 35 mm: Wait 5 days (n = 17)
• 35-50 mm: Wait 3-5 days (n = 42)
• 50 mm: Surgery possible within 1 day (n = 27)

These subjects were compared with 95 clopidogrel-naive patients who underwent CABG.

Comparable Results

At 24 hours after CABG, the primary endpoint of chest-tube drainage was equivalent between the stratified patients and the clopidogrel-naive patients at 650 mL (interquartile range [IQR], 480-1,010 mL) and 780 mL (IQR, 570-953 mL), respectively (P = 0.080).

Adjustment for demographic variables, intraoperative characteristics, and clinical and laboratory parameters did not show any difference in blood loss between the 2 cohorts (P = 0.496) or across the 3 TEG categories of clopidogrel-treated patients (P = 0.27). Chest-tube drainage in the clopidogrel group was 93.3% (95% CI 81.0%-107.4%) of the amount observed in the clopidogrel-naive group.

Moreover, the total amount of red blood cells transfused was 2 units (IQR, 0-3) irrespective of clopidogrel use (P = 0.540). Adjustment for potential confounders did not change the results, with clopidogrel-treated patients receiving 86.6% (95% CI 56.3%-116.9%) of the amount of red blood cells transfused to clopidogrel-naive patients.

The mean delay before CABG amounted to 2.7 days per patient. Prespecified waiting was associated with higher platelet reactivity in clopidogrel-treated patients at the time of surgery. But irrespective of clopidogrel use, reactivity began to decrease on ICU arrival and returned to normal 24 hours after surgery (P < 0.001 for trend).

Median length of hospital stay was significantly higher in patients who received clopidogrel compared with those who did not (8 days vs. 6 days, P < 0.001). Although 1 clopidogrel-treated patient had a preoperative MI during withdrawal from the drug, there was no difference in duration of intubation, ICU stay, re-thoracotomy rates, 30-day mortality, and 30-day readmission rates between the 2 groups. One patient in each cohort underwent re-catheterization for clinical signs of ischemia.

Other Potential Applications

Dr. Gurbel told TCTMD in a telephone interview that he was unsurprised by the lack of increased bleeding, given that patients only underwent CABG before 5 days if platelet function testing showed they were pharmacodynamically unresponsive to clopidogrel.

When asked if these findings would hold up with other similar drugs, Dr. Gurbel predicted that if a patient is nonresponsive to antiplatelet therapy in general, the waiting time to CABG can be shortened.

“New antiplatelet drugs are associated with much less time responsiveness than clopidogrel,” he said. “[Y]ou can’t directly extrapolate our data and our findings to other drugs, but it’s possible that with [ticagrelor] you may be able to safely operate on these patients even sooner because the drug has a faster onset.”

Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), agreed. “You can measure the reactivity of the other drugs but you would have to adapt the protocol based upon the half-life of the other drugs,” he told TCTMD in a telephone interview. “In other words, you might be able to actually go sooner with ticagrelor and longer with prasugrel.”

Economic Implications

According to Dr. Kirtane, this study is one of the first to measure platelet responsiveness through a formalized protocol with the goal of predicting bleeding complications. This practice has been “somewhat controversial, with some studies showing that lower platelet reactivity did not correlate with bleeding and other studies showing it did,” he said. “What’s nice is that they employed this strategy, they studied it prospectively and looked at outcomes. And sure enough, they were able to find outcomes that eventually paralleled those of clopidogrel-naive patients.”

Still, Dr. Kirtane said it is important to note that the assay used here is different from the more widely known VerifyNow (Accumetrics, San Diego, CA), a discrepancy that might affect outcomes.

“This is a somewhat of a proof-of-concept type of study,” he continued. “In conjunction with the BRIDGE trial, which was published earlier this year, these 2 studies demonstrate that there may be a clear role for platelet function testing in terms of mitigating bleeding risk.”

After further validation from a larger clinical trial or an expanded prospective protocol including other platelet function assays and drugs, Dr. Kirtane said, these findings could have a substantial economic effect.

“The scope of the problem is that there are a fair number of patients who have to wait 5 to 7 days before surgeons feel comfortable operating on them,” he said. “There are data that say you can operate on the drugs, but that may increase bleeding. So this type of protocol has the ability to reduce hospital stays for a significant proportion of patients.”

Study Details

Clopidogrel-naive patients were more often male, and on average had lower body mass index, a less frequent history of MI and coronary artery stenting, less beta-blocker usage, and treatment with lower aspirin doses. More patients treated with clopidogrel presented with ACS.

 

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Source:
Mahla E, Suarez TA, Bliden KP, et al. Platelet function measurement-based strategy to reduce bleeding and waiting time in clopidogrel-treated patients undergoing coronary bypass graft surgery: The timing based on platelet function strategy to reduce clopidogrel-associated bleeding related to CABG (TARGET-CABG) study. Circ Cardiovasc Interv. 2012;Epub ahead of print.

 

 

Related Stories:

• Platelet Testing May Shorten Waiting Time to CABG in Clopidogrel-Treated Patients
• GRAVITAS Analysis: Lower Cutpoint May Enhance Functional Platelet Testing
• Data Accumulating on Clopidogrel Nonresponsiveness, More Needed

 

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