Platelet Tests Pre-CABG May Safely Shorten Washout Waits, Cut Costs

Use of platelet reactivity testing in ACS patients coming off P2Y12 inhibitors who may be at risk for perioperative bleeding can safely shorten the waiting time before CABG, potentially cutting hospital costs, according to a new randomized study.

The findings are in line with results from TARGET-CABG and other observational studies looking at the use of platelet function tests to guide decisions on timing, its authors note, but they represent the first randomized data in this space.

“Despite the fact that our hospital is one of the biggest in the world in cardiology, available beds for new hospitalizations is always a problem for the institution,” senior author José Nicolau, MD, PhD (Universidade de Sao Paulo, Brazil), told TCTMD in an email. “We know that many patients on clopidogrel have platelet reactivity normalized before the 5-7 day waiting days after withdrawing the drug before CABG. So, if we could safely shorten this waiting time, it would have a great impact on the hospital’s capacity for new patients.”

Additionally, “the United States spends an estimated $6.5 billion per year on CABG procedures; the implementation of the strategy tested in the current study could save between $416,000,000 (6.4% decrease obtained in the intention to treat analyses) and $728,000,000 (11.2% obtained in the as-protocol analyses),” write Nicolau, Carlos Nakashima, MD (Universidade de Sao Paulo, Brazil), and colleagues in their paper, which was published in the March 16, 2021, issue of the Journal of the American College of Cardiology.

However, logistical issues abound with using platelet reactivity testing in the real world, according to Anders Jeppsson, MD, PhD (Sahlgrenska University Hospital, Gothenburg, Sweden), who commented on the study for TCTMD. “It's very problematic to wait until you have a test that says if the patients can be safely operated on or not, because the speed is very different from patient to patient—the recovery of the platelet function,” he said. “We want to use all our spots in the OR for patients. So, it's difficult to ‘maybe’ operate on patients.”

In addition, researchers have tinkered with various cutoff points to find the optimal predictive ability of platelet reactivity and questions remain regarding the true link to bleeding.

Because of all this, “using platelet reactivity testing to shorten the waiting time for CABG is a plausible approach, but [it] is too inaccurate to be the linchpin for deciding when to proceed with surgery,” John Bittl, MD (AdventHealth Ocala, Ocala, FL), writes in an editorial accompanying the paper.

Multiplate Analysis

For their study, the researchers randomized 190 ACS patients scheduled for CABG at their institution who had been on dual antiplatelet therapy (99% with clopidogrel and 1% with ticagrelor) to either undergo their surgeries the next workday after normalization of platelet reactivity as measured by the Multiplate analyzer (Roche Diagnostics) or to delayed CABG 5 to 7 days after drug cessation.

Median chest tube drainage at 24 hours after CABG (primary endpoint) was similar for both the intervention and control arms (350 vs 350 mL; P < 0.001 for noninferiority). There were also no differences between groups in the amount of red blood cell, platelet, and fresh plasma infusions.

The waiting time to CABG was 24 hours shorter in those whose platelet reactivity was measured versus controls (112 vs 136 hours; P < 0.001), and the median length of hospital stay time was similar between the groups.

Three patients in each group died in the hospital—all in the intervention arm were due to sepsis, while the causes of death in the control group were cardiogenic shock, hemorrhagic shock, and sepsis, respectively.

Costs were calculated in Brazilian real. Overall, median hospital expenses were 6.4% lower for the intervention versus control groups in the intention-to-treat analysis (R$15,202.33 [US $2,613] vs R$16,251.37 [US $2,794]; P = 0.014) and 11.2% lower for the per-protocol analysis (R$14,248.41 [US $2,449] vs R$16,039.55 [US $2,757]; P = 0.003).

“This technique can be easily implemented—the point-of-care Multiplate device utilized for platelet reactivity evaluation is very friendly and needs only a short training for utilization,” Nicolau said, adding that the main limitation to its use may be price, although the associated savings would eventually cover those costs.

Superiority Needed Before Widespread Use

Bittl, however, has some concerns, noting that the study “was based on the tenuous premise that platelet reactivity testing predicts postoperative bleeding.” Post-CABG bleeding, he says, can be caused by a multitude of factors unrelated to platelet function.

As such, “is unlikely that a single test of a pathway of platelet activation blocked by one drug could predict systemic bleeding risk or even overall platelet reactivity,” Bittl continues. “Platelet reactivity testing is based on solid science but only weakly predicts outcomes in selected populations and has failed to predict events on an individual level.” Other concerns include the different cutoffs used in different studies. “Writing committees,” he predicts, “will not likely give platelet reactivity testing a higher recommendation than Class IIb for predicting bleeding.”

Jeppsson said he uses platelet reactivity testing in select patients. “For example, if we have patients with an urgent but not acute indication, like myxoma, and they are on dual antiplatelet therapy, we use it to decide when we should operate on them because we want to operate on them as early as possible,” he explained. Swedish cardiologists have not used this approach for ACS patients since 2016 when, based on available evidence, they decided not to pretreat with antiplatelets, so it has become a nonissue, Jeppsson added.

For a platelet-function-based strategy to take hold, it would need to be proven superior to the current standard of waiting 5 days for clopidogrel and 3 days for ticagrelor, Jeppsson said, which warrants further study.

Nicolau agreed. “I would like to see a multicenter trial testing the same hypothesis tested in the present study, preferentially with hard clinical endpoints in addition to bleeding in order to give us a definitive answer,” he said.

Correction: An earlier version of this story incorrectly stated that the 2016 European guidelines advised cardiologists not to pretreat with antiplatelets. This did not happen until 2020.