Courtesy of Dr. Agustín Vecchia.

Nearly 10% of patients with acute coronary syndrome (ACS) require surgery. Managing periprocedural dual antiplatelet therapy (DAPT) in ACS patients is controversial and, to date, there are no randomized trials in this regard. Guidelines recommend ticagrelor discontinuation five days prior surgery and in the most emblematic work on this drug discontinuation was 24 to 72 hours prior surgery.

The following multicenter, prospective study used patients form the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry. It included consecutive patients with ACS undergoing CABG alone between January and September 2015.

Propensity score matching provided two groups of 215 patients of similar characteristics: one of them received ticagrelor with or without aspirin, the other aspiring alone.

Primary end point was severe bleeding according to the Universal Definition of Perioperative Bleeding (UDPB) and E-CABG registry bleeding classification criteria. Secondary end points included drainage debt 12 hours after surgery, re-exploration with excessive bleeding or tamponade, use of hemoderivatives, prolonged intensive care, wound infection, in-hospital mortality and postoperative renal, cardiac and neurological complications.

Out of 2,482 E-CABG patients, 786 were included (31.7%). Population mean age was 67.1 years and 16.8% were women. Patients in the ‘aspirin alone’ group were older (mean age 68.3 vs. 65.1 years; p <0.001) and had higher EuroSCORE preoperative risk (3.6% vs. 3.1%; p< 0.001). Patients in the ticagrelor group received emergency surgery more often.

Population mean age

Aspirin alone: 68.3

Ticagrelor: 65.1

Higher preoperative risk by EuroSCORE

Aspirin alone: 3.6%

Ticagrelor: 3.1%

Globally, preoperative use of ticagrelor was associated to a similar risk of bleeding by both definitions, and after propensity matching, the same bleeding rates were seen, but there was a higher platelet transfusion rate for the ticagrelor group vs. the control group (13.5% [29 de 215] vs. 6.0% [13 of 215]).

Compared to patients receiving aspirin alone, using ticagrelor up until surgery or discontinuing ticagrelor within 48 hours prior surgery were associated to a significant increase of platelet transfusion rates (22.7% [5 of 22] vs. 6.4% [12 of 187]) and E-CABG bleeding grades 2 and 3 (18.2% [4 of 22] vs 5.9% [11 of 187]).

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“Continuing ticagrelor up to the time of surgery or discontinuing its use less than 48 hours before surgery were associated to a significant increase in platelet transfusion and bleeding rates”.

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In addition, in the ticagrelor group, there was a higher UDPB bleeding grades 3 and 4 (22.7% [5 of 22] vs 9.6% [18 of 187]). In patients discontinued at least 48 hours prior surgery, there was higher platelet transfusion rate in the ticagrelor + aspirin group vs. aspirin alone (12.4% (24 of 193) vs 3.6% (1 of 28). When analyzing subgroups discontinued from 2 to 3 days and from 4 to 14 days, no differences were found.

Conclusion

Authors concluded that perioperative use of ticagrelor with or without aspirin compared to aspirin alone was associated to a higher rate of platelet transfusion but with similar bleeding rate. Patients receiving ticagrelor within 24 hours prior surgery, saw increased severe bleeding rate.

Editorial Comment

Despite the limitations of a retrospective study and the chance of confounders, outcomes make sense, since “safe” discontinuation times were similar to those of PLATO’s. Looking at PLATO patients undergoing CABG (bearing in mind ticagrelor was discontinued 24-72 hours prior surgery and clopidogrel was discontinued five days before) outcomes were the same as those of the global study (less total and cardiovascular mortality with no excess bleeding associated to CABG).

As negative points, despite its prospective character, the study is still observational, and therefore may be biased. Note that this is a small sample and, most importantly, the number of patients that remained on ticagrelor or were not early discontinued, is small. Moreover, it was not a blind trial and consequently the higher rate of hemoderivatives used in the ticagrelor group may have been influenced by this. Lastly, only surgery survivors were included; this study does not assess the consequences of waiting for surgery.

These findings call into question the guideline recommended times for ticagrelor discontinuation prior CABG. Clearly, randomized studies are required.

Courtesy of Dr. Agustín Vecchia. German Hospital, Buenos Aires, Argentina.

Original Title: Safety of Preoperative Use of Ticagrelor with or without Aspirin Compared with Aspirin Alone in Patients with Acute Coronary Syndromes Undergoing Coronary Artery Bypass Grafting

Reference: Riccardo Gherli et al. JAMA Cardiol. Published online September 21, 2016.

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