No Gain With Upstream P2Y12 Inhibitors in STEMI PCI

Patrice Wendling

August 30, 2017

BARCELONA, SPAIN — Frontloading STEMI patients with P2Y12 receptor antagonists before primary PCI provides no benefits or added risks, a new analysis of the SCAAR registry suggests[1].

Among 44,804 patients, the primary end point of death at 30 days occurred in 5.2% of pretreated patients and 7.6% of those not pretreated (adjusted odds ratio 1.07, P=0.313).

Dr Elmir Omerovic

There were no differences in any secondary outcomes, senior author Dr Elmir Omerovic (Sahlgrenska University Hospital, Gothenburg, Sweden) reported here at the European Society of Cardiology (ESC) 2017 Congress.

"We haven't found any important subgroups where this treatment strategy would be associated with improved outcomes, so just don't use it. The argument is ethical. It seems to be a futile exercise," he said in an interview.

Not so, according to recent STEMI guidelines. The 2017 ESC STEMI guidelines[2], released during the meeting, update the 2014 recommendation to use P2Y12 inhibitors at the time of "first medical contact" to a class 1A recommendation for prasugrel (Effient, Lilly/Daiichi-Sankyo), ticagrelor (Brilinta, AstraZeneca), or clopidogrel (Plavix, Bristol-Myers Squibb) if the first two are unavailable or contraindicated, before or "at least at the time of PCI."

Similarly, US STEMI guidelines recommend a loading dose of a P2Y12 inhibitor as early as possible or at the time of primary PCI.

Omerovic argued that the evidence in support of pretreatment in the setting of STEMI patients undergoing primary PCI "is indirect and weak" and there's the potential for increased bleeding.

The randomized trial that most directly addressed the issue, the ATLANTIC study, failed to show a benefit with prehospital ticagrelor in STEMI patients on its co–primary end points, although rates of definite stent thrombosis within 30 days were lower, he noted. But prehospital treatment was also associated with a trend for increased 30-day mortality and a significantly higher risk of death within 24 hours.

SCAAR Registry Data

Against this background, the investigators evaluated data for all consecutive patients who underwent primary PCI between January 2005 and November 2016 in the nationwide SCAAR registry, of whom 37,840 underwent routine P2Y12 pretreatment and 6964 did not.

Propensity score-adjusted multilevel mixed effects logistic regression was performed, with the hospital as a random effect variable. To adjust for differences in patient characteristics, roughly 30 variables were used to estimate the propensity score.

The time from symptom onset to first medical contact was 113 minutes and 74 minutes to start of PCI.

After adjustment, there was no significant benefit with P2Y12 pretreatment over no pretreatment on infarct-related artery occlusion (67.9% vs 67.5%, OR 1.01; P=0.635), definite stent thrombosis at 30 days (0.6% both, OR 0.99; P=0.941), or cardiogenic shock (2.7% vs 5.3%, OR 0.87; P=0.105), he said.

At the same time, pretreatment did not increase in-hospital bleeding (2.6% vs 3.4%, OR 1.04; P=0.604) or in-hospital neurogenic complications (0.2% vs 0.5%, OR 0.66; P=0.129).

No significant differences were observed in a sensitivity analysis with propensity score matching.

Limitations of the observational study, Omerovic said, include the potential for selection bias and residual confounding, missing data on 1171 patients, and a lack of information on cause-specific mortality, TIMI flow in the infarct-related artery, and patients who died before hospitalization.

The study also does not address the issue of P2Y12 pretreatment in non-STEMI patients. In 2013, the ACCOAST trial was prematurely stopped because prasugrel pretreatment showed no clinical benefit and was associated with a near doubling of major bleeding in non-STEMI patients.

During a discussion of the findings, Omerovic repeated his assertion that he could find no clinical setting in which he'd pretreat with P2Y12 inhibitors, prompting session cochair and ESC press committee chair Dr Steen Dalby Kristensen (Aarhus University Hospital, Skejby, Denmark) to counter: "For patients who have a clear-cut STEMI and are really high risk, I would still probably recommend treatment with a P2Y12 inhibitor."

Commenting for | Medscape Cardiology, Dr Clemens von Birgelen (University of Twente, Enschede, the Netherlands) urged caution in interpreting the results, noting that despite the huge amount of data, it is unclear why some patients were treated and others were not, there was no information on aortic dissections, and the study actually showed the procedure was safe.

"Future research is warranted but I wouldn't draw any premature conclusions; we pretreat and will continue to pretreat."

Omerovic reported no relevant financial relationships. Birgelen reported institutional research grants from AstraZeneca, Boston Scientific, Biotronic, Medtronic. Kristensen reported no relevant financial relationships. von Birgelen has consulting for Boston Scientific and Medtronic; and received lecture fees from AstraZeneca.

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