ACCOAST Analysis Identifies Factors Tied to Higher Bleeding Risks in NSTE-ACS


Pretreatment with prasugrel is one of the strongest predictors of bleeding in patients with NSTE-ACS being managed invasively, according to a post hoc analysis of the ACCOAST trial published online June 9, 2015, ahead of print in Heart. Age, sex, and procedural variables also are tied to bleeding risk.

Implications: ACCOAST Analysis Identifies Factors Tied to Higher Bleeding Risks in NSTE-ACS

The ACCOAST trial randomized 4,033 NSTE-ACS patients to pretreatment with prasugrel (Effient; Eli Lilly/Daiichi Sankyo)—a 30-mg loading dose administered shortly after diagnosis, followed by coronary angiography and an additional 30-mg dose at the time of PCI—or no pretreatment. The latter group received a placebo loading dose, followed by angiography and a 60-mg prasugrel dose at the time of PCI. The second doses were given only when the patient actually underwent PCI.

The main results showed that the rates of the primary endpoint (cardiovascular death, MI, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor [GPI] bailout) did not differ between groups at 7 days, although major bleeding was increased in the pretreatment arm.

In this post hoc analysis, Zuzana Motovska, MD, PhD, of University Hospital Kralovske Vinohrady (Prague, Czech Republic), and colleagues looked for predictors of non–CABG-related TIMI major bleeding (primary outcome) and non–CABG-related TIMI major or minor bleeding among the 3,839 patients with complete data.

TIMI major bleeding was seen in 0.9% of patients—mostly in the periprocedural period—and TIMI major or minor bleeding was observed in 2.4%.

TIMI major bleeding was fatal in 1 patient and was considered life-threatening in 20 patients. The most common type of TIMI major bleed, accounting for 30.6% of events, was major vascular access site bleeding, followed by GI bleeding at 19.4%. Six patients had pericardial bleeding and none had intracranial bleeding.

Pretreatment with prasugrel was the strongest independent predictor of non–CABG-related TIMI major bleeding through 7 days (table 1).

Table 1.  Predictors of Non–CABG-Related TIMI Major Bleeding Through 7 days


The factors associated with an increased risk of non–CABG-related major or minor bleeding were similar, with the addition of the receipt of PCI and GPI use (table 2).

Table 2. Predictors of Non–CABG-Related TIMI Major/Minor Bleeding Through 7 Days

Many of the predictors were the same when the analysis was restricted to the patients who underwent PCI (68.7% of the cohort). Unique to the PCI group were associations between switching from unfractionated heparin to low molecular weight heparin (and vice versa) and TIMI major bleeding and between low body weight or hypertension and TIMI major or minor bleeding.

Findings Question P2Y12 Pretreatment

Discussing the predictors identified in the study, the authors note that female sex was identified as a strong predictor of bleeding and vascular complications in a prior study. “It is unclear whether the sex-specific risk of bleeding complications persists after adjustment for comorbidities,” they write. “Female sex-specific mechanisms surrounding access vessel anatomy and platelet biology may play a role.”

Femoral access also has been consistently linked to higher rates of bleeding compared with radial access. For example, in the MATRIX program, which included ACS patients with or without ST-segment elevation, femoral procedures carried higher risks of major bleeding and all-cause mortality.

Placing more than 1 stent may increase bleeding by increasing the length of the procedure, the authors note. “Duration of PCI was identified as independently associated with bleeding complications,” they write. “Moreover, multiple lesion intervention carries higher potential for intraprocedural complications. Longer procedure duration and emergence of intraprocedural complications may increase the risk of overdosing of antithrombotic agents.”

Dr. Motovska and colleagues acknowledge that the study was limited by the post hoc design with testing of numerous variables and by the lack of data for some randomized patients.

Nevertheless, they conclude, “the use and timing of pretreatment with P2Y12 antagonists is further questioned by this study.”


Source:

Widimsky P, Motovska Z, Bolognese L, et al. Predictors of bleeding in patients with acute coronary syndromes treated with prasugrel. Heart. 2015;Epub ahead of print.

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Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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Disclosures
  • The study was supported by Daiichi Sankyo and Eli Lilly.
  • Dr. Motovska reports receiving payments for advisory board membership from Bayer, lecture fees from AstraZeneca, Bayer, and Eli Lilly, and travel support from Eli Lilly.

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