ACCOAST Substudy: Prasugrel Pretreatment Linked With Increased Bleeding in NSTEMI Patients

BARCELONA, Spain—Pretreatment with prasugrel before coronary angiography in patients with non-ST-segment elevation myocardial infarction (NSTEMI) is an additional risk factor for bleeding on top of already known procedural variables, according to a subanalysis of the ACCOAST trial presented on September 2, 2014, at the European Society of Cardiology Congress.

Methods
Presented at last year’s meeting, ACCOAST showed that pretreatment with prasugrel does not reduce the rate of major ischemic events at 30 days in NSTE-ACS patients undergoing coronary angiography within 2 to 48 hours after randomization to pretreatment with either prasugrel (n = 2,037; 30-mg loading dose plus an additional 30 mg with PCI) or placebo (n = 1,996; followed by 60-mg prasugrel given with PCI). The second prasugrel dose in the pretreatment arm was not administered in patients treated with medical management (25.1%) or CABG (5.9%).
For the substudy, Petr Widimský, MD, DSc, of Charles University (Prague, Czech Republic), and colleagues looked at early bleeding outcomes.


At 30 days, all TIMI major bleeding was higher in the pretreatment arm (2.9%) than the placebo arm (1.5%; P = .002). Incidence of any TIMI major or minor bleeding was 2.4% over 30 days, and 84% of these bleeds were presented in the first 7 days.

Median time from randomization to angiography did not differ between patients with and without non-CABG TIMI major bleeding. Older age, female sex, and low body weight were related to the risk of overall major bleeding, and hypertension enhanced the risk of major and minor non-CABG bleeding, especially in patients who underwent PCI. Additionally, use of multiple stents and GPIs were associated with more periprocedural bleeding complications, and transradial access twice as often in patients without bleeding (table 1).

Table 1. Factors Associated with Non-CABG TIMI Major Bleeding at 7 Days

 

Bleeding 
 (n = 36) 

No Bleeding 
 (n = 3,997) 

P Value

Age ≥ 75 Years

36.1%

17.6%

.004

Male Sex

47.2%

72.7%

.0007

Weight < 65 kg

11.1%

5.0%

.1

Hypertension

75.0%

62.0%

.1

Median Time From Randomization to Coronary Angiography, hours

4.3

3.9

.4

PCI

77.8%

69.1%

.3

Radial Access

22.2%

42.6%

.01

Multiple Stents

36.1%

19.1%

.01

 

Importantly, prasugrel pretreatment tripled the risks of non-CABG TIMI major (HR 3.02; 95% CI 1.42-6.43) and major or minor bleeding (HR 3.07; 95% CI 1.85-5.11) through 7 days. Other predictors of major bleeding included:

 

  • Female sex (HR 2.56; 95% CI 1.32-5.00)
  • Femoral access (HR 2.45; 95% CI 1.11-5.37)
  • Multiple stents (HR 2.50; 95% CI 1.26-4.95)
  • Age, per year (HR 1.05; 95% CI 1.02-1.09)

 

Within the PCI cohort, predictors of major bleeding were similar but also included switching from unfractionated heparin to low molecular weight heparin (HR 2.36; 95% CI 1.08-5.15). For major or minor bleeding, body weight was indirectly associated with risk (HR 1.03; 95% CI 1.01-1.05).

Discussant Kurt Huber, MD, of Wilhelminenhospital (Vienna, Austria), noted the importance of establishing prasugrel pretreatment as an additional bleeding risk factor in NSTEMI. In order to prevent bleeding, he said, “We need to stratify for bleeding risk, reduce dosage if necessary, and—if possible—avoid excessive dosing, avoid crossover of antithrombins, avoid antithrombotic combination therapies, eventually use safer antithrombotic agents, stop anticoagulants [during] sheath removal, use the radial vascular approach, and now avoid pretreatment with prasugrel in NSTEMI patients.”

 


Source: 
Widimský P. Predictors of bleeding in ACS patients treated with prasugrel: analysis from the ACCOAST study. Presented at: European Society of Cardiology Congress; September 2, 2014; Barcelona, Spain.

 

Disclosures:

 

  • ACCOAST was supported by Daiichi Sankyo and Eli Lilly.
  • Dr. Widimský reports receiving consultant fees and speaker honoraria from AstraZeneca, Bayer, Boehringer Engelheim, Daiichi Sankyo, Eli Lilly, and Sanofi.
  • Dr. Huber reports receiving lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Sanofi Aventis, and The Medicines Company.

 

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