Prasugrel Improves Outcomes vs Clopidogrel After Primary PCI with Bivalirudin

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In patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) with bivalirudin, antiplatelet therapy with prasugrel was associated with improved efficacy compared with clopidogrel, according to a post-hoc analysis of randomized trial data published online February 13, 2014, ahead of print in the American Journal of Cardiology. However, safety outcomes were comparable between the newer and older agents.

For the study, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), and colleagues looked at 452 STEMI patients from the INFUSE-AMI trial who underwent PCI with adjunctive bivalirudin. All patients received aspirin and either clopidogrel (65.7%) or prasugrel (34.3%) at physician discretion. Additionally, they were randomized to receive abciximab vs no abciximab and thrombus aspiration vs no thrombus aspiration.

Patients in the prasugrel group had higher rates of procedural success, TIMI 3 flow, and lower corrected TIMI frame counts. At 30 days, infarct size on cardiac MRI (primary endpoint) trended lower in those treated with prasugrel (table 1). However, this result was not maintained after controlling for the propensity to use prasugrel.

Table 1. Angiographic Parameters and Infarct Size

 

Clopidogrel
(n = 297)

Prasugrel
(n = 155)

P Value

Corrected TIMI Frame Count

22.79 ± 10.94

20.51 ± 6.26

0.008

Procedural Success

87.8%

94.2%

0.03

Infarct Size, % LV mass

17.6%

16.4%

0.06

LVEF

48.6%

51.1%

0.004

 
Both 30-day MACE (1.9% vs 8.8%; P = 0.005) and MACCE (0.7% vs 5.8%; P = 0.009) were lower in the prasugrel cohort than the clopidogrel group. Both remained lower in the prasugrel group at 1 year, driven by lower mortality (P = 0.004) and fewer episodes of new onset severe heart failure (P = 0.02). There were no differences in terms of stent thrombosis and major bleeding, with results persisting after propensity score adjustment (table 2).

Table 2. Adjusted 1-Year Outcomes

 

Clopidogrel
(n = 297)

Prasugrel
(n = 155)

Adjusted HR
(95% CI)

P Value

Death

8.3%

1.3%

0.18
(0.04-0.86)

0.03

MACE

14%

3.3%

0.33
(0.12-0.96)

0.04

MACCE

11.4%

4.1%

0.01

Definite/Probable Stent Thrombosis

2.5%

0

0.054

Major Bleeding

5.3%

5.6%

2.09
(0.70-6.21)

0.18


Study Design Likely Encouraged Bias

Dr. Brener and colleagues acknowledge several limitations of the study design. The nonrandomized nature of the current analysis “probably led to the selection of younger and healthier patients for [prasugrel] over clopidogrel,” the researchers note. “Yet, the experience of using prasugrel with bivalirudin is rather limited and we have adjusted as much as possible for these differences by using a propensity score derived from a robust series of variables.”

As such, “these data can only be considered hypothesis generating,” they write. “Additional studies from large-scale randomized clinical trials and registries regarding this combination are warranted.”

Prasugrel Pretreatment Remains the Issue

In a telephone interview with TCTMD, Neal S. Kleiman, MD, of Methodist DeBakey Heart and Vascular Center (Houston, TX) said the current analysis confirmed the results of the larger, randomized TRITON TIMI 38 study in a group of higher risk patients.

Because of the positive findings seen in both this and the aforementioned studies, he said he is convinced of the benefits of prasugrel over clopidogrel in this patient group without the need for additional randomized studies. However, there remains an unanswered question: “what happens when you give prasugrel in the ambulance [to confirmed STEMI patients]?” Dr. Kleiman observed. “The ACCOAST study is not very encouraging, but that was a different patient group. I think there’s still room to explore that.”

Study Details

Baseline characteristics between the groups were well-matched, except prasugrel-treated patients were younger, had no prior stroke and higher LVEF, and were more likely to receive DES.

Note: Dr. Brener and several study coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 


Source:
Brener SJ, Oldroyd KF, Maehara A, et al. Outcomes in patients with ST-segment elevation myocardial infarction treated with clopidogrel vs. prasugrel (from the INFUSE-AMI trial). Am J Cardiol. 2014;Epub ahead of print.

 

 

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Disclosures
  • The paper contains no statement regarding conflicts of interest for Dr. Brener.
  • Dr. Kleiman reports serving as an advisor to AstraZeneca and Lilly.

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