CardioExchange Archive

CardioExchange, an NEJM practice community for medical professionals dedicated to improving cardiac patient care, was active from 2009 to 2015. CardioExchange fostered discussion between clinicians from across the globe.

July 12th, 2010

Clopidogrel vs. Prasugrel: How Effective? How Risky?

Here are the issues:

  1. The FDA has posted a black box warning that people with reduced CYP2C19 liver enzyme function (2% to 14% of the U.S. population) cannot effectively convert clopidogrel to its active form, which reduces its effectiveness in ACS patients. CYP2C19 function doesn’t influence prasugrel’s effectiveness.
  2. The AHA and ACC do not support routine CYP2C19 genetic testing (and the test is not readily available).
  3. Prasugrel (10 mg) is ≈2.5 times more potent than clopidogrel (75 mg); in TRITON-TIMI 38, ACS patients treated with prasugrel had a 50% higher rate of life-threatening hemorrhage and a 4-fold higher rate of fatal hemorrhage than those treated with clopidogrel.
  4. Prasugrel was recently reported to be associated with an increase in cancer rates, prompting the authors of the report to recommend that  “physicians should consider the potential cancer risks before prescribing prasugrel, especially with prolonged use and in patients with known cancer.”

So, how do you decide which agent to prescribe for your ACS patients?

Categories: General


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4 Responses to “Clopidogrel vs. Prasugrel: How Effective? How Risky?”

  1. Audrey Sernyak, MD says:
    July 13, 2010 at 7:20 am

    I have yet to jump on the prasugrel bandwagon- maybe I am just old fashioned. I have yet to see my patients clotting stents off left and right when they are on Plavix. I do however, repeatedly see them showing up with bleeding complications even on this less potent medication. Sticking with the first of all do no harm, I am holding off for now. I also find the marketing ploy of “well if you go back to the study you can see that if we had excluded the old, prior strokes and low body mass all the adverse effects would have been equal in the two arms”. Since when do we get to retrospectively cull out patienbts who do poorly in a randomized trial????

  2. Gregory Dehmer, MD says:
    July 13, 2010 at 6:40 pm

    Clopidogrel vs. Prasugrel

    As with any new drug, time will ultimately determine it’s role in patient care. Currently, we are very selective in its use. We are a large STEMI referral center and and have switched to prasugrel for the patient with STEMI unless there is a contraindication (body weight < 60 kg, any prior CVA, TIA, or age > 75 years). Previously, patients would get 600 mg of clopidogrel at the referring hospital ED or our ED, heparin and maybe a glycoprotein IIb/IIIa inhibitor. A small portion of patients would be best served by CABG rather than PCI and several of our surgeons are very reluctant to operate for several days in a patient who has receive clopidogrel. Now we wait until the first angiograms are done and we know that CABG is out of the picture. We then give 60 mg prasugrel (faster onset of action than clopidogrel) plus bivalirudin as our antithrombotic antiplatelet therapy. So far this seems to be working well in our clinical management. Since up to 50% of Asians are low responders to clopidogrel, I now use prasugrel as a first choice. So in summary, some limited use, but it has not been completely substituted for clopidogrel. Although we have the ability to do genotyping and phenotyping at our facility, it is not practical and is expensive to do in every patient.

    Competing Interests: Although a co-author of the recent ACCF/AHA statement on clopidogrel (J Am Coll Cardiol, 2010; 56:321-341), the opinions expressed herein are my own and not those of any professional organization.

  3. John Ryan, MD says:
    July 16, 2010 at 2:31 pm

    Platelet assay

    Although there is no recommendation to do genetic testing, is there any benefit from doing platelet function analysis on all patients in order to decide if they should be treated with clopidogrel vs prasugrel?

  4. Rick Stouffer, MD says:
    July 20, 2010 at 2:59 pm

    The recently added black box warning for clopidogrel (Plavix) was driven by research suggesting that genetic variation at the CYP450 2C19 locus may result in decreased metabolic activation of clopidogrel and increased risk of adverse cardiovascular events. In particular, individuals who have two abnormal alleles at the CYP 2C19 locus (approximately 2-4%) are ‘poor’ metabolizers and have more adverse cardiovascular outcomes. Individuals with one abnormal allele have intermediate metabolism of clopidogrel to the active metabolite and some of these patients may be at risk.

    The best strategy for platelet inhibition in patients who are poor or intermediate metabolizers was not mandated by the ‘black box’ warning and is left to the discretion of the treating physician. Some physicians have advocated using prasugrel for all patients in whom an adenosine diphosphate receptor P2Y12 receptor antagonist is indicated to avoid the potential problems associated with poor metabolism of clopidogrel. Before adopting this strategy, it is important to remember that: 1) prasugrel is also a prodrug and thus there maybe ‘poor metabolizers’ of this drug (although this has not been established) and 2) prasugrel carries a black box warning recommending against its use in patients who are 75 years of age or older, who weigh less than 60 kg, or who have had a prior cerebrovascular event. While a reduced daily dose (5 mg) is recommended in patients who weigh less than 60 kg, there is limited data on use of this dosage.

    Our practice at UNC has been to perform genetic testing on patients admitted with acute coronary syndromes and/or patients undergoing PCI, as these patients are at the highest risk for ischemic events. Patients who are homozygote for *2 or *3 allelle are changed to prasugrel. For patients with a contraindication to prasugrel, we consider increasing the daily dose of clopidogrel to 150 mg qD. Since there are limited data on the best anti-platelet treatment in patients with impaired clopidogrel metabolism, we have launched the UNC Clopidogrel Pharmacogenomics Project (under the direction of Joe Rossi), a clinical research study exploring the effects of increased clopidogrel doses on platelet inhibition in patients who are intermediate metabolizers. We await results of other clinical trials that are currently underway and more data on ticagrelor, a reversible antagonist of the ADP receptor.

    Competing interests pertaining specifically to this post, comment, or both:
    none