Although the PLATO trial demonstrated the overall superiority of ticagrelor (Brilinta, AstraZeneca) to clopidogrel in more than 18,000 acute coronary syndrome patients worldwide, approval of the drug in the U.S. has been delayed because of ticagrelor’s lack of effect in the prespecified subgroup of patients from North America. Now, two analyses of the trial, presented…

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A 77-year-old man with metformin-treated type 2 diabetes, high blood pressure, moderate renal insufficiency, stable angina, and a history of phlebitis stopped taking aspirin in preparation for palpebral surgery. A day after the surgery, he presented to the ER with two transient ischemic attacks (TIAs) affecting the left arm. The patient complained to the examining neurologist…

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The PROSPECT trial provides some interesting insights about the mechanisms of thrombotic coronary artery disease, but how, if at all, should it change practice? Here are what the findings do and do not demonstrate: What the PROSPECT study says: In ACS patients treated with PCI, major adverse cardiovascular events that occurred during a median follow-up of 3.4 years were…

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From time to time, a sales representative visits my office promoting clopidogrel (Plavix) as a drug that patients who present with unstable angina/non–ST-segment-elevation MI (UA/NSTEMI) should start immediately as an up-front load. That strategy hasn’t been uniformly accepted in my clinician community because of concern about using an irreversible antiplatelet agent to treat patients who…

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You’ve heard a lot lately about so-called “clopidogrel resistance.” That sounds straightforward, but the underlying reason can be complex, possibly related to how the drug is metabolized by subjects with a certain genetic profile. We seek here to provide some perspective about clopidogrel’s metabolic and gene-related complexities. First, some brief background: Clopidogrel, a thienopyridine, is…

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I recently read an article in the journal Circulation that contained an alarming finding about patients who receive drug-eluting stents. Apparently, 1 in 6 did not fill their clopidogrel prescriptions immediately after discharge from a hospital in one of three large integrated health care systems. The median delay was 3 days. Furthermore, during a median…

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In many clinical trials, researchers investigate whether an overall effect of an intervention is consistent across various subgroups, as I discussed in this Journal Club Series last week. Such subgroup analyses require assessment of what is called an interaction — that is, whether the effect in one group differs from that in another. Do the benefits differ,…

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In the CURRENT-OASIS 7 trial, more than 25,000 patients with ACS for whom an interventional strategy was planned were randomized to either double-dose clopdiogrel (a 600-mg loading dose on the first day followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300-mg loading dose, followed by 75 mg…

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CardioExchange welcomes Guillaume Paré to discuss his team’s work on the  utility of clopidogrel genotyping. The researchers genotyped for CYP2C19 alleles associated with loss-of-function or gain-of-function of clopidogrel in some 5,000 patients with ACS or A-fib from two large randomized trials. In both studies, clopidogrel had similar efficacy over placebo regardless of whether patients had…

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Genetic substudies across a broad range of large clinical trials that used clopidogrel raise questions about the clinical utility of clopidogrel genotyping. The substudies come from large and important trials like PLATO, TRITON-TIMI 38, CURE, and ACTIVE A. A genetic substudy of PLATO finds that ticagrelor is superior to clopidogrel irrespective of genetic subtype. Therefore,…

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