Key Antiplatelet Presentations Yield More Questions Than Answers

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 - Paul A. Gurbel, MD
Paul A. Gurbel, MD

The Dual Antiplatelet Therapy (DAPT) study presented at the American Heart Association (AHA) conference shows that knowledge gaps still exist.

Cardiologists have debated how long to treat patients with dual antiplatelet therapy (DAPT) after stenting. The DAPT Study sought to answer that question by following patients who had drug-eluting stents (DES) implanted and were on DAPT for a year. After the first year, those free of adverse events were randomized to two groups: DAPT for a 30-month period or a placebo. Both groups received daily aspirin.

The results showed that patients on long-term DAPT had less MI and stent thrombosis compared with patients who were on DAPT for 12 months. Still, questions remain. Among 22,866 patients treated with DES, less than half were randomized although over half were eligible.

Most of the patients randomized were not troponin-positive acute coronary syndrome patients. This group would be expected to have a lower incidence of stent thrombosis than patients with STEMI or NSTEMI. It’s likely that treating physicians assessed thrombosis risk and excluded the patients from randomization whom they perceived were at highest risk. Similarly, for patients they felt were at the lowest risk for cardiac events or the most risk for bleeding, they stopped the drug altogether. 

Additionally, there was no assessment of patient thrombogenicity or assessment of antiplatelet effect of clopidogrel or prasugrel. Clopidogrel has been shown to have unpredictable antiplatelet effects and patients with high platelet reactivity during clopidogrel have a higher risk for long-term thrombotic events, including stent thrombosis.

At the end of the study period, patients treated with prasugrel had significantly lower incidences of thrombotic events compared with clopidogrel and had a similar rate of bleeding events. These observations support the importance of measuring platelet function and selectively treating patients with high platelet reactivity on clopidogrel with prasugrel.   

There was a greater incidence of stent thrombosis and major adverse events in patients who were on prasugrel at the start of the study and randomized to placebo compared with patients on clopidogrel and randomized to placebo. It is likely that the former group was of high risk.  

The DAPT study used an arbitrary cutoff of 30 months or 12 months without any assessment of intrinsic thrombogenicity. Perhaps a better strategy would employ laboratory methods to identify individual patient risk for thrombosis and bleeding. We are really no closer to answering these key questions.

An important takeaway from the DAPT study and a consideration for future research is the potential signal for higher mortality for nonselective prolonged DAPT. The cause of noncardiovascular death needs to be studied in more detail.

A personalized assessment of the propensity for thrombosis may improve the identification of patients for prolonged DAPT. Point-of-care genetic and platelet function testing devices are available. Thrombelastography (TEG) has been widely used to assess global hemostasis as well as antiplatelet therapy effect.

Conventional TEG is a labor intensive and time-consuming method. My team presented validation study results for the new CORA (TEG 6S) point-of-care device at AHA, demonstrating greater precision and ease of use compared with traditional TEG. It likely will serve as a valuable tool in future trials of personalized antiplatelet therapy and improve assessment of bleeding and thrombotic risk in cardiovascular, surgical and trauma patients.

Despite advancements in testing and treatment options, much more work is needed to determine individual patient thrombogenicity and the optimal antithrombotic regimen after drug-eluting stenting.