JAMA: Platelet testing shows promise, but still no reason for widespread adoption
Several studies have shown that high residual platelet reactivity during clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) treatment is predictive of major cardiovascular events in patients undergoing PCI, according to the study authors. However, it has not yet been proven that the risk of thrombotic events increases markedly above a critical cut point of platelet reactivity on in vitro platelet function tests.
Guido Parodi, MD, and colleagues from the Careggi Hospital in Florence, Italy, conducted the RECLOSE 2–ACS (Responsiveness to Clopidogrel and Stent Thrombosis 2–ACS) study to examine whether high residual platelet reactivity (HRPR) after clopidogrel loading (a comparatively larger dose of the drug given at the beginning of treatment) is an independent prognostic marker of risk of long-term thrombotic events in patients with ACS undergoing an invasive procedure and receiving long-term antithrombotic treatment adjusted according to the results of platelet function tests.
The study included 1,789 patients with ACS undergoing PCI from April 2005 to April 2009 and who had platelet reactivity assessed via testing. All patients received 325 mg of aspirin and a 600 mg loading dose of clopidogrel, followed by a maintenance dosage of 325 mg per day of aspirin and 75 mg per day of clopidogrel for at least six months.
Patients with HRPR as assessed by adenosine diphosphate test (70 percent platelet aggregation or greater) received an increased dose of clopidogrel or switched to the antiplatelet drug ticlopidine under adenosine diphosphate test guidance, Parodi et al wrote.
The primary outcome measure was a composite of cardiac death, heart attack, any urgent coronary revascularization and stroke at two-year follow-up. Secondary measured outcomes were stent thrombosis and each component of the primary endpoint.
The researchers found that the primary endpoint event rate was 14.6 percent in the HRPR group and 8.7 percent in the low residual platelet reactivity group (LRPR). The difference in the event rate was driven by the difference in cardiac mortality, which was 9.7 percent in the HRPR group and 4.3 percent in the LRPR group.
The stent thrombosis rate was two-fold higher in the HRPR group (6.1 percent vs. 2.9 percent), Parodi and colleagues reported. Additional analysis indicated that HRPR was independently associated with a 49 percent increased risk of the primary endpoint and a 81 percent increased risk of cardiac mortality.
“To our knowledge, this is the first study to explore the association of high residual platelet reactivity after clopidogrel loading with long-term clinical outcome in patients with ACS undergoing an invasive procedure,” the researchers noted. “Consistent with previous studies, our study shows that high residual platelet reactivity is likely to be associated with a worse patient risk profile. However, after adjusting for differences in baseline characteristics between low and high residual platelet reactivity groups, high residual platelet reactivity remained an independent predictor of cardiac death.”
The study authors suggested that "the results of this study should be considered only as hypothesis generating for further studies of tailored therapy using new antithrombotic agents."
In the accompanying editorial, Dominick J. Angiolillo, MD, PhD, of the University of Florida College of Medicine-Jacksonville, commented on the use of platelet function testing.
“Tailored antiplatelet therapy may have more value in populations characterized by higher event rates, such as ACS patients as investigated in the RECLOSE 2–ACS study,” Angiolillo wrote. “However, the lack of significant benefit on the primary ischemic endpoint with adjusted therapies in this study leaves unsolved the pivotal dilemma of whether platelet reactivity is simply a marker of risk or if it is a modifiable risk factor that can affect prognosis.”
"[D]espite promising research conducted to date, currently available evidence cannot support routine use of platelet function testing [PFT] in clinical practice,” he concluded. “Until results of appropriately powered randomized controlled trials demonstrate efficacy and safety (in particular, low bleeding risk) of adjustment of antiplatelet treatment, PFT should be reserved mostly as a research tool."