New data from ADAPT-DES, published in JACC: Cardiovascular Interventions, indicate that higher platelet reactivity units (PRU) is associated with an increased risk of ischaemic stroke. Therefore, study authors Gennaro Giustino (The Zena and Michael A Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA) and others suggest that risk of ischaemic stroke should be taken into consideration when making decisions about antiplatelet therapy after percutaneous coronary intervention (PCI).
Data from ADAPT-DES, Giustino et al report, have already shown that high on-platelet reactivity is a strong independent predictor of both stent thrombosis and myocardial infarction after PCI. Noting that coronary artery disease patients are at increased of ischaemic stroke because of concomitant atherosclerotic disease, the authors add that the influence of residual P2Y12 receptor inhibition on the risk of ischaemic stroke is unknown. “We sought to investigate the association between platelet reactivity on clopidogrel and aspirin and the risk of ischaemic stroke in patients with coronary artery disease who underwent successful drug-eluting stent PCI,” they comment.
In a post-hoc analysis of ADAPT-DES, Giustino et al identified 7,649 patients (of 8,582 originally enrolled) who had two-year follow-up data. Of these, 68 patients had an ischaemic stroke and 14 had a haemorrhagic stroke (82 in total). According to the authors, this two-year incidence is comparable to that of stent thrombosis.
Patients with ischaemic stroke had higher levels of PRU, identified using the VerifyNow assay (Accriva Diagnostics), compared with those without ischaemic stroke. There were no differences in level of PRU between patients with haemorrhagic stroke and those without haemorrhagic stroke. Giustino et al observe: “Patients with PRU >208 had a higher risk of ischaemic stroke at two years (1.2% vs. 0.5%; univariate hazards ratio [HR] 2.18; p=0.01); an association that persisted following multivariate adjustment (HR 1.84; p=0.02).” They add that, after modelling ischaemic stroke as a time-dependent covariate and by adjusting for baseline confounders, it was strongly associated with two-year all-cause mortality (p<0.001) and cardiovascular mortality (p=0.0009).
As well as the incidence of ischaemic stroke being similar to that of stent thrombosis at two years, the authors say, the risks of all-cause mortality and cardiovascular mortality are also similar. “Our findings imply that the risk of ischaemic stroke should be taken into consideration when risk-stratifying patients and selecting antiplatelet regimens after PCI,” Giustino et al comment. They add: “The results of the present investigation suggest that ensuring optimal platelet inhibition may reduce the risk for ischaemic stroke in this patient population.”
Study investigator Gregg Stone (Columbia University Medical Center, and The Cardiovascular Research Foundation, New York, USA) told Cardiovascular News: “Our study demonstrates an association between inadequate inhibition of the platelet adenosine diphosphate receptor and ischaemic stroke. Subsequent randomised trials are required to determine whether more potent platelet inhibition in such patients will reduce the risk of stroke without excessively increasing bleeding.”