Silent Cerebral Infarcts After Angiography Linked to Insufficient Platelet Inhibition

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Patients who have insufficient platelet inhibition after administration of antiplatelet therapy may be more likely to develop silent embolic cerebral infarctions following coronary angiography, researchers conclude in a study published online December 29, 2011, ahead of print in Stroke.

Investigators led by Sun U. Kwon, MD, PhD, of the University of Ulsan College of Medicine (Seoul, South Korea), conducted a phase 1 study that retrospectively analyzed the location of silent embolic cerebral infarctions occurring in 272 patients after coronary angiography. All patients had also undergone CABG. In a phase 2 study, 102 patients who were recommended for CABG were prospectively recruited to compare the extent of platelet inhibition as measured by VerifyNow (Accumetrics, San Diego, CA) assay among patients with and without cerebral infarctions.

Patients were classified into 3 groups according to their responsiveness to antiplatelet agents:

• Nonresponders (resistant to both aspirin and clopidogrel)
• Partial responders (resistant to either aspirin or clopidogrel)
• Responders (no resistance to any antiplatelet agent)

More Resistance Equals More Emboli

A similar percentage of patients in phase 1 (16.5%) and phase 2 (16.7%) had silent cerebral infarctions. Overall, lesions in patients from both phases were more frequent in the right hemisphere. Additionally, the majority of the lesions were located at the cerebral cortex.

In the phase 2 study, aspirin reaction units and P2Y12 reaction units were higher in patients with cerebral infarctions compared with those without such events (table 1).

Table 1. Antiplatelet Resistance

Furthermore, the incidence of cerebral infarctions increased with antiplatelet agent resistance. Nonresponders had the highest incidence (50%) followed by partial responders (22.2%) and responders (3.6%; P = 0.023).

In logistic regression analysis, higher aspirin reaction units, white blood cell count, low hemoglobin, and nonresponsiveness to antiplatelet agents were independent risk factors for silent emboli.

Silent But Still Important

According to Dr. Kwon and colleagues, studies of patients with vascular dementia have implied that small clinically silent lesions may contribute to cognitive deterioration. While these lesions are silent on routine neurological examination, significant postcatheterization cognitive impairment has been demonstrated on neuropsychological assessment, validating the clinical relevance of silent infarctions, they write.

“The plausible embolic sources of [silent cerebral infarctions], suggested from the previous studies, are thrombus formed from the catheter by platelet activation, dislodgement of the atheroma from the aortic arch by mechanical stress, and air embolism,” the study authors say.

Studies also have shown that activation of platelets by catheterization can be seen with platelet flow cytometry. In addition, platelet membrane activation markers have been shown to be predictive of an increased risk of ischemic events after cardiac catheterization. However, studies have been mixed with regard to the importance of platelet activation in the pathogenic mechanism that leads to cerebral infarcts.

Dr. Kwon and colleagues suggest that administering a higher dosage of antiplatelet agents and sufficiently inhibiting platelet activation can reduce the occurrence of silent emboli.

“However, loading a higher dose of antiplatelet agents may increase the risk of bleeding, including intracerebral hemorrhage,” they write. “Therefore, measuring resistance of antiplatelet agents and selectively administering a high dose to patients with resistance may be a more logical option to reduce the occurrence of [silent embolic cerebral infarction] after [coronary angiography].”

No Real Clinical Relevance

Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), told TCTMD in a telephone interview that while the study is “fascinating” and consistent with literature showing that cardiac catheterization can mobilize emboli, there is no evidence that this results in clinical events.

“If they had shown that patients go on to develop strokes once these emboli have been documented, then that would have some relevance, but they did not show that,” he said. “All of these patients were asymptomatic, so what is being demonstrated is at the subclinical level. However, it is very important to understand that this procedure carries risk and you should think about whether you need to do it or not. What this study really shows is that vascular disease is a diffuse disease.”

Dr. Brener added that the patient population in the study is somewhat unusual in terms of resistance to antiplatelets, which makes it difficult to extrapolate to other populations.

“Their PRUs are at least 100 units higher than any other study we’ve seen,” he said. “This is important because 88% of those with emboli and 64% without it in this study had a PRU ≥ 275. Now when you consider that a PRU of 208 is the new standard for adequate platelet inhibition, [the majority of patients] are unresponsive.”

Dr. Brener added that although the study raises important issues, it does not present sufficient evidence to suggest that platelet inhibition should be checked in all patients prior to coronary angiography or that different antiplatelet strategies such as aspirin and prasugrel are warranted to try to avoid development of silent emboli.

Playing devil’s advocate, Dr. Brener concluded that there also is no proof that some patients did not have the emboli prior to angiography.

Study Details

Patients received aspirin and clopidogrel at least 1 day before undergoing coronary angiography. During the procedure, patients received heparin with a bolus dose of 8,000 U and a repeat bolus of 2000 U if necessary to maintain the activated clotting time over 250 seconds.

Platelet inhibition was measured within 6 hours of angiography. After angiography, patients also underwent diffusion-weighted imaging and magnetic resonance angiography.

 

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Source:
Kim BJ, Lee S-W, Park S-W, et al. Insufficient platelet inhibition is related to silent embolic cerebral infarctions after coronary angiography. Stroke. 2012;Epub ahead of print.

 

 

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