Platelet‐reactivity tests identify patients at risk of secondary cardiovascular events: a systematic review and meta‐analysis

Abstract

To cite this article: Wisman PP, Roest M, Asselbergs FW, de Groot PG, Moll FL, van der Graaf Y, de Borst GJ. Platelet-reactivity tests identify patients at risk of secondary cardiovascular events: a systematic review and meta-analysis. J Thromb Haemost 2014; 12: 736-47.Summary. Background: Antiplatelet therapy is the standard treatment for the prevention of cardiovascular events (CVEs). High on-treatment platelet reactivity (HPR) is a risk factor for secondary CVEs in patients prescribed aspirin and/or clopidogrel. The present review and meta-analysis was aimed at assessing the ability of individual platelet-function tests to reliably identify patients at risk of developing secondary CVEs. Methods and Results: A systematic literature search was conducted to identify studies on platelet-reactivity measurements and CVEs. The main inclusion criteria were: (i) prospective study design; (ii) study medication, including aspirin and/ or clopidogrel; and (iii) a platelet-function test being performed at baseline, before follow-up started. Of 3882 identified studies, 102 (2.6%; reporting on 44 098 patients) were included in the meta-analysis. With regard to high on-aspirin platelet reactivity (HAPR), 22 different tests were discussed in 55 studies (22 441 patients). Pooled analysis showed that HAPR was diagnosed in 22.2% of patients, and was associated with an increased CVE risk (relative risk [RR] 2.09; 95% confidence interval [CI] 1.77-2.47). Eleven HAPR tests independently showed a significantly increased CVE risk in patients with HAPR as compared with those with normal on-aspirin platelet reactivity. As regards high on-clopidogrel platelet reactivity (HCPR), 59 studies (34 776 patients) discussed 15 different tests, and reported that HCPR was present in 40.4% of patients and was associated with an increased CVE risk (RR 2.80; 95% CI 2.40-3.27). Ten tests showed a significantly increased CVE risk. Conclusions: Patients with HPR are suboptimally protected against future cardiovascular complications. Furthermore, not all of the numerous platelet tests proved to be able to identify patients at increased cardiovascular risk.

Validation of a New ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay to Assess Platelet Reactivity Index in a Chinese Population

“…However, a considerable number of patients demonstrate HPR. 14,15 Recently, the level of PR inhibition measured by platelet assays has been shown to predict the risk of recurrent thrombotic events following PCI. 16,17 Therefore, the calculation of platelet aggregation is useful for guiding the choice of antiplatelet drugs and individualizing treatment.…”

Clinical Implications of Changes in Individual Platelet Reactivity to Aspirin Over Time in Acute Ischemic Stroke

“…16 Although various platelet reactivity assays have not been considered accurate or consistent, 17 in separate HAPR analyses using END is defined as an increase in the NIHSS score of ≥1 point, and END 4 is defined as an increase in the NIHSS score of ≥4 points. END and END 4 were more frequently observed in patients in the fourth quartile based on ∆ARU than in patients in the other quartiles (by Pearson χ 2 ; P=0.003 in the END column and 0.009 in the END 4 column, and P for trends=0.003 and 0.007, respectively).…”

“…16 However, our study focused on the acute period of ischemic stroke. Few studies have focused on this period or on the platelet reactivity after aspirin administration during the first several days after acute ischemic stroke.…”

“…different tests, the results of 12 tests have independently shown that patients with HAPR exhibit a significantly increased risk for cardiovascular events, particularly coronary artery disease, compared with patients with NAPR. 16 However, our study focused on the acute period of ischemic stroke. Few studies have focused on this period or on the platelet reactivity after aspirin administration during the first several days after acute ischemic stroke.…”

High On-Treatment Platelet Reactivity in Peripheral Arterial Disease: A Pilot Study to Find the Optimal Test and Cut Off Values

“…1 Clopidogrel, a P2Y 12 inhibitor, is often the first choice APT added to aspirin, although previous trials have shown that 40% of patients show high platelet reactivity, despite additional clopidogrel treatment. 8 The few trials reporting on high on-clopidogrel platelet reactivity (HCPR) in PAD patients indicate an even higher incidence. 9e11 In some patients, this phenomenon can be caused by a mutation in the genes coding for cytochrome P450 2C19 (CYP2C19) activity, a liver enzyme that converts the clopidogrel prodrug into its active metabolite.…”