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      Effect of gender difference on platelet reactivity

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          Abstract

          Background

          Previous studies have suggested that women do not accrue equal therapeutic benefit from antiplatelet medication as compared with men. The physiological mechanism and clinical implications behind this gender disparity have yet to be established.

          Methods

          On-treatment platelet reactivity was determined in 717 men and 234 women on dual antiplatelet therapy, undergoing elective coronary stent implantation. Platelet function testing was performed using arachidonic acid and adenosine diphosphate-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 and Aspirin assays. Also the incidence of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and ischaemic stroke was evaluated.

          Results

          Women had higher baseline platelet counts than men. Women exhibited a higher magnitude of on-aspirin platelet reactivity using LTA, but not using the VerifyNow Aspirin assay. The magnitude of on-clopidogrel platelet reactivity was significantly higher in women as compared with men with both tests used. The cut-off value to identify patients at risk as well as the incidence of clinical endpoints was similar between women and men (16/234[6.8%] vs. 62/717[8.6%], p = 0.38).

          Conclusion

          Although the magnitude of platelet reactivity was higher in women, the absolute difference between genders was small and both the cut-off value to identify patients at risk and the incidence of the composite endpoint were similar between genders. Thus, it is unlikely that the difference in platelet reactivity accounts for a worse prognosis in women.

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          Most cited references23

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          Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate.

          The addition of clopidogrel to aspirin treatment reduces ischemic events in a wide range of patients with cardiovascular disease. However, recurrent ischemic event occurrence during dual antiplatelet therapy, including stent thrombosis, remains a major concern. Platelet function measurements during clopidogrel treatment demonstrated a variable and overall modest level of P2Y(12) inhibition. High on-treatment platelet reactivity to adenosine diphosphate (ADP) was observed in selected patients. Multiple studies have now demonstrated a clear association between high on-treatment platelet reactivity to ADP measured by multiple methods and adverse clinical event occurrence. However, the routine measurement of platelet reactivity has not been widely implemented and recommended in the guidelines. Reasons for the latter include: 1) a lack of consensus on the optimal method to quantify high on-treatment platelet reactivity and the cutoff value associated with clinical risk; and 2) limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes. This review provides a consensus opinion on the definition of high on-treatment platelet reactivity to ADP based on various methods reported in the literature and proposes how this measurement may be used in the future care of patients. Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation.

            Context High on-treatment platelet reactivity is associated with atherothrombotic events following coronary stent implantation. Objective To evaluate the capability of multiple platelet function tests to predict clinical outcome. Design, Setting, and Patients Prospective, observational, single-center cohort study of 1069 consecutive patients taking clopidogrel undergoing elective coronary stent implantation between December 2005 and December 2007. On-treatment platelet reactivity was measured in parallel by light transmittance aggregometry, Verify Now P2Y12 and Platelet works assays, and the IMPACT-R and the platelet function analysis system (PFA-100) (with the Dade PFA collagen/adenosine diphosphate (ADP) cartridge and Innovance PFA P2Y). Cutoff values for high on-treatment platelet reactivity were established by receiver operating characteristic curve (ROC) analysis. Main Outcome Measurement The primary end point was defined as a composite of all-cause death, nonfatal acute myocardial infarction, stent thrombosis, and ischemic stroke. The primary safety end point included TIMI (Thrombolysis In Myocardial Infarction) criteria major and minor bleeding. Results Kaplan-Meier analysis demonstrated that at 1-year follow-up, the primary end point occurred more frequently in patients with high on-treatment platelet reactivity when assessed by light transmittance aggregometry (52 [11.7%; 95% confidence interval {CI}, 8.9%-15.0%] vs 36 [6.0%;95%CI, 4.2%-8.2%] P.001; n=1049),Verify Now (54 [13.3%; 95% CI, 10.2%-17.0%] vs 37 [5.7%; 95% CI, 4.1%-7.8%]P.001; n=1052), Platelet works (33 [12.6%; 95% CI, 8.8%-17.2%] vs 21 [6.1%;95% CI, 3.8%-9.2%] P=.005; n=606), and Innovance PFA P2Y (18 [12.2%; 95%CI; 7.4%-18.6%] vs 28 [6.3%; 95% CI, 4.3%-8.9%] P=.02; n=588). ROC-curve analysis demonstrated that light transmittance aggregometry (area under the curve[AUC], 0.63; 95% CI, 0.58-0.68), Verify Now (AUC, 0.62; 95% CI, 0.57-0.67), and Platelet works (AUC, 0.61; 95% CI, 0.53-0.69) had modest ability to discriminate between patients with and without primary end point at 1-year follow-up. The IMPACT-R(n=905) and the Siemens PFA Collagen/ADP (n=812) were unable to discriminate between patients with and without the primary end point at 1-year follow-up (all AUCs included 0.50 in the CI). None of the tests identified patients at risk for bleeding. Conclusions Of the platelet function tests assessed, light transmittance aggregometry,Verify Now, Platelet works, and Innovance PFA P2Y were significantly associated with the primary end point. However, the predictive accuracy of these 4 tests was only modest. None of the tests provided accurate prognostic information to identify patients at higher risk of bleeding following stent implantation. Trial Registration clinical trials.gov Identifier: NCT00352014 [corrected].
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              Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials.

              Aspirin therapy reduces the risk of cardiovascular disease in adults who are at increased risk. However, it is unclear if women derive the same benefit as men. To determine if the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease vary by sex. MEDLINE and the Cochrane Central Register of Controlled Trials databases (1966 to March 2005), bibliographies of retrieved trials, and reports presented at major scientific meetings. Eligible studies were prospective, randomized controlled trials of aspirin therapy in participants without cardiovascular disease that reported data on myocardial infarction (MI), stroke, and cardiovascular mortality. Six trials with a total of 95 456 individuals were identified; 3 trials included only men, 1 included only women, and 2 included both sexes. Studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points (a composite of cardiovascular events [nonfatal MI, nonfatal stroke, and cardiovascular mortality], each of these individual components separately, and major bleeding). Among 51,342 women, there were 1285 major cardiovascular events: 625 strokes, 469 MIs, and 364 cardiovascular deaths. Aspirin therapy was associated with a significant 12% reduction in cardiovascular events (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.79-0.99; P = .03) and a 17% reduction in stroke (OR, 0.83; 95% CI, 0.70-0.97; P = .02), which was a reflection of reduced rates of ischemic stroke (OR, 0.76; 95% CI, 0.63-0.93; P = .008). There was no significant effect on MI or cardiovascular mortality. Among 44,114 men, there were 2047 major cardiovascular events: 597 strokes, 1023 MIs, and 776 cardiovascular deaths. Aspirin therapy was associated with a significant 14% reduction in cardiovascular events (OR, 0.86; 95% CI, 0.78-0.94; P = .01) and a 32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P = .001). There was no significant effect on stroke or cardiovascular mortality. Aspirin treatment increased the risk of bleeding in women (OR, 1.68; 95% CI, 1.13-2.52; P = .01) and in men (OR, 1.72; 95% CI, 1.35-2.20; P<.001). For women and men, aspirin therapy reduced the risk of a composite of cardiovascular events due to its effect on reducing the risk of ischemic stroke in women and MI in men. Aspirin significantly increased the risk of bleeding to a similar degree among women and men.
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                Author and article information

                Contributors
                +31-30-6099111 , +31-30-6034420 , j.ten.berg@antoniusziekenhuis.nl
                Journal
                Neth Heart J
                Netherlands Heart Journal
                Bohn Stafleu van Loghum (Heidelberg )
                1568-5888
                1876-6250
                7 September 2011
                7 September 2011
                November 2011
                : 19
                : 11
                : 451-457
                Affiliations
                [1 ]St Antonius Center for Platelet Function Research, St Antonius Hospital, Nieuwegein, the Netherlands
                [2 ]Department of Cardiology, St Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands
                [3 ]Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, the Netherlands
                [4 ]Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands
                [5 ]Department of Clinical Chemistry, St Antonius Hospital, Nieuwegein, the Netherlands
                Article
                189
                10.1007/s12471-011-0189-y
                3203982
                21901505
                984ad17b-0b93-429e-b75c-145a91212111
                © The Author(s) 2011
                History
                Categories
                Original Article
                Custom metadata
                © Springer Media / Bohn Stafleu van Loghum 2011

                Cardiovascular Medicine
                antiplatelet therapy,clopidogrel,aspirin,gender,platelet function testing
                Cardiovascular Medicine
                antiplatelet therapy, clopidogrel, aspirin, gender, platelet function testing

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