Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 2/2016

01-04-2016 | ORIGINAL ARTICLE

Gender Differences in Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy

Authors: Monica Verdoia, Patrizia Pergolini, Roberta Rolla, Matteo Nardin, Lucia Barbieri, Veronica Daffara, Paolo Marino, Giorgio Bellomo, Harry Suryapranata, Giuseppe De Luca, on behalf of the Novara Atherosclerosis Study Group (NAS)

Published in: Cardiovascular Drugs and Therapy | Issue 2/2016

Login to get access

Abstract

Background

Cardiovascular risk is still underestimated in women, experiencing higher mortality and worse prognosis after acute cardiovascular events. Gender differences have been reported in thrombotic and hemorrhagic risk during dual antiplatelet therapy (DAPT), thus suggesting a potential variability in platelet reactivity according to sex. The aim of the present study was to assess the role of gender on platelet function and the prevalence of high-on treatment residual platelet reactivity (HRPR) during DAPT in patients with recent acute coronary syndrome or percutaneous coronary revascularization.

Methods

Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30–90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥417 AU*min (for ADP-antagonists).

Results

We included 541 patients on DAPT, 122 (22.6 %) of whom were females. Females were older (p < 0.001), displayed more frequently hypercholesterolemia (p = 0.003), renal failure (p = 0.04), acute presentation (p < 0.001), higher cholesterol levels and platelets count (p < 0.001). Inverse association was demonstrated with smoking (p < 0.001), previous PCI (p = 0.04) and statin use (p = 0.03), creatinine and haemoglobin (p < 0.001). Female gender did not influence mean platelet reactivity or the prevalence of HRPR for ASA (1.7 % vs 1.4 %, OR[95%CI] = 1.14[0.17–4.36], p = 0.99, adjusted OR[95%CI] = 1.54[0.20–11.6], p = 0.68) or ADP-antagonists (26.3 % vs 22.8 %, OR[95%CI] = 1.17[0.52–1.34], p = 0.45, adjusted OR[95%CI] = 1.05[0.59–1.86], p = 0.87). Results did not change when considering separately the 309 patients treated with clopidogrel (34 % vs 31.3 %, OR[95%CI] = 1.13[0.62–2.07], p = 0.76, adjusted OR[95%CI] = 1.35[0.63–2.9], p = 0.44 for females vs males), or patients (n = 232) on ticagrelor (20.4 % vs 11.1 %, OR[95%CI] = 2.27[0.99–5.17], p = 0.06 for females vs males), confirmed after correction for baseline differences (adjusted OR[95%CI] = 1.21[0.28–2.29], p = 0.68).

Conclusion

In patients receiving dual antiplatelet therapy, gender does not impact on the prevalence of high-on treatment residual platelet reactivity (HRPR) with the major antiplatelet agents ASA, clopidogrel or ticagrelor.
Literature
1.
De Luca G, Biondi-Zoccai G, Marino P. Transferring patients with ST-segment elevation myocardial infarction for mechanical reperfusion: a meta-regression analysis of randomized trials. Ann Emerg Med. 2008;52(6):665–76.CrossRefPubMed
2.
De Luca G, Suryapranata H. Recent advances in optimal adjunctive antithrombotic therapy in STEMI patients undergoing primary angioplasty: an overview. Curr Vasc Pharmacol 2014
3.
Landes U, Kornowski R, Assali A, Vaknin-Assa H, Greenberg G, Lev EI, Bental T. Predictors of long term outcomes in 11,441 consecutive patients following percutaneous coronary interventions. Am J Cardiol 2015
4.
Pancholy SB, Shantha GP, Patel T, Cheskin LJ. Sex differences in short-term and long-term all-cause mortality among patients with ST-segment elevation myocardial infarction treated by primary percutaneous intervention: a meta-analysis. JAMA Intern Med. 2014;174:1822–30.CrossRefPubMed
5.
De Luca G, Suryapranata H, Dambrink JH, JP O, AW v 't H, Zijlstra F, JC H, AT G, MJ d B. Sex-related differences in outcome after st-segment elevation myocardial infarction treated by primary angioplasty: data from the zwolle myocardial infarction. Study Am Heart J. 2004;148:852–6.CrossRefPubMed
6.
De Luca G, Verdoia M, Dirksen MT, Spaulding C, Kelbæk H, Schalij M, Thuesen L, Bv H, MA V, Kaiser C, Musto C, Chechi T, Spaziani G, LS D d l l, Pasceri V, Di Lorenzo E, Violini R, Suryapranata H, GW S. DESERT Cooperation gender-related differences in outcome after bms or des implantation in patients with st-segment elevation myocardial infarction treated by primary angioplasty: insights from the DESERT cooperation. Atherosclerosis. 2013;230:12–6.CrossRefPubMed
7.
De Luca G, Parodi G, Sciagrà R, Bellandi B, Verdoia M, Vergara R, Migliorini A, Valenti R, Antoniucci D. Relation of gender to infarct size in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty. Am J Cardiol. 2013;111:936–40.CrossRefPubMed
8.
Chieffo A, Buchanan GL, Mauri F, Mehilli J, Vaquerizo B, Moynagh A, Mehran R, Morice MC. ACS and STEMI treatment: gender-related issues. EuroIntervention. 2012 Aug;8 Suppl P:P27-35
9.
Gutiérrez-Chico JL, Mehilli J. Gender differences in cardiovascular therapy: focus on antithrombotic therapy and percutaneous coronary intervention. Drugs. 2013;73(17):1921–33.CrossRefPubMed
10.
DB D, KP O, MC K, Blomkalns A, AY C, Miller C, Wiviott S, ED P. Gender differences in time to presentation for myocardial infarction before and after a national women's cardiovascular awareness campaign: a temporal analysis from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation (CRUSADE) and the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network-Get with the Guidelines (NCDR ACTION Registry-GWTG). Am Heart J. 2010;160(1):80–7.CrossRef
11.
Becker DM, Segal J, Vaidya D, Yanek LR, Herrera-Galeano JE, Bray PF, Moy TF, Becker LC, Faraday N. Sex differences in platelet reactivity and response to low-dose aspirin therapy. J Am Med Assoc. 2006;295(12):1420–7.CrossRef
12.
Gremmel T, Kopp CW, Eichelberger B, Koppensteiner R, Panzer S. Sex differences of leukocyte-platelet interactions and on-treatment platelet reactivity in patients with atherosclerosis. Atherosclerosis. 2014;237(2):692–5.CrossRefPubMed
13.
Mayer K, Bernlochner I, Braun S, Schulz S, Orban M, Morath T, Cala L, Hoppmann P, Schunkert H, Laugwitz KL, Kastrati A, Sibbing D. Aspirin treatment and outcomes after percutaneous coronary intervention: results of the ISAR-ASPI registry. J Am Coll Cardiol. 2014;64(9):863–71.CrossRefPubMed
14.
Tantry US, Bonello L, Aradi D, Price MJ, Jeong YH, Angiolillo DJ, Stone GW, Curzen N, Geisler T, Ten Berg J, Kirtane A, Siller-Matula J, Mahla E, Becker RC, Bhatt DL, Waksman R, Rao SV, Alexopoulos D, Marcucci R, Reny JL, Trenk D, Sibbing D. Gurbel PA; working group on On-treatment platelet reactivity. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013;62(24):2261–73.CrossRefPubMed
15.
Harrison MJ, Weisblatt E. A sex difference in the effect of aspirin on “spontaneous” platelet aggregation in whole blood. Thromb Haemost. 1983;50(4):773–4.PubMed
16.
Jochmann N, Stangl K, Garbe E, Baumann G, Stangl V. Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases. Eur Heart J. 2005;26(16):1585–95.CrossRefPubMed
17.
De Luca G, Secco GG, Santagostino M, Venegoni L, Iorio S, Cassetti E, Verdoia M, Coppo L, Di Mario C, Bellomo G, Marino P. Uric acid does not affect the prevalence and extent of coronary artery disease. Results from a prospective study. Nutr Metab Cardiovasc Dis. 2012;22:426–33.CrossRefPubMed
18.
De Luca G, Venegoni L, Iorio S, Secco GG, Cassetti E, Verdoia M, Schaffer A, Coppo L, Bellomo G, Marino P, Group NAS. Platelet distribution width and the extent of coronary artery disease: results from a large prospective study. Platelets. 2010;21:508–14.CrossRefPubMed
19.
Verdoia M, Pergolini P, Camaro C, Restifo M, Rolla R, Schaffer A, Di Giovine G, Marino P, Bellomo G, Suryapranata H. De Luca G; Novara AtherosclerosisStudy group (NAS). PlA(1)/PlA(2) polymorphism does not influence response to GpIIb-IIIa inhibitors in patients undergoing coronary angioplasty. Blood Coagul Fibrinolysis. 2013;24:411–8.CrossRefPubMed
20.
Vidali M, Rolla R, Parrella M, Cassani C, Manzini M, Portalupi MR, Serino R, Prando MD, Bellomo G, Pergolini P. Role of the laboratory in monitoring patients receiving dual antiplatelet therapy. Int J Lab Hematol. 2012;34:484–94.CrossRefPubMed
21.
Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, Bhatt DL, Cattaneo M, Collet JP, Cuisset T, Gachet C, Montalescot G, Jennings LK, Kereiakes D, Sibbing D, Trenk D, JW v W, Paganelli F, MJ P, Waksman R, PA G. Working group on high On-treatment platelet reactivity. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010;56:919–33.CrossRefPubMed
22.
Authors/Task Force members, Windecker S, Kolh P, Alfonso F, JP C, Cremer J, Falk V, Filippatos G, Hamm C, SJ H, Jüni P, AP K, Kastrati A, Knuuti J, Landmesser U, Laufer G, FJ N, DJ R, Schauerte P, Sousa Uva M, GG S, DP T, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS guidelines on myocardial revascularization: the task force on myocardial revascularization of the European society of cardiology (ESC) and the European association for cardio-thoracic surgery (EACTS) developed with the special contribution of the European association of percutaneous cardiovascular interventions (EAPCI). Eur Heart J. 2014;35(37):2541–619.CrossRef
23.
De Luca G, Marino P. Antithrombotic therapies in primary angioplasty: rationale, results and future directions. Drugs. 2008;68(16):2325–44.CrossRefPubMed
24.
Verdoia M, Schaffer A, Barbieri L, Cassetti E, Piccolo R, Galasso G, Marino P, Sinigaglia F, De Luca G. Benefits from new ADP antagonists as compared with clopidogrel in patients with stable angina or acute coronary syndrome undergoing invasive management: a meta-analysis of randomized trials. J Cardiovasc Pharmacol. 2014;63(4):339–50.CrossRefPubMed
25.
De Luca G, Bellandi F, Huber K, Noc M, Petronio AS, Arntz HR, Maioli M, Gabriel HM, Zorman S, DE Carlo M, Rakowski T, Gyongyosi M, Dudek D. Early glycoprotein IIb-IIIa inhibitors in primary angioplasty-abciximab long-term results (EGYPT-ALT) cooperation: individual patient's data meta-analysis. J Thromb Haemost. 2011;9(12):2361–70.CrossRef
26.
Gurbel PA, Tantry US. Clopidogrel response variability and the advent of personalised antiplatelet therapy. A bench to bedside journey. Thromb Haemost. 2011;106(2):265–71.CrossRefPubMed
27.
Migliorini A, Valenti R, Marcucci R, Parodi G, Giuliani G, Buonamici P, Cerisano G, Carrabba N, Gensini GF, Abbate R, Antoniucci D. High residual platelet reactivity after clopidogrel loading and long-term clinical outcome after drug-eluting stenting for unprotected left main coronary disease. Circulation. 2009;120:2214–21.CrossRefPubMed
28.
Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schömig A, Kastrati A, von Beckerath N. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol. 2009;53:849–56.CrossRefPubMed
29.
Marcucci R, Cioni G, Giusti B, Fatini C, Rossi L, Pazzi M, Abbate R. Gender and anti-thrombotic therapy: from biology to clinical implications. J Cardiovasc Transl Res. 2014;7:72–81.CrossRefPubMed
30.
De Luca G, Gibson CM, Gyöngyösi M, Zeymer U, Dudek D, Arntz HR, Bellandi F, Maioli M, Noc M, Zorman S, Gabriel HM, Emre A, Cutlip D, Rakowski T, Huber K, van't Hof AW. Gender-related differences in outcome after ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb-IIIa inhibitors: insights from the EGYPT cooperation. J Thromb Thrombolysis. 2010;30:342–6.CrossRefPubMed
31.
Capodanno D, Angiolillo DJ. Impact of race and gender on antithrombotic therapy. Thromb Haemost. 2010;104:471–84.CrossRefPubMed
32.
Johnson M, Ramey E, Ramwell PW. Sex and age differences in human platelet aggregation. Nature. 1975;253(5490):355–7.CrossRefPubMed
33.
Singla A, Bliden KP, Jeong YH, Abadilla K, Antonino MJ, Muse WC, Mathew DP, Bailon O, Tantry US, Gurbel PA. Platelet reactivity and thrombogenicity in postmenopausal women. Menopause. 2013;20(1):57–63.CrossRefPubMed
34.
Kjeldsen SE, Kolloch RE, Leonetti G, Mallion JM, Zanchetti A, Elmfeldt D, Warnold I, Hansson L. Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study. Hypertension optimal treatment. J Hypertens. 2000;18(5):629–42.CrossRefPubMed
35.
Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl JMed. 2005;352:1293–304.CrossRef
36.
Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. J Am Med Assoc. 2006;295(3):306–13.CrossRef
37.
Franconi F, Carru C, Spoletini I, Malorni W, Vella S, Mercuro G, Deidda M, Rosano G. A GENS-based approach to cardiovascular pharmacology: impact on metabolism, pharmacokinetics and pharmacodynamics. Ther Deliv. 2011;2(11):1437–53.CrossRefPubMed
38.
Budaj A, Yusuf S, Mehta SR, Fox KA, Tognoni G, Zhao F, Chrolavicius S, Hunt D, Keltai M. Franzosi MG; clopidogrel in unstable angina to prevent recurrent events (CURE) trial investigators. Benefit of clopidogrel in patients with acute coronary syndromes without ST-segment elevation in various risk groups. Circulation. 2002;106(13):1622–68.CrossRefPubMed
39.
Hobson AR, Qureshi Z, Banks P, Curzen N. Gender and responses to aspirin and clopidogrel: insights using short thrombelastography. Cardiovasc Ther. 2009;27(4):246–52.CrossRefPubMed
40.
Breet NJ, Sluman MA, van Berkel MA, van Werkum JW, Bouman HJ, Harmsze AM, Kelder JC, Zijlstra F, Hackeng CM, Ten Berg JM. Effect of gender difference on platelet reactivity. Neth Hear J. 2011;19(11):451–7.CrossRef
41.
Alexopoulos D, Xanthopoulou I, Storey RF, Bliden KP, Tantry US, Angiolillo DJ, Gurbel PA. Platelet reactivity during ticagrelor maintenance therapy: a patient-level data meta-analysis. Am Heart J. 2014;168(4):530–6.CrossRefPubMed
42.
Chen HY, Saczynski JS, McManus DD, Lessard D, Yarzebski J, Lapane KL, Gore JM, Goldberg RJ. The impact of cardiac and noncardiac comorbidities on the short-term outcomes of patients hospitalized with acute myocardial infarction: a population-based perspective. Clin Epidemiol. 2013;5:439–48.PubMedPubMedCentral
43.
Koltai K, Papp J, Kenyeres P, Feher G, Tibold A, Alexy T, Marton Z, Kesmarky G, Toth K. Gender differences in hemorheological parameters and in in vitro platelet aggregation in acetylsalicylic acid and clopidogrel treated vascular patients. Biorheology. 2014;51(2–3):197–206.PubMed
44.
D'Ascenzo F, Colombo F, Barbero U, Moretti C, Omedè P, Reed MJ, Tarantini G, Frati G, Di Nicolantonio JJ, Biondi Zoccai G, Gaita F. Discontinuation of dual antiplatelet therapy over 12 months after acute coronary syndromes increases risk for adverse events in patients treated with percutaneous coronary intervention: systematic review and meta-analysis. J Interv Cardiol. 2014;27(3):233–41.CrossRefPubMed
45.
Butler K, Teng R. Effect of ticagrelor on the pharmacokinetics of ethinyl oestradiol and levonorgestrel in healthy volunteers. Curr Med Res Opin. 2011;27(8):1585–93.CrossRefPubMed
46.
Guo LZ, Kim MH, Jin CD, Lee JY, Yi SJ, Park MK, Cho YR, Park TH. Comparison of pharmacodynamics between low dose ticagrelor and clopidogrel after loading and maintenance doses in healthy Korean subjects. Platelets. 2014;2:1–7.
47.
Siller-Matula JM, Delle-Karth G, Lang IM, Neunteufl T, Kozinski M, Kubica J, Maurer G, Linkowska K, Grzybowski T, Huber K, Jilma B. Phenotyping vs. genotyping for prediction of clopidogrel efficacy and safety: the PEGASUS-PCI study. J Thromb Haemost. 2012;10(4):529–42.CrossRefPubMed
48.
Siller-Matula JM, Gruber C, Francesconi M, Dechant C, Jilma B, Delle-Karth G, Grohs K, Podczeck-Schweighofer A, Christ G. The net clinical benefit of personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention. Clin Sci (Lond). 2015;128(2):121–30.CrossRef
Metadata
Title
Gender Differences in Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy
Authors
Monica Verdoia
Patrizia Pergolini
Roberta Rolla
Matteo Nardin
Lucia Barbieri
Veronica Daffara
Paolo Marino
Giorgio Bellomo
Harry Suryapranata
Giuseppe De Luca
on behalf of the Novara Atherosclerosis Study Group (NAS)
Publication date
01-04-2016
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 2/2016
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-016-6646-5

Other articles of this Issue 2/2016

Cardiovascular Drugs and Therapy 2/2016 Go to the issue

ORIGINAL ARTICLE

Clinical Significance of Laboratory-determined Aspirin Poor Responsiveness After Primary Percutaneous Coronary Intervention

Erratum

Erratum to: Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers in Coronary Artery Disease without Heart Failure in the Modern Statin Era: a Meta-Analysis of Randomized-Controlled Trials

REVIEW ARTICLE

Lipophilic Statin Versus Rosuvastatin (Hydrophilic) Treatment for Heart Failure: a Meta-Analysis and Adjusted Indirect Comparison of Randomised Trials

ORIGINAL ARTICLE

ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism

ORIGINAL ARTICLE

Aleglitazar, a Balanced Dual PPARα and -γ Agonist, Protects the Heart Against Ischemia-Reperfusion Injury

ORIGINAL ARTICLE

Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Regulate the Phenotype of Smooth Muscle Cells to Limit Intimal Hyperplasia

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits