Effects of Ramadan fasting on platelet reactivity in diabetic patients treated with clopidogrel

W Bouida, H Baccouche, M Sassi, Z Dridi, T Chakroun, I Hellara, R Boukef, M Hassine, F Added, R Razgallah, I Khochtali, S Nouira, Ramadan Research Group, W Bouida, H Baccouche, M Sassi, Z Dridi, T Chakroun, I Hellara, R Boukef, M Hassine, F Added, R Razgallah, I Khochtali, S Nouira, Ramadan Research Group

Abstract

Background: The effects of Ramadan fasting (RF) on clopidogrel antiplatelet inhibition were not previously investigated. The present study evaluated the influence of RF on platelet reactivity in patients with high cardiovascular risk (CVR) in particular those with type 2 diabetes mellitus (DM).

Methods: A total of 98 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking clopidogrel at a maintenance dose of 75 mg. Clinical findings and serum lipids data were recorded before Ramadan (Pre-R), at the last week of Ramadan (R) and 4 weeks after the end of Ramadan (Post-R). During each patient visit, nutrients intakes were calculated and platelet reactivity assessment using Verify Now P2Y12 assay was performed.

Results: In DM patients, the absolute PRU changes from baseline were +27 (p = 0.01) and +16 (p = 0.02) respectively at R and Post-R. In addition, there was a significant increase of glycemia and triglycerides levels with a significant decrease of high-density lipoprotein. In non DM patients there was no significant change in absolute PRU values and metabolic parameters. Clopidogrel resistance rate using 2 cut-off PRU values (235 and 208) did not change significantly in DM and non DM patients.

Conclusions: RF significantly decreased platelet sensitivity to clopidogrel in DM patients during and after Ramadan. This effect is possibly related to an increase of glycemia and serum lipids levels induced by fasting.

Trial registration: Clinical Trials.gov NCT02720133. Registered 24 July 2014.Retrospectively registered.

Keywords: Clopidogrel; Diabetes mellitus; Fasting; Platelet activation; Platelet aggregation inhibitors.

Figures

Fig. 1
Fig. 1
Study profile
Fig. 2
Fig. 2
Median of absolute PRU change from baseline during and after Ramadan. *p < 0.05 between Ramadan and Post-Ramadan

References

    1. Barkia A, Mohamed K, Smaoui M, Zouari N, Hammami M, Nasri M. Change of diet, plasma lipids, lipoproteins, and fatty acids during Ramadan: a controversial association of the considered Ramadan model with atherosclerosis risk. J Health Popul Nutr. 2011;29:486–493. doi: 10.3329/jhpn.v29i5.8902.
    1. Benaji B, Mounib N, Roky R, Aadil N, Houti IE, Moussamih S, et al. Diabetes and Ramadan: review of the literature. Diabetes Res Clin Pract. 2006;73:117–25.
    1. Salti I, Bénard E, Detournay B, Bianchi-Biscay M, Le Brigand C, Voinet C, et al., EPIDIAR study group. A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care. 2004;27:2306–11.
    1. Aslam M, Assad A. Drug regimens and fasting during Ramadan: a survey in Kuwait. Public Health. 1986;100:49–53. doi: 10.1016/S0033-3506(86)80086-5.
    1. Rashed AH. The fast of Ramadan. BMJ. 1992;304:521–522. doi: 10.1136/bmj.304.6826.521.
    1. Addad F, Amami M, Ibn Elhadj Z, Chakroun T, Marrakchi S, Kachboura S. Does Ramadan fasting affect the intensity of acenocoumarol-induced anticoagulant effect? Br J Haematol. 2014;166:792–794. doi: 10.1111/bjh.12897.
    1. Lai YF, Cheen MH, Lim SH, Yeo FH, Nah SC, Kong MC, et al. The effects of fasting in Muslim patients taking warfarin. J Thromb Haemost. 2014;12:349–54.
    1. Farooq S, Nazar Z, Akhtar J, Irfan M, Subhan F, Ahmed Z, et al. Effect of fasting during Ramadan on serum lithium level and mental state in bipolar affective disorder. Int Clin Psychopharmacol. 2010;25:323–7.
    1. Sharma RK, Voelker DJ, Sharma R, Reddy HK, Dod H, Marsh JD. Evolving role of platelet function testing in coronary artery interventions. Vasc Health Risk Manag. 2012;8:65–75. doi: 10.2147/VHRM.S28090.
    1. Tantry US, Gesheff M, Liu F, Bliden KP, Gurbel PA. Resistance to antiplatelet drugs: what progress has been made? Expert Opin Pharmacother. 2014;15:2553–2564. doi: 10.1517/14656566.2014.968126.
    1. Siller-Matula JM, Trenk D, Schrör K, Gawaz M, Kristensen SD, Storey RF, et al., EPA (European Platelet Academy). Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv. 2013;6:1111–28.
    1. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003;107:2908–2913. doi: 10.1161/01.CIR.0000072771.11429.83.
    1. Matetzky S, Shenkman B, Guetta V, Shechter M, Beinart R, Goldenberg I, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004;109:3171–5.
    1. Schuette C, Steffens D, Witkowski M, Stellbaum C, Bobbert P, Schultheiss HP, et al. The effect of clopidogrel on platelet activity in patients with and without type-2 diabetes mellitus: a comparative study. Cardiovasc Diabetol. 2015;14:15.
    1. Angiolillo DJ, Suryadevara S. Aspirin and clopidogrel: efficacy and resistance in diabetes mellitus. Best Pract Res Clin Endocrinol Metab. 2009;23:375–388. doi: 10.1016/j.beem.2008.12.001.
    1. Price MJ. Diabetes mellitus and clopidogrel response variability. J Am Coll Cardiol. 2014;64:1015–1018. doi: 10.1016/j.jacc.2014.07.003.
    1. Aradi D, Collet JP, Mair J, Plebani M, Merkely B, Jaffe AS, et al., Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association of the European Society of Cardiology, Working Group on Thrombosis of the European Society of Cardiology. Platelet function testing in acute cardiac care - is there a role for prediction or prevention of stent thrombosis and bleeding? Thromb Haemost. 2015;113:221–30.
    1. Grundy SM, Pasternak R, Greenland P, Smith S, Jr, Fuster V. Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. Circulation. 1999;100:1481–1492. doi: 10.1161/01.CIR.100.13.1481.
    1. Price MJ, Endemann S, Gollapudi RR, et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J. 2008;29:992–1000. doi: 10.1093/eurheartj/ehn046.
    1. Price M, Angiolillo D, Teirstein P, et al. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: impact on thrombosis and safety (GRAVITAS) trial. Circulation. 2011;124:1132–1137. doi: 10.1161/CIRCULATIONAHA.111.029165.
    1. Ferroni P, Basili S, Falco A, Davì G. Platelet activation in type 2 diabetes mellitus. J Thromb Haemost. 2004;2:1282–1291. doi: 10.1111/j.1538-7836.2004.00836.x.
    1. Grant PJ. Diabetes mellitus as a prothrombotic condition. J Intern Med. 2007;262:157–172. doi: 10.1111/j.1365-2796.2007.01824.x.
    1. Demirtunc R, Duman D, Basar M, Bilgi M, Teomete M, Garip T. The relationship between glycemic control and platelet activity in type 2 diabetes mellitus. J Diabetes Complicat. 2009;23:89–94. doi: 10.1016/j.jdiacomp.2008.01.006.
    1. Singla A, Antonino MJ, Bliden KP, Tantry US, Gurbel PA. The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy. Am Heart J. 2009;158:784.e1–784.e6. doi: 10.1016/j.ahj.2009.08.013.
    1. Watala C, Golanski J, Pluta J, Boncler M, Rozalski M, Luzak B, et al. Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)-its relation to metabolic control. Thromb Res. 2004;113:101–13.
    1. Winocour PD, Watala C, Perry DW, Kinlough-Rathbone RL. Decreased platelet membrane fluidity due to glycation or acetylation of membrane proteins. Thromb Haemost. 1992;68:577–582.
    1. Geisler T, Mueller K, Aichele S, Bigalke B, Stellos K, Htun P, et al. Impact of inflammatory state and metabolic control on responsiveness to dual antiplatelet therapy in type 2 diabetics after PCI: prognostic relevance of residual platelet aggregability in diabetics undergoing coronary interventions. Clin Res Cardiol. 2010;99:743–52.
    1. Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010;303:754–62.
    1. Price MJ, Endemann S, Gollapudi RR, Valencia R, Stinis CT, Levisay JP, et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J. 2008;29:992–1000.
    1. Stone GW, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, et al., ADAPT-DES Investigators. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet. 2013;382:614–23.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅