替格瑞洛与氯吡格雷药品不良反应/不良事件对比分析
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摘要
目的对比分析替格瑞洛和氯吡格雷致药品不良反应/不良事件(ADR/AE),为临床安全、合理选择抗血小板药物提供参考。方法对深圳市2014～2017年间共上报的怀疑替格瑞洛和氯吡格雷的病例报告进行统计分析。结果共筛选出31例怀疑替格瑞洛所致ADR/AE报告、43例怀疑氯吡格雷所致的ADR/AE报告;均以男性为主,但替格瑞洛男女比例更明显;替格瑞洛ADR多发生在用药2～7 d内(35.48%),而氯吡格雷ADR多发生在1 d及2～7d内(分别为32.56%、30.23%);替格瑞洛ADR/AE以出血(56.46%)及呼吸困难(33.33%)多见,氯吡格雷不良反应涉及系统器官及不良反应表现较多;在ADR/AE结果中,替格瑞洛与氯吡格雷ADR多数较轻微,易于好转和治愈,但患者对替格瑞洛不良反应耐受性更好,同时氯吡格雷出现了1例ADR/AE导致死亡报告。结论临床医师和药师在患者开始使用替格瑞洛或氯吡格雷一周内应加强关注其不良反应,密切监测服用替格瑞洛患者的出血及呼吸系统的不良反应,注意氯吡格雷的安全用药,积极防范ADR/AE的发生。
Objective To compare the adverse drug reactions/adverse events(ADRs/AEs) caused by ticagrelor and clopidogrel, in order to provide reference for clinical safe and rational use of the antiplatelet agents. Methods ADR/AE cases caused by ticagrelor and clopidogrel were screened and analyzed statistically from ADR/AE cases reported in Shenzhen city from 2014 to 2017. Results 31 ADR/AE cases caused by ticagrelor and 43 caused by clopidogrel were screened out. All of the ADR/AE cases were mainly male, however, the ratio of ticagrelor males and females was more obvious. The onset time of most ADRs/AEs by ticagrelor was within 2 to 7 days after oral medication(35.48%), and that of clopidogrel was mostly within 1 day and 2 to 7 days(32.56%, 30.23%). The main clinical manifestations by ticagrelor were bleeding(56.46%) and dyspnea(33.33%). The involved system-organs and clinical manifestations by clopidogrel were more than that by ticagrelor. Most clinical manifestations by ticagrelor and clopidogrel were mild and had good prognosis, but the patients were more tolerant to ticagrelor compared with clopidogrel. One fatal case was reported by clopidogrel. Conclusion Clinicians and clinical pharmacists should pay more attention to monitor ADRs/AEs by tigrelor and copidogrel within one week. The bleeding and dyspnea by tigrelor should be more concerned. Clinic should strengthen medication monitoring to reduce ADRs and ensure drug safety.
Objective To compare the adverse drug reactions/adverse events(ADRs/AEs) caused by ticagrelor and clopidogrel, in order to provide reference for clinical safe and rational use of the antiplatelet agents. Methods ADR/AE cases caused by ticagrelor and clopidogrel were screened and analyzed statistically from ADR/AE cases reported in Shenzhen city from 2014 to 2017. Results 31 ADR/AE cases caused by ticagrelor and 43 caused by clopidogrel were screened out. All of the ADR/AE cases were mainly male, however, the ratio of ticagrelor males and females was more obvious. The onset time of most ADRs/AEs by ticagrelor was within 2 to 7 days after oral medication(35.48%), and that of clopidogrel was mostly within 1 day and 2 to 7 days(32.56%, 30.23%). The main clinical manifestations by ticagrelor were bleeding(56.46%) and dyspnea(33.33%). The involved system-organs and clinical manifestations by clopidogrel were more than that by ticagrelor. Most clinical manifestations by ticagrelor and clopidogrel were mild and had good prognosis, but the patients were more tolerant to ticagrelor compared with clopidogrel. One fatal case was reported by clopidogrel. Conclusion Clinicians and clinical pharmacists should pay more attention to monitor ADRs/AEs by tigrelor and copidogrel within one week. The bleeding and dyspnea by tigrelor should be more concerned. Clinic should strengthen medication monitoring to reduce ADRs and ensure drug safety.
引文
[1] Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes[J]. N Engl J Med, 2009,361(11):1045-1057.
[2] James S, Angiolillo D J, Cornel J H, et al. Ticagrelor vs. clopidogrel in patients with acute coronary syndromes anddiabetes:a substudy from the platelet inhibition and patient outcomes(PLATO)trial[J].Eur Heart J, 2010, 31(24):3006-3016.
[3] Husted S, James S, Becker R C, et al. Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes:a substudy from the prospective randomized platelet inhibition and patient outcomes(PLATO)trial[J]. Circ Cardiovasc Qual Outcomes, 2012,5(5):680-688.
[4] Bonaca M P, Bhatt D L, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction[J]. N Engl J Med, 2015,372(19):1791-1800.
[5] Sch mig A.Ticagrelor-isthereneedforanewplayerintheantiplatelettherapy field[J]. N Engl J Med, 2009, 361(11):1108-1111.
[6] Mega J L, Simon T. Pharmacology of antithrombotic drugs:an assessment of oral antiplatelet and anticoagu-lant treatments[J].Lancet, 2015, 386(9990):281-291.
[7]张建红,朱立勤,田丹丽,等.替格瑞洛致不良反应国内外文献分析[J].中国新药杂志, 2017, 26(11):1335-1338.
[8]谢立,张文颖.我院替格瑞洛致不良反应108例分析[J].中国药房,2016, 27(29):4085-4087.
[9]胡爱虹,李小明. 33例氯吡格雷致不良反应文献分析[J].海峡药学, 2011, 23(5):260-261.üo
[10] Becker R C, Bassand J P, Budaj A, et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes(PLATO)trial[J].Eur Heart J, 2011, 32(23):2933-2944.
[11] Dobesh P P, Oestreich J H. Ticagrelor:pharmacokinetics, pharmacodynamics, clinical efficacy, and safety[J]. Pharmacotherapy, 2014, 34(10):1077-1090.
[12]杨玉辉,郑卫星,黄明方,等.替格瑞洛在中国急性冠脉综合征患者中的早期疗效及安全性观察[J].中国药物警戒, 2014,11(7):390-393.
[13] Buchanan A, Newton P, Pehrsson S, et al. Structural and functional characterization of a specific antidote for ticagrelor[J].Blood. 2015, 125(22):3484-3490.
[14] Storey R F, Bliden K P, Patil S B, et al. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study[J]. J Am Coll Cardiol, 2010, 56(3):185-193.
[15]张怡,钱皎,曹爱霖.替格瑞洛致呼吸困难两例并文献分析[J].药学服务与研究, 2015, 15(3):224-229.
[16]邵春丽,颜红兵,乔树宾,等.替格瑞洛相关呼吸困难的调查分析[J].中国介入心脏病学杂志, 2015, 23(2):85-88.
[17] Parodi G, Storey R F. Dyspnoea management in acute coronary syndrome patients treated with ticagrelor[J]. Eur Heart J Acute Cardiovasc Care, 2015, 4(6):555.
[18] Storey R F, Becker R C, Harrington R A, et al. Pulmonary function in patients with acute coronary syndrome treated with ticagrelor or clopidogrel(from the Platelet Inhibition and Patient Outcomes[PLATO] pulmonary function substudy)[J]. Am J Cardiol, 2011,108(11):1542-1546.
[19] van Giezen J J, Sidaway J, Glaves P, et al. Ticagrelor inhibits adenosine uptake in vitro and enhances adenosine-mediated hyperemia responses in a canine model[J]. J Cardiovasc Pharmacol Ther, 2012, 17(2):164-172.
[20] Cattaneo M, Faioni E M. Why does ticagrelor induce dyspnea[J].Thromb Haemost, 2012, 108(6):1031-1036.
[21]张志,高航,陶贵周.氯吡格雷致血小板减少性紫癜1例[J].中国心血管病研究杂志, 2005, 3(3):240.
[22]陈五波.氢氯吡格雷致两上肢血小板减少性紫癜1例[J].药物流行病学杂志, 2007, 6(4):214.
[2] James S, Angiolillo D J, Cornel J H, et al. Ticagrelor vs. clopidogrel in patients with acute coronary syndromes anddiabetes:a substudy from the platelet inhibition and patient outcomes(PLATO)trial[J].Eur Heart J, 2010, 31(24):3006-3016.
[3] Husted S, James S, Becker R C, et al. Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes:a substudy from the prospective randomized platelet inhibition and patient outcomes(PLATO)trial[J]. Circ Cardiovasc Qual Outcomes, 2012,5(5):680-688.
[4] Bonaca M P, Bhatt D L, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction[J]. N Engl J Med, 2015,372(19):1791-1800.
[5] Sch mig A.Ticagrelor-isthereneedforanewplayerintheantiplatelettherapy field[J]. N Engl J Med, 2009, 361(11):1108-1111.
[6] Mega J L, Simon T. Pharmacology of antithrombotic drugs:an assessment of oral antiplatelet and anticoagu-lant treatments[J].Lancet, 2015, 386(9990):281-291.
[7]张建红,朱立勤,田丹丽,等.替格瑞洛致不良反应国内外文献分析[J].中国新药杂志, 2017, 26(11):1335-1338.
[8]谢立,张文颖.我院替格瑞洛致不良反应108例分析[J].中国药房,2016, 27(29):4085-4087.
[9]胡爱虹,李小明. 33例氯吡格雷致不良反应文献分析[J].海峡药学, 2011, 23(5):260-261.üo
[10] Becker R C, Bassand J P, Budaj A, et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes(PLATO)trial[J].Eur Heart J, 2011, 32(23):2933-2944.
[11] Dobesh P P, Oestreich J H. Ticagrelor:pharmacokinetics, pharmacodynamics, clinical efficacy, and safety[J]. Pharmacotherapy, 2014, 34(10):1077-1090.
[12]杨玉辉,郑卫星,黄明方,等.替格瑞洛在中国急性冠脉综合征患者中的早期疗效及安全性观察[J].中国药物警戒, 2014,11(7):390-393.
[13] Buchanan A, Newton P, Pehrsson S, et al. Structural and functional characterization of a specific antidote for ticagrelor[J].Blood. 2015, 125(22):3484-3490.
[14] Storey R F, Bliden K P, Patil S B, et al. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study[J]. J Am Coll Cardiol, 2010, 56(3):185-193.
[15]张怡,钱皎,曹爱霖.替格瑞洛致呼吸困难两例并文献分析[J].药学服务与研究, 2015, 15(3):224-229.
[16]邵春丽,颜红兵,乔树宾,等.替格瑞洛相关呼吸困难的调查分析[J].中国介入心脏病学杂志, 2015, 23(2):85-88.
[17] Parodi G, Storey R F. Dyspnoea management in acute coronary syndrome patients treated with ticagrelor[J]. Eur Heart J Acute Cardiovasc Care, 2015, 4(6):555.
[18] Storey R F, Becker R C, Harrington R A, et al. Pulmonary function in patients with acute coronary syndrome treated with ticagrelor or clopidogrel(from the Platelet Inhibition and Patient Outcomes[PLATO] pulmonary function substudy)[J]. Am J Cardiol, 2011,108(11):1542-1546.
[19] van Giezen J J, Sidaway J, Glaves P, et al. Ticagrelor inhibits adenosine uptake in vitro and enhances adenosine-mediated hyperemia responses in a canine model[J]. J Cardiovasc Pharmacol Ther, 2012, 17(2):164-172.
[20] Cattaneo M, Faioni E M. Why does ticagrelor induce dyspnea[J].Thromb Haemost, 2012, 108(6):1031-1036.
[21]张志,高航,陶贵周.氯吡格雷致血小板减少性紫癜1例[J].中国心血管病研究杂志, 2005, 3(3):240.
[22]陈五波.氢氯吡格雷致两上肢血小板减少性紫癜1例[J].药物流行病学杂志, 2007, 6(4):214.