Clinical relevance of clopidogrel-proton pump inhibitors interaction

Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal(GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient’s bleeding and cardiovascular risk.     

Clinical evidence of interaction between clopidogrel and proton pump inhibitors

Clopidogrel is approved for reduction of atherothrombotic events in patients with cardiovascular(CV)and cerebrovascular disease.Dual antiplatelet therapy with aspirin and clopidogrel decreases the risk of major adverse cardiac events after acute coronary syndrome or percutaneous coronary intervention,compared with aspirin alone.Due to concern about gastrointestinal bleeding in patients who are receiving clopidogrel and aspirin therapy,current guidelines recommend combined use of a proton pump inhibitor(PPI)to decrease the risk of bleeding.Data from previous pharmacological studies have shown that PPIs,which are extensively metabolized by the cytochrome system,may decrease the ADP-induced platelet aggregation of clopidogrel. Results from retrospective cohort studies have shown a higher incidence of major CV events in patients re-ceiving both clopidogrel and PPIs than in those without PPIs.However,other retrospective analyses of randomized clinical trials have not shown that the concomitant PPI administration is associated with increased CV events among clopidogrel users.These controversial results suggest that large specific studies are needed. This article reviews the metabolism of clopidogrel and PPIs,existing clinical data regarding the interaction between clopidogrel and PPIs,and tries to provide recommendations for health care professionals.     

Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

Low-dose aspirin(LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society.On the other hand,a very low dose of aspirin(10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage.The incidence of LDAinduced gastrointestinal mucosal injury and bleeding has increased.It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug(NSAID)-induced lesions.The pathogenesis related to inhibition of cyclooxygenase(COX)-1 includes reduced mucosal flow,reduced mucus and bicarbonate secretion,and impaired platelet aggregation.The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence.The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation.The factors associated with an increased risk of upper gastrointestinal(GI) complications in subjects taking LDA are aspirin dose,history of ulcer or upper GI bleeding,age > 70 years,concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs,and Helicobacter pylori(H.pylori) infection.Moreover,no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea,acid regurgitation,heartburn,and bloating.It has been shown that the ratios of ulcers located in the body,fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA.Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers.In contrast to NSAIDinduced gastrointestinal ulcers,a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers.The eradication of H.pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding.Continuous aspirin therapy for patie     

老年人消化性溃疡出血的相关危险因素分析

Objective To explore the risk factors for peptic ulcer bleeding in elderly patients.Methods The 414 patients with upper gastrointestinal ulcer bleeding in Xuanwu Hospital from January 2001 to January 2006 were enrolled.The patients were divided into elderly group (≥ 60years,n= 183 ) and non-elderly group ( ＜ 60 years,n= 231 ).The coexisting diseases and hemorrhage causes were compared and analyzed.Results The detection rate of coexisting diseases was significantly higher in elderly group than in non-elderly group (68.9% vs.10.0% ).The hemorrhage causes included the taking of drugs for cardiovascular and cerebrovascular diseases or osteoarthropathy in elderly group.And the fatigue,stress and dietary upset were the main causes in non-elderly group.Helicobacter pylori infection rate was 35.0% in the elderly and 58.0% in young patients.Conclusions It is very important to promote rational use of anticoagulant drugs and analgesic agents in elderly patients for managing peptic ulcer complication.     

老年人消化性溃疡出血的相关危险因素分析

Objective To explore the risk factors for peptic ulcer bleeding in elderly patients.Methods The 414 patients with upper gastrointestinal ulcer bleeding in Xuanwu Hospital from January 2001 to January 2006 were enrolled.The patients were divided into elderly group (≥ 60years,n= 183 ) and non-elderly group ( ＜ 60 years,n= 231 ).The coexisting diseases and hemorrhage causes were compared and analyzed.Results The detection rate of coexisting diseases was significantly higher in elderly group than in non-elderly group (68.9% vs.10.0% ).The hemorrhage causes included the taking of drugs for cardiovascular and cerebrovascular diseases or osteoarthropathy in elderly group.And the fatigue,stress and dietary upset were the main causes in non-elderly group.Helicobacter pylori infection rate was 35.0% in the elderly and 58.0% in young patients.Conclusions It is very important to promote rational use of anticoagulant drugs and analgesic agents in elderly patients for managing peptic ulcer complication.     

Bleeding risk with clopidogrel and percutaneous endoscopic gastrostomy

AIM To compare bleeding within 48 h in patients undergoing percutaneous endoscopic gastrostomy(PEG) with or without clopidogrel.METHODS After institutional review board approval, a retrospective study involving a single center was conducted on adult patients having PEG(1/08-1/14). Patients were divided into two groups: Clopidogrel group consisting of those patients taking clopidogrel within 5 d of PEG and the non-clopidogrel group including those patients not taking clopidogrel within 5 d of the PEG.RESULTS Three hundred and nineteen PEG patients were found. One hundred and sixty-eight males and 151 females with mean body mass index 28.47 ± 9.75 kg/m2 and mean age 65.03 ± 16.11 years were identified. Thirtythree patients were on clopidogrel prior to PEG with 286 patients not on clopidogrel. No patients in either group developed hematochezia, melena, or hematemesiswithin 48 h of percutaneous endoscopic gastrostomy(PEG). No statistical differences were observed between the two groups with 48 h for hemoglobin decrease of 2 g/dL(2 vs 5 patients; P = 0.16), blood transfusions(2 vs 7 patients; P = 0.24), and repeat endoscopy for possible gastrointestinal bleeding(no patients in either group). CONCLUSION Based on the results, no significant post-procedure bleeding was observed in patients undergoing PEG with recent use of clopidogrel.     

Is the AIMS65 score useful in predicting outcomes in peptic ulcer bleeding?

AIM:To evaluate the applicability of AIMS65 scores in predicting outcomes of peptic ulcer bleeding.METHODS:This was a retrospective study in a single center between January 2006 and December 2011.We enrolled 522 patients with upper gastrointestinal haemorrhage who visited the emergency room.Highrisk patients were regarded as those who had rebleeding within 30 d from the first endoscopy as well as those who died within 30 d of visiting the Emergency room.A total of 149 patients with peptic ulcer bleeding were analysed,and the AIMS65 score was used to retrospectively predict the high-risk patients.RESULTS:A total of 149 patients with peptic ulcer bleeding were analysed.The poor outcome group comprised 28 patients[male:23(82.1%)vs female:5(10.7%)]while the good outcome group included 121patients[male:93(76.9%)vs female:28(23.1%)].The mean age in each group was not significantly different.The mean serum albumin levels in the poor outcome group were slightly lower than those in the good outcome group(P=0.072).For the prediction of poor outcome,the AIMS65 score had a sensitivity of35.5%(95%CI:27.0-44.8)and a specificity of 82.1%(95%CI:63.1-93.9)at a score of 0.The AIMS65 score was insufficient for predicting outcomes in peptic ulcer bleeding(area under curve=0.571;95%CI:0.49-0.65).CONCLUSION:The AIMS65 score may therefore not be suitable for predicting clinical outcomes in peptic ulcer bleeding.Low albumin levels may be a risk factor associated with high mortality in peptic ulcer bleeding.     

Long-term prognosis in patients continuing taking antithrombotics after peptic ulcer bleeding

AIM To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. METHODS All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t- or χ2-test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the differencewas compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. RESULTS A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups(70.8 ± 11.4 vs 62.4 ± 12.0, P 0.001; 8(8.2%) vs 15(21.7%), P 0.05; 65(66.3%) vs 13(18.8%), P 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant(P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients in the continuing group, and the risk of death and developing acute cardiovascular disease was higher in patients in the discontinuing group(log-rank test, P = 0.000 for both). Furthermore, COX regression multivariate analysis revealed that the hazard ratio(HR) for recurrent bleeding was 2.986(95%CI: 067-8.356, P = 0.015) in the continuing group, while HR for death or acute cardiovascular disease was 5.216(95%CI: 1.035-26.278, P = 0.028).CONCLUSION After the occurrence of peptic ulcer bleeding, continuing antithrombotics increases the risk of recurrent bleeding events, while discontinuing antithrombotics would increase the risk of death and developing cardiovascular disease. This suggests that clinicians should comprehensively consider the use of antithrombotics after peptic ulcer bleeding.     

The risk of bleeding of triple therapy with vitamin K-antagonists, aspirin and clopidogrel after coronary stent implantation: Facts and questions

Background Triple therapy (TT) with vitamin K-antagonists (VKA), aspirin and clopidogrel is the recommended antithrombotic treatment following percutaneous coronary intervention with stent implantation (PCI-S) in patients with an indication for oral anticoagulation. TT is associated with an increased risk of bleeding, but available evidence is flawed by important limitations, including the limited size and the retrospective design of most of the studies, as well as the rare reporting of the incidence of in-hospital bleeding and the treatment which was actually ongoing at the time of bleeding. Since the perceived high bleeding risk of TT may deny patients effective strategies, the determination of the true safety profile of TT is of paramount importance. Methods All the 27 published studies where the incidence of bleeding at various time points during follow-up has been reported separately for patients on TT were reviewed, and the weakness of the data was analyzed. Results The absolute incidence of major bleeding upon discharge at in-hospital, ≤ 1 month, 6 months, 12 months and ≥ 12 months was: 3.3% ± 1.9%, 5.1% ± 6.7%, 8.0% ± 5.2%, 9.0% ± 8.0, and 6.2% ± 7.8%, respectively, and not substantially different from that observed in previous studies with prolonged dual antiplatelet treatment with aspirin and clopidogrel. Conclusions While waiting for the ongoing, large-scale, registries and clinical trials to clarify the few facts and to answer the many questions regarding the risk of bleeding of TT, this treatment should not be denied to patients with an indication for VKA undergoing PCI-S provided that the proper measures and cautions are implemented.     

NSAIDs and the GI Tract： Past, Present and Future

The gastroscopic demonstration of gastrotoxicity of aspirin was first demonstrated a century ago and the gastrointestinal adverse events of non-steroidal antiinflammatory drugs (NSAIDs) have been increasingly reported in the literature ever since. Despite their undoubted efficacy for the treatment of joint inflammation and musculoskeletal injury, a significant proportion of patients taking NSAIDs may experience gastrointestinal symptoms, usually dyspepsia, and endoscopic abnormalities, which range from petechial hemorrhages to fatal complications of peptic ulcer.     

幽门螺杆菌感染和长期服用阿司匹林与上消化道出血关系研究

目的:探讨幽门螺杆菌(Hp)感染患者长期服用阿司匹林与上消化道出血的关系。方法:选取门诊每日服用100mg阿司匹林的患者,进行胃镜检查并检测Hp。根据Hp检测结果将3809例入选对象分为Hp阳性组和Hp阴性组,随访2年,观察上消化道出血情况;Hp阳性伴上消化道出血患者抗Hp治疗根除Hp后分组,分别给予法莫替丁40mg睡前顿服(干预组),或不加干预者作为对照组,2组均继续服用阿司匹林,随访2年,观察其再出血情况。结果:60岁以上老年患者服用小剂量阿司匹林上消化道出血率明显高于60岁以下患者(P<0.05);Hp阳性组2802例患者中上消化道出血146例(5.21%),Hp阴性组共1007例患者,上消化道出血为30例(2.98%),2组相比差异有统计学意义(P<0.05);144例患者根除Hp法莫替丁干预组72例,上消化道再出血2例(2.78%),对照组72例,上消化道再出血8例(11.1%),2组相比差异有统计学意义(P<0.05)。结论:60岁以上老年患者服用小剂量阿司匹林增加上消化道出血风险;Hp感染并长期服用小剂量阿司匹林可增加患者上消化道出血风险;法莫替丁干预能有效降低长期服用小剂量阿司匹林患者上消化道再出血风险。     

Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications.

BACKGROUND AND AIMS: The role of clopidogrel in patients at risk for gastrointestinal complications is uncertain, although it has been recommended for patients who have gastrointestinal intolerance to aspirin. We tested the hypothesis that clopidogrel is as effective as esomeprazole and aspirin in preventing recurrences of ulcer complications. METHODS: This was a prospective, double-blind, randomized, controlled study of 170 patients who developed ulcer bleeding after the use of low-dose aspirin between November 2002 and January 2005. After healing of ulcers and eradication of Helicobacter pylori, if present, patients were assigned randomly to treatment with esomeprazole 20 mg/day and aspirin 100 mg/day (n = 86) or clopidogrel 75 mg/day (n = 84) for 52 weeks. The primary end point was recurrent ulcer complications. RESULTS: During a median follow-up period of 52 weeks, no patient in the esomeprazole group, as compared with 9 patients in the clopidogrel group, developed recurrent ulcer complications. The cumulative incidences of recurrent ulcer complications were 0% in patients receiving esomeprazole and aspirin and 13.6% in patients receiving clopidogrel (absolute difference, 13.6%; 95% confidence interval for the difference, 6.3-20.9; log-rank test, P = .0019). CONCLUSIONS: The combination of esomeprazole and aspirin is superior to clopidogrel in preventing ulcer complications in patients who have a past history of aspirin-related peptic ulcer bleeding.     

New look at antiplatelet agent-related peptic ulcer: an update of prevention and treatment

Patients taking antiplatelet agents for the prevention of cardiovascular diseases who develop gastrointestinal bleeding represent a serious challenge in clinical practice. The initial step in reducing gastrointestinal risk of antiplatelet therapy is to assess whether the patient has a continued need for antiplatelet therapy. The next step is to eliminate the risk factors that may place the patient at increased gastrointestinal risk. In the management of bleeding ulcer patients with high-risk stigmata of recent hemorrhage, resuming antiplatelet agents at 3-5 days after the last dosing is a reasonable strategy. However, patients with low-risk stigmata can keep taking antiplatelet agents immediately following endoscopy. In the management of aspirin-related uncomplicated peptic ulcers in patients requiring antiplatelet therapies, continuing aspirin plus a powerful proton pump inhibitor is the choice of treatment. Patients who require antiplatelet agents for the prevention of cardiovascular diseases should be tested and treated for Helicobacter pylori infection before starting antiplatelet therapy. Additionally, those with high risks for upper gastrointestinal bleeding should receive co-therapy with a gastroprotective drug, preferably a proton pump inhibitor at standard dose. H2-receptor antagonist can significantly reduce upper gastrointestinal bleeding risk in patients taking low-dose aspirin but it is ineffective in the prevention of upper gastrointestinal bleeding in clopidogrel users. Although several retrospective studies reported that patients prescribed clopidogrel who also took proton pump inhibitors had significant increases in cardiovascular events, the current evidence from a prospective randomized trial does not justify a conclusion that proton pump inhibitors are associated with cardiovascular events among clopidogrel users.     

雷贝拉唑预防心血管病患者阿司匹林引起的消化性溃疡

目的 探讨雷贝拉唑对小剂量阿司匹林引起消化性溃疡的预防作用.方法 纳入2010年6月~2012年2月,患心血管病需抗血小板治疗的患者166例,随机分为对照组（n=83）和观察组（n=83）.对照组单用阿司匹林（100 mg,qd）;观察组在服用等剂量阿司匹林肠溶片同时服用雷贝拉唑钠肠溶胶囊（20 mg,qd）.对比两组患者出现上腹不适、上腹痛、烧心、反酸等消化道不适症状,同时比较两组胃镜下黏膜表现变化和呕血、黑便等消化道出血临床症状.结果 对照组和观察组分别出现消化道症状37例（44.6%）和4例（4.8%）,对照组胃肠黏膜损伤患者29例（34.9%）,其中消化性溃疡12例（14.5%）,观察组发生胃黏膜损伤患者仅6例（7.2%）,其中消化性溃疡1例（1.2%）,观察组的消化道症状发生率、胃肠粘膜损伤率以及消化性溃疡发生率均显著低于对照组,差异均有统计学意义（P均＜0.05）.随访3个月和6个月时患者呕血、黑便等消化道出血情况观察组均小于对照组,差异有统计学意义（P＜0.05）.结论 雷贝拉唑钠肠溶可降低小剂量阿司匹林治疗中发生溃疡出血的风险.     

不同的质子泵抑制剂与氯吡格雷相互作用的研究进展

大量研究表明阿司匹林和氯吡格雷联合抗血小板可以降低急性冠状动脉综合征及冠状动脉支架植入术后复发心血管事件的概率。但由于联合抗血小板治疗会增加出血的风险,所以目前临床推荐加用质子泵抑制剂以预防胃肠道溃疡和出血。氯吡格雷和质子泵抑制剂均通过细胞色素P450同工酶系统代谢,质子泵抑制剂通过竞争性抑制细胞色素P450同工酶CYP2C19,而降低氯吡格雷的抗血小板活性,增加复发心血管事件的概率。最近的研究发现不同的质子泵抑制剂影响程度不同,泮托拉唑和埃索美拉唑对氯吡格雷作用影响较小,而奥美拉唑、雷贝拉唑和兰索拉唑对氯吡格雷的抗血小板活性抑制作用较大。     

Upper gastrointestinal haemorrhage complicating antiplatelet treatment with aspirin and/or clopidogrel: where we are now?

A large number of patients require antiplatelet therapy (mainly aspirin and/or clopidogrel). Recent studies suggest that the combination of these agents is useful in patients with acute coronary syndrome and after percutaneous coronary intervention with stent placement. On the other hand, bleeding complications, most of which arise from the upper gastrointestinal (UGI) tract, can limit the use of antiplatelet drugs. Clopidogrel appears to be associated with fewer UGI side effects and bleeding compared with aspirin. However, a history of previous UGI bleeding is a major risk factor for clopidogrel-associated bleeding. The use of proton-pump inhibitors (PPIs) decreases the rate of UGI bleeding in patients receiving aspirin or clopidogrel. Furthermore, a recent study suggested that the administration of low-dose aspirin plus high-dose esomeprazole (a potent PPI) was associated with fewer episodes of UGI bleeding than clopidogrel alone in patients with a history of recent UGI haemorrhage. However, this study had several limitations and its results should be cautiously extrapolated into clinical practice. The combination of aspirin plus clopidogrel increases the risk of UGI bleeding. Unfortunately, there are no data on the effect of PPI prophylaxis in this setting. Available evidence suggests that where aspirin and/or clopidogrel are to be started or continued in patients with a recent history of UGI ulceration or bleeding (after ulcer healing and eradication of H. pylori infection), treatment with a PPI is a useful precaution. The patients should also be carefully monitored for recurrence of UGI bleeding.     

Management and outcome of peptic ulcers or erosions in patients receiving a combination of aspirin plus clopidogrel

BACKGROUND: This multicenter retrospective study investigated the management and outcome of patients with peptic ulcer/erosion-related aspirin and clopidogrel (A + C) cotherapy. METHODS: From January 2002 to September 2006, patients with endoscopically proven peptic ulcers/erosions after receiving A + C cotherapy were analyzed. RESULTS: This group consisted of 106 patients (age, 69.3 +/- 11.7 years). Ulcers/erosions developed in 27 patients during hospitalization for cardiac events and in 79 patients after hospital discharge. Of 27 patients hospitalized for acute cardiac events, gastrointestinal (GI) bleeding and dyspepsia occurred in 24 and three, respectively. The most common lesion was gastric ulcer. Of 79 discharged patients, GI bleeding and dyspepsia occurred in 64 and 15, respectively. The most common bleeding and dyspeptic lesions were gastric ulcer and gastritis, respectively. Overall, 17 patients underwent endoscopic hemostasis all successfully. A + C cotherapy was continued in 57 patients for a median (interquartile range) of 3.0 (6.2) months. Most were coprescribed a proton pump inhibitor (PPI) (53, 93%). No recurrent GI bleeding was observed. CONCLUSIONS: After A + C cotherapy, gastric ulcer or gastritis were the most common endoscopic lesions. The combination of a PPI and endoscopic treatment for ulcer bleeding was highly successful. After patient stabilization, continuation of A + C cotherapy with a PPI appears to be safe.     

Endoscopy in Asymptomatic Minidose Aspirin Consumers

Aspirin is widely used for its antiplatelet activity, but it harbors a risk of severe adverse gastrointestinal effects, such as bleeding and perforation, especially in elderly people. Our aim to assess the prevalence of upper gastrointestinal lesions and the effect of aspirin on the gastrointestinal mucosa in asymptomatic subjects taking minidose aspirin (100 to 325 mg per day) for more than 3 months. A prospective, open design was used. Patients attending the ophthalmology and cardiology outpatient clinics who had a medical history of more than 3 months of regular aspirin consumption were referred for esophagogastroduodenoscopy (EGD). Of the 90 patients referred for EGD, 44 were symptomatic (epigastric pain or dyspepsia) and were excluded from the study. The 46 asymptomatic patients included 22 men and 24 women of mean age 70 ± 10 years (range, 36 to 87 years); 32% were current or former smokers. Mean daily aspirin dose was 129.34 ± 76.61 mg. Only 24% were taking a gastroprotective agent. EGD revealed ulcer or erosions in 47.83% of the patients: erosive gastroduodenitis in 13 patients, gastric ulcer in 14, duodenal ulcer in 2, and gastric and duodenal ulcers in 2. Urease test for Helicobacter pylori infection was positive in 26%. Univariate and multivariate analysis revealed no factor other than aspirin predictive of a positive endoscopy. Minidose aspirin treatment is associated with a high prevalence of ulcerations of the stomach and duodenum.     

Platelet receptor redox regulation

A large number of patients require antiplatelet therapy (mainly aspirin and/or clopidogrel). Recent studies suggest that the combination of these agents is useful in patients with acute coronary syndrome and after percutaneous coronary intervention with stent placement. On the other hand, bleeding complications, most of which arise from the upper gastrointestinal (UGI) tract, can limit the use of antiplatelet drugs. Clopidogrel appears to be associated with fewer UGI side effects and bleeding compared with aspirin. However, a history of previous UGI bleeding is a major risk factor for clopidogrel-associated bleeding. The use of proton-pump inhibitors (PPIs) decreases the rate of UGI bleeding in patients receiving aspirin or clopidogrel. Furthermore, a recent study suggested that the administration of low-dose aspirin plus high-dose esomeprazole (a potent PPI) was associated with fewer episodes of UGI bleeding than clopidogrel alone in patients with a history of recent UGI haemorrhage. However, this study had several limitations and its results should be cautiously extrapolated into clinical practice. The combination of aspirin plus clopidogrel increases the risk of UGI bleeding. Unfortunately, there are no data on the effect of PPI prophylaxis in this setting. Available evidence suggests that where aspirin and/or clopidogrel are to be started or continued in patients with a recent history of UGI ulceration or bleeding (after ulcer healing and eradication of H. pylori infection), treatment with a PPI is a useful precaution. The patients should also be carefully monitored for recurrence of UGI bleeding.     

精准医疗在经皮冠状动脉介入术后抗血小板药物选择中的作用

目的:探讨精准医疗、个体化给药在经皮冠状动脉介入术(PCI)后抗血小板药物选择中的作用。方法:入选PCI后服用常规剂量阿司匹林(100 mg/d)和氯吡格雷(75 mg/d)且疗程在3个月左右的患者,根据CYP2C19基因多态性检测结果,将患者分为快代谢组、中代谢组和低代谢组,并给予个体化干预治疗。快代谢组继续服用常规剂量的阿司匹林和氯吡格雷;中代谢组将氯吡格雷调整为1.5倍剂量;低代谢组分为两组,氯吡格雷组将氯吡格雷调整为2倍剂量,替格瑞洛组将氯吡格雷改换为替格瑞洛(90 mg、2次/d)。检测各组个体化干预治疗前后凝血指标和血小板聚集率的变化及干预治疗后的出血事件。结果:各组患者干预治疗前后组间和组内比较,凝血指标差异均无统计学意义(P均0.05)。干预治疗前,血小板聚集率为快代谢组中代谢组低代谢组,3组间差异均有统计学意义(P均0.05);干预治疗后,中代谢组患者血小板聚集率较干预治疗前明显下降(P0.05),低代谢组中氯吡格雷组血小板聚集率与干预治疗前比较差异无统计学意义,替格瑞洛组血小板聚集率较干预治疗前明显下降(P0.05)。干预治疗后快代谢组、中代谢组血小板聚集率差异无统计学意义;低代谢组中替格瑞洛组血小板聚集率明显低于快/中代谢组,氯吡格雷组仍明显高于快/中代谢组(P均0.05)。干预治疗后,中代谢组、低代谢组与快代谢组比较出血风险均未增加(P均0.05)。结论:根据CYP2C19基因多态性检测结果个体化给药,可提高抗血小板治疗效果,且不增加出血风险。对于CYP2C19基因型为低代谢型的患者建议改用替格瑞洛治疗。