Clopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS.
MEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622).
Six trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD -0.00023, 95% CI -0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI -0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI -0.00096 to 0.00177) when Asian ratio of the population was elevated.
We raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care.
https://www.crd.york.ac.uk/prospero, identifier CRD42022299622.

BACKGROUND: Clopidogrel resistance is a well-described phenomenon that has been linked to adverse cardiovascular events in patients with coronary artery disease. The impact of clopidogrel resistance in patient outcomes after vascular and endovascular surgery is not well-established.
METHODS: Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a literature review with the medical subject headings (MeSH) terms \"(clopidogrel resistance) and (vascular)\", \"(clopidogrel resistance) and (vascular surgery)\", \"(clopidogrel resistance) and (endovascular)\", and \"(clopidogrel resistance) and (endovascular surgery)\" was performed in PubMed and Cochrane databases, to identify all peer-reviewed studies performed on clopidogrel resistance in vascular and endovascular surgery. Studies written in the English language from inception to 2022 were included. Case reports, studies with limited information, nonhuman studies, and studies not pertaining to vascular or endovascular surgery were excluded from analysis. Each study was independently reviewed by 2 qualified researchers to assess eligibility.
RESULTS: Of the 691 studies identified through the MeSH strategy, 16 studies met the inclusion criteria and were reviewed and summarized. These studies focused on extracranial cerebrovascular disease (n = 5) and peripheral arterial disease (PAD, n = 11), encompassing a total of 1,716 patients. The prevalence of clopidogrel resistance ranged from 0% to 83.3%, depending on the diagnostic assay and cutoff values used. In cerebrovascular disease, clopidogrel resistance may be associated with cerebral embolization, ischemic neurologic events, and vascular-related mortality. In PAD, clopidogrel resistance has been linked to recurrent stent thrombosis, target lesion revascularization, amputation-free survival, and all-cause mortality.
CONCLUSIONS: This systematic review provides an up-to-date summary of clopidogrel resistance in vascular and endovascular surgery. The impact of clopidogrel resistance remains incompletely investigated, and future studies are needed to clarify the role of resistance testing in patients with vascular disease.

Dual antiplatelet therapy (DAPT) has remained the cornerstone for management of acute coronary syndrome (ACS) over the years. Clopidogrel has been the quintessential P2Y12 receptor (platelet receptor for Adenosine 5\' diphosphate) inhibitor for the past two decades. With the demonstration of unequivocal superior efficacy of prasugrel/ticagrelor over clopidogrel, guidelines now recommend these agents in priority over clopidogrel in current management of ACS. Cangrelor has revived the interest in injectable antiplatelet therapy too. Albeit the increased efficacy of these newer agents comes at the cost of increased bleeding and this becomes more of a concern when combined with aspirin. Which P2Y12i is superior over another has been intensely debated over last few years after the ISAR-REACT 5 study with inconclusive data. Three novel antiplatelet agents are already in the pipeline for ACS with all of them succeeding in phase II studies. The search for an ideal antiplatelet remains a need of the hour for optimal reduction of ischemic events in ACS.

BACKGROUND: Antiplatelet therapy is used to prevent stent thrombosis in intracranial stents, but the optimal dose of aspirin is unknown. This study sought to determine whether the degree of platelet inhibition with aspirin is affected by bodyweight as observed through a platelet reactivity assay.
METHODS: This is a retrospective review of patients who underwent neurovascular stent placement and had a VerifyNow Aspirin assay result. The primary outcome was the correlation between the VerifyNow Aspirin result, bodyweight, and the initial dose of aspirin. Secondary outcomes included the impact of the VerifyNow P2Y12 result and of weight on the incidence of bleeding or a thrombotic event.
RESULTS: Of the 142 included patients, 62.7% weighed ≥70 kg and 88.7% were initiated on aspirin 300-325 mg daily. 83.8% achieved a therapeutic VerifyNow Aspirin result. There was minimal correlation between the VerifyNow Aspirin result, bodyweight, and aspirin dose (R2=0.02). Between patients who weighed <70 kg versus ≥70 kg, there was no difference in the mean aspirin reaction units (ARU) (449 vs 435, p=0.32) or in the incidence of bleeding (28% vs 17.1%, p=0.14) or a thrombotic event (4% vs 5.3%, p=0.59). No patient experienced stent thrombosis and eight patients experienced in-stent stenosis. In a multivariate analysis, only the VerifyNow P2Y12 result predicted the development of either bleeding or a thrombotic event (p<0.01).
CONCLUSIONS: Bodyweight did not influence the likelihood of obtaining a therapeutic VerifyNow Aspirin result. The clinical utility of obtaining VerifyNow Aspirin assays for this patient population is unknown.

Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention.
In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients\' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037).
A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used.
Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality.
Italian Ministry of Education.

暂无摘要。

BACKGROUND: Limitations have been observed with the use of clopidogrel following percutaneous coronary intervention (PCI) indicating the urgent need of a more potent anti-platelet agent. We aimed to compare the efficacy and safety of ticagrelor versus clopidogrel following PCI.
METHODS: Online databases were searched for relevant studies (published between the years 2007 and 2017) comparing ticagrelor versus clopidogrel following coronary stenting. Primary outcomes assessed efficacy whereas secondary outcomes assessed safety. Odds ratios (OR) with 95% confidence intervals (CIs) based on a random effect model were calculated and the analysis was carried out by the RevMan 5.3 software.
RESULTS: A total number of 25,632 patients with acute coronary syndrome (ACS) [12,992 patients with ST segment elevation myocardial infarction (STEMI) and 14,215 patients with non-ST segment elevation myocardial infarction (NSTEMI)] were included in this analysis, of whom 23,714 patients were revascularized by PCI. Results of this analysis did not show any significant difference in all-cause mortality, major adverse cardiac events (MACEs), myocardial infarction, stroke and stent thrombosis observed between ticagrelor and clopidogrel with (OR: 0.83, 95% CI: 0.67-1.03; P = .09), (OR: 0.64, 95% CI: 0.41-1.01; P = .06), (OR: 0.77, 95% CI: 0.57-1.03; P = .08), (OR: 0.85, 95% CI: 0.57-1.26; P = .42) and (OR: 0.70, 95% CI: 0.47-1.05; P =.09).However, ticagrelor was associated with a significantly higher minor and major bleeding with (OR: 1.57, 95% CI: 1.30-1.89; P = .00001) and (OR: 1.52, 95% CI: 1.01-2.29; P = 0.04) respectively. Dyspnea was also significantly higher in the ticagrelor group (OR: 2.64, 95% CI: 1.87-3.72; P = .00001).
CONCLUSIONS: Ticagrelor and clopidogrel were comparable in terms of efficacy in these patients with ACS. However, the safety outcomes of ticagrelor should further be investigated.

暂无摘要。

BACKGROUND: The relationship of CYP2C19 genotype and clinical efficacy in stroke or transient ischemic attack (TIA) patients treated with clopidogrel monotherapy or clopidogrel plus aspirin remains unknown. We thus aim to conduct a meta-analysis to appraise evidence on the association of CYP2C19 genotype and clinical efficacy for stroke or TIA.
METHODS: An electronic search will be performed for clinical trials that reported the interested efficacy data (stroke, myocardial infarction, or vascular death) and safety data (any bleeding) in clopigogrel-treated patients with stroke or TIA. Odds ratios (ORs) with their confidence intervals (CIs) will be calculated using a meta-analysis.
RESULTS: This study will provide the evidence of the relationship between CYP2C19 genotype and clinical efficacy and safety in stroke/TIA patients taking clopidogrel by pooling the results of individual studies.
CONCLUSIONS: The results will bring about vigorous evidence in this issue and guide both clinical decision-making and future research.

There is a lack of age-specific evidence regarding the efficacy and safety of dual antiplatelet therapy (DAPT). A systematic review and meta-analysis was conducted for dual versus mono antiplatelet therapy in elderly patients with ischaemic stroke (IS) or transient ischaemic attack (TIA).
PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Risk ratios (RRs) for the outcomes of stroke recurrence, major bleeding and intracranial bleeding were calculated based on the DerSimonian and Laird random effects model. Subgroup analyses were conducted.
In seven multicentre, randomized controlled trials comprising 24 873 patients with IS or TIA, aged 65 years or older, a significant reduction in the risk of recurrent stroke was observed using DAPT in comparison with aspirin monotherapy [RR 0.79, 95% confidence interval (95% CI) 0.69-0.91; P = 0.001]. DAPT was not associated with a significant reduction in recurrent stroke compared with clopidogrel monotherapy (RR 1.01, 95% CI 0.93-1.10; P = 0.800). In addition, the results from two studies showed that DAPT significantly increased the risk of major bleeding and intracranial bleeding in elderly patients over younger patients (RR 2.18, 95% CI 1.02-4.69; and RR 2.13, 95% CI 1.18-3.86, respectively).
For stroke prevention in elderly patients with IS or TIA, DAPT is superior to aspirin monotherapy but appears to be equivalent to clopidogrel monotherapy, and is accompanied by an increased risk of bleeding. The balance between the benefits and risks of DAPT is important to consider when choosing antiplatelet strategy.