Dataset Information

Gut microbiota induces high platelet response in patients with ST segment elevation myocardial infarction after ticagrelor treatment.

ABSTRACT:

Background

Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear.

Methods

To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokinetic assessment result showed that the plasma concentrations of ticagrelor and its metabolism production, AR-C124910XX, were lower in HPR patients than controls. Further single nucloetide polymorphism (SNP) analysis identified that there is no difference in ATP binding cassette subfamily B member 1 (ABCB1) gene expression between the NPR group and the HPR group. Metagenomic and metabolomic analyses of fecal samples showed that HPR patients had higher microbial richness and diversity. Transplantation of the gut microbiota from HPR donors to microbiota-depleted mice obviously decreased plasma concentration of ticagrelor.

Results

Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with STEMI and support that modify gut microbiota is a potential therapeutic option for STEMI.

Conclusions

Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with ST elevation myocardial infarction (STEMI) and support that modify gut microbiota is a potential therapeutic option for STEMI.

Funding

NSFC 82170297 and 82070300 from the National Natural Science Foundation of China.

SUBMITTER: Zhang X

PROVIDER: S-EPMC8903831 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Gut microbiota induces high platelet response in patients with ST segment elevation myocardial infarction after ticagrelor treatment.

Zhang Xi X Zhang Xiaolin X Tong Fangnian F Cai Yi Y Zhang Yujie Y Song Haixu H Tian Xiaoxiang X Yan Chenghui C Han Yaling Y

eLife 20220308

<h4>Background</h4>Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear.<h4>Methods</h4>To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokin ...[more]

PMID: 35258452

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Project description:ImportanceDual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation.ObjectiveTo evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI.Design, setting, and participantsA randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat.InterventionsFifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose.Main outcomes and measuresP2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD.ResultsBaseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, -103.77 to -19.75; P = .003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P = .005), and 43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P > .99).Conclusions and relevanceChewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes.Trial registrationclinicaltrials.gov Identifier: NCT02725099.

Project description:ImportanceChallenges to improving ST-segment elevation myocardial infarction (STEMI) care are formidable in low- to middle-income countries because of several system-level factors.ObjectiveTo examine access to reperfusion and percutaneous coronary intervention (PCI) during STEMI using a hub-and-spoke model.Design, setting, and participantsThis multicenter, prospective, observational study of a quality improvement program studied 2420 patients 20 years or older with symptoms or signs consistent with STEMI at primary care clinics, small hospitals, and PCI hospitals in the southern state of Tamil Nadu in India. Data were collected from the 4 clusters before implementation of the program (preimplementation data). We required a minimum of 12 weeks for the preimplementation data with the period extending from August 7, 2012, through January 5, 2013. The program was then implemented in a sequential manner across the 4 clusters, and data were collected in the same manner (postimplementation data) from June 12, 2013, through June 24, 2014, for a mean 32-week period.ExposuresCreation of an integrated, regional quality improvement program that linked the 35 spoke health care centers to the 4 large PCI hub hospitals and leveraged recent developments in public health insurance schemes, emergency medical services, and health information technology.Main outcomes and measuresPrimary outcomes focused on the proportion of patients undergoing reperfusion, timely reperfusion, and postfibrinolysis angiography and PCI. Secondary outcomes were in-hospital and 1-year mortality.ResultsA total of 2420 patients with STEMI (2034 men [84.0%] and 386 women [16.0%]; mean [SD] age, 54.7 [12.2] years) (898 in the preimplementation phase and 1522 in the postimplementation phase) were enrolled, with 1053 patients (43.5%) from the spoke health care centers. Missing data were common for systolic blood pressure (213 [8.8%]), heart rate (223 [9.2%]), and anterior MI location (279 [11.5%]). Overall reperfusion use and times to reperfusion were similar (795 [88.5%] vs 1372 [90.1%]; P = .21). Coronary angiography (314 [35.0%] vs 925 [60.8%]; P < .001) and PCI (265 [29.5%] vs 707 [46.5%]; P < .001) were more commonly performed during the postimplementation phase. In-hospital mortality was not different (52 [5.8%] vs 85 [5.6%]; P = .83), but 1-year mortality was lower in the postimplementation phase (134 [17.6%] vs 179 [14.2%]; P = .04), and this difference remained consistent after multivariable adjustment (adjusted odds ratio, 0.76; 95% CI, 0.58-0.98; P = .04).Conclusions and relevanceA hub-and-spoke model in South India improved STEMI care through greater use of PCI and may improve 1-year mortality. This model may serve as an example for developing STEMI systems of care in other low- to middle-income countries.

Dataset Information

Gut microbiota induces high platelet response in patients with ST segment elevation myocardial infarction after ticagrelor treatment.

Background

Methods

Results

Conclusions

Funding

Publications

Gut microbiota induces high platelet response in patients with ST segment elevation myocardial infarction after ticagrelor treatment.

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