Predicting perioperative myocardial injury/infarction after noncardiac surgery in patients under surgical and medical co-management: a prospective cohort study.

BACKGROUND: Perioperative myocardial injury/infarction (PMI) following noncardiac surgery is a frequent cardiac complication. This study aims to evaluate PMI risk and explore preoperative assessment tools of PMI in patients at increased cardiovascular (CV) risk who underwent noncardiac surgery under the surgical and medical co-management (SMC) model. METHODS: A prospective cohort study that included consecutive patients at increased CV risk who underwent intermediate- or high-risk noncardiac surgery at the Second Medical Center, Chinese PLA General Hospital, between January 2017 and December 2022. All patients were treated with perioperative management by the SMC team. The SMC model was initiated when surgical intervention was indicated and throughout the entire perioperative period. The incidence, risk factors, and impact of PMI on 30-day mortality were analyzed. The ability of the Revised Cardiac Risk Index (RCRI), frailty, and their combination to predict PMI was evaluated. RESULTS: 613 eligible patients (mean [standard deviation, SD] age 73.3[10.9] years, 94.6% male) were recruited consecutively. Under SMC, PMI occurred in 24/613 patients (3.9%). Patients with PMI had a higher rate of 30-day mortality than patients without PMI (29.2% vs. 0.7%, p = 0.00). The FRAIL Scale for frailty was independently associated with an increased risk for PMI (odds ratio = 5.91; 95% confidence interval [CI], 2.34-14.93; p = 0.00). The RCRI demonstrated adequate discriminatory capacity for predicting PMI (area under the curve [AUC], 0.78; 95% CI, 0.67-0.88). Combining frailty with the RCRI further increased the accuracy of predicting PMI (AUC, 0.87; 95% CI, 0.81-0.93). CONCLUSIONS: The incidence of PMI was relatively low in high CV risk patients undergoing intermediate- or high-risk noncardiac surgery under SMC. The RCRI adequately predicted PMI. Combining frailty with the RCRI further increased the accuracy of PMI predictions, achieving excellent discriminatory capacity. These findings may aid personalized evaluation and management of high-risk patients who undergo intermediate- or high-risk noncardiac surgery.

A risk score to predict postdischarge bleeding among acute coronary syndrome patients undergoing percutaneous coronary intervention: BRIC-ACS study.

BACKGROUND: Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) prevents ischemic events while increasing bleeding risk. Real-world-based metrics to accurately predict postdischarge bleeding (PDB) occurrence and its potential impact on postdischarge major cardiovascular event (MACE) remain undefined. This study sought to evaluate the impact of PDB on MACE occurrence, and to develop a score to predict PDB risk among Chinese acute coronary syndrome (ACS) patients after PCI. METHODS AND RESULTS: From May 2014 to January 2016, 2496 ACS patients who underwent PCI were recruited consecutively from 29 nationally representative Chinese tertiary hospitals. Among 2,381 patients (95.4%, 2,381/2,496) who completed 1-year follow-up, the cumulative incidence of PDB (bleeding academic research consortium type [BARC] ≥2) and postdischarge MACE (a composite of all-cause death, nonfatal myocardial infarction, ischemic stroke, or urgent revascularization) was 4.9% (n = 117) and 3.3% (n = 79), respectively. The association between PDB and MACE during 1-year follow-up, as well as the impact of DAPT with ticagrelor or clopidogrel on PDB were evaluated. PDB was associated with higher risk of postdischarge MACE (7.7 vs. 3.1%; adjusted hazard ratio: 2.59 [95% confidence interval: 1.17-5.74]; p = .02). For ticagrelor versus clopidogrel, PDB risk was higher (8.0 vs. 4.4%; 2.05 [1.17-3.60]; p = .01), while MACE risk was similar (2.0 vs. 3.4%; 0.70 [0.25-1.93]; p = .49). Based on identified PDB predictors, the constructed bleeding risk in real world Chinese acute coronary syndrome patients (BRIC-ACS) score for PDB was established. C-statistic for the score for PDB was 0.67 (95% CI: 0.62-0.73) in the overall cohort, and >0.70 in subgroups with non-ST- and ST-segment elevation myocardial infarction, diabetes and receiving more than two drug eluting stents. CONCLUSIONS: In Chinese ACS patients, PDB with BARC ≥2 was associated with higher risk for MACE after PCI. The constructed BRIC-ACS risk score provides a useful tool for PDB discrimination, particularly among high ischemic and bleeding risk patients.

Switching between ticagrelor and clopidogrel in patients who underwent percutaneous coronary intervention: insight into contemporary practice in Chinese patients.

Ticagrelor has been proved to be more effective than clopidogrel; however, little is known about the switching between ticagrelor and clopidogrel in real-world clinical practice. We assessed the prevalence, related factors, dose bridging, compliance, and short-term outcomes of in-hospital switching between ticagrelor and clopidogrel in consecutively recruited patients treated by ticagrelor after percutaneous coronary intervention (PCI). A total of 417 eligible patients administrated with ticagrelor in-hospital after PCI were recruited. Switching between ticagrelor and clopidogrel occurred in 362 (86.8%) patients, with 318 (76.3%) from clopidogrel to ticagrelor occurring mainly after PCI and 44 (10.6%) from ticagrelor to clopidogrel primarily at discharge. History of cerebrovascular disease, final diagnosis of acute coronary syndrome, left main disease, ostial lesion, co-administration with warfarin, CYP2C19 loss-of-function alleles' carriage status, and ticagrelor-related dyspnoea emerged as related factors for the switching between clopidogrel and ticagrelor. Dose bridging between clopidogrel loading dose and ticagrelor maintenance dose (MD) was more frequent in patients switching from clopidogrel to ticagrelor, while the bridging between ticagrelor MD and clopidogrel MD was more likely to occur in patients switched from ticagrelor to clopidogrel. At 6 month follow-up, poor compliance was observed in patients from clopidogrel to ticagrelor (64.8%) or treated only by ticagrelor (50.9%), but perfect compliance in patients from ticagrelor to clopidogrel (100%). After excluding the cases with incompliance, patients switching from ticagrelor to clopidogrel had a relatively lower bleeding risk in comparison with patients with constant ticagrelor treatment and those switching from clopidogrel to ticagrelor (29.5% vs. 50.0% vs. 46.6%, adjusted P = 0.02). In-hospital switching between ticagrelor and clopidogrel is frequent in patients undergoing PCI. In comparison with constant ticagrelor treatment, switching from clopidogrel to ticagrelor in ischaemic high-risk patients confers similar antiplatelet efficacy and safety, while switching from ticagrelor to clopidogrel in ischaemic low-risk patients relates to lower hazard for bleeding events.

Comparison of Performances among Four Bleeding-Prediction Scores in Elderly Cancer Patients with Venous Thromboembolism.

The performances of RIETE, VTE-BLEED, SWITCO65 + , and Hokusai-VTE scores for predicting major bleeding events in hospitalized elderly cancer patients with venous thromboembolism (VTE) have not been evaluated. This study validated the performances of these scoring systems in a cohort of elderly cancer patients with VTE. Between June 2015 and March 2021, a total of 408 cancer patients (aged ≥ 65 years) with acute VTE were consecutively enrolled. The overall rates of in-hospital major bleeding and clinically relevant bleeding (CRB) were 8.3% (34/408) and 11.8% (48/408), respectively. RIETE score could categorize patients with increasing rate of major bleeding and CRB into low-/intermediate- and high-risk categories (7.1 vs. 14.1%, p = 0.05 and 10.1 vs. 19.7%, p = 0.02, respectively). The discriminative power of the four scores for predicting major bleeding was poor to moderate, indicated by areas under the receiver operating characteristic curves (0.45 [95% confidence interval, CI: 0.35-0.55] for Hokusai-VTE, 0.54 [95% CI: 0.43-0.64] for SWITCO65 + , 0.58 [95% CI: 0.49-0.68] for VTE-BLEED, and 0.61 [95% CI: 0.51-0.71] for RIETE). RIETE score might be used to predict major bleeding in hospitalized elderly cancer patients with acute VTE.

Genotype-guided personalization of antiplatelet treatment: A meta-analysis of patients with ACS or undergoing PCI.

INTRODUCTION: Personalized antiplatelet treatment in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) remains challenging in clinical practice. The present study aimed to explore the benefit of genotype-guided antiplatelet treatment with P2Y12 inhibitors in patients with ACS or undergoing PCI. METHODS: A literature search was conducted (from inception to September 2018) in the PUBMED, EMBASE and Cochrane databases. Studies were included in which the genotype-guided P2Y12 inhibitor antiplatelet strategy was compared with the standard strategy in patients with ACS or undergoing PCI. The endpoints were high on-treatment platelet reactivity (HTPR), major adverse cardiovascular events including all-cause mortality, myocardial infarction (MI), stent thrombosis (ST), stroke and target-vessel revascularization (TVR), and major bleedings. RESULTS: A total of 3377 patients in 9 studies (5 RCTs and 4 non-RCTs) were included, in which 91% of the patients were diagnosed with ACS and 88.5% underwent PCI. A total of 1639 patients (48.5%) were assigned to the genotype-guided group, and 1738 (51.4%) assigned to the conventional or standard (STD) group, with an average follow-up time of 7.6 months. After the pooled analysis, significantly lower risks of HTPR (HR: 0.32, 95% CI: 0.18-0.55, P < 10-4), all-cause mortality (HR: 0.55, 95% CI: 0.37-0.83, p = 0.005), MI (HR: 0.43, 95% CI: 0.27-0.67, p = 0.0002) and ST (HR: 0.39, 95% CI: 0.16-0.97, p = 0.004) were observed in the genotype-guided group compared to the STD group. No significant between-group difference was found for the risk of stroke, TVR, and major bleedings after the pooled analysis. CONCLUSION: Genotype-guided antiplatelet treatment could decrease the risks of HTPR, all-cause mortality, MI and ST in patients with ACS or undergoing PCI.

Interaction between platelet-derived microRNAs and CYP2C19*2 genotype on clopidogrel antiplatelet responsiveness in patients with ACS.

BACKGROUND: Both platelet-derived microRNAs and the genotype of CYP2C19*2 were implicated for the variability of clopidogrel antiplatelet responsiveness. However, their interaction on the antiplatelet responsiveness of clopidogrel in patients with acute coronary syndrome (ACS) remains unknown. METHODS: Consecutive clopidogrel-treated patients with ACS were recruited, with their antiplatelet responsiveness evaluated by the relative platelet inhibition (RI), as measured by light transmittance aggregometry (LTA) at baseline and 5days' after the maintenance treatment of clopidogrel. Extreme cases were selected according to the octiles of RI value. Expression of the microRNAs targeting the mRNAs of P2RY12 was analyzed in the platelet of the extreme cases. Genotyping of CYP2C19*2 was performed for each extreme case. RESULTS: Among the included 272 ACS patients, 21 cases were screened as the extremely high-responders with RI>84%, and 18 as the extremely low-responders with RI<10%. Bioinformatics tools predicted the candidate microRNAs of miR-223, miR-221, and miR-21 could bind directly to the mRNA of P2RY12. Compared with the extremely low-responders, the expression of miR-223, miR-221, and miR-21 was significantly higher in the extremely high-responders (miR-223: 7.18±2.95 vs. 0.99±0.64, p=0.022; miR-221: 3.60±2.54 vs. 1.14±0.81, p=0.004; miR-21: 4.36±3.33 vs. 2.31±1.69, p=0.01). ROC curve showed ideal discriminatory power of the platelet-derived miRNAs for the prediction of clopidogrel antiplatelet responsiveness (c-index=0.70 for miR-223; c-index=0.76 for miR-221; c-index=0.79 for miR-21). After stratified by the carrier status of CYP2C19*2, the association between platelet-derived miRNAs and clopidogrel antiplatelet responsiveness could be found only in CYP2C19*2 carriers, but not in non-carriers. CONCLUSIONS: Platelet-derived miRNAs (miR-223, miR-221 and miR-21) are independently associated with clopidogrel antiplatelet responsiveness in ACS patients. However, the association could be influenced by the interaction with CYP2C19*2 genotype.

Integrating genotypes in the SAMe-TT2R2 score for the prediction of anticoagulation control in Chinese patients with atrial fibrillation on warfarin.

INTRODUCTION: The SAMe-TT2R2 score has been proposed to predict whether patients with atrial fibrillation (AF) would be well anti-coagulated with warfarin or not. However, it might over-estimate the number of patients under suboptimal warfarin treatment in non-Caucasians. This study was designed to modify the SAMe-TT2R2 score with genotypes and validate it in Chinese AF patients treated with warfarin. MATERIAL AND METHODS: Consented Chinese-Han patients (n=510) with AF under the treatment of warfarin for at least 3months were randomly divided into a derivation (n=310) and a validation cohort (n=200). For each patient, CYP2C9*3 and VKORC1 -1639 A/G genotyping was performed, and the time in therapeutic range (TTR) was calculated over this period. RESULTS: The modified SAMe-TT2R2 score was established by adding "warfarin genotype bins" to replace "the non-white race" variable. In the validation cohort, the discrimination performance of the modified score for good anticoagulation control (TTR≥70%) was significantly improved (c- index increased from 0.60 to 0.67). Significantly increased risks of major bleedings (HR: 4.91; 95% CI: 1.03-23.37; adjusted p=0.04) and all bleedings (HR: 1.93; 95% CI: 1.14-3.25; adjusted p=0.01) were found in patients with modified scores ≥2, as compared with patients with modified scores of 0-1. CONCLUSIONS: The modified SAMe-TT2R2 score could improve the ability for the identification of good anticoagulation control, and the prediction of major bleeding events in Chinese patients with AF treated by warfarin.

The Performance of CRUSADE and ACUITY Bleeding Risk Scores in Ticagrelor-Treated ACS Patients Who Underwent PCI.

The performance of the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) and ACUITY (Acute Catheterization and Urgent Intervention Triage strategy) risk scores for the prediction of major bleeding in ticagrelor-treated acute coronary syndrome (ACS) patients who underwent percutaneous coronary intervention (PCI) is unknown. The aim of the present study is to validate the performance of both scores in a contemporary Chinese cohort of ACS patients hospitalized for PCI and administrated with ticagrelor. From January 2013 to December 2014, a total of 629 ticagrelor-treated ACS patients who underwent PCI were recruited consecutively. The overall rate of major bleeding defined by the BARC (Bleeding Academic Research Consortium) criteria was 1.7%. This incidence increased with the risk category of both the CRUSADE (very low, 0.6%; low, 1.3%; moderate, 1.1%; high, 7.0%; and very high, 13.0%; p = 0.001) and the ACUITY score (low, 0.6%; moderate, 1.4%; high, 4.9%; and very high, 7.0%; p = 0.003). The CRUSADE score demonstrated adequate calibration and discriminatory capacity for the patients as a whole (HL-p [Hosmer-Lemeshow goodness-of-fit test p-value] >0.3; AUC [area under the curve]: 0.78), with the excellent performance in the subgroups of acute myocardial infarction, men, diabetes and those implanted with more than two DESs (AUC: 0.85, 0.80, 0.93 and 0.93, respectively). For the ACUITY score, adequate calibration and discriminatory capacity could be observed for the whole patients (HL-p > 0.3; AUC: 0.78), with excellent performance for the patients with diabetes or those implanted with more than two DESs (AUC: 0.90 and 0.97, respectively). In conclusion, both CRUSADE and ACUITY risk scores performed adequate discriminatory power for the prediction of major bleeding within 30 days in ticagrelor-treated ACS patients who underwent PCI.

Relationship between ADP-induced platelet-fibrin clot strength and anti-platelet responsiveness in ticagrelor treated ACS patients.

BACKGROUND: Ticagrelor provides enhanced antiplatelet efficacy but increased risk of bleeding and dyspnea. This study aimed to display the relationship between ADP-induced platelet-fibrin clot strength (MAADP) and clinical outcomes in acute coronary syndrome (ACS) patients treated by ticagrelor. METHODS: Consecutive Chinese-Han patients with ACS who received maintenance dose of ticagrelor on top of aspirin were recruited. After 5-day ticagrelor maintenance treatment, MAADP measured by thrombelastography (TEG) were recorded for the evaluation of ticagrelor anti-platelet reactivity. Pre-specified cutoffs of MAADP > 47 mm for high on-treatment platelet reactivity (HTPR) and MAADP < 31 mm for low on-treatment platelet reactivity (LTPR) were applied for evaluation. The occurrences of primary ischemic cardiovascular events (including a composite of cardiac death, non-fatal myocardial infarction and stroke), the Thrombolysis in Myocardial Infarction (TIMI) defined bleeding events, and ticagrelor related dyspnea were recorded after a follow-up of three months. RESULTS: Overall, 176 ACS patients (Male: 79.55%, Age: 59.91 ± 10.54 years) under ticagrelor maintenance treatment were recruited. The value of MAADP ranged from 4.80% to 72.90% (21.27% ± 12.07% on average), with the distribution higher skewed towards the lower values. Using the pre-specific cutoffs for HTPR and LTPR, seven patients (3.98%) were identified as HTPR and 144 patients (81.82%) as LTPR. After a follow-up of three months in 172 patients, major cardiovascular events occurred in no patient, but TIMI bleeding events in 81 (47.09%) with major bleedings in three patients. All patients with major bleedings were classified as LTPR. Ticagrelor related dyspnea occurred in 31 (18.02%) patients, with 30 (21.28%) classified as LTPR and no one as HTPR (P = 0.02). CONCLUSIONS: In ticagrelor treated ACS patients, MAADP measured by TEG might be valuable for the prediction of major bleeding and ticagrelor related dyspnea. Due to the small number of patients with HTPR after ticagrelor maintenance treatment, larger scale study should be warranted to verify the relationship between MAADP defined HTPR and ticagrelor related ischemic events.