The efficacy and safety of cilostazol as an alternative to aspirin in Chinese patients with aspirin intolerance after coronary stent implantation: a combined clinical study and computational system pharmacology analysis

Xue, Ying; Feng, Zhiwei; Li, Xiaoye; Hu, Ziheng; Xu, Qing; Wang, Zi; Cheng, Jia-Hui; Shi, Hongtao; Wang, Qibing; Wu, Hongyi; Xie, Xiang‐Qun; Lv, Qianzhou

doi:10.1038/aps.2017.85

Cited by 25 publications

(27 citation statements)

References 47 publications

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“…Ultimately, the efficacy of cilostazol-based DAPT for preventing MACCE was at least similar to the traditional aspirin-based DAPT, and it even reached a "better" level in our study. This conclusion was consistent with the study conducted by Xue et al, 10 although their comparisons did not reach statistical significance. Interestingly, we found an obvious intersection when plotting the cumulative incidence curves of MACCE.…”

Section: Discussionsupporting

confidence: 91%

“…We assumed cilostazol-based DAPT was superior to aspirinbased DAPT with respect to the occurrence of MACCE after DES implantation based on a previous study. 10 The rate of MACCE was estimated to be 5% in the cilostazol group and 9% in the aspirin group at about 1 year of follow-up. With a sample size of 730 in each group, the study would have 85% power to detect the difference with a two-sided α level of 0.05.…”

Section: Discussionmentioning

confidence: 96%

“…It should be admitted that some sporadic studies have explored the efficacy and safety of cilostazol-based DAPT in China, but most of them have been small scale and published domestically. At present, the only one published internationally was conducted by Xue et al 10 In their study, only 205 patients with aspirin intolerance were enrolled, and it eventually focused on pharmacologic analysis. For the first time, we used a relatively large-sample real-world cohort study to explore the efficacy and safety of cilostazol-based DAPT in patients with aspirin intolerance after DES implantation in China.…”

Section: Discussionmentioning

confidence: 99%

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Cilostazol for Chinese Patients with Aspirin Intolerance after Coronary Drug-Eluting Stent Implantation

Dai

Chen

et al. 2020

Thromb Haemost

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Background Cilostazol-based dual antiplatelet therapy (DAPT) is widely used in patients with aspirin intolerance after coronary drug-eluting stent (DES) implantation in China. However, this empirical strategy is not recommended or even mentioned in Chinese or international guidelines due to a lack of evidence from large-scale studies. We aimed to explore the efficacy and safety of cilostazol-based DAPT in this special population. Methods In this cohort study, patients were grouped according to the DAPT strategy that they received after coronary DES implantation. The primary efficacy endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs). Angiographic follow-up and major bleeding events were also recorded. Results A total of 918 patients receiving cilostazol-based DAPT due to aspirin intolerance were enrolled, matched with 918 patients receiving aspirin-based DAPT. After 15-month prospective follow-up, the cilostazol group had lower risk of MACCE (5.1% vs. 7.6%, propensity score adjusted hazard ratio = 0.671 [95% confidence interval 0.462–0.974], p = 0.036) compared with the aspirin group. Lower rate of coronary lesion progression was also found through follow-up angiography in the cilostazol group (17.4% vs. 23.6%, p = 0.022), especially in nontarget lesions (12.1% vs. 17.6%, p = 0.019). The two groups had the same risk of major bleeding events (0.8% vs. 0.4%, p = 0.364). Conclusion In the current study, cilostazol is a good substitute for aspirin in patients who have aspirin intolerance but need DAPT after coronary DES implantation in China. However, large-scale randomized controlled trials were still required to further confirm its efficacy and safety.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Cilostazol for Chinese Patients with Aspirin Intolerance after Coronary Drug-Eluting Stent Implantation

Dai

Chen

et al. 2020

Thromb Haemost

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“…targets with higher docking scores may have higher binding affinities and therefore a greater chance of interacting with Captagon. Next, we mapped out a pharmacological network of interactions between drug compounds and target proteins at the molecular level [54,55]. Cytoscape 3.4.0 [56] was used to generate, analyze, and visualize the network of targets and drugs/ compounds, as described previously [55].…”

Section: Simulationsmentioning

confidence: 99%

Structural insight into the serotonin (5-HT) receptor family by molecular docking, molecular dynamics simulation and systems pharmacology analysis

Wang

Lin

et al. 2019

Acta Pharmacol Sin

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Serotonin (5-HT) receptors are proteins involved in various neurological and biological processes, such as aggression, anxiety, appetite, cognition, learning, memory, mood, sleep, and thermoregulation. They are commonly associated with drug abuse and addiction due to their importance as targets for various pharmaceutical and recreational drugs. However, due to a high sequence similarity/identity among 5-HT receptors and the unavailability of the 3D structure of the different 5-HT receptor, no report was available so far regarding the systematical comparison of the key and selective residues involved in the binding pocket, making it difficult to design subtype-selective serotonergic drugs. In this work, we first built and validated three-dimensional models for all 5-HT receptors based on the existing crystal structures of 5-HT 1B , 5-HT 2B , and 5-HT 2C. Then, we performed molecular docking studies between 5-HT receptors agonists/inhibitors and our 3D models. The results from docking were consistent with the known binding affinities of each model. Sequentially, we compared the binding pose and selective residues among 5-HT receptors. Our results showed that the affinity variation could be potentially attributed to the selective residues located in the binding pockets. Moreover, we performed MD simulations for 12 5-HT receptors complexed with ligands; the results were consistent with our docking results and the reported data. Finally, we carried out off-target prediction and blood-brain barrier (BBB) prediction for Captagon using our established hallucinogen-related chemogenomics knowledgebase and in-house computational tools, with the hope to provide more information regarding the use of Captagon. We showed that 5-HT 2C , 5-HT 5A , and 5-HT 7 were the most promising targets for Captagon before metabolism. Overall, our findings can provide insights into future drug discovery and design of medications with high specificity to the individual 5-HT receptor to decrease the risk of addiction and prevent drug abuse.

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“…The primary efficacy outcome was major adverse cardiac events (MACE), defined as the composite of cardiac death, non‐fatal myocardial infarction (MI), stroke, restenosis and target vessel revascularization (TVR) at 12‐month follow‐up 19 . Secondary efficacy outcome included cardiovascular re‐hospitalization 20 and need for urgent repeat percutaneous coronary intervention (urgent re‐PCI) 21 .…”

Section: Methodsmentioning

confidence: 99%

Efficacy assessment of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention by data mining and machine‐learning decision tree approaches

Xue

Jing

et al. 2020

J Clin Pharm Ther

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What is known and Objective Although ticagrelor has been well‐known to improve clinical outcomes in patients undergoing percutaneous coronary intervention (PCI), and its effectiveness and safety have not been well evaluated in Chinese patients. This study aimed to evaluate the effectiveness and safety of ticagrelor in Chinese patients. In order to find potential effect modifiers on the drug effects, a decision tree method was performed to detect interactions between treatment and patient characteristics in an automatic and systematic manner. Methods This retrospective study included acute coronary syndrome (ACS) patients who underwent PCI and received either ticagrelor (N = 250) or clopidogrel (N = 291) while hospitalized between August 2014 and August 2015. After propensity score matching, Kaplan‐Meier analysis was used to study the event‐free survival against major adverse cardiovascular events (MACE, primary efficacy outcome, defined as the composite of cardiac death, non‐fatal myocardial infarction [MI], stroke, restenosis and target vessel revascularization [TVR]), re‐hospitalization, the need for urgent re‐PCI (secondary efficacy outcome) and bleeding events (safety outcome) within 12 months of the PCI date. To search for effect modifiers of the two antiplatelet therapies, a machine‐learning decision tree algorithm was conducted to predict re‐hospitalization status. Results After propensity score matching (N = 442), ticagrelor and clopidogrel had no significant difference in MACE, re‐hospitalization and bleeding. The decision tree analysis showed that the number of diseased vessels modulated the effect of ticagrelor and clopidogrel on re‐hospitalization rates. In single‐vessel disease (SVD) patients, ticagrelor was associated with lower hazards than clopidogrel for all efficacy outcomes: MACE (HR = 0.190, 95% CI: 0.042–0.866), re‐hospitalization (HR = 0.296, 95% CI: 0.108–0.808), urgent re‐PCI (HR = 0.249, 95% CI: 0.069–0.895), bleeding (HR = 1.006, 95% CI: 0.063–16.129). However, in multi‐vessel disease (MVD) patients, the two treatments did not show significant difference. What is New and Conclusion In the general patient population, there was no significant difference between ticagrelor and clopidogrel on the hazard of MACE. However, ticagrelor achieved a better effectiveness than clopidogrel in patients with SVD. This pilot study provides scientific basis to call for a large‐scale prospective study in this population.

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The efficacy and safety of cilostazol as an alternative to aspirin in Chinese patients with aspirin intolerance after coronary stent implantation: a combined clinical study and computational system pharmacology analysis

Cited by 25 publications

References 47 publications

Cilostazol for Chinese Patients with Aspirin Intolerance after Coronary Drug-Eluting Stent Implantation

Cilostazol for Chinese Patients with Aspirin Intolerance after Coronary Drug-Eluting Stent Implantation

Structural insight into the serotonin (5-HT) receptor family by molecular docking, molecular dynamics simulation and systems pharmacology analysis

Efficacy assessment of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention by data mining and machine‐learning decision tree approaches

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