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Comparison of Shear Stress-Induced Thrombotic and Thrombolytic Effects Among 3 Different Antithrombotic Regimens in Patients With Acute Coronary Syndrome.

ABSTRACT: Shear stress (SS)-induced platelet activation is suggested as an essential mechanism of the acute coronary syndrome (ACS). We aimed to compare SS-induced thrombotic and thrombolytic activities among 3 treatment regimens in patients with ACS who underwent percutaneous coronary intervention (PCI). Patients were nonrandomly enrolled and treated with one of 3 regimens (TICA: ticagrelor 180 mg/d; RIVA: clopidogrel 75 mg/d and rivaroxaban 5 mg/d; CLP: clopidogrel 75 mg/d), administered in addition to aspirin (100 mg/d) for 30 days. The global thrombosis test was applied to measure SS-induced thrombotic (occlusion time [OT]) and thrombolytic activity (lysis time [LT]) at day 2 and 30. Aspirin reaction unit (ARU) and P2Y12 reaction unit (PRU) were simultaneously measured using VerifyNow. Group differences in the OT, LT, ARU, and PRU were evaluated. Seventy-five patients (25 patients in each group) finished 30 days of follow-up. Clinical and angiographic characteristics did not differ among the 3 groups, except ACS subtype and pre-PCI coronary flow. No major adverse cardiovascular events occurred in any group during follow-up. The OT and LT did not differ among the 3 groups at day 30 (OT: TICA, 447.2 ± 87.1 vs RIVA, 458.5 ± 70.3, vs CLP, 471.9 ± 90.7, LT: 1522.3 ± 426.5 vs 1734.6 ± 454.3 vs 1510.2 ± 593.9) despite significant differences in the PRU among the 3 groups. Shear stress-induced thrombotic and thrombolytic activities did not differ among the 3 investigated antithrombotic treatments.

SUBMITTER: Kim M

PROVIDER: S-EPMC7289065 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Comparison of Shear Stress-Induced Thrombotic and Thrombolytic Effects Among 3 Different Antithrombotic Regimens in Patients With Acute Coronary Syndrome.

Kim Minsuk M Kang Si-Hyuck SH Kim Jeong-Ran JR Park Jin Joo JJ Cho Young-Seok YS Youn Tae-Jin TJ Chae In-Ho IH Suh Jung-Won JW

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20200101

Shear stress (SS)-induced platelet activation is suggested as an essential mechanism of the acute coronary syndrome (ACS). We aimed to compare SS-induced thrombotic and thrombolytic activities among 3 treatment regimens in patients with ACS who underwent percutaneous coronary intervention (PCI). Patients were nonrandomly enrolled and treated with one of 3 regimens (TICA: ticagrelor 180 mg/d; RIVA: clopidogrel 75 mg/d and rivaroxaban 5 mg/d; CLP: clopidogrel 75 mg/d), administered in addition to ...[more]

PMID: 32191493

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Project description:BackgroudAntithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS.MethodsWe used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality.ResultsFive trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low.ConclusionsThese results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.

Project description:AimsAtherosclerotic plaque development has been associated with wall shear stress (WSS). However, the multidirectionality of blood flow, and thus of WSS, is rarely taken into account. The purpose of this study was to comprehensively compare five metrics that describe (multidirectional) WSS behaviour and assess how WSS multidirectionality affects coronary plaque initiation and progression.Methods and resultsAdult familial hypercholesterolaemic pigs (n = 10) that were fed a high-fat diet, underwent imaging of the three main coronary arteries at three-time points [3 (T1), 9 (T2), and 10-12 (T3) months]. Three-dimensional geometry of the arterial lumen, in combination with local flow velocity measurements, was used to calculate WSS at T1 and T2. For analysis, arteries were divided into 3 mm/45° sectors (n = 3648). Changes in wall thickness and final plaque composition were assessed with near-infrared spectroscopy-intravascular ultrasound, optical coherence tomography imaging, and histology. Both in pigs with advanced and mild disease, the highest plaque progression rate was exclusively found at low time-averaged WSS (TAWSS) or high multidirectional WSS regions at both T1 and T2. However, the eventually largest plaque growth was located in regions with initial low TAWSS or high multidirectional WSS that, over time, became exposed to high TAWSS or low multidirectional WSS at T2. Besides plaque size, also the presence of vulnerable plaque components at the last time point was related to low and multidirectional WSS. Almost all WSS metrics had good predictive values for the development of plaque (47-50%) and advanced fibrous cap atheroma (FCA) development (59-61%).ConclusionThis study demonstrates that low and multidirectional WSS promote both initiation and progression of coronary atherosclerotic plaques. The high-predictive values of the multidirectional WSS metrics for FCA development indicate their potential as an additional clinical marker for the vulnerable disease.

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Dataset Information

Comparison of Shear Stress-Induced Thrombotic and Thrombolytic Effects Among 3 Different Antithrombotic Regimens in Patients With Acute Coronary Syndrome.

Publications

Comparison of Shear Stress-Induced Thrombotic and Thrombolytic Effects Among 3 Different Antithrombotic Regimens in Patients With Acute Coronary Syndrome.

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