scholarly journals Temporal Trends of Bleeding Episodes during Half- vs. Standard-Dose Ticagrelor in Acute Coronary Syndrome Patients with Low Platelet Reactivity: A Randomized BLEEDING-ACS Trial

2021 ◽  
Vol 10 (6) ◽  
pp. 1159
Author(s):  
Laeun Kim ◽  
Jeong Cheon Choe ◽  
Jin Hee Ahn ◽  
Hye Won Lee ◽  
Jun-Hyok Oh ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Standard Dose ◽  
Temporal Trends ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
Half Dose ◽  
Bleeding Episodes ◽  
Ischemic Events ◽  
Over Time

To assess the temporal trends of bleeding episodes during half- vs. standard-dose ticagrelor in acute coronary syndrome (ACS) patients with low platelet reactivity (LPR) during standard-dose ticagrelor (90 mg bid). ACS Patients with LPR (<85 P2Y12 reaction units) (n = 122) were randomly assigned to receive either half-dose (45 mg bid) or standard-dose ticagrelor (90 mg bid). The primary endpoint was incidence of Bleeding Academic Research Consortium (BARC) bleeding at 1 week, 1, 3 and 6 months. Dyspnea and ischemic events were also evaluated. Bleeding episodes were most commonly observed at 1 month and then decreased over time. Half-dose ticagrelor did not reduce any BARC bleeding (odds ratio [OR] 0.900, 95% confidence interval [CI] 0.563–1.440, p = 0.661). However, serious bleeding (BARC type ≥2) occurred less often in half-dose ticagrelor (OR 0.284, 95% CI 0.088–0.921, p = 0.036). The rate of moderate-to-severe dyspnea was highest at 1 month, then decreased over time. Half-dose ticagrelor did not decrease moderate-to-severe dyspnea (Borg scale ≥ 3) (OR 1.066, 95% CI 0.322–3.530, p = 0.916). The risk of ischemic events was also similar between the groups. In conclusions, compared with standard-dose ticagrelor, half-dose ticagrelor reduced serious bleeding events during early period of dual-antiplatelet therapy in ACS patients with LPR; however, the risk of any bleeding events and dyspnea did not differ according to ticagrelor dose. Clinical registration: KCT0004640.

scholarly journals Antithrombotic Strategy for Patients with Acute Coronary Syndrome: A Perspective from East Asia

2020 ◽  
Vol 9 (6) ◽  
pp. 1963 ◽  
Author(s):  
Yohei Numasawa ◽  
Mitsuaki Sawano ◽  
Ryoma Fukuoka ◽  
Kentaro Ejiri ◽  
Toshiki Kuno ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
East Asian ◽  
Standard Of Care ◽  
Coronary Intervention ◽  
Hemorrhagic Diathesis ◽  
Bleeding Events ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Ischemic Events

Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention has become the standard of care, particularly in patients with acute coronary syndrome (ACS). Current clinical guidelines recommend novel P2Y12 inhibitors (e.g., prasugrel or ticagrelor) in addition to aspirin based on the results of representative randomized controlled trials conducted predominantly in Western countries. These agents were superior to clopidogrel in reducing the composite ischemic events, with a trade-off of the increased bleeding events. However, multiple differences exist between East Asian and Western patients, especially with respect to their physique, thrombogenicity, hemorrhagic diathesis, and on-treatment platelet reactivity. Recent studies from East Asian countries (e.g., Japan or South Korea) have consistently demonstrated that use of novel P2Y12 inhibitors is associated with a higher risk of bleeding events than use of clopidogrel, despite borderline statistical difference in the incidence of composite ischemic events. Additionally, multiple studies have shown that the optimal duration of DAPT may be shorter in East Asian than Western patients. This review summarizes clinical studies of antithrombotic strategies in East Asian patients with ACS. Understanding these differences in antithrombotic strategies including DAPT and their impacts on clinical outcomes will aid in selection of the optimal tailored antithrombotic therapy for patients with ACS.

A Randomized Non-Inferiority Study of Low-dose and Standard-dose Ticagrelor After Intervention for Acute Coronary Syndrome : Study Protocol for the TIGER STUDY

2021 ◽  
Author(s):  
Yanan Pang ◽  
Minglu Ma ◽  
Dong Wang ◽  
Hongyi Wu ◽  
Wei Hu ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Low Dose ◽  
Dual Antiplatelet Therapy ◽  
Standard Dose ◽  
Academic Research ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
Risk Of Bleeding ◽  
Research Consortium ◽  
Ischemic Events

Abstract BackgroundCurrent guidelines recommend that patients with acute coronary syndrome (ACS) who have successfully undergone percutaneous coronary intervention (PCI) should continue to use dual antiplatelet therapy (DAPT) for 12 months. The long-term use of standard-dose dual antiplatelet therapy will increase the risk of bleeding. An optimized antiplatelet strategy that can prevent ischemic events and reduce the risk of bleeding remains to be explored.MethodsThe study is a prospective, multicenter, randomized, open-label, controlled study involving 2120 patients from six clinical centers in China. Through the Interactive Web Response System (IWRS), ACS patients undergoing successful PCI will be randomly divided into the low-dose ticagrelor group or the normal-dose ticagrelor group, after taking 100 mg aspirin and 90 mg ticagrelor bid for 1 week. The primary endpoint is a composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, repeat revascularization, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria at one year. The secondary endpoints are bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria at one year.DiscussionRecent studies have confirmed that 90 mg ticagrelor alone can safely and effectively reduce bleeding without increasing ischemic events of patients with ACS after PCI. Compared with standard-dose DAPT, whether low-dose ticagrelor combined with aspirin can ensure the anti-ischemic effect while reducing the bleeding risk remains unclear in Chinese patients.The Tiger study will be the first large-scale, multicenter study to compare the efficacy and safety of low-dose and standard-dose ticagrelor combined with aspirin in ACS patients one week after successful PCI.Trial registrationClinicaltrials.gov, NCT04255602. Registered on 5 February 2020.

Pharmacodynamic comparison of optimal platelet reactivity by multiple platelet function tests in Korean acute coronary syndrome patients with half-dose ticagrelor or prasugrel treatment

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.H Kim ◽  
C.D Jin ◽  
K Song ◽  
G.M Lee ◽  
H.Y Moon ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Standard Dose ◽  
Light Transmittance ◽  
Funding Source ◽  
Platelet Function Tests ◽  
Coronary Syndrome ◽  
Function Tests ◽  
Half Dose

Abstract Background East Asians treated with potent P2Y12 inhibitors, prasugrel or ticagrelor exhibit more potent platelet inhibition than clopidogrel. Whether half-dose de-escalation strategy would improve optimal platelet reactivity at maintenance in East Asian patients with acute coronary syndrome (ACS) remains uncertain. Method In de-escalation strategy single center study, eligible Korean ACS patients (n=96) were assigned to receive standard-dose ticagrelor (n=33), prasugrel (n=28), followed by half-dose reduction at 1 month for maintenance, and clopidogrel (n=35) as control. Platelet reactivity was measured by VerifyNow, light transmittance aggregometry (LTA) and multiple electrode aggregometry (MEA). The investigators aim to compare optimal platelet reactivity status (OPR, defined as 85–208 P2Y12 reaction unit [PRU] for VerifyNow (VN), 16%–47% for LTA and 19–46 U for MEA) among 3 different platelet function tests at 3 months post PCI. Results At 3 months, ticagrelor achieved significantly lower PRU (17 [6–51] vs. 95 [61–151] vs. 172 [111–204]) than prasugrel and clopidogrel, resulting OPR rate 10% vs. 57.7% vs. 60.0%, respectively. Similar results were observed at LTA method (2% [0–12] in ticagrelor vs. 18% [13–22] in prasugrel vs. 18% [11–30] in clopidogrel), with OPR rate 11.8% vs. 69.2% vs. 50.0%, respectively. However, platelet reactivity was similar by MEA method (16 [13–20] in ticagrelor vs. 17 [13–22] in prasugrel vs. 19 [14–28] in clopidogrel), with OPR rate 33.3% vs. 40.0% vs. 42.0%, respectively (all p&gt;0.005). Among the three tests, resulting higher correlation between VN and LTA (r=0.745), MEA and LTA vs. MEA and VN showed lower correlations (r=0.412 and r=0.303). (Fig.) Conclusion In Korean ACS patients with half-dose de-escalation strategy after 1 month, OPR rate in ticagrelor is still rare during 3-month treatment by VN and LTA methods, however, prasugrel appears comparable to clopidogrel. VN/LTA might overestimate platelet function than MEA or MEA underestimate OPR rate than VN/LTA. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): National Research Foundation of Korea

A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study

Cardiology ◽  
2017 ◽  
Vol 138 (4) ◽  
pp. 201-206 ◽  
Author(s):  
Cai De Jin ◽  
Moo Hyun Kim ◽  
Junghee Bang ◽  
Victor Serebruany
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Academic Research ◽  
P2y12 Receptor ◽  
Drug Eluting Stent ◽  
Platelet Response ◽  
Open Label ◽  
Korean Patients ◽  
Coronary Syndrome ◽  
Half Dose

Background: The optimal dosing of novel oral P2Y12 receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. Design: HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y12 flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). Conclusion: HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y12 receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017.

Pharmacodynamic profile in East Asian patients with ACS treated with prasugrel standard-dose v de-escalation strategy: a randomized A-MATCH trial

2021 ◽  
Author(s):  
Young-Hoon Jeong ◽  
Ju Hyeon Oh ◽  
Hyuck-Jun Yoon ◽  
Yongwhi Park ◽  
Jon Suh ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Standard Dose ◽  
East Asian ◽  
Therapeutic Window ◽  
Bleeding Events ◽  
Match Trial ◽  
Asian Patients ◽  
Pharmacodynamic Profile ◽  
Bleeding Episodes ◽  
East Asian Patients

Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACS) treated with prasugrel standard-dose vs. de-escalation strategy. Before discharge, ACS patients with age <75 year or weight ≥60 kg (n=250) were randomly assigned to the standard-dose (10-mg group) or de-escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 Reaction Units [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85≤PRU≤208). The percentage of patients within the therapeutic window was significantly lower in the 10-mg group compared to the 5-mg and PFT-guided groups (35.3% vs. 67.5% vs. 65.9%) (Odds ratio [OR], 3.80 and 3.54; 95% confidence interval [CI], 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with de-escalation strategies (35.3% vs. 24.1% vs. 23.2%) (Hazard ratio [HR], 0.58 and 0.55; 95% CI, 0.30-1.14 and 0.28-1.09, respectively). ‘PRU<127’ was the optimal cut-off for predicting one-month bleeding events (area under curve, 0.616; 95% CI, 0.543-0.689; p= 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR, 2.00; 95% CI, 1.28-3.03; p= 0.001). In conclusion, compared with the standard-dose prasugrel, prasugrel de-escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes.

scholarly journals Ischemic and Bleeding Events Among Patients With Acute Coronary Syndrome Associated With Low-Dose Prasugrel vs Standard-Dose Clopidogrel Treatment

2020 ◽  
Vol 3 (4) ◽  
pp. e202004 ◽  
Author(s):  
Satoshi Shoji ◽  
Mitsuaki Sawano ◽  
Alexander T. Sandhu ◽  
Paul A. Heidenreich ◽  
Yasuyuki Shiraishi ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Low Dose ◽  
Standard Dose ◽  
Bleeding Events ◽  
Coronary Syndrome

scholarly journals De-escalation strategy with half-dose prasugrel or ticagrelor on pharmacodynamics and outcome in East Asians patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.H Kim ◽  
C.D Jin ◽  
K Song ◽  
K.M Lee ◽  
H.Y Moon ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Dose Reduction ◽  
Standard Dose ◽  
Inhibitory Response ◽  
Funding Source ◽  
East Asians ◽  
Pharmacodynamic Response ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Half Dose

Abstract Background East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) are exposed to more potent platelet inhibitory response. Whether half-dose de-escalation strategy would be benefit for chronic antiplatelet strategy in East Asian patients with acute coronary syndrome (ACS) remain uncertain. Method In half-dose de-escalation strategy, 129 Korean ACS patients were assigned to receive standard-dose potent P2Y12 inhibitors (n=86, prasugrel [n=38], ticagrelor [n=48]), followed by half-dose reduction at 1 month for maintenance, and was compared to clopidogrel (n=43) as control. The primary safety outcome was any clinically significant bleeding according to BARC (Bleeding Academic Research Consortium) criteria at 12 months. The pharmacodynamic response is accessed by VerifyNow P2Y12 reaction unit (PRU) at 1 month and 3 months post PCI. Results Ticagrelor achieved significantly lower PRU (7 [4–32] vs. 11 [5–76] vs. 167 [97–212]) than prasugrel and clopidogrel, resulting OPR rate 0% vs. 21.6% vs. 58.5%, respectively at 1 month post PCI. Similar results were observed at 3 months (PRU 12 [6–43] in ticagrelor vs. 88 [58–148] in prasugrel vs. 169 [107–199] in clopidogrel), with OPR rate 7.1% vs. 51.5% vs. 65.9%, respectively. At 12 months, the incidence of BARC type-1 or -2 bleeding was significantly higher in potent P2Y12 inhibitors (37.5% in ticagrelor, 34.2% in prasugrel) than in clopidogrel (36.0 vs. 14.0%; HR, 2.86; 95% CI, 1.19–6.87; p=0.018). Conclusion In Korean ACS patients, pharmacodynamic response (OPR rate) with half-dose prasugrel appears comparable to that with clopidogrel, whereas ticagrelor still exhibit potent platelet inhibition either standard or half doses. De-escalation strategy with half-dose potent P2Y12 inhibitor was associated with higher incidence of clinically insignificant bleeding compared with clopidogrel. Optimal dose reduction strategies in potent P2Y12 inhibitors to balance safety and effectiveness remain uncertain, and require further studies. Pharmcodynamics to oral P2Y12 inhibitors Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): National Research Foundation of Korea

scholarly journals Efficacy and safety of low dose ticagrelor in patients with acute coronary syndrome: a systematic review and meta-analysis

2020 ◽  
Vol 96 (1141) ◽  
pp. 693-702
Author(s):  
Qing Chen ◽  
Yuanyuan Zhang ◽  
Zhen Wang ◽  
Shuai Wang ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Major Bleeding ◽  
Low Dose ◽  
Standard Dose ◽  
Left Ventricular ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
Major Bleeding Events

Our aim was to examine clinical trials, provide guidance to practitioners and estimate the efficacy and safety of two agents by comparing low dose ticagrelor with standard dose clopidogrel in patients with acute coronary syndrome. We systematically looked through Pubmed, Embase, the Cochrane Library, Wanfang data and CNKI for trials comparing low dose ticagrelor with standard dose clopidogrel for the treatment of patients with ACS since the database was created. The primary endpoint for efficacy was the rate of major adverse cardiac events (MACEs). The primary endpoint for safety was the rate of major bleeding events. We also evaluated platelet function between low dose ticagrelor and standard dose clopidogrel in ACS patients. From 6744 articles, 16 studies including 1629 patients met the inclusion criteria. In contrast with standard dose clopidogrel, low dose ticagrelor significantly reduced MACEs (OR 0.39, 95% CI 0.26, 0.58) and the difference was statistically significant (p<0.01). No difference was noted for major bleeding events (OR 1.16, 95% CI 0.43, 3.08) between the two agents (p=0.77). In addition, low dose ticagrelor showed lower platelet aggregation rate than clopidogrel (standardised mean difference (SMD) −0.68, 95% CI −0.83 to 0.53) (p<0.01). Platelet reaction units for low dose ticagrelor were much lower than those for standard dose clopidogrel (SMD −2.46, 95% CI −2.85 to −2.07) (p<0.01). In comparison with standard dose clopidogrel, low dose ticagrelor significantly lowered the incidence of MACEs, improved left ventricular ejection fraction, decreased left ventricular end diastolic dimension and did not expand the risk of major bleeding events or minor or minimal bleeding events in ACS patients with a considerable safety and efficacy profile. In addition, low dose ticagrelor was associated with dramatically lower platelet aggregation compared with standard dose clopidogrel.

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