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.

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 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.

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.

Triflusal in Patients with Acute Coronary Syndrome and Acetylsalicylic Acid Hypersensitivity

Cardiology ◽  
2021 ◽  
pp. 447-451
Author(s):  
Georgina Fuertes Ferre ◽  
Ainhoa Pérez Guerrero ◽  
Jose Antonio Linares Vicente ◽  
Javier Jimeno Sánchez ◽  
Vanesa Alonso-Ventura ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Acetylsalicylic Acid ◽  
Stent Implantation ◽  
Academic Research ◽  
Bleeding Events ◽  
Good Tolerability ◽  
Coronary Syndrome ◽  
History Of ◽  
Research Consortium

Background: Acetylsalicylic acid hypersensitivity (ASAH) limits therapeutic options in patients with acute coronary syndrome (ACS), who benefit from dual antiplatelet therapy (DAPT), especially when undergoing stent implantation. Our aim was to evaluate the safety and efficacy of triflusal in patients with ACS and ASAH. Methods and Results: Two-center retrospective study of patients diagnosed with ACS and ASAH from January 1, 2000, to May 1, 2020. Sixty-six patients were treated with triflusal. ASAH was confirmed with tests in 15 patients (22.7%). Forty-nine patients (74.2%) presented history of other drug allergies. Fifty-nine patients (89.4%) underwent stent implantation. DAPT was prescribed for ≥12 months in 54 patients. No adverse reactions to triflusal were reported. During a median follow-up of 5.12 years [IQR 2.7–9.9], rate of cardiovascular (CV) mortality was 6.1%, nonfatal myocardial infarction 12.1%, and ischemic stroke 4.5%. No cases of definite stent thrombosis occurred. Bleeding Academic Research Consortium grade ≥2 was observed in 3 patients during follow-up. Conclusion: In this series of patients presenting with ACS and ASA hypersensitivity, triflusal showed good tolerability and was associated with a low rate of CV and bleeding events.

scholarly journals Apixaban or Vitamin K Antagonists and Aspirin or Placebo According to Kidney Function in Patients with Atrial Fibrillation After Acute Coronary Syndrome or PCI: Insights from The AUGUSTUS Trial

Circulation ◽  
2021 ◽  
Author(s):  
Ziad Hijazi ◽  
John H. Alexander ◽  
Zhuokai Li ◽  
Daniel M. Wojdyla ◽  
Roxana Mehran ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Acute Coronary Syndrome ◽  
Kidney Function ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Exclusion Criterion ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
Risk Of Bleeding ◽  
Ischemic Events

Background: In the AUGUSTUS trial, apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists (VKA), and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y 12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function. Methods: In 4456 patients, the CKD-EPI formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban vs. VKA and aspirin vs. placebo was assessed across kidney function categories using Cox models. The primary outcome was ISTH major or clinically relevant non-major bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance below 30 mL/min was an exclusion criterion in the AUGUSTUS trial. Results: Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30-50 mL/min/1.73m 2 , respectively. During 6-months follow-up a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with VKA, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30-50 mL/min/1.73m 2 for bleeding events with rates of 13.1% vs. 21.3%; HR (95% CI) 0.59 (0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL/min/1.73m 2 : 16.6% vs. 5.6%; HR 3.22 (2.19-4.74); p for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable with aspirin and placebo across eGFR categories with HR ranging from 0.97 (0.76-1.23) to 1.28 (1.02-1.59) and from 0.75 (0.48-1.17) to 1.34 (0.81-2.22), respectively. Conclusions: The safety and efficacy of apixaban was consistent irrespective of kidney function, as compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT02415400

Assessing bleeding in acute coronary syndrome using the Bleeding Academic Research Consortium definition

2019 ◽  
Vol 20 (12) ◽  
pp. 818-824
Author(s):  
Federico Fortuni ◽  
Gabriele Crimi ◽  
Nuccia Morici ◽  
Giuseppe De Luca ◽  
Luca Paolo Alberti ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Academic Research ◽  
Coronary Syndrome ◽  
Research Consortium

scholarly journals Risk of Major Bleeding With Potent Antiplatelet Agents After an Acute Coronary Event: A Comparison of Ticagrelor and Clopidogrel in 5116 Consecutive Patients in Clinical Practice

2021 ◽  
Author(s):  
Liam Mullen ◽  
Mohammed N. Meah ◽  
Ahmed Elamin ◽  
Suneil Aggarwal ◽  
Adeel Shahzad ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Clinical Practice ◽  
Coronary Artery ◽  
Major Bleeding ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Academic Research ◽  
Artery Bypass Graft ◽  
Coronary Syndrome ◽  
Research Consortium

Background Major bleeding after acute coronary syndrome predicts a poor outcome but is challenging to define. The choice of antiplatelet influences bleeding risk. Methods and Results Major bleeding, subsequent myocardial infarction (MI), and all‐cause mortality to 1 year were compared in consecutive patients with acute coronary syndrome treated with clopidogrel (n=2491 between 2011 and 2013) and ticagrelor (n=2625 between 2012 and 2015) in 5 English hospitals. Clinical outcomes were identified from national hospital episode statistics. Bleeding and MI events were independently adjudicated by 2 experienced clinicians, blinded to drug, sequence, and year. Bleeding events were categorized using Bleeding Academic Research Consortium 3 to 5 and PLATO (Platelet Inhibition and Patient Outcomes) criteria and MI by the Third Universal Definition. Multivariable regression analysis was used to adjust outcomes for case mix. The median age was 68 years and 34% were women. 39% underwent percutaneous coronary intervention and 13% coronary artery bypass graft surgery. Clinical outcome data were 100% complete for bleeding and 99.7% for MI. No statistically significant difference was seen in crude or adjusted major bleeding for ticagrelor compared with clopidogrel (Bleeding Academic Research Consortium 3–5, hazard ratio [HR], 1.23; 95% CI, 0.90–1.68; P =0.2, PLATO major adjusted HR, 1.30; 95% CI, 0.98–1.74; P =0.07) except in the non‐coronary artery bypass graft cohort (n=4464), where bleeding was more frequent with ticagrelor (Bleeding Academic Research Consortium 3–5, adjusted HR, 1.58; 95% CI, 1.09–2.31; P =0.017; and PLATO major HR, 1.67; 95% CI, 1.18–2.37; P =0.004). There was no difference in crude or adjusted subsequent MI (adjusted HR, 1.20; 95% CI, 0.87–1.64; P =0.27). Crude mortality was higher in the clopidogrel group but not after adjustment, using either Cox proportional hazards or propensity matched population (HR, 0.90; 95% CI, 0.76–1.10; P =0.21) as was the case for stroke (HR, 0.82; 95% CI, 0.52–1.32; P =0.42). Conclusions This observational study indicates that the apparent benefit of ticagrelor demonstrated in a clinical trial population may not be observed in the broader population encountered in clinical practice. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02484924.

scholarly journals The Safety and Efficacy of Aspirin Discontinuation on a Background of a P2Y 12 Inhibitor in Patients After Percutaneous Coronary Intervention

Circulation ◽  
2020 ◽  
Vol 142 (6) ◽  
pp. 538-545 ◽  
Author(s):  
Michelle L. O’Donoghue ◽  
Sabina A. Murphy ◽  
Marc S. Sabatine
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Coronary Intervention ◽  
Major Adverse Cardiovascular Events ◽  
Coronary Syndrome ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Percutaneous Coronary

Background: Dual antiplatelet therapy with aspirin and a P2Y 12 inhibitor has been shown to reduce the risk of major adverse cardiovascular events (MACE) compared with aspirin alone after percutaneous coronary intervention (PCI) or acute coronary syndrome but with increased risk of bleeding. The safety of discontinuing aspirin in favor of P2Y 12 inhibitor monotherapy remains disputed. Methods: A meta-analysis was conducted from randomized trials (2001–2020) that studied discontinuation of aspirin 1 to 3 months after PCI with continued P2Y 12 inhibitor monotherapy compared with traditional dual antiplatelet therapy. Five trials were included; follow-up duration ranged from 12 to 15 months after PCI. Primary bleeding and MACE outcomes were the prespecified definitions in each trial. Results: The study population included 32 145 patients: 14 095 (43.8%) with stable coronary artery disease and 18 046 (56.1%) with acute coronary syndrome. In the experimental arm, background use of a P2Y 12 inhibitor included clopidogrel in 2649 (16.5%) and prasugrel or ticagrelor in 13 408 (83.5%) patients. In total, 820 patients experienced a primary bleeding outcome and 937 experienced MACE. Discontinuation of aspirin therapy 1 to 3 months after PCI significantly reduced the risk of major bleeding by 40% compared with dual antiplatelet therapy (1.97% versus 3.13%; hazard ratio [HR], 0.60 [95% CI, 0.45–0.79]), with no increase observed in the risk of MACE (2.73% versus 3.11%; HR, 0.88 [95% CI, 0.77–1.02]), myocardial infarction (1.08% versus 1.27%; HR, 0.85 [95% CI, 0.69–1.06]), or death (1.25% versus 1.47%; HR, 0.85 [95% CI, 0.70–1.03]). Findings were consistent among patients who underwent PCI for an acute coronary syndrome, in whom discontinuation of aspirin after 1 to 3 months reduced bleeding by 50% (1.78% versus 3.58%; HR, 0.50 [95% CI, 0.41–0.61]) and did not appear to increase the risk of MACE (2.51% versus 2.98%; HR, 0.85 [95% CI, 0.70–1.03]). Conclusions: Discontinuation of aspirin with continued P2Y 12 inhibitor monotherapy reduces risk of bleeding when stopped 1 to 3 months after PCI. An increased risk of MACE was not observed after discontinuation of aspirin, including in patients with acute coronary syndrome.

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