Comparison between preoperative loading dose with Ticagrelor and Clopidogrel on myocardial perfusion during intervention in patients with STsegment elevation myocardial infarction undergoing primary percutaneous coronary intervention
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Abstract Aim and Objectives The aim of this study is to compare between clopidogrel and ticagrelor loading doses used prior to primary PCI in patients presenting with acute STEMI (ST-elevation Myocardial Infarction) on myocardial perfusion and in-hospital MACE (major adverse cardiac events). Patients and Methods The study included 170 patients who presented with acute STEMI to the cardiology department of Ain Shams university hospitals and underwent primary PCI. They were divided into 2 groups where the1st group 85 patients received clopidogrel loading dose (600mg) and the 2nd group 85 patients received ticagrelor loading dose (180mg). Post interventional thrombolysis in myocardial infarction (TIMI) flow grade and myocardial blush grade (MBG) were recorded. Results The majority of patients in both groups had the LAD as the culprit vessel for their presentation (71.8% in the clopidogrel group and 50.6% in ticagrelor group). In the clopidogrel group there were 4 patients with TIMI I flow and MBG I, 13 with TIMI II flow and MBG II and 68 with TIMI III flow and MBG III. Meanwhile in the ticagrelor group there was 2 patients with TIMI I flow and MBG I, s with TIMI II flow and MBG II and 81 with TIMI III flow and MBG III. There was no statistical significance between the two groups regarding in-hospital death of all causes and stroke after primary PCI. Conclusion Ticagrelor loading before primary PCI resulted in improved TIMI flow, MBG but did not decrease incidence of in-hospital MACE.Keywords:
TIMI
Mace
Loading dose
<p>The PLATO trial demonstrated significantly lower mortality and myocardial infarction in acute coronary syndrome (ACS) patients treated with ticagrelor and aspirin compared to clopidogrel and aspirin. Ticagrelor is a direct acting P2Y12 receptor antagonist, and is a more potent inhibitor of platelet reactivity than clopidogrel, and this is believed to be the main cause of its superior efficacy in the PLATO trial. A range of factors have been associated with high on-treatment platelet reactivity (HOTPR) on clopidogrel, including genetic factors, drug interactions and clinical risk factors. HOTPR on clopidogrel has been associated with a higher risk of adverse outcomes following ACS. On the basis of the PLATO trial results, and the theoretical limitations associated with clopidogrel, ticagrelor was funded by PHARMAC in July 2013, and has been recommended for use in patients with ACS in New Zealand. This thesis examined the use of ticagrelor in a real world ACS population being managed through Wellington Hospital cardiology department. We examined platelet reactivity in patients treated with ticagrelor compared to clopidogrel, factors associated with clinician choice to use ticagrelor versus clopidogrel and the incidence of side effects of ticagrelor that may have implications for compliance with the drug outside the setting of a randomized controlled trial. We found that ticagrelor significantly reduced both platelet reactivity (30.3 AU ± 17.5 versus 43.7 AU ± 24.8, p= 0.0001) and the proportion of patients classified as having HOTPR (15.9% versus 37.7%, p= 0.0001), in comparison to clopidogrel. The clinical variables associated with HOTPR differ between clopidogrel and ticagrelor, suggesting that different factors were driving residual platelet reactivity on the two agents. Over a 2 year period, clopidogrel (68%) was used more commonly than ticagrelor (42%), and in a different cohort of patients. Patients treated with ticagrelor were younger (61 years ± 10 versus 65 years ± 12, p=0.0001), less likely to present with STEMI (12% versus 31%, p=0.0001), less likely to have a history of prior myocardial infarction (15.8% versus 22.7%, p=0.05), and had lower GRACE (98 ± 24 versus 108 ± 28, p=0.0001) and CRUSADE (25 ± 9 versus 28 ± 12, p=0.001) risk scores compared to those treated with clopidogrel. Prescription of ticagrelor was therefore not driven by clinical risk. Antiplatelet prescription varied significantly according to the patients’ admitting hospital. Bleeding rates on ticagrelor and clopidogrel within 30 days of study enrolment were low and were not significantly different. There was 1 patient on clopidogrel who had the drug discontinued due to bleeding. At 30 day follow up, significantly more patients treated with ticagrelor reported dyspnoea (43.3% versus 27.1%, p=0.001), however discontinuation of the drug due to dyspnoea on ticagrelor was infrequent (1.7%). In this real world cohort of ACS patients, we observed that ticagrelor was associated with more potent platelet inhibition than clopidogrel, but was not associated with factors leading to increased discontinuation at 30 days. Despite the proven benefits of ticagrelor compared to clopidogrel, the majority of patients, including the highest risk patients appear to be preferentially treated with clopidogrel. The causes contributing to underuse of ticagrelor need to be examined and addressed.</p>
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Aim: To evaluate the 6-month recurrent major adverse cardiac events (MACE) in acute coronary syndrome (ACS) patients, in relation to region and clopidogrel treatment separately for men and women. Material and Methods: During 2016, n =1,194 consecutive ACS patients hospitalized in various Cardiology Clinics in Aegean islands and Attica region, were enrolled. Clopidogrel treatment was recorded either as original product clopidogrel hydrogen sulphate (Plavix®/Iscover®) (branded) or clopidogrel besylate formulation (generic). Six-month follow-up evaluation was performed and recurrent MACE incidence and hemorrhage event were recorded. Results: The 6-month MACE incidence was 3.9% (4.6% in Aegean islands and 3.5% in Attica area, p>0.05 ). The respective incidence in men was 4.0% and in women 3.8% ( p>0.05 ). Overall generic and branded clopidogrel use was 87% and 13%, respectively. No significant differences were observed between branded and generic clopidogrel use and 6-month MACE incidence; subgroup analysis with gender as strata, did not reveal any significant outcomes as well. Hemorrhage incidence did not exceed the 1% in the total sample. Conclusions: The low incidence of recurrent MACE in ACS patients along with the low rate of bleeding events, irrespective of type of clopidogrel used, support the clinical and safety equivalence of generic and branded clopidogrel in the cardiac rehabilitation of ACS men and women patients.
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Loading dose
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Objective
To investigate the clinical efficacy and safety of ticagrelor in the treatment of patients with acute coronary syndrome(ACS).
Methods
From January 2016 to June 2017, 112 patients with ACS in the Central Hospital of Maanshan were selected as study objects, and according to the digital table they were randomized divided into two groups: ticagrelor group(n=57) and clopidogrel group(n=55). The clopidogrel group received clopidogrel treatment, and the clopidogrel group was treated with clopidogrel.The time of short-term curative effect was 3 months after taking medcine.The differences of platelet inhibition rate, efficacy of platelet inhibition, main adverse cardiovascular events and hemorrhage complication in medication after 1d and 3 months after PCI of patients in two groups were observed.
Results
The platelet inhibition rate and efficacy of platelet inhibition in medication after 1 d and 3 months after PCI in the ticagrelor group were (83.2±15.4)% and (78.4±19.6)%, respectively, which were significantly higher than those in the clopidogrel group[(69.5±19.9)% and (41.3±14.6)%](t=2.555, 4.468, all P 0.05).
Conclusion
Compared with clopidogrel, the application of ticagrelor in the treatment of ACS is more efficient and safe.
Key words:
Coronary disease; Ticagrelor; Clopidogrel; Controlled clinical trial
Loading dose
Clinical efficacy
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Objective: To report the use of ticagrelor in a patient with a documented hypersensitivity reaction to clopidogrel. Case Summary: A 64-year-old woman presented with non-ST-segment elevation myocardial infarction (NSTEMI) with a history significant for a hypersensitivity reaction to clopidogrel and was medically managed. Based on the patient’s past medical history and current evidence available, the determination was made to use ticagrelor in this patient. Ticagrelor was administered without reaction during the hospital stay and on assessment at 2 and 4 weeks postdischarge. Discussion: Hypersensitivity occurs in approximately 1% of patients receiving clopidogrel. Although the risk of hypersensitivity reaction to clopidogrel is low, evidence to support alternative antiplatelets in this setting is relatively limited. Prasugrel has a similar structure to clopidogrel and, therefore, may cross-react. Furthermore, prasugrel is not recommended in the medical management of NSTEMI. Ticagrelor is a newer P2Y12 inhibitor that contains a cyclopentyltriazolopyrimidine structure. Because of the difference in structure, a lower theoretical risk of cross-reactivity with the thienopyridines would be anticipated. However, there are no reports to date that investigate the use of this agent in patients with a documented thienopyridine allergy. Conclusions: The current case report describes the use of ticagrelor in a patient with documented hypersensitivity to clopidogrel. In this patient, ticagrelor was well tolerated during hospital admission and at 2 and 4 weeks postdischarge following administration.
Thienopyridine
Hypersensitivity reaction
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Advances in antiplatelet technologies to improve cardiovascular disease morbidity and mortality: a review of ticagrelor Estella M Davis, Jon T Knezevich, Robyn M Teply Department of Pharmacy Practice, Creighton University School of Pharmacy and Health Professions, Omaha, NE, USA Abstract: Antiplatelet therapy is widely used with proven benefit for the prevention of further ischemic cardiac complications in patients with acute coronary syndrome. Treatment guidelines for acute coronary syndrome and percutaneous coronary intervention now recommend the use of oral antiplatelet agents including ticagrelor, prasugrel, or clopidogrel in combination with aspirin to comprise dual antiplatelet therapy for the prevention of recurrent ischemic events. The limitations of conventional antiplatelet therapy with clopidogrel or prasugrel include the potential for low response to clopidogrel identified through platelet reactivity or genetic testing, increased risk of bleeding with prasugrel, or slower return to normal platelet activity in patients who received either prasugrel or clopidogrel prior to emergent or planned surgical procedures. This review will discuss the pharmacokinetic and pharmacodynamic properties of ticagrelor in comparison to conventional P2Y12 receptor inhibitors and its utility in patients identified as low responders to clopidogrel. Completed clinical studies and substudies comparing ticagrelor to clopidogrel and ongoing clinical trials evaluating ticagrelor in acute coronary syndrome patients will also be reviewed. Keywords: ticagrelor, antiplatelet, acute coronary syndrome, ST elevation myocardial infarction, non-ST elevation MI, percutaneous coronary intervention
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Loading dose
Adenosine diphosphate
Maintenance dose
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No published information exists to support the safe use of ticagrelor in patients with a clopidogrel allergy. This study involved an institutional review board–approved retrospective review of patients with a documented clopidogrel allergy who subsequently received ticagrelor between July 2011 and February 2014. We report the cases of two patients with a history of hypersensitivity to clopidogrel in whom ticagrelor was used successfully without documented incident. In addition, principles suggesting a lack of cross‐sensitivity between ticagrelor and clopidogrel are reviewed. These cases combined with theoretical evidence support the use of ticagrelor in patients with hypersensitivity to clopidogrel.
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Dual antiplatelet treatment is recommended by current clinical practice guidelines for patients undergoing PCI. The PLATO trial showed superiority of ticagrelor to clopidogrel in reducing the rate of death from vascular causes, myocardial infarction and stroke without increase in the rate of overall major bleeding in ACS patients. However, real world evidence in Indian patients is limited. The objective of this study is to compare safety profile of ticagrelor with clopidogrel in real world settings.In this single centered retrospective observational study, a total of 1208 serial patient records undergoing PCI (ACS and stable angina patients as well) treated with Ticagrelor or Clopidogrel were collected and analyzed to look into in hospital outcomes. We excluded the patient's data that were incomplete.In total of 1208 patients, 604 patients received ticagrelor and similarly 604 patient received clopidogrel. No significant differences in the rates of major life threatening bleeding and any major bleeding were observed between ticagrelor and clopidogrel group (0.2% (n = 1) vs. 0.7% (n = 4), p = 0.18 and 2.8% (n = 17) vs. 3% (n = 18), p = 0.86 respectively). There was increase in minor bleeding rate with ticagrelor compared to clopidogrel (21.4% & 13.6%, p = 0.00).In the real world settings, patients undergoing PCI treated with ticagrelor showed similar safety profile compared to clopidogrel but with increase in minor bleeding rate. The observed results were in alignment with PLATO clinical trial.
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<p>The PLATO trial demonstrated significantly lower mortality and myocardial infarction in acute coronary syndrome (ACS) patients treated with ticagrelor and aspirin compared to clopidogrel and aspirin. Ticagrelor is a direct acting P2Y12 receptor antagonist, and is a more potent inhibitor of platelet reactivity than clopidogrel, and this is believed to be the main cause of its superior efficacy in the PLATO trial. A range of factors have been associated with high on-treatment platelet reactivity (HOTPR) on clopidogrel, including genetic factors, drug interactions and clinical risk factors. HOTPR on clopidogrel has been associated with a higher risk of adverse outcomes following ACS. On the basis of the PLATO trial results, and the theoretical limitations associated with clopidogrel, ticagrelor was funded by PHARMAC in July 2013, and has been recommended for use in patients with ACS in New Zealand. This thesis examined the use of ticagrelor in a real world ACS population being managed through Wellington Hospital cardiology department. We examined platelet reactivity in patients treated with ticagrelor compared to clopidogrel, factors associated with clinician choice to use ticagrelor versus clopidogrel and the incidence of side effects of ticagrelor that may have implications for compliance with the drug outside the setting of a randomized controlled trial. We found that ticagrelor significantly reduced both platelet reactivity (30.3 AU ± 17.5 versus 43.7 AU ± 24.8, p= 0.0001) and the proportion of patients classified as having HOTPR (15.9% versus 37.7%, p= 0.0001), in comparison to clopidogrel. The clinical variables associated with HOTPR differ between clopidogrel and ticagrelor, suggesting that different factors were driving residual platelet reactivity on the two agents. Over a 2 year period, clopidogrel (68%) was used more commonly than ticagrelor (42%), and in a different cohort of patients. Patients treated with ticagrelor were younger (61 years ± 10 versus 65 years ± 12, p=0.0001), less likely to present with STEMI (12% versus 31%, p=0.0001), less likely to have a history of prior myocardial infarction (15.8% versus 22.7%, p=0.05), and had lower GRACE (98 ± 24 versus 108 ± 28, p=0.0001) and CRUSADE (25 ± 9 versus 28 ± 12, p=0.001) risk scores compared to those treated with clopidogrel. Prescription of ticagrelor was therefore not driven by clinical risk. Antiplatelet prescription varied significantly according to the patients’ admitting hospital. Bleeding rates on ticagrelor and clopidogrel within 30 days of study enrolment were low and were not significantly different. There was 1 patient on clopidogrel who had the drug discontinued due to bleeding. At 30 day follow up, significantly more patients treated with ticagrelor reported dyspnoea (43.3% versus 27.1%, p=0.001), however discontinuation of the drug due to dyspnoea on ticagrelor was infrequent (1.7%). In this real world cohort of ACS patients, we observed that ticagrelor was associated with more potent platelet inhibition than clopidogrel, but was not associated with factors leading to increased discontinuation at 30 days. Despite the proven benefits of ticagrelor compared to clopidogrel, the majority of patients, including the highest risk patients appear to be preferentially treated with clopidogrel. The causes contributing to underuse of ticagrelor need to be examined and addressed.</p>
Antiplatelet drug
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