Ticagrelor Treatment Research Articles

Clinical impact and predictors of complete ST segment resolution after primary percutaneous coronary intervention: A subanalysis of the ATLANTIC Trial.

In the ATLANTIC (Administration of Ticagrelor in the catheterization laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery) trial the early use of aspirin, anticoagulation, and ticagrelor coupled with very short medical contact-to-balloon times represent good indicators of optimal treatment of ST-elevation myocardial infarction and an ideal setting to explore which factors may influence coronary reperfusion beyond a well-established pre-hospital system. This study sought to evaluate predictors of complete ST-segment resolution after percutaneous coronary intervention in ST-elevation myocardial infarction patients enrolled in the ATLANTIC trial. ST-segment analysis was performed on electrocardiograms recorded at the time of inclusion (pre-hospital electrocardiogram), and one hour after percutaneous coronary intervention (post-percutaneous coronary intervention electrocardiogram) by an independent core laboratory. Complete ST-segment resolution was defined as ≥70% ST-segment resolution. Complete ST-segment resolution occurred post-percutaneous coronary intervention in 54.9% ( n=800/1456) of patients and predicted lower 30-day composite major adverse cardiovascular and cerebrovascular events (odds ratio 0.35, 95% confidence interval 0.19-0.65; p<0.01), definite stent thrombosis (odds ratio 0.18, 95% confidence interval 0.02-0.88; p=0.03), and total mortality (odds ratio 0.43, 95% confidence interval 0.19-0.97; p=0.04). In multivariate analysis, independent negative predictors of complete ST-segment resolution were the time from symptoms to pre-hospital electrocardiogram (odds ratio 0.91, 95% confidence interval 0.85-0.98; p<0.01) and diabetes mellitus (odds ratio 0.6, 95% confidence interval 0.44-0.83; p<0.01); pre-hospital ticagrelor treatment showed a favorable trend for complete ST-segment resolution (odds ratio 1.22, 95% confidence interval 0.99-1.51; p=0.06). This study confirmed that post-percutaneous coronary intervention complete ST-segment resolution is a valid surrogate marker for cardiovascular clinical outcomes. In the current era of ST-elevation myocardial infarction reperfusion, patients' delay and diabetes mellitus are independent predictors of poor reperfusion and need specific attention in the future.

Temporal Trends in the Use of Antiplatelet Therapy in Patients With Acute Coronary Syndromes.

Current clinical guidelines of acute coronary syndromes (ACS) recommend the use of potent antiplatelet therapy, prasugrel or ticagrelor, because both drugs consistently reduce cardiovascular events. The aim of this study was to examine temporal changes in the use of optimal antiplatelet therapy in patients with ACS. A total of 1717 consecutive patients admitted for ACS in 3 tertiary hospitals from February 2014 to December 2015 were enrolled. We divided these 23 months into 4 semesters: period I (0-5 months), period II (6-11 months), period III (12-17 months), and period IV (17-23 months). Demographic, clinical, and treatment data were collected both at admission and at discharge. Treatment with clopidogrel remained constant throughout the periods (52%, 50%, 44%, and 50% for periods I, II, III, and IV, respectively), whereas a progressive increase in ticagrelor treatment was observed (15%, 25%, 26%, and 28%; P = .001). Indeed, new P2Y12 agents showed an increase from 47% at the first semester to 65% in patients with ST-segment elevation myocardial infarction (STEMI), and in patients younger than 75 years from 36% to 53%. However, for patients older than 75 years, diabetic, and patients with end-stage kidney disease, clopidogrel was the second most commonly used antiplatelet agent. In this real-life registry of patients with ACS, we observed there is still a high rate of use of clopidogrel, despite guidelines recommendations, and our analyses also showed a trend toward the use of ticagrelor. Patients who received new antiplatelet agents were patients with STEMI, younger than 75 years, and with less comorbidities. However, the use of ticagrelor and prasugrel remains low, highlighting a therapeutic inertia with considerable gap between evidence-based clinical guidelines and daily clinical practice.

Comparison of the Antiplatelet Effects of Once and Twice Daily Low-Dose Ticagrelor and Clopidogrel After Percutaneous Coronary Intervention

Although Asian people are believed to be more susceptible to bleeding on currently recommended dose of ticagrelor, there is limited evidence supporting low-dose ticagrelor. We prospectively randomized patients receiving dual antiplatelet therapy with aspirin and clopidogrel into 3 groups; aspirin plus clopidogrel 75mg versus aspirin plus ticagrelor 90mg once daily versus aspirin plus ticagrelor 45mg twice daily. Platelet function assessments were conducted using VerifyNow P2Y12 assay at baseline and 28days after randomization. No differences in baseline P2Y12 reaction unit (PRU) values were observed among the 3 groups. PRU values at the end of the treatment periods were significantly lower in low-dose ticagrelor (90mg QD group, 98.6 ± 73.4 and 45mg BID group, 65.5 ± 58.8) compared with clopidogrel (221.2 ± 50.1, both p <0.001). There was no significant difference in PRU values between 2 groups of low-dose ticagrelor (p= 0.208). The rates of high on-treatment platelet reactivity were significantly lower in low-dose ticagrelor compared with clopidogrel, whereas clopidogrel showed higher rate of optimal on-treatment platelet reactivity than ticagrelor 45mg BID. However, similar rate of optimal on-treatment platelet reactivity was observed in clopidogrel and ticagrelor 90mg QD. In conclusion, low-dose ticagrelor treatment, either with 90mg QD or 45mg BID, was associated with a more potent antiplatelet effect compared with clopidogrel treatment and once daily dose provided similar antiplatelet effect but favorable effect on optimal plateletinhibition compared with twice daily dose.

INFLAMMATORY RESPONSE AND INFARCTION SIZE ARE DECREASED WITH TICAGRELOR COMPARED TO CLOPIDOGREL IN PRIMARY PERCUTANEOUS CORONARY INTERVENTION

Background: It is unknown whether ticagrelor treatment before and after primary percutaneous coronary intervention (pPCI) can reduce the inflammatory response and infarction size compared to clopidogrel. Methods: Four hundred and sixty consecutive patients with ST-segment elevation myocardial

Efficacy and Safety of Novel Oral P2Y12 Receptor Inhibitors in Patients With ST-Segment Elevation Myocardial Infarction Undergoing PCI: A Systematic Review and Meta-Analysis.

:The efficacy and safety of novel oral P2Y12 receptor inhibitors (prasugrel and ticagrelor) are subjects of contention in patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI, and the optimal duration of therapy remains uncertain. We searched PubMed, Embase, Cochrane Library, CNKI, VIP, and WanFang Data to identify randomized controlled trials comparing novel oral P2Y12 receptor inhibitors with clopidogrel in patients with STEMI undergoing PCI until February 2016. The primary efficacy and safety endpoint were all-cause mortality and major/minor bleeding. Twelve studies were included. Novel oral P2Y12 inhibitors significantly reduced the incidence of all-cause death (relative risk: 0.65, 95% confidence interval, 0.53–0.78), major adverse cardiac events [0.68 (0.56–0.83)], and stent thrombosis [0.56 (0.43–0.75)] without significant difference in bleeding (P = 0.11) compared with clopidogrel. Identical results were observed in the longer dual antiplatelet therapy (DAPT) and shorter-DAPT subgroups, albeit Chinese patients with ticagrelor treatment had a slight increase in bleeding (P = 0.08). Furthermore, the pooled relative risk ratio for each endpoint showed no significant difference between the longer-DAPT and shorter-DAPT subgroups. In conclusion, prasugrel and ticagrelor decreased the risk of all-cause death, major adverse cardiac events, and stent thrombosis without causing more bleeding events compared with clopidogrel in patients with STEMI undergoing PCI.

734 - Safety of device implantation under antipatelet therapy with ticagrelor: about 20 cases

Introduction Management of antiplatelet therapy at the time of device implantation remains controversial. This study aimed to assess the risk of bleeding complications in patients receiving ticagrelor at the time of cardiac device surgery. Methods We performed a multicentre ( N = 4), retrospective study from January 2015 to January 2016. The survey included all patients (pts) treated with ticagrelor before undergoing pacemaker, implantable–cardioverter defibrillator (ICD) implantation or generator replacement. We report haemorrhagic post-procedural complications at 1 month. A significant bleeding complication was defined as pocket hematoma requiring a surgical evacuation or prolonged hospitalization, hemothorax, pericardial effusion or tamponade. Results A total of 20 patients underwent a permanent pacemaker or ICD implantation while taking a combination of antipatelet therapy with ticagrelor and aspirin. The mean age of the patients was 65 ± 9 years, 95% were male, 25% of patients were diabetics, 55% had hypertension and 50% presented a history of heart failure. All the patients had a history of acute coronary syndrome (6 [4–26] months before the procedure). The majority of implanted devices were ICDs (17, 85%) with 5 single chamber, 4 dual chambers and 9 triple chambers ICDs. Subclavian venous approach was utilized in 9 patients. The mean duration of procedure was 60 minutes. One per-procedure bleeding was described due to high venous pressure, without post-procedure hematoma. A post-procedure pocket hematoma has been experienced by one patient. The subclavian approach was used for the 2 patients. No blood transfusion was needed for these 2 cases. Conclusion Ticagrelor treatment at the time of heart rhythm device procedures does not seem to be associated with an increased risk of significant bleeding complications. In our study, 2 patients experienced non significant bleeding complications.

Platelet function recovery after ticagrelor withdrawal in patients awaiting urgent coronary surgery.

Dual antiplatelet therapy with ticagrelor and aspirin is associated with an increased risk of perioperative bleeding complications. Current guidelines recommend therefore discontinuation of ticagrelor 5 days before surgery to allow sufficient recovery of platelet function. It is not known how the time to recovery varies between individual patients after discontinuation of ticagrelor. Twenty-five patients accepted for urgent coronary artery bypass surgery and treated with ticagrelor and aspirin were included in a prospective observational study. Platelet aggregation was evaluated with impedance aggregometry at five timepoints 12-96 h after discontinuation of ticagrelor. In a subset of patients ( n = 15), we also tested the ex vivo efficacy of platelet concentrate supplementation on platelet aggregation. There was a gradual increase in mean adenosine diphosphate-induced platelet aggregation after discontinuation of ticagrelor. After 72 h, mean aggregation was 38 ±23 aggregation units (U), which is above a previously suggested cut-off of 22 U, when patients can be operated without increased bleeding risk. However, there was a large interindividual variability (range 4‒88 U at 72 h) and 6/24 patients (25%) had <22 U after 72 h. Ex vivo administration of platelet concentrate did not improve adenosine diphosphate-induced aggregation at any timepoint after ticagrelor discontinuation. Adenosine diphosphate-induced aggregation was acceptable after 72 h in the majority of patients but with a large interindividual variability. Due to the large variability, platelet function testing may prove to be a valuable tool in timing of surgery in patients with ongoing or recently stopped ticagrelor treatment. Adenosine diphosphate-induced aggregation was not improved by addition of platelet concentrate.

Safety of device implantation under antipatelet therapy with ticagrelor: About 20 cases

Management of antiplatelet therapy at the time of device implantation remains controversial. This study aimed to assess the risk of bleeding complications in patients receiving ticagrelor at the time of cardiac device surgery. We performed a multicentre (N=4), retrospective study from January 2015 to January 2016. The survey included all patients (pts) treated with ticagrelor before undergoing pacemaker, implantable-cardioverter defibrillator (ICD) implantation or generator replacement. We report haemorrhagic post-procedural complications at 1 month. A significant bleeding complication was defined as pocket hematoma requiring a surgical evacuation or prolonged hospitalization, hemothorax, pericardial effusion or tamponade. A total of 20 patients underwent a permanent pacemaker or ICD implantation while taking a combination of antipatelet therapy with ticagrelor and aspirin. The mean age of the patients was 65±9 years, 95% were male, 25% of patients were diabetics, 55% had hypertension and 50% presented a history of heart failure. All the patients had a history of acute coronary syndrome (6 [4-26] months before the procedure). The majority of implanted devices were ICDs (17, 85%) with 5 single chamber, 4 dual chambers and 9 triple chambers ICDs. Subclavian venous approach was utilized in 9 patients. The mean duration of procedure was 60minutes. One per-procedure bleeding was described due to high venous pressure, without post-procedure hematoma. A post-procedure pocket hematoma has been experienced by one patient. The subclavian approach was used for the 2 patients. No blood transfusion was needed for these 2 cases. Ticagrelor treatment at the time of heart rhythm device procedures does not seem to be associated with an increased risk of significant bleeding complications. In our study, 2 patients experienced non significant bleeding complications.

PCV107 - Ticagrelor Treatment for Prevention of Cardiovascular Events in High Risk Post Myocardial Infarction Patients: Cost-Effectiveness Analysis Using Evidence From The Pegasus-Timi 54 Trial

PCV107 - Ticagrelor Treatment for Prevention of Cardiovascular Events in High Risk Post Myocardial Infarction Patients: Cost-Effectiveness Analysis Using Evidence From The Pegasus-Timi 54 Trial

Lack of Evidence for Deterioration in Endothelial Function Following Ticagrelor Treatment Cessation.

Ticagrelor may exert pleiotropic actions, beyond platelet inhibition, which are possibly adenosine-mediated. It has been suggested that in patients with coronary artery disease (CAD) ticagrelor may influence endothelial function. We aimed to assess the possibility of endothelial function deterioration following ticagrelor treatment cessation. This was a prospective, observational study, in stable CAD patients with prior percutaneous coronary intervention (PCI) for acute coronary syndrome manifested 1 year earlier, under ticagrelor maintenance dose (90 mg bid) and due to discontinue ticagrelor. Endothelial function was assessed by Peripheral Arterial Tonometry (EndoPat 2000 system, Itamar Medical, Caesarea, Israel) immediately after receiving the last tablet of ticagrelor (Day 0) and at Day 2 and Day 5 post-ticagrelor cessation. Reactive hyperaemia index (RHI) was calculated by automated software and endothelial dysfunction (ED) was defined as a RHI <1.67. We identified 30 eligible patients with endothelial function assessment pre- and post-ticagrelor cessation (86.7% men, 13.3% with diabetes and 33.3% current smokers; mean age: 63.6±11.5 years). The study's primary endpoint of RHI at Day 5 did not differ significantly compared with RHI at Day 0, 1.69 (1.45-2.23) vs 1.81 (1.59-2.13). ED rate did not differ significantly between Day 5 and Day 0, 40 vs 33.3%, p=0.8, respectively. No differences in RHI or ED rate were observed between Day 2 and Day 0, 1.64 (1.54-2.04) vs 1.8 1(1.59-2.13), p=0.3 and 53.3 vs 33.3%, p=0.2, respectively. In stable CAD patients there is no evidence of deterioration in endothelial function after discontinuing ticagrelor.

Preoperative platelet function predicts perioperative bleeding complications in ticagrelor-treated cardiac surgery patients: a prospective observational study

BackgroundTreatment with P2Y12 receptor antagonists increases the risk for perioperative bleeding, but there is individual variation in the antiplatelet effect and time to offset of this effect. We investigated whether preoperative platelet function predicts the risk of bleeding complications in ticagrelor-treated cardiac surgery patients. MethodsNinety patients with ticagrelor treatment within <5 days of surgery were included in a prospective observational study. Preoperative platelet aggregation was assessed with impedance aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating peptide (TRAP) as initiators. Severe bleeding complications were registered using a new universal definition of perioperative bleeding. The accuracy of aggregability tests for predicting severe bleeding was assessed using receiver operating characteristic (ROC) curves, which also identified optimal cut-off values with respect to sensitivity and specificity, based on Youden's index. ResultsThe median time from the last ticagrelor dose to surgery was 35 (range 4–108) h. The accuracy of platelet function tests to predict severe bleeding was highest for ADP [area under the ROC curve 0.73 (95% confidence interval 0.63–0.84, P<0.001); TRAP 0.61 (0.49–0.74); AA 0.53 (0.40–0.66)]. The optimal cut-off for ADP-induced aggregation was 22 U. In subjects with ADP-induced aggregation below the cut-off value, 24/38 (61%) developed severe bleeding compared with 8/52 (14%) when aggregation was at or above the cut-off value (P<0.001). The positive and negative predictive values for this cut-off value were 63 and 85%, respectively. ConclusionsPreoperative ADP-induced platelet aggregability predicts the risk for severe bleeding complications in ticagrelor-treated cardiac surgery patients.

Ticagrelor

Ticagrelor

Efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome in Taiwan: A multicenter retrospective pilot study

BackgroundThe efficacy and safety of ticagrelor compared with clopidogrel in acute coronary syndrome has not previously been evaluated in an Eastern Asian population, which is recognized to have a different response to P2Y12 antagonists compared with the Caucasian population in real-life situations. MethodsA multicenter retrospective pilot study was performed to evaluate 928 consecutive patients with acute coronary syndrome, receiving aspirin and one P2Y12 antagonist (324 ticagrelor or 604 clopidogrel). Using propensity score matching, 448 patients were selected and divided into two equal groups. Kaplan–Meier analysis was used to study patient survival and event-free status using the log-rank test. Independent covariates were identified using univariate in a multivariate Cox proportional hazard model. ResultsIn the overall cohort, significant differences were observed for certain variables between the two groups. During the mean 164.3 (±116.4)-day follow-up in the overall cohort, ticagrelor treatment had no significant effect on the primary efficacy endpoint (myocardial infarction, stroke, or vascular death); however, in the matched cohort, ticagrelor showed a lower incidence of primary endpoint (hazard ratio: 0.56; 95% confidence interval: 0.30–1.04; p = 0.07) and stroke (hazard ratio: 0.15; 95% confidence interval: 0.02–1.24; p = 0.08) with marginal statistical significance, and a similar bleeding rate. The protective effect of ticagrelor treatment was consistent for all subgroups. More patients treated with ticagrelor experienced dyspnea (21.0% vs. 11.6%, p = 0.007), and P2Y12 antagonist treatment was consequently discontinued. ConclusionTicagrelor treatment could provide a marginally favorable effect at the expense of an increased risk of dyspnea in real-life situations. This pilot study provides a scientific basis to call for a larger, suitably powered Phase 4 prospective or observational study in this ethnic population.

Initiation and persistence with dual antiplatelet therapy after acute myocardial infarction: a Danish nationwide population-based cohort study

ObjectivesThe study investigated dual antiplatelet therapy (DAPT) patterns over time and patient characteristics associated with the various treatments in a myocardial infarction (MI) population.DesignA registry-based observational cohort study was performed...

Switching between ticagrelor and clopidogrel in patients who underwent percutaneous coronary intervention: insight into contemporary practice in Chinese patients.

Ticagrelor has been proved to be more effective than clopidogrel; however, little is known about the switching between ticagrelor and clopidogrel in real-world clinical practice. We assessed the prevalence, related factors, dose bridging, compliance, and short-term outcomes of in-hospital switching between ticagrelor and clopidogrel in consecutively recruited patients treated by ticagrelor after percutaneous coronary intervention (PCI). A total of 417 eligible patients administrated with ticagrelor in-hospital after PCI were recruited. Switching between ticagrelor and clopidogrel occurred in 362 (86.8%) patients, with 318 (76.3%) from clopidogrel to ticagrelor occurring mainly after PCI and 44 (10.6%) from ticagrelor to clopidogrel primarily at discharge. History of cerebrovascular disease, final diagnosis of acute coronary syndrome, left main disease, ostial lesion, co-administration with warfarin, CYP2C19 loss-of-function alleles' carriage status, and ticagrelor-related dyspnoea emerged as related factors for the switching between clopidogrel and ticagrelor. Dose bridging between clopidogrel loading dose and ticagrelor maintenance dose (MD) was more frequent in patients switching from clopidogrel to ticagrelor, while the bridging between ticagrelor MD and clopidogrel MD was more likely to occur in patients switched from ticagrelor to clopidogrel. At 6 month follow-up, poor compliance was observed in patients from clopidogrel to ticagrelor (64.8%) or treated only by ticagrelor (50.9%), but perfect compliance in patients from ticagrelor to clopidogrel (100%). After excluding the cases with incompliance, patients switching from ticagrelor to clopidogrel had a relatively lower bleeding risk in comparison with patients with constant ticagrelor treatment and those switching from clopidogrel to ticagrelor (29.5% vs. 50.0% vs. 46.6%, adjusted P = 0.02). In-hospital switching between ticagrelor and clopidogrel is frequent in patients undergoing PCI. In comparison with constant ticagrelor treatment, switching from clopidogrel to ticagrelor in ischaemic high-risk patients confers similar antiplatelet efficacy and safety, while switching from ticagrelor to clopidogrel in ischaemic low-risk patients relates to lower hazard for bleeding events.

Serum uric acid levels during dual antiplatelet therapy with ticagrelor or clopidogrel: Results from a single-centre study

Background and aimsNew antithrombotic therapies have significantly improved the outcomes of patients with acute coronary syndrome (ACS), where the introduction of ticagrelor has provided the greatest mortality benefits. However, ticagrelor treatment has been associated with a potential increase in the serum uric acid (SUA) levels, which may influence endothelial dysfunction and prothrombotic status, thereby affecting the risk of acute cardiovascular events in patients requiring dual antiplatelet therapy (DAPT). The present study aimed to compare the impact of antiplatelet agents such as ticagrelor or clopidogrel on SUA levels and their effect on platelet reactivity. Methods and resultsWe included patients admitted for ACS or elective percutaneous coronary intervention (PCI) and discharged with ASA (acetylsalicylic acid; 100–160 mg) and clopidogrel (75 mg) or ticagrelor (90 mg twice a day). Chemistry was assessed at admission (baseline) and after a 30–90-day period of DAPT (together with platelet reactivity). The absolute and percentage variations of SUA after DAPT introduction were considered. Multiple-electrode aggregometry was used to assess platelet function.A total of 378 patients were enrolled, with 145 treated with aspirin and clopidogrel (AC) and 233 with aspirin and ticagrelor (AT). The AC patients were older (p = 0.003) and more often showed elective PCI as an indication to DAPT (<0.001); they received chronic therapy with ARB (angiotensin II receptor blocker; p = 0.001), nitrates (p = 0.044), CCB (calcium channel blocker; p = 0.005) and diuretics (p = 0.044). The AT patients displayed a higher percentage of ACS diagnosis (p < 0.001) and received chronic therapy with ACE (angiotensin-converting enzyme) inhibitors (p = 0.001), beta blockers (p = 0.001) and statins (p = 0.013).The AC patients displayed higher platelet reactivity at COL (collagen) test, ASPI test and ADP (adenosine diphosphate) test (p = 0.03, 0.001 and <0.001, respectively) and a higher percentage of HRPR (high residual platelet reactivity) in the ADP test (p = 0.001).No difference was found in the baseline uric acid and creatinine levels between AC and AT patients. At 30–90 days, a significant absolute and percentage increase in the SUA levels was found in AT as compared to AC patients (0.204 mg/dl vs. −0.165 mg/dl, p = 0.034; 6.26% vs. −0.005%, p = 0.018, respectively). Results were not influenced by variations in renal function. At multivariate analysis, in fact, ticagrelor therapy emerged as an independent predictor of increase in the uric acid levels (odds ratio (OR; 95% confidence interval (CI)) = 2.79 (1.66–4.67), p < 0.001). However, the variation in the SUA levels did not affect platelet reactivity or HRPR in both AC and AT patients. ConclusionAn increase in the SUA levels at 30–90 days was observed in patients receiving chronic DAPT with ticagrelor, but not clopidogrel treatment. However, the changes in the SUA levels do not influence platelet aggregation.

Effect of Modifying Antiplatelet Treatment to Ticagrelor in High-Risk Coronary Patients With Low Response to Clopidogrel (MATTIS)

BackgroundTreatment with clopidogrel is subject to wide variability in response, and high on-treatment platelet reactivity (HTPR) is associated with increased risk of ischemic events. Ticagrelor has been shown to have antiplatelet effects superior to those of clopidogrel, with subsequent reduced clinical ischemic events. However, the efficacy of ticagrelor in high-risk patients with coronary disease who have high on-treatment platelet reactivity (HTPR) with clopidogrel has not been examined. MethodsWe recruited 201 patients (mean age, 64 ± 10 years; 20% women) with stable/unstable angina who were receiving clopidogrel treatment and in whom coronary catheterization was planned. Platelet reactivity was tested using VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) (HTPR defined as P2Y12 reaction units [PRU] ≥ 208). Patients with HTPR were randomized to receive either additional clopidogrel 300 mg or ticagrelor 180 mg before coronary angiography, and persisted with the respective treatment after percutaneous coronary intervention (PCI). The primary end point was the rate of troponin elevation after PCI, and the secondary end point was the change in platelet reactivity 24 hours after PCI. In addition, clinical outcomes at 30 days were evaluated. ResultsEighty-four (42%) patients had HTPR (mean PRU, 270.8 ± 46.5) and were randomly assigned to clopidogrel or ticagrelor treatment. Subsequently, 49 patients underwent percutaneous coronary intervention (PCI) (26 receiving ticagrelor and 23 receiving clopidogrel). After PCI, the mean PRU in the ticagrelor group declined significantly (ticagrelor, 59.3 ± 49 vs clopidogrel, 202.4 ± 60.4; P < 0.0001). The rate of cardiac troponin elevation and clinical ischemic events were similar between the groups. ConclusionsIn high-risk patients with coronary disease and HTPR on clopidogrel, ticagrelor was highly effective in platelet inhibition and overcoming HTPR compared with continued clopidogrel treatment but had no apparent effect on troponin release or short-term clinical outcomes.

Cost-effectiveness of clopidogrel, prasugrel and ticagrelor for dual antiplatelet therapy after acute coronary syndrome: a decision-analytic model.

The use of prasugrel or ticagrelor as part of dual antiplatelet therapy with acetylsalicylic acid after acute coronary syndrome (ACS) improves clinical outcomes relative to clopidogrel. The relative cost-effectiveness of these agents are unknown. We conducted an economic analysis evaluating 12 months of treatment with clopidogrel, prasugrel or ticagrelor after ACS. We developed a fully probabilistic Markov cohort decision-analytic model using a lifetime horizon, from the perspective of the Ontario Ministry of Health and Long-Term Care. The model incorporated risks of death, recurrent ACS, heart failure, major bleeding and other adverse effects of treatment. Data on probabilities and utilities were obtained from the published literature where available. The primary outcome was quality-adjusted life-years (QALYs). Treatment with clopidogrel was associated with the lowest effectiveness (7.41 QALYs, 95% confidence interval [CI] 1.05-14.79) and the lowest cost ($39 601, 95% CI $8434-$111 186). Ticagrelor treatment had an effectiveness of 7.50 QALYs (95% CI 1.13-14.84) at a cost of $40 649 (95% CI $9327-$111 881). The incremental cost-effectiveness ratio (ICER) for ticagrelor relative to clopidogrel was $12 205 per QALY gained. Prasugrel had an ICER of $57 630 per QALY gained relative to clopidogrel. Ticagrelor was the preferred option in 90% of simulations at a willingness-to-pay threshold of $50 000 per QALY gained. Ticagrelor was the most cost-effective agent when used as part of dual antiplatelet therapy after ACS. This conclusion was robust to wide variations in model parameters.

Inter-patient variability of platelet reactivity in patients treated with prasugrel and ticagrelor

The aim of this study was to evaluate the distribution of platelet reactivity values in patients treated with prasugrel and ticagrelor. This prospective observational study enrolled 200 patients treated with prasugrel or ticagrelor. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) in the maintenance phase of treatment with prasugrel or ticagrelor. Only 3% of patients in the prasugrel group and 2% of study participants in the ticagrelor group had high on treatment platelet reactivity (HTPR). The majority of patients displayed low on treatment platelet reactivity (LTPR; prasugrel: 69%; ticagrelor: 64%). The pharmacodynamic effect was similar in patients treated with prasugrel and ticagrelor: the median level of ADP-induced platelet aggregation was 15U (interquartile range IQR 9-21U) under prasugrel treatment and 17U (IQR 8–24U) under ticagrelor treatment (p=0.370). In conclusion, our study suggests that there is some degree of variability in ADP-induced platelet aggregation under treatment with prasugrel and ticagrelor.

Preoperative Ticagrelor administration leads to a higher risk of bleeding during and after coronary bypass surgery in a case-matched analysis.

To evaluate the effect of Ticagrelor on intra- and postoperative bleeding complications in patients undergoing coronary bypass surgery. For this study, patients who underwent on-pump or off-pump coronary bypass surgery with preoperative acetylsalicylic acid (ASA) and Ticagrelor administration, between January 2014 and December 2014, were included. In the matched control group, continued dual antiplatelet therapy (DAPT) consisted of Clopidogrel and ASA. A total of 28 consecutive patients (24 males; 73 ± 6.6 years) with preoperative Ticagrelor intake underwent elective (n = 22), urgent (n = 2) or emergency (n = 4) cardiac bypass surgery. The postoperative blood loss, red blood cell units given and intra- and postoperative bleeding complications were documented. To evaluate the effect of Ticagrelor treatment on bleeding during and after coronary bypass surgery in a non-randomized study, we used a case-matched analysis. Baseline parameters showed no important differences between the study group and the control group regarding the matching variables, left ventricular function, preoperative clinical status and risk stratification. The preoperative laboratory analysis showed no important differences regarding coagulation and blood cell count parameters. Overall blood loss was significantly higher in the study group with a mean loss of 1028.8 ± 735.5 ml (P = 0.0002). Accordingly, units of red blood cells administered were also significantly higher in the study group (P = 0.0002). In the Ticagrelor group, there were six rethoracotomies due to postoperative bleeding with a blood loss of more than 1200 ml in the first 3 h. With no rethoracotomies in the Clopidogrel group, this also showed statistical significance for the postoperative course (P = 0.02). There were no differences found regarding ICU stay and ventilation time. Comparing the mean hospital stay, the study group presented a significantly longer stay than the control group (P = 0.001). Recent studies about bleeding complications in patients with Ticagrelor intake undergoing CABG in a real-life scenario presented inconsistent data. We were able to show in a case-matched analysis that Ticagrelor administration leads to significantly higher blood loss, more red blood cell units transfused and a higher rate of rethoracotomies. The data also present a longer hospital stay to the disadvantage of the study group. Consequently, Ticagrelor intake before CABG procedures should be avoided or at least discontinued 3 days before cardiac surgery.