ticagrelor and Ischemia

In the peripheral arteries, a thrombus superimposed on atherosclerosis contributes to the progression of peripheral artery disease (PAD), producing intermittent claudication (IC), ischemic necrosis, and, potentially, loss of the limb. PAD with IC is often undiagnosed and, in turn, undertreated. The low percentage of diagnosis (∼30%) in this setting of PAD is of particular concern because of the potential worsening of PAD (amputation) and the high risk of adverse vascular outcomes (vascular death, coronary artery disease, stroke). A Medline literature search of the highest-quality systematic reviews and meta-analyses of randomized controlled trials documents that, due to risk of bias, imprecision, and indirectness, the overall quality of the evidence concerning diagnostic tools and antithrombotic interventions in PAD is generally low. Areas of research emerge from the information collected. Appropriate treatments for PAD patients will only derive from ad-hoc studies. Innovative imaging techniques are needed to identify PAD subjects at the highest vascular risk. Whether IC unresponsive to physical exercise and smoking cessation identifies those with a heritable predisposition to more severe vascular events deserves to be addressed. Devising ways to improve prevention of vascular events in patients with PAD implies a co-ordinated approach in vascular medicine.

Topics: Adenosine; Aspirin; Asymptomatic Diseases; Cilostazol; Clopidogrel; Fibrinolytic Agents; Humans; Intermittent Claudication; Ischemia; Lower Extremity; Meta-Analysis as Topic; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Primary Prevention; Review Literature as Topic; Secondary Prevention; Stroke; Tetrazoles; Thrombosis; Ticagrelor; Ticlopidine

The two newer antiplatelet drugs, prasugrel and ticagrelor have both been incorporated in various national guidelines and are both under consideration for approval or have already been approved by various drug regulatory authorities. Mortality benefits with clopidogrel were comparable to newer anti-platelets, and prasugrel had great anti-ischemic potency than ticagrelor. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials' databases for randomized controlled trials conducted between 1990 and 2012 that assessed clinical outcomes with prasugrel or ticagrelor. The comparator was standard dosage of clopidogrel. Outcomes assessed were the risk of all causes mortality, TIMI non-CABG major bleeding, and a composite of stent thrombosis, recurrent ischemia and serious recurrent ischemia in the intervention groups versus the comparator groups. Event rates were compared using a forest plot of relative risk using a random effects model (Mantel-Haenszel); and Odd's ratio was calculated in the absence of significant heterogeneity. Prasugrel was indirectly compared with ticagrelor using network meta-analysis. Four studies (total N = 34,126) met the inclusion/exclusion criteria. Both drugs had improved mortality and greater risk of bleeding compared to clopidogrel; but outcomes were comparable for both (p = NS). However a composite of recurrent ischemic events, including rates of stent thrombosis (p = 0.045) was reduced to a modest degree with prasugrel compared with ticagrelor. This systematic review suggests greater clinical efficacy of both prasugrel and ticagrelor compared with clopidogrel and an indirect comparison indicates prasugrel may be more effective than ticagrelor for preventing stent thrombosis and recurrent ischemic events.

Topics: Adenosine; Clopidogrel; Hemorrhage; Humans; Ischemia; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; PubMed; Randomized Controlled Trials as Topic; Stents; Thiophenes; Thrombosis; Ticagrelor; Ticlopidine

Platelets play a pivotal role in the pathogenesis of acute coronary syndromes (ACS) and their inhibition remains a mainstay therapy in this setting. We aimed to perform a meta-analysis of randomized trials to evaluate the benefits of new oral antiplatelet regimens to block platelet ADP-receptors compared to standard-dose clopidogrel (300 mg loading dose followed by 75 mg/daily).. We obtained results from all randomized trials enrolling patients with ACS. Primary endpoint was mortality. Secondary endpoints were myocardial infarction and definite in-stent thrombosis. Safety endpoint was the risk of major bleeding complications. We prespecified subanalyses according to new antiplatelet drugs (prasugrel/ticagrelor), high-dose clopidogrel (600 mg) and patients undergoing percutaneous coronary intervention.. A total of seven randomized trials were finally included in the meta-analysis (n = 58 591). We observed a significant reduction in mortality (2.9% vs. 3.4%, OR = 0.87, 95% CI 0.79-0.95, P = 0.002), recurrent myocardial infarction (4.2% vs. 5.2%, OR = 0.80, 95% CI 0.74-0.87, P < 0.0001), definite in-stent thrombosis (0.9% vs. 1.7%, OR = 0.52, 95% CI 0.43-0.63, P < 0.0001). The benefits in mortality and reinfarction were driven by the treatment with prasugrel or ticagrelor, without a significant difference in terms of major bleeding complications as compared to standard-dose clopidogrel (5% vs. 4.7%, OR = 1.06 95% CI 0.96-1.17, P = 0.25).. This meta-analysis showed that new oral antiplatelet regimens are associated with a significant reduction in mortality, reinfarction and in-stent thrombosis in ACS patients without an overall increase of major bleeding when treated with new antiplatelet drugs.

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Clopidogrel; Hemorrhage; Humans; Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Ticlopidine

Regional variations exist in the epidemiology of peripheral artery disease (PAD), in comorbidities, use of secondary prevention, and outcomes. Large studies of these variations in worldwide populations are rare. The EUCLID (Examining Use of tiCagreLor In peripheral artery Disease) trial included 13,885 patients with PAD from four geographical regions (Central/South America, Europe, Asia, North America) and compared monotherapy with ticagrelor and clopidogrel. Inclusion criteria were either an ankle-brachial index < 0.80 or a prior revascularization. The primary efficacy endpoint was time to first occurrence of any event in the composite of cardiovascular death, myocardial infarction, or ischemic stroke and did not differ between the study arms. This post hoc analysis of EUCLID confirmed that regional differences occurred in the inclusion criteria with more prior revascularization in North America (73.9%) and Asia (72.5%) compared with Central/South America (34.0%) and Europe (51.6%). The characteristics of patients also differed. Prior amputation at baseline was most frequent in Central/South America (6.3%) compared with other regions (1.6-2.8%). A history of stroke was most common in Asia, coronary heart disease in North America, and diabetes in Central/South America compared with other regions. The incidence of outcomes in patients with PAD varied by region. North America had the highest rate of the primary combined endpoint (5.97 events/100 patient-years). Corresponding rates were 4.80, 3.95, and 3.87 for Asia, Europe, and Central/South America, respectively. Hospitalization for acute limb ischemia (events/100 patient-years) was most frequent in Europe (0.75) and North America (0.74) compared with Asia (0.60) and Central/South America (0.33). Adjustment for inclusion criteria and relevant PAD characteristics did not have a major impact on these regional differences. Further adjustment for concomitant disease, risk factors, and preventive medication modified the regional differences only marginally. In conclusion, substantial regional differences were found in cardiovascular and limb outcomes in patients with PAD and were not explained by variation in the category of included patients, concomitant disease, risk factors, and prevention. Such differences, which may be due to variation in other factors such as background population rates or clinical care, need to be considered when designing and interpreting large international studies (

Topics: Clopidogrel; Humans; Internationality; Ischemia; Ischemic Stroke; Myocardial Infarction; Peripheral Arterial Disease; Ticagrelor; Treatment Outcome

Peripheral artery disease (PAD) is associated with increased risk of mortality, cardiovascular morbidity, and major amputation. Data on major amputation from a large randomized trial that included a substantial cohort of patients without critical limb ischemia (CLI) have not been described. The objective was to describe the incidence and types of amputations in the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease) population, subcategorize amputations in the CLI versus no CLI cohorts, and describe the events surrounding major amputation.. Postrandomization major amputation was analyzed in the EUCLID trial. Patients were stratified by baseline CLI status. The occurrence of major amputation was ascertained and defined as the highest level. Perioperative events surrounding major amputation were obtained including acute limb ischemia, revascularization, and all-cause mortality. All variables were assessed for significance in univariable and multivariable models. The rate of major amputation during the course of the trial was 1.6% overall, 8.4% in the CLI at baseline group, and 1.2% in the no CLI at baseline group. The annualized rate of major amputation was 0.6% in PAD overall, 3.9% in the CLI at baseline group, and 0.5% in the no CLI at baseline group. Several factors were associated with increased risk of major amputation, including history of amputation, the presence of diabetes mellitus, baseline Rutherford category 4 to 6, and an ankle-brachial index <0.8. Factors associated with a lower risk for major amputation included prior statin use. The 30-day mortality rate after major amputation was 6.5% overall, 5.6% in the CLI at baseline group, and 6.8% in the no CLI at baseline group. The annual mortality rate following major amputation was 22.8% in the CLI at baseline group and 16.0% in the no CLI at baseline group.. The risk factors for major amputation in EUCLID patients are similar to previous large registries' reports except for diabetes mellitus in patients with CLI. The mortality following major amputation is lower in the EUCLID trial compared with registry data. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01732822.

Topics: Aged; Amputation, Surgical; Critical Illness; Female; Humans; Incidence; Ischemia; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Patients with peripheral artery disease (PAD) are at high risk for myocardial infarction (MI).. To characterize the incidence and types of MI in a PAD population, identify factors associated with MI, and determine the association of MI with cardiovascular mortality and acute limb ischemia.. The Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID) was a double-blind randomized clinical trial conducted at 811 sites in 28 countries that randomized 13 885 patients with symptomatic PAD to monotherapy with ticagrelor or clopidogrel. Participants had an ankle-brachial index (ABI) of 0.80 or less or previous lower extremity revascularization. Median follow-up was 30 months. For these analyses, patients were evaluated for MI occurrence during follow-up irrespective of treatment. Data were analyzed from June 2017 to September 2018.. An adjudication clinical events committee classified MI as type 1 (spontaneous), type 2 (secondary), type 3 (sudden cardiac death), type 4a (less than 48 hours after percutaneous coronary intervention), type 4b (definite stent thrombosis), or type 5 (less than 72 hours after coronary artery bypass graft). A multivariate regression model was developed by stepwise selection to identify factors associated with MI, and a time-dependent multivariate Cox regression analysis was performed to determine the association of MI with cardiovascular death and acute limb ischemia requiring hospitalization.. Of the 13 885 patients included in this analysis, 9997 (72.0%) were male, and the median (interquartile range) age was 66 (60-73) years. Myocardial infarction occurred in 683 patients (4.9%; 2.4 events per 100 patient-years) during a median follow-up of 30 months. Patients experiencing MI were older (median [interquartile range] age, 69 [62-75] vs 66 [60-72] years), more likely to have diabetes (349 of 683 [51.1%] vs 4996 of 13 202 [37.8%]) or a previous lower extremity revascularization (466 of 683 [68.2%] vs 7409 of 13 202 [56.1%]), and had a lower ABI (if included by ABI) compared with censored patients. Of the 683 patients with MI during follow-up, the most common MI type was type 1 (405 [59.3%]), followed by type 2 (236 [34.6%]), type 4a (14 [2.0%]), type 3 (12 [1.8%]), type 4b (11 [1.6%]), and type 5 (5 [0.7%]). Postrandomization MI was independently associated with cardiovascular death (adjusted hazard ratio, 9.0; 95% CI, 7.3-11.2; P < .001) and acute limb ischemia requiring hospitalization (adjusted hazard ratio, 2.5; 95% CI, 1.3-5.0; P = .008).. Approximately 5% of patients with symptomatic PAD had an MI during a median follow-up of 30 months. Type 1 MI (spontaneous) was the most common MI type; however, one-third of MIs were type 2 MI (secondary). More research is needed to identify therapies to reduce the risk of MI in patients with PAD and to improve management of type 2 MI.. ClinicalTrials.gov Identifier: NCT01732822.

Topics: Aged; Ankle Brachial Index; Clopidogrel; Coronary Artery Bypass; Death; Extremities; Female; Hospitalization; Humans; Incidence; Ischemia; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor

Physician behavior in response to knowledge of a patient's CYP2C19 clopidogrel metabolizer status is unknown.. To investigate the association of mandatory reporting of CYP2C19 pharmacogenomic testing, provided to investigators with no direct recommendations on how to use these results, with changes in P2Y12 inhibitor use, particularly clopidogrel, in the Randomized Trial to Compare the Safety of Rivaroxaban vs Aspirin in Addition to Either Clopidogrel or Ticagrelor in Acute Coronary Syndrome (GEMINI-ACS-1) clinical trial.. The GEMINI-ACS-1 trial compared rivaroxaban, 2.5 mg twice daily, with aspirin, 100 mg daily, plus open-label clopidogrel or ticagrelor (provided), in patients with recent acute coronary syndromes (ACS). The trial included 371 clinical centers in 21 countries and 3037 patients with ACS. Data were analyzed between May 2017 and February 2019.. Investigators were required to prestipulate their planned response to CYP2C19 metabolizer status. In response to a regulatory mandate, results for all patients were reported to investigators approximately 1 week after randomization.. Reasons for switching P2Y12 inhibitors and occurrence of bleeding and ischemic events were collected.. Of 3037 patients enrolled (mean [SD] age, 62.8 [9.0] years; 2275 men [74.9%], and 2824 white race/ethnicity [93.0%]), investigators initially treated 1704 (56.1%) with ticagrelor and 1333 (43.9%) with clopidogrel. Investigators prestipulated that they would use CYP2C19 metabolizer status to change P2Y12 inhibitor in 48.5% of genotyped clopidogrel-treated patients (n = 642 of 1324) and 5.5% of genotyped ticagrelor-treated patients (n = 93 of 1692). P2Y12 inhibitor switching for any reason occurred in 197 patients and was more common in patients treated with ticagrelor (146 of 1704 [8.6%]) compared with clopidogrel (51 of 1333 [3.8%]). Of patients initially treated with ticagrelor, only 1 (0.1% overall; 0.7% of all who switched) was switched based on CYP2C19 status. Of patients initially treated with clopidogrel, 23 (1.7% overall,;45.1% of all who switched) were switched owing to metabolizer status. Of 48 patients (3.6%) with reduced metabolizer status treated initially with clopidogrel, 15 (31.3%) were switched based on metabolizer status, including 48.1% (13 of 27) in which switching was prestipulated.. Physicians were evenly split on how to respond to knowledge of CYP2C19 metabolizer status in clopidogrel-treated patients. Mandatory provision of this information rarely prompted P2Y12 inhibitor switching overall, including a minority of patients with reduced metabolizer status. These findings highlight the clinical equipoise among physicians regarding use of this information and the reluctance to use information from routine genotyping in the absence of definitive clinical trial data demonstrating the efficacy of this approach.. ClinicalTrials.gov identifier: NCT02293395.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Administration Schedule; Drug Substitution; Drug Therapy, Combination; Hemorrhage; Humans; Ischemia; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Ticagrelor

Acute limb ischemia (ALI) is an important clinical event and an emerging cardiovascular clinical trial outcome. Risk factors for and outcomes after ALI have not been fully evaluated.. EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized patients with peripheral artery disease to ticagrelor versus clopidogrel. Enrollment criteria included an ankle-brachial index ≤0.80 or previous lower extremity revascularization. Patients were grouped according to the primary outcome, postrandomization ALI hospitalization. Baseline factors associated with ALI were identified using Cox proportional hazards modeling. Models with ALI hospitalization as a time-dependent covariate were developed for secondary outcomes of major adverse cardiovascular events (myocardial infarction, cardiovascular death, ischemic stroke), all-cause mortality, and major amputation.. Among 13 885 patients, 1.7% (n=232) had 293 ALI hospitalizations (0.8 per 100 patient-years). Patients with versus without ALI were younger and more often had previous peripheral revascularization and lower baseline ankle-brachial index. Treatment during ALI hospitalization included endovascular revascularization (39.2%, n=115), surgical bypass (24.6%, n=72), and major amputation (13.0%, n=38). After multivariable adjustment, any previous peripheral revascularization (Hazard Ratio [HR] 4.7, 95% CI 3.3-6.8, P<0.01), baseline atrial fibrillation (HR 1.8, 95% CI 1.1-3.2, P=0.03), and baseline ankle-brachial index ≤0.60 (HR 1.3 per 0.10 decrease, 95% CI 1.1-1.5, P<0.01) were associated with higher ALI risk. Older age (HR 0.8 per 10-year increase, 95% CI 0.7-1.0, P=0.02) and baseline statin use (HR 0.7, 95% CI 0.5-0.9, P<0.01) were associated with lower risk for ALI. There was no relationship between randomized treatment to ticagrelor or clopidogrel and ALI. Among patients with previous revascularization, surgical versus endovascular procedures performed more than 6 months prior were associated with ALI (adjusted HR 2.63, 95% CI 1.75-3.96). In the overall population, ALI hospitalization was associated with subsequent MACE (adjusted HR 1.4, 95% CI 1.0-2.1, P=0.04), all-cause mortality (adjusted HR 3.3, 95% CI 2.4-4.6, P<0.01), and major amputation (adjusted HR 34.2, 95% CI 9.7-20.8, P<0.01).. Previous peripheral revascularization, baseline atrial fibrillation, and lower ankle-brachial index identify peripheral artery disease patients at heightened risk for ALI, an event associated with subsequent cardiovascular and limb-related morbidity and mortality.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01732822.

Topics: Acute Disease; Aged; Double-Blind Method; Female; Hospitalization; Humans; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Ticagrelor

Critical limb ischaemia (CLI) implies an increased risk of cardiovascular morbidity and mortality, and the optimal antithrombotic treatment is not established.. The EUCLID trial investigated the effect of monotherapy with ticagrelor versus clopidogrel in 13,885 patients with peripheral artery disease (PAD); the primary endpoint was cardiovascular death, myocardial infarction, or ischaemic stroke. Patients planned for revascularisation or amputation within 3 months, were excluded. This analysis focuses on the subgroup with CLI, defined by rest pain (58.8%), major (9.0%) or minor (32.2%) tissue loss.. In EUCLID, 643 patients (4.6%) had CLI at baseline. Diabetes mellitus was more common in the CLI group, while coronary disease, carotid disease, and hypertension were more common in the non-CLI group. A majority of CLI patients (62.1%) had only lower extremity PAD. In patients enrolled on the ankle brachial index (ABI) criteria, ABI was 0.55 ± 0.21 (mean ± SD) for those with CLI versus 0.63 ± 0.15 for those without CLI. The primary efficacy endpoint significantly increased among patients with CLI compared with those without CLI with a rate of 8.85 versus 4.28/100 patient years (adjusted for baseline characteristics hazard ratio [HR] 1.43 [95% CI 1.16-1.76]; p = 0.0009). When acute limb ischaemia requiring hospitalisation was added to the model, significant differences remained (adjusted HR 1.38, [95% CI 1.13-1.69]; p = 0.0016). The 1 year mortality was 8.9%. A trend towards increased lower limb revascularisation among those with CLI was observed. Bleeding (TIMI major, fatal, intracranial) did not differ between those with and without CLI.. Nearly 5% of patients enrolled in EUCLID had CLI at baseline. Milder forms of CLI dominated, a result of the trial design. Patients with CLI had a significantly higher rate of cardiovascular mortality and morbidity versus those without CLI. Further efforts are required to reduce the risk of cardiovascular events in PAD, especially in patients with CLI. CLINICALTRIALS.GOV: NCT01732822.

Topics: Adenosine; Aged; Clopidogrel; Female; Hospitalization; Humans; Hypertension; Incidence; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Proportional Hazards Models; Prospective Studies; Purinergic P2Y Receptor Antagonists; Risk Factors; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome; Vascular Surgical Procedures

Topics: Aged; Blood Platelets; Clopidogrel; Female; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stents; Thrombosis; Ticagrelor; Time Factors; Treatment Outcome

Diabetes confers an increased risk for atherosclerotic cardiovascular disease, but less is known about the independent risk diabetes confers on major cardiovascular and limb events in patients with symptomatic peripheral artery disease (PAD) on contemporary management.. The authors sought to assess the risk of cardiovascular and limb events in patients with PAD and diabetes as compared with those with PAD alone.. In the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial, 13,885 patients with symptomatic PAD were evaluated with a primary endpoint of an adjudicated composite of major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, ischemic stroke) followed over a median of ∼30 months. The diabetes subgroup was analyzed compared with the subgroup without diabetes, and further examined for diabetes-specific factors such as glycosylated hemoglobin (HbA. A total of 5,345 patients (38.5%) had diabetes; the majority (n = 5,134 [96.1%]) had type 2 diabetes. The primary endpoint occurred in 15.9% of patients with PAD and diabetes as compared with 10.4% of those without diabetes (absolute risk difference 5.5%; adjusted hazard ratio: 1.56; 95% confidence interval [CI]: 1.41 to 1.72; p < 0.001). Every 1% increase in HbA. Patients with PAD and diabetes are at high risk for cardiovascular and limb ischemic events, even on contemporary therapies. Every 1% increase in HbA

Topics: Aged; Diabetes Mellitus, Type 2; Female; Humans; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease.. In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months.. The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49).. In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).

Topics: Adenosine; Aged; Cardiovascular Diseases; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Leg; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI).. This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI.. PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up.. A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026).. Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562).

Topics: Adenosine; Aged; Aspirin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hemorrhage; Humans; Ischemia; Lower Extremity; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Stroke; Ticagrelor; Vascular Grafting

Topics: Adenosine; Clopidogrel; Coronary Artery Disease; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Ischemia; Male; Platelet Aggregation Inhibitors; Proportional Hazards Models; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

The role of platelets during myocardial ischemia/reperfusion (I/R) is ambivalent. They contribute to injury but also to cardioprotection. Repeated blood flow restriction and reperfusion in a tissue/organ remote from the heart (remote ischemic conditioning, RIC) reduce myocardial I/R injury and attenuate platelet activation. Whether or not platelets mediate RIC's cardioprotective signal is currently unclear.. Platelets serve as carriers for RIC's cardioprotective signal through an aspirin-sensitive and thus cyclooxygenase-dependent mechanism. The P2Y

Topics: Animals; Aspirin; Dialysis Solutions; Humans; Infarction; Ischemia; Rats; Ticagrelor

The first 3 months after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) is a high-risk period for adverse events, including ischemic and bleeding events, which decrease greatly with time. It is worth investigating whether the use of potent P2Y12 inhibitors is necessary after the early stage. The purpose of this study was to investigate the differences in clinical outcomes between clopidogrel and ticagrelor in stable patients without ischemic or major bleeding events during the first 3 months after PCI.. Data for this study were obtained from the PHARM-ACS registry (NCT04184583). Patients who were free from ischemic and major bleeding events in the first 3 months after PCI were enrolled. Inverse probability of treatment weighting (IPTW) and Cox proportional hazards model were applied to compare the differences in clinical outcomes between the 2 groups. Major adverse cardiovascular and cerebrovascular events (MACCE) were considered the primary end point, and major bleeding was considered the secondary end point.. A total of 6662 patients were included in this study. Of these, 3465 were treated with clopidogrel plus aspirin (clopidogrel group) and 3197 with ticagrelor plus aspirin (ticagrelor group). There were no significant differences in MACCE after IPTW adjustment for baseline variables (IPTW-adjusted HR, 1.06; 95% CI, 0.90-1.25) or major bleeding events (IPTW-adjusted HR, 0.97; 95% CI, 0.67-1.41) between the 2 groups. However, the incidence of minor bleeding in the clopidogrel group was significantly lower than that in the ticagrelor group (IPTW-adjusted HR, 0.65; 95% CI, 0.59-0.71).. In patients with ACS who were free from ischemic or major bleeding events during the first 3 months after PCI, the subsequent clopidogrel treatment might reduce minor bleeding events without increasing the risk of MACCE compared with ticagrelor. However, the results still need to be confirmed by large randomized controlled studies in the future.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Ticagrelor; Treatment Outcome

Randomized trials have shown superiority of the novel P2Y12 inhibitors over clopidogrel in patients with acute coronary syndrome (ACS), but clinical benefit in the community remains controversial. Our objective was to compare the safety and efficacy of clopidogrel to ticagrelor and prasugrel in patients with ACS undergoing percutaneous coronary intervention (PCI) in a real-world population.. We conducted a retrospective cohort study of patients with ACS who underwent PCI and were discharged with clopidogrel, ticagrelor, or prasugrel from 2012 to 2018 within Kaiser Permanente Northern California. We used Cox proportional hazard models with propensity-score matching to evaluate the association of the P2Y12 agent with the primary outcomes of all-cause mortality, myocardial infarction (MI), stroke, and bleeding events.. The study included 15,476 patients (93.1% on clopidogrel, 3.6% on ticagrelor and 3.2% on prasugrel). Compared to the clopidogrel group, ticagrelorand prasugrel patients were younger with less comorbidities. In multivariable models with propensity-score matching, we found a lower risk of all-cause mortality in the ticagrelor vs the clopidogrel group (HR (95% CI) 0.43 (0.20-0.92)), but no differences in the other endpoints, and no difference between prasugrel and clopidogrel among any endpoints. A larger proportion of patients on ticagrelor or prasugrel switched to an alternative P2Y12 agent vs. clopidogrel (. Among patients with ACS who underwent PCI, we observed a lower risk of all-cause mortality in patients treated with ticagrelor vs clopidogrel, but no difference in other clinical endpoints nor any differences in endpoints between prasugrel vs. clopidogrel users. These results suggest that further study is needed to identify an optimal P2Y12 inhibitor in a real-world population.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor; Treatment Outcome

Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR.. This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score ≥25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect.. We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

Topics: Clopidogrel; Hemorrhage; Humans; Ischemia; Myocardial Infarction; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

To investigate the effect of different DAPTs in patients with ACS undergoing PCI, and to identify the most efficient DAPT to reduce the risk of ischemia and bleeding after PCI. Between March 2017 and December 2021, 1598 patients with ACS who underwent PCI were included in the study. The DAPT protocol included the clopidogrel group (aspirin 100 mg + clopidogrel 75 mg), ticagrelor group (aspirin 100 mg + ticagrelor 90 mg), de-escalation Group 1 (reduced dose of ticagrelor [from 90 mg to 60 mg]) after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]), and de-escalation Group 2 (switched from ticagrelor to clopidogrel after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]). All patients received a 12-month follow-up. The primary endpoint was net adverse clinical events (NACEs) that included the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, stroke, and bleeding events. There were 2 secondary endpoints, major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding. No statistically significant difference was found in the incidence of NACEs between the 4 groups at the average 12-month follow-up (15.7% vs 19.2% vs 16.7% vs 20.4%). Cox regression analysis revealed that DAPT ticagrelor group regimen (hazard ratio [HR] 0.547; 95% confidence interval [CI]: 0.334-0.896; P  = .017) were associated with a lower risk of MACCEs. Age (HR 1.024; 95% CI: 1.003-1.046; P  = .022). DAPT de-escalation Group 2 regimen (HR 1.665; 95% CI: 1.001-2.767; P  = .049) were marginally associated with a higher risk of MACCEs. Ticagrelor group regimen (HR 1.856; 95% CI: 1.376-2.504; P  < .001) was associated with higher risk of bleeding events. Ticagrelor group regimen (HR 1.606; 95% CI: 1.179-2.187; P  = .003) were associated with a higher risk of minor bleeding events. For patients with ACS underwent PCI, there were no significant difference in the incidence of NACEs between 3 and 12 months after PCI between de-escalation and non-de-escalation therapies. Compared with ticagrelor-based 12-month DAPT, there was no significant difference in MACCEs and bleeding events in patients receiving de-escalation treatment (ticagrelor reduction from 90 to 60 mg, 3 months after PCI).

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

To evaluate potential gains in outcomes from ticagrelor-based strategy according to risk stratification by Global Registry of Acute Coronary Events (GRACE) score.. A total of 19,704 patients discharged alive post-acute coronary syndrome who underwent percutaneous coronary intervention and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, composed of cardiac death, myocardial infarction, and/or stroke. Secondary outcomes included all-cause mortality and Bleeding Academic Research Consortium type 2 to 5 and 3 to 5 bleeding.. The ticagrelor group comprised 6432 (32.6%) patients and the clopidogrel group comprised 13,272 (67.4%) patients. During the follow-up period, there was a significant reduction in the incidence of ischemic events in patients treated using ticagrelor who had excessive risk of bleeding. According to the GRACE score, among low-risk patients, ticagrelor use compared with clopidogrel was not associated with decreased ischemic events (HR, 0.82; 95% CI, 0.57 to 1.17; P=.27) with excessive risk of Bleeding Academic Research Consortium type 3 to 5 bleeding (HR, 1.59; 95% CI, 1.16 to 2.17; P=.004). The risk of ischemic events (HR, 0.60; 95% CI, 0.41 to 0.89; P=.01) were lower in the intermediate- to high-risk patients treated with ticagrelor without significant difference in BARC type 3 to 5 bleeding risk (HR, 1.11; 95% CI, 0.75 to 1.65; P=.61).. There was still a gap between guideline-indicated therapy and the clinical practice in a sizable subset of patients with acute coronary syndrome who underwent percutaneous coronary intervention. The GRACE risk score could identify patients who would derive benefit from the ticagrelor-based antiplatelet strategy.

Topics: Acute Coronary Syndrome; China; Clopidogrel; Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Risk Factors; Ticagrelor; Treatment Outcome

To date, no studies have specifically examined the efficacy of P2Y12 inhibitor monotherapy in patients with acute coronary syndrome (ACS) exhibiting a high risk of gastrointestinal (GI) bleeding following percutaneous coronary intervention (PCI). This was a retrospective cohort study of ACS exhibiting a high GI bleeding risk after PCI admitted to the Affiliated Hospital of the Jiangnan University from August 2016 to December 2019. Of the 308 enrolled patients, 269 were found eligible and were assigned to the ticagrelor monotherapy (TIC) arm (n = 128) and to ticagrelor plus aspirin (TIC + ASP) arm (n = 141) treatment for a 1-year period. The primary study outcome was a composite end point, including bleeding academic research consortium (BARC) type 2, 3, or 5 bleeding and adverse cardiac or cerebrovascular events; 8 (6.3%) in the TIC group and 14 (9.9%) in the combination treatment group reached the primary ischemic end point within 1 year with no significant difference between these groups. BARC type 2, 3, and 5 bleeding events affected significantly more patients in the combination group relative to the TIC group (38 [27.0%] vs. 11 [8.6%], P < 0.001). As the follow-up interval was prolonged, the cumulative BARC type 2, 3, and 5 bleeding incidence in the TIC group remained significantly below than that in the combination treatment group ( P < 0.05). These results indicate that TIC is associated with a lower risk of clinically relevant bleeding events among ACS with a high risk of GI bleeding after PCI relative to combination TIC + ASP treatment, although ischemic outcomes in these 2 groups were similar.

Topics: Acute Coronary Syndrome; Aspirin; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor; Treatment Outcome

It is unknown whether there are age- and gender-related differences in the safety and efficacy of potent P2Y12 inhibitors in East Asian populations with a different bleeding or ischemic propensity. Using data from the TICAKOREA (Ticagrelor Versus Clopidogrel in Asian/Korean Patients with ACS Intended for Invasive Management) trial comparing ticagrelor versus clopidogrel for 800 Korean patients with acute coronary syndrome, the safety and efficacy outcomes were compared according to age (<75 vs ≥75 years) and gender (men vs women). The primary bleeding end point was clinically significant bleeding, and the primary ischemic end point was a major adverse cardiovascular event (MACE) at 12 months. The incidences of clinically significant bleeding were significantly higher after ticagrelor than after clopidogrel in patients aged <75 years (adjusted hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.40 to 4.67) but not in patients aged ≥75 years (adjusted HR 1.1, 95% CI 0.40 to 3.38). The incidences of MACEs were significantly higher after ticagrelor than after clopidogrel in patients aged ≥75 years (adjusted HR 6.14, 95% CI 1.40 to 26.90) but not in patients aged <75 years (adjusted HR 0.93, 95% CI 0.50 to 1.73). The incidences of clinically significant bleeding were significantly higher after ticagrelor than after clopidogrel in men (adjusted HR 2.69, 95% CI 1.38 to 5.24) but not in women (adjusted HR 1.49, 95% CI 0.64 to 3.46). The adjusted risks of MACEs after ticagrelor or clopidogrel were not significantly different between men and women. In conclusion, there were substantial age- and gender-related differences in bleeding and ischemic outcomes after ticagrelor or clopidogrel in Korean patients with acute coronary syndrome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT02094963.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; East Asian People; Female; Hemorrhage; Humans; Ischemia; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

The goal of this work was to investigate the short-term time-course benefit and risk of ticagrelor with aspirin in acute mild-moderate ischemic stroke or high-risk TIA in The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial.. In an exploratory analysis of the THALES trial, we evaluated the cumulative incidence of irreversible efficacy and safety outcomes at different time points during the 30-day treatment period. The efficacy outcome was major ischemic events defined as a composite of ischemic stroke or nonhemorrhagic death. The safety outcome was major hemorrhage defined as a composite of intracranial hemorrhage and fatal bleedings. Net clinical impact was defined as the combination of these 2 endpoints.. This analysis included a total of 11,016 patients (5,523 in the ticagrelor-aspirin group, 5,493 in the aspirin group) with a mean age of 65 years, and 39% were women. The reduction of major ischemic events by ticagrelor occurred in the first week (4.1% vs 5.3%; absolute risk reduction 1.15%, 95% CI 0.36%-1.94%) and remained throughout the 30-day treatment period. An increase in major hemorrhage was seen during the first week and remained relatively constant in the following weeks (absolute risk increase ≈0.3%). Cumulative analysis showed that the net clinical impact favored ticagrelor-aspirin in the first week (absolute risk reduction 0.97%, 95% CI, 0.17%-1.77%) and remained constant throughout the 30 days.. In patients with mild-moderate ischemic stroke or high-risk TIA, the treatment effect of ticagrelor-aspirin was present from the first week. The ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the treatment period, which may support the use of 30-day treatment with ticagrelor and aspirin in these patients.. This study provides Class II evidence that, for patients with mild-moderate ischemic stroke or high-risk TIA, the ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the 30-day treatment period.

Topics: Aged; Aspirin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Ischemia; Ischemic Attack, Transient; Ischemic Stroke; Male; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

In patients with prior myocardial infarction (MI) on aspirin, the addition of ticagrelor reduces ischaemic risk but increases bleeding risk. The simultaneous assessment of baseline ischaemic and bleeding risk may assist clinicians in selecting patients who are most likely to have a favourable risk/benefit profile with long-term ticagrelor.. PEGASUS-TIMI 54 randomized 21 162 prior MI patients, 13 956 of which to the approved 60 mg dose or placebo and who had all necessary data. The primary efficacy endpoint was cardiovascular death, MI, or stroke, and the primary safety outcome was TIMI major bleeding; differences in Kaplan-Meier event rates at 3 years are presented. Post-hoc subgroups based on predictors of bleeding and ischaemic risk were merged into a selection algorithm. Patients were divided into four groups: those with a bleeding predictor (n = 2721, 19%) and then those without a bleeding predictor and either 0-1 ischaemic risk factor (IRF; n = 3004, 22%), 2 IRF (n = 4903, 35%), or ≥3 IRF (n = 3328, 24%). In patients at high bleeding risk, ticagrelor increased bleeding [absolute risk difference (ARD) +2.3%, 95% confidence interval (CI) 0.6, 3.9] and did not reduce the primary efficacy endpoint (ARD +0.08%, 95% CI -2.4 to 2.5). In patients at low bleeding risk, the ARDs in the primary efficacy endpoint with ticagrelor were -0.5% (-2.2, 1.3), -1.5% (-3.1, 0.02), and -2.6% (-5.0, -0.24, P = 0.03) in those with ≤1, 2, and 3 risk factors, respectively (P = 0.076 for trend across groups). There were significant trends for greater absolute risk reductions for cardiovascular death (P-trend 0.018), all-cause mortality (P-trend 0.027), and net outcomes (P-trend 0.037) with ticagrelor across these risk groups.. In a post-hoc exploratory analysis of patients with prior MI, long-term ticagrelor therapy appears to be best suited for those with prior MI with multiple IRFs at low bleeding risk.. NCT01225562 ClinicalTrials.gov.

Topics: Adenosine; Hemorrhage; Humans; Ischemia; Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Secondary Prevention; Ticagrelor; Treatment Outcome

Studies on ischemia/reperfusion injury remain the focus of interest. Ticagrelor and enoxaparin, which are antiaggregant and anticoagulant drugs developed for use in many cardiovascular pathologies, are still included in many ischemia/reperfusion studies. Remarkably, their new protective effects, especially with regard to ticagrelor, continue to be reported in the current literature. The aim of this study was to evaluate the beneficial effects of ticagrelor and enoxaparin pretreatments on the rat heart with histological and immunohistochemical markers in an ischemia/reperfusion model.. Wistar-albino rats (weighing 350-400 g) were divided into four groups as follows: Sham-Control (Group 1), Control-Saline+ischemia/reperfusion (Group 2), Ticagrelor+ischemia/reperfusion (Group 3), and Enoxaparin+ischemia/reperfusion (Group 4). The ischemia/reperfusion injury model was applied to Group 2, Group 3 and Group 4. Heart tissue sections were stained with hematoxylin and eosin for histological examinations. Caspase 3 immunostaining was evaluated to detect apoptosis in the heart tissue sections.. Both pretreatments ameliorated the ischemic damage but especially tissue sections belonging to Group 3 were nearly similar to control levels. The results indicated that ischemia/reperfusion-induced myocardial damage was significantly increased in Group 2, whereas ticagrelor and enoxaparin pretreatments in Group 3 and Group 4 significantly decreased apoptotic scores and the histological appearance of the Group 3 close to the normal myocardium (p<0.001).. As supported by histological findings in our study, ticagrelor and enoxaparin have protective properties for heart tissue in this ischemia/reperfusion injury model.

Topics: Animals; Apoptosis; Enoxaparin; Ischemia; Rats; Rats, Wistar; Reperfusion; Ticagrelor

Postischemic inflammation induces angiogenesis, while platelet P2Y. Laser Doppler perfusion imaging and capillary density measurement were used for angiogenesis quantified. Immunofluorescence was used to detect the level of CD31. The mice muscle was harvested for enzyme-linked immunosorbent (ELISA) assay of interleukin- (IL) 10 activity and Western blot determination of vascular endothelial growth factor (VEGF) production.. The study underscores that the effect of ticagrelor antiangiogenic function is related with the higher IL-10 expression.

Topics: Angiogenesis Inducing Agents; Animals; Capillaries; Hindlimb; Interleukin-10; Ischemia; Male; Mice, Inbred C57BL; Muscles; Neovascularization, Physiologic; Perfusion; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Vascular Endothelial Growth Factors

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Guanine Nucleotide Exchange Factors; Ischemia; Kidney Function Tests; Male; Purinergic P2Y Receptor Antagonists; rap1 GTP-Binding Proteins; Rats; Rats, Wistar; Renal Circulation; Reperfusion Injury; Signal Transduction; Ticagrelor

Critical limb-threatening ischemia (CLTI) is associated with an increased risk of major adverse limb events and mortality. High on-treatment platelet reactivity (HPR) is associated with an increased risk of ischemic events, while low on-treatment platelet reactivity (LPR) is associated with an increased risk of bleeding. This study investigates the frequency with which patients with CLTI on clopidogrel or ticagrelor achieve a "therapeutic window" (TW) of platelet inhibition.. Data from the "Switch To Ticagrelor in Critical Limb Ischemia Anti-Platelet Study" were assessed retrospectively to determine the incidence of TW of on-treatment platelet reactivity in 50 consecutive patients with CLTI (mean age: 65.2 ± 10.5 years, 54% male). The data included 4 measurements of patients' platelet reactivity using the VerifyNow P2Y12 Assay: baseline and steady state platelet reactivity on clopidogrel 75 mg daily and on ticagrelor 90 mg twice daily.. At baseline, 46% of patients on clopidogrel were within TW of on-treatment platelet reactivity compared to 10% of patients on ticagrelor (. Although ticagrelor has been proposed as an alternative for patients with HPR on clopidogrel, the current study observes an excess of platelet inhibition with ticagrelor in most patients with CLTI at a dose of 90 mg twice daily.

Topics: Aged; Clopidogrel; Critical Illness; Drug Administration Schedule; Drug Monitoring; Female; Humans; Ischemia; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; Ticagrelor; Time Factors; Treatment Outcome

The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies.. BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup.. A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively).. In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Female; Hemorrhage; Humans; Ischemia; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Recurrence; Registries; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors

Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention.. To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice.. A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019.. Ticagrelor vs clopidogrel.. The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis.. After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group.. Among patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Algorithms; Aspirin; Case-Control Studies; Cause of Death; Clopidogrel; Databases, Factual; Dyspnea; Female; Hemorrhage; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Network Meta-Analysis; Percutaneous Coronary Intervention; Propensity Score; Purinergic P2Y Receptor Antagonists; Recurrence; Republic of Korea; Retrospective Studies; Stroke; Ticagrelor; United States

Clinical outcomes in acute coronary syndrome patients treated with P2Y. We examined clinical outcomes in acute coronary syndrome patients in relation to the timing of CABG following P2Y. Among 508 patients (95 ticagrelor, 413 clopidogrel), the timing of CABG following P2Y. CABG within 72 h after P2Y

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Case-Control Studies; Clopidogrel; Coronary Angiography; Coronary Artery Bypass; Female; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Postoperative Hemorrhage; Prospective Studies; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Time Factors; Treatment Outcome; Withholding Treatment

The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy (DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry.. Retrospective multicenter study with voluntary participation of 11 centers in 6 European countries. We studied 4310 patients with ACS discharged with DAPT with ticagrelor or prasugrel. Ischemic events were defined as stent thrombosis or spontaneous myocardial infarction, and hemorrhagic events as BARC (Bleeding Academic Research Consortium) type 3 or 5 bleeding. Discrimination and calibration were calculated for both PARIS scores (PARIS. During a period of 17.2 ± 8.3 months, there were 80 ischemic events (1.9% per year) and 66 bleeding events (1.6% per year). PARIS. In patients with ACS treated with DAPT with ticagrelor or prasugrel, the PARIS model helps to properly evaluate the ischemic-hemorrhagic risk.

Topics: Acute Coronary Syndrome; Aged; Dose-Response Relationship, Drug; Drug Therapy, Combination; Europe; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Ischemia; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Retrospective Studies; Risk Assessment; Ticagrelor; Treatment Outcome

Coronary artery disease is the top cause of death among the Chinese population. With the establishment of a Chinese prediction model, it is urgent to assess factors related to the prognosis of patients with acute coronary syndrome at extremely high risk.. In this retrospective study, we enrolled 601 patients assessed as being of extremely high risk, according to specific criteria from the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk) project, and investigated various clinical parameters using Cox multivariate analysis to establish a risk nomogram. C-index and calibration curves were involved to assess the internal identification. By using the all-cause death risk model, we stratified patients by risk level and compared the effects of clopidogrel and ticagrelor on end points.. We identified several factors, including body mass index, angiopathy, smoking status, β-blocker usage, history of myocardial infarction, total number of stents, and usage of antiplatelet agents, related to ischemic end points, all-cause death, cardiovascular events, and cardiac death. A C-index of >0.7 and the calibration curve demonstrated good concordance. In a subsequent analysis, we used the all-cause death model to stratify patients by risk level, and compared the effects of clopidogrel and ticagrelor. In the subgroup with a 2-year death rate of >50%, ticagrelor showed a positive effect (P = 0.045), but in the subgroup with a 2-year death rate of <50%, the difference between clopidogrel and ticagrelor was not significant. Considering the duration of effect of antiplatelet agents, we also compared these 2 agents at 1-year follow up, with ticagrelor showing no advantage.. We determined the probability of ischemic risk in patients at extremely high ischemic risk and developed new risk models for this specific group. Ticagrelor, compared with clopidogrel, may improve the prognosis of patients at high risk for death after 2 years.

Topics: Acute Coronary Syndrome; Aged; China; Clopidogrel; Female; Humans; Ischemia; Male; Middle Aged; Models, Biological; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prognosis; Risk; Ticagrelor

Topics: Humans; Inflammation; Ischemia; Purinergic P2Y Receptor Antagonists; Ticagrelor

There are few data on ticagrelor in Asian patients. This study evaluated clinical outcomes with ticagrelor and clopidogrel in Taiwanese patients with acute myocardial infarction (AMI).Methods and Results:We used the Taiwan National Health Insurance Research Database to identify 27,339 AMI patients aged ≥18 years between January 2012 and December 2014, and only patients who survived greater than or equal to 30 days after AMI and took dual antiplatelet therapy were included. Cohorts of ticagrelor and clopidogrel were matched 1:8, based on propensity score matching, to balance baseline covariates. The primary efficacy endpoints were death from any cause, AMI, or stroke. The safety endpoints consisted of major gastrointestinal bleeding or intracerebral hemorrhage. Following propensity matching, the primary efficacy endpoint rate was 22% lower in the ticagrelor group than in the clopidogrel group (10.6% and 16.2%, respectively; adjusted HR, 0.779; 95% CI: 0.684-0.887). The safety endpoint rate was similar between the ticagrelor and clopidogrel groups (3.2% and 4.1% respectively; adjusted HR, 0.731; 95% CI: 0.522-1.026).. In real-world AMI Taiwanese patients, ticagrelor seemed to offer better anti-ischemic protection than clopidogrel, without an increase in the rate of major bleeding. A large-scale randomized trial is needed to assess the efficacy and safety of ticagrelor in East Asian AMI patients.

Topics: Aged; Asian People; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Ischemia; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Propensity Score; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Risk; Taiwan; Ticagrelor; Treatment Outcome