ticagrelor and Coronary-Restenosis

New P2Y12 inhibitors can be classified as oral (prasugrel and ticagrelor) and intravenous drugs (cangrelor and elinogrel). These P2Y12 inhibitors might be superior to clopidogrel for reducing ischemic events in patients with coronary artery disease (CAD). We performed a meta-analysis of randomized trials that compared new oral or intravenous P2Y12 inhibitors with clopidogrel to determine their efficacy and safety in patients.. Twelve randomized, placebo-controlled studies and two subgroup analyses of included studies on ST-segment elevation myocardial infarction (STEMI) were included. The database consisted of 82,784 patients, with 43,875 (53%) on new oral P2Y12 inhibitors and 38909 (47%) on intravenous P2Y12 inhibitors compared with clopidogrel. The primary efficacy endpoint was major adverse cardiac events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding. New oral P2Y12 inhibitors significantly decreased MACEs (odds ratio: 0.85, p<0.0001 for the whole cohort; OR: 0.77, p=0.04 for STEMI) and all-cause death (OR: 0.88, p=0.04 for the whole cohort; OR: 0.77, p=0.01 for STEMI). Among new intravenous P2Y12 inhibitors, only cangrelor significantly decreased the risk of MACEs. An increase in TIMI major bleeding was observed only by prasugrel among the new P2Y12 inhibitors.. New oral P2Y12 inhibitors reduce ischemic events, but there is no obvious increase in major bleeding in patients with CAD, and the risk/benefit ratio is particularly favorable for STEMI patients. Moreover, only cangrelor is beneficial for ischemic events in patients on new intravenous P2Y12 inhibitors.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Administration, Oral; Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Fibrinolytic Agents; Hemorrhage; Humans; Injections, Intravenous; Multicenter Studies as Topic; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Stents; Stroke; Sulfonamides; Thiophenes; Thrombolytic Therapy; Ticagrelor; Ticlopidine

Topics: Adenosine; Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Clopidogrel; Coronary Angiography; Coronary Disease; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Foramen Ovale, Patent; Hospital Mortality; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Radiology, Interventional; Thiophenes; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Treatment Outcome

The efficacy with aspirin and clopidogrel treatment has been demonstrated in various clinical trials. Laboratory evaluation of platelet response in recent studies revealed that a distinctive response variability and nonresponsiveness/resistance in selected patients were associated with these antiplatelet agents. Moreover, some studies have correlated this nonresponsiveness/resistance phenomenon to the occurrence of thrombotic events. At this time there are no uniformly established methods to quantify exvivo platelet reactivity after clopidogrel and aspirin treatment of the extent of platelet inhibition by clopidogrel and aspirin. Therefore, specific treatment recommendations for patients exhibiting high platelet reactivity or poor platelet inhibition during clopidogrel or aspirin therapy are not established. A higher aspirin dose and strict compliance to therapy may overcome the occurrence of "aspirin resistance" in selected patients. A higher clopidogrel dose may be considered in patients exhibiting clopidogrel nonresponsiveness.

Topics: Adenosine; Adenosine Monophosphate; Angioplasty, Balloon, Coronary; Aspirin; Clinical Trials as Topic; Clopidogrel; Coronary Restenosis; Drug Resistance; Humans; Membrane Proteins; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Thiophenes; Ticagrelor; Ticlopidine

The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown.. To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG.. Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017.. Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation.. Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography.. Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P < .001), whereas the difference between ticagrelor alone vs aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with ticagrelor + aspirin; 2 with ticagrelor alone).. Among patients undergoing elective CABG with saphenous vein grafting, ticagrelor + aspirin significantly increased graft patency after 1 year vs aspirin alone; there was no significant difference between ticagrelor alone and aspirin alone. Further research with more patients is needed to assess comparative bleeding risks.. clinicaltrials.gov Identifier: NCT02201771.

Topics: Adenosine; Adult; Aged; Aspirin; Coronary Artery Bypass; Coronary Restenosis; Drug Therapy, Combination; Elective Surgical Procedures; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Saphenous Vein; Ticagrelor; Vascular Patency

Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y. TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81-100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA.. TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aspirin; Coronary Restenosis; Double-Blind Method; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Adjustment; Ticagrelor; Treatment Outcome

High on-treatment platelet reactivity (HTPR) is accompanied by an increased risk of adverse outcomes. Direct comparison of the antiplatelet effects between ticagrelor and high-dose clopidogrel has not yet been reported in acute myocardial infarction (AMI) or coronary artery in-stent restenosis (ISR) patients with HTPR. Consecutive patients with AMI or coronary artery ISR treated with standard-dose clopidogrel (75 mg/day) were screened with the VerifyNow assay, defining HTPR as P2Y12 reaction units (PRUs)>208. Of the 102 screened patients, 48 (47.06%) patients with HTPR were randomly assigned to either ticagrelor (180 mg/90 mg twice daily) or high-dose clopidogrel (150 mg/day) for 24 hours. Baseline characteristics and mean PRUs were similar in both groups. After 24 hours, ticagrelor was associated with a significantly lower platelet reactivity than high-dose clopidogrel (44.38±40.26  vs. 212.58±52.34 PRU, P<0.05). No patient receiving ticagrelor exhibited HTPR, whereas 15 (62.50%) patients after treatment with high-dose clopidogrel remained HTPR (P<0.05). During the follow-up (mean, 138.42±53.59 days), no patient exhibited a major bleeding event in either treatment group. In conclusion, in patients with AMI or coronary artery ISR exhibiting HTPR after standard clopidogrel treatment, ticagrelor is significantly more effective compared with high-dose clopidogrel in overcoming HTPR.

Topics: Adenosine; Aged; Clopidogrel; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome

A 41-year-old woman with chest pain for 6 hours was admitted to our chest pain center, presenting with acute myocardial infarction. Coronary angiography showed acute total occlusion in the proximal left anterior descending artery due to late stent thrombosis. After thrombus aspiration and intracoronary administration of 0.5 mg tirofiban, repeated angiography showed that no obvious residual stenosis remained. The patient underwent drug-coated balloon angioplasty 69 days ago and was then administered dual antiplatelet treatment (aspirin and clopidogrel) uninterruptedly. Genetic testing found that both cytochrome P450 2C19 (CYP2C19) (G681A) and glycoprotein Ia (GPIa) (C807T, G873A) were hybrid mutant types, demonstrating that the patient was possibly resistant to clopidogrel and aspirin simultaneously. Thus, clopidogrel was replaced by ticagrelor and no more cardiovascular adverse events occurred during the 2-year follow-up.

Topics: Acute Disease; Adult; Aftercare; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Cytochrome P-450 CYP2C19; Dual Anti-Platelet Therapy; Female; Fibrinolytic Agents; Humans; Integrin alpha2; Mutation; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Stents; Thrombectomy; Thrombosis; Ticagrelor; Tirofiban; Treatment Outcome

Topics: Acute Coronary Syndrome; Clopidogrel; Coronary Restenosis; Coronary Vessels; Hemodynamics; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Spectroscopy, Near-Infrared; Switzerland; Ticagrelor; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Prasugrel and ticagrelor both reduce ischaemic endpoints in high-risk acute coronary syndromes, compared with clopidogrel. However, comparative outcomes of these two newer drugs in the context of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) remains unclear. We sought to examine this question using the British Cardiovascular Interventional Society national database in patients undergoing primary PCI for STEMI.. Data from January 2007 to December 2014 were used to compare use of P2Y12 antiplatelet drugs in primary PCI in >89 000 patients. Statistical modelling, involving propensity matching, multivariate logistic regression (MLR) and proportional hazards modelling, was used to study the association of different antiplatelet drug use with all-cause mortality.. In our main MLR analysis, prasugrel was associated with significantly lower mortality than clopidogrel at both 30 days (OR 0.87, 95% CI 0.78 to 0.97, P=0.014) and 1 year (OR 0.89, 95% CI 0.82 to 0.97, P=0.011) post PCI. Ticagrelor was not associated with any significant differences in mortality compared with clopidogrel at either 30 days (OR 1.07, 95% CI 0.95 to 1.21, P=0.237) or 1 year (OR 1.058, 95% CI 0.96 to 1.16, P=0.247). Finally, ticagrelor was associated with significantly higher mortality than prasugrel at both time points (30 days OR 1.22, 95% CI 1.03 to 1.44, P=0.020; 1 year OR 1.19 95% CI 1.04 to 1.35, P=0.01).. In a cohort of over 89 000 patients undergoing primary PCI for STEMI in the UK, prasugrel is associated with a lower 30-day and 1-year mortality than clopidogrel and ticagrelor. Given that an adequately powered comparative randomised trial is unlikely to be performed, these data may have implications for routine care.

Topics: Aged; Clopidogrel; Coronary Restenosis; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Prasugrel Hydrochloride; Retrospective Studies; ST Elevation Myocardial Infarction; Survival Rate; Ticagrelor; United Kingdom

Topics: Angioplasty, Balloon, Coronary; Aspirin; Coronary Angiography; Coronary Restenosis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Stents; Ticagrelor

Several investigations have been conducted to evaluate the off-target effects of ticagrelor. The aim of the present study was to evaluate the off-target effects of ticagrelor such as neointimal formation and endothelial function after drug-eluting stent implantation in a porcine restenosis model.. A total of 30 pigs were randomly allocated based on the following P2Y. Regarding vasomotor responses to acetylcholine infusion, there were significant vasoconstrictions to maximal acetylcholine infusion in the clopidogrel and prasugrel group compared with those in the ticagrelor group. The mean neointimal area were significantly lower in the ticagrelor group (1.0±0.3 by OCT, 0.9±0.3 by histology), than in the clopidogrel (1.8±0.7, p=0.003, 1.6±0.8, p=0.030) and prasugrel (1.8±0.5, p=0.001, 1.5±0.5, p=0.019) groups. Percentages of moderate to dense peri-strut inflammatory cell infiltration were significantly lower in the ticagrelor group (9.0%) compared with the clopidogrel (17.3%, p<0.001) and prasugrel groups (15.7%, p=0.002). There were no significant differences in all findings between clopidogrel and prasugrel groups.. Compared to clopidogrel and prasugrel, ticagrelor reduced neointimal formation, endothelial dysfunction, and peri-strut inflammation.

Topics: Adenosine; Animals; Clopidogrel; Coronary Restenosis; Drug-Eluting Stents; Endothelium, Vascular; Hyperplasia; Male; Neointima; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Random Allocation; Swine; Ticagrelor; Ticlopidine; Tomography, Optical Coherence; Treatment Outcome

The purpose of the research is to give the effectiveness and safety of ticagrelor in combination with acetylsalicylic acid as preoperative treatment of primary stenting in patients with ACS. We have investigated 42 patients with ACS, 3 of which were diagnosed with cardiogenic shock, age from 38 to 82 years (63 ± 6.5 years). The ACS diagnosis was verified using the results of the ECG, a troponin test and x-ray contrast coronary angiography. The purpose of preoperative antiplatelet treatment prior to primary PCI ticagrelor was administered in the dose of 180 mg and aspirin at a dose of 200 mg. Emergency coronary angiography and primary PCI was performed 15-90 minutes from the time of diagnosis. TIMI III flow in the infarct-related coronary arteries was achieved in all patients. None of the patients the phenomenon of "No-Reflow" has not developed. The appointment of the antiplatelet drug ticagrelor before primary PCI contributes to the achievement of full blood flow restoration in the infarct-related coronary artery, and also reduces the risk of intraoperative and postoperative complications.

Topics: Acute Coronary Syndrome; Adenosine; Adult; Aged; Aged, 80 and over; Coronary Restenosis; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clopidogrel; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Electrocardiography; Female; Humans; Male; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine

Topics: Adenosine; Animals; Blood Coagulation; Blood Platelets; Carotid Artery Injuries; Carotid Artery, Common; Carotid Stenosis; Cell Proliferation; Coronary Restenosis; Fibrinolytic Agents; Humans; Mice; P-Selectin; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Thrombosis; Ticagrelor; Tunica Intima