ABSTRACT
Background: The study assessed the outcomes of patients undergoing percutaneous coronary intervention (PCI) to bypass grafts, focusing on all-cause mortality and target vessel failure (TVF) rates. Methods: A single-centre registry analysis included 364 patients who underwent PCI on coronary bypass grafts between 2008 and 2019. The study analyzed all-cause mortality and TVF, which encompassed target lesion revascularization, target vessel revascularization, and medically treated occluded target graft post-PCI. Results: The median age of the patients was 71 years (interquartile range: [IQR] 65-78), with 82.1% being male. Most patients (94.8%) received PCI on saphenous vein grafts, and the median graft age was 13.0 years (IQR: 8.4-17.6). Drug-eluting stents were used more frequently (54.4%) than bare-metal stents (45.6%), with a median stent diameter of 3.5 mm (IQR: 3-4) and length of 19 mm (IQR: 18-28). Outcome differences were not significant for PCI sites (aorto-ostial, graft body, anastomosis), use of drug-eluting stents, or use of protection devices. The 1-year mortality rate was 3.3%, whereas the combined rate of TVF or death was 20.3%. After 5 years, the mortality rate increased to 14.9%, and the combined TVF or death rate rose to 40.3%. Multivariable analyses revealed that chronic kidney disease was independently associated with mortality (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.16-2.61, P = 0.007), whereas hypertension (HR 2.42, 95% CI 1.32-4.42, P = 0.004) and increased stent length (HR 1.01, 95% CI 1.00-1.02, P = 0.007) were independently associated with the TVF-or-mortality outcome. Conclusions: Patients undergoing PCI to bypass grafts experience considerable adverse outcomes over a 5-year period, highlighting the need for further strategies in managing this high-risk population.
Contexte: L'étude visait à évaluer l'issue des patients ayant subi une intervention coronarienne percutanée (ICP) sur un greffon coronarien, en mettant l'accent sur le taux de mortalité toutes causes confondues et le taux d'échecs de revascularisation du vaisseau cible (EVC). Méthodologie: Une analyse du registre d'un seul établissement a porté sur 364 patients ayant subi une ICP sur un greffon coronarien de 2008 à 2019. L'étude a analysé la mortalité toutes causes confondues et les EVC, qui comprenaient la revascularisation de la lésion cible, la revascularisation du vaisseau cible et le traitement médical de l'occlusion du greffon coronarien cible après l'ICP. Résultats: L'âge médian des patients était de 71 ans (intervalle interquartile [IIQ] de 65 à 78) et 82,1 % d'entre eux étaient de sexe masculin. La plupart des patients (94,8 %) avaient subi une ICP sur un greffon de veine saphène; l'âge médian des greffons était de 13,0 ans (IIQ de 8,4 à 17,6). Les endoprothèses médicamentées avaient été utilisées plus fréquemment (54,4 %) que les endoprothèses non médicamentées (45,6 %), le diamètre médian de l'endoprothèse étant de 3,5 mm (IIQ de 3 à 4) et sa longueur, de 19 mm (IIQ de 18 à 28). Les différences pour ce qui est de l'issue clinique n'étaient pas significatives à l'égard des sites d'ICP (aorto-ostial, corps du greffon, anastomose), de l'utilisation d'une endoprothèse médicamentée, ou encore de l'utilisation de dispositifs de protection. Le taux de mortalité à 1 an était de 3,3 %, alors que le taux combiné d'EVC ou de décès était de 20,3 %. Après 5 ans, le taux de mortalité avait augmenté à 14,9 %, alors que le taux combiné d'EVC ou de décès s'élevait à 40,3 %. Les analyses multivariables ont révélé que la néphropathie chronique était indépendamment associée au décès (rapport des risques instantanés [RRI] de 1,74, intervalle de confiance [IC] à 95 % de 1,16 à 2,61, p = 0,007), alors que l'hypertension (RRI de 2,42, IC à 95 % de 1,32 à 4,42, p = 0,004) et une longueur accrue de l'endoprothèse (RRI de 1,01, IC à 95 % de 1,00 à 1,02, p = 0,007) étaient indépendamment associées à une issue d'EVC ou de décès. Conclusions: Les patients qui ont subi une ICP sur un greffon coronarien présentent des complications considérables sur une période de 5 ans, ce qui souligne le besoin de mettre en place davantage de stratégies de prise en charge pour cette population à risque élevé.
ABSTRACT
BACKGROUND: Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging, and the optimal antithrombotic therapy remains uncertain. The potential of non-vitamin K antagonist oral anticoagulants (NOACs) to prevent ischaemic cardiovascular events is promising, but the evidence remains limited. OBJECTIVES: To evaluate the efficacy and safety of non-vitamin-K-antagonist oral anticoagulants (NOACs) in addition to background antiplatelet therapy, compared with placebo, antiplatelet therapy, or both, after acute myocardial infarction (AMI) in people without an indication for anticoagulation (i.e. atrial fibrillation or venous thromboembolism). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science, and two clinical trial registers in September 2022 with no language restrictions. We checked the reference lists of included studies for any additional trials. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that evaluated NOACs plus antiplatelet therapy versus placebo, antiplatelet therapy, or both, in people without an indication for anticoagulation after an AMI. DATA COLLECTION AND ANALYSIS: Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random-effects pairwise analyses using Review Manager Web, and network meta-analysis using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons and allow ranking of treatments on a continuous 0-to-1 scale. MAIN RESULTS: We identified seven eligible RCTs, including an ongoing trial that we could not include in the analysis. Of the six RCTs involving 33,039 participants, three RCTs compared rivaroxaban with placebo, two RCTs compared apixaban with placebo, and one RCT compared dabigatran with placebo. All participants in the six RCTs received concomitant antiplatelet therapy. The available evidence suggests that rivaroxaban compared with placebo reduces the rate of all-cause mortality (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.69 to 0.98; number needed to treat for an additional beneficial outcome (NNTB) 250; 3 studies, 21,870 participants; high certainty) and probably reduces cardiovascular mortality (RR 0.83, 95% CI 0.69 to 1.01; NNTB 250; 3 studies, 21,870 participants; moderate certainty). There is probably little or no difference between apixaban and placebo in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35; number needed to treat for an additional harmful outcome (NNTH) 334; 2 studies, 8638 participants; moderate certainty) and cardiovascular mortality (RR 0.99, 95% CI 0.77 to 1.27; number needed to treat not applicable; 2 studies, 8638 participants; moderate certainty). Dabigatran may reduce the rate of all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06; NNTB 63; 1 study, 1861 participants; low certainty). Dabigatran compared with placebo may have little or no effect on cardiovascular mortality, although the point estimate suggests benefit (RR 0.72, 95% CI 0.34 to 1.52; NNTB 143; 1 study, 1861 participants; low certainty). Two of the investigated NOACs were associated with an increased risk of major bleeding compared to placebo: apixaban (RR 2.41, 95% CI 1.44 to 4.06; NNTH 143; 2 studies, 8544 participants; high certainty) and rivaroxaban (RR 3.31, 95% CI 1.12 to 9.77; NNTH 125; 3 studies, 21,870 participants; high certainty). There may be little or no difference between dabigatran and placebo in the risk of major bleeding (RR 1.74, 95% CI 0.22 to 14.12; NNTH 500; 1 study, 1861 participants; low certainty). The results of the network meta-analysis were inconclusive between the different NOACs at all individual doses for all primary outcomes. However, low-certainty evidence suggests that apixaban (combined dose) may be less effective than rivaroxaban and dabigatran for preventing all-cause mortality after AMI in people without an indication for anticoagulation. AUTHORS' CONCLUSIONS: Compared with placebo, rivaroxaban reduces all-cause mortality and probably reduces cardiovascular mortality after AMI in people without an indication for anticoagulation. Dabigatran may reduce the rate of all-cause mortality and may have little or no effect on cardiovascular mortality. There is probably no meaningful difference in the rate of all-cause mortality and cardiovascular mortality between apixaban and placebo. Moreover, we found no meaningful benefit in efficacy outcomes for specific therapy doses of any investigated NOACs following AMI in people without an indication for anticoagulation. Evidence from the included studies suggests that rivaroxaban and apixaban increase the risk of major bleeding compared with placebo. There may be little or no difference between dabigatran and placebo in the risk of major bleeding. Network meta-analysis did not show any superiority of one NOAC over another for our prespecified primary outcomes. Although the evidence suggests that NOACs reduce mortality, the effect size or impact is small; moreover, NOACs may increase major bleeding. Head-to-head trials, comparing NOACs against each other, are required to provide more solid evidence.
Subject(s)
Dabigatran , Myocardial Infarction , Humans , Rivaroxaban , Network Meta-Analysis , Platelet Aggregation Inhibitors , Anticoagulants , HemorrhageABSTRACT
A novel enoxaparin regimen consisting of intra-arterial bolus (0.75 mg/kg) followed by intravenous infusion (0.75 mg/kg/6 hours) has been developed as a possible solution to the delayed absorption of oral P2Y12 inhibitors in opiate-treated ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. We aimed to study the feasibility of this regimen as an alternative to standard-of-care treatment (SOC) with unfractionated heparin ± glycoprotein IIb/IIIa antagonist (GPI). One hundred opiate-treated patients presenting with STEMI and accepted for primary angioplasty were randomized (1:1) to either enoxaparin or SOC. Fifty patients were allocated enoxaparin (median age 61, 40% females) and 49 allocated SOC (median age 62, 22% females). One developed stroke before angiography and was withdrawn. One SOC patient had a gastrointestinal bleed resulting in 1 g drop in hemoglobin and early cessation of GPI infusion. Two enoxaparin patients had transient minor bleeding: one transient gingival bleed and one episode of coffee ground vomit with no hemoglobin drop or hemodynamic instability. Two SOC and no enoxaparin group patients had acute stent thrombosis. These preliminary data support further study of this novel 6-hour enoxaparin regimen in opiate-treated PPCI patients.
Subject(s)
Enoxaparin/therapeutic use , Fibrinolytic Agents/therapeutic use , Opiate Alkaloids/therapeutic use , Percutaneous Coronary Intervention/methods , Enoxaparin/pharmacology , Feasibility Studies , Female , Fibrinolytic Agents/pharmacology , Humans , Male , Opiate Alkaloids/pharmacologyABSTRACT
Hypofibrinolysis is a key abnormality in diabetes but the role of impaired clot lysis in predicting vascular events and mortality in this population is yet to be determined. We aimed to investigate the relationship between fibrin clot properties and clinical outcomes in patients with diabetes and recent acute coronary syndrome (ACS). Plasma samples were collected at hospital discharge from 974 ACS patients with diabetes randomised to clopidogrel or ticagrelor in the PLATO trial. A validated turbidimetric assay was employed to study fibrin clot lysis and maximum turbidity. One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were determined using Cox proportional analysis. After adjusting for CV risk factors, each 50% increase in lysis time was associated with increased risk of CV death/MI (HR 1.21; 95% confidence interval [CI] 1.02-1.44; p = 0.026) and CV death alone (HR 1.38; 1.08-1.76; p = 0.01). Similarly, each 50% increase in maximum turbidity was associated with increased risk of CV death/MI (HR 1.25; 1.02-1.53; p = 0.031) and CV death alone (HR 1.49; 1.08-2.04; p = 0.014). The relationship between lysis time and the combined outcome of CV death and MI remained significant after adjusting for multiple prognostic vascular biomarkers (p = 0.034). Neither lysis time nor maximum turbidity was associated with major bleeding events. Impaired fibrin clot lysis predicts 1-year CV death and MI in diabetes patients following ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier NCT00391872.
Subject(s)
Acute Coronary Syndrome/blood , Acute Coronary Syndrome/complications , Diabetes Complications/therapy , Fibrinolysis , Aged , Biomarkers/metabolism , Cardiovascular Diseases/mortality , Clopidogrel/therapeutic use , Double-Blind Method , Female , Fibrin/chemistry , Hemorrhage , Humans , International Cooperation , Male , Middle Aged , Myocardial Infarction/mortality , Nephelometry and Turbidimetry , Patient Discharge , Platelet Aggregation Inhibitors/therapeutic use , Prognosis , Risk Factors , Thrombosis , Ticagrelor/therapeutic use , Treatment OutcomeABSTRACT
Antithrombotic treatment is a key component of secondary prevention following acute coronary syndromes (ACS). Although dual antiplatelet therapy is standard therapy post-ACS, duration of treatment is the subject of ongoing debate. Prolonged dual antiplatelet therapy in high-risk patients with history of myocardial infarction reduced the risk of recurrent myocardial infarction, stroke or cardiovascular death. Similarly, in patients with stable coronary artery disease, two-thirds of whom had a history of myocardial infarction, dual antithrombotic therapy with very-low-dose rivaroxaban and aspirin also resulted in improved ischaemic outcomes. In the absence of head-to-head comparison, choosing the most appropriate treatment strategy can be challenging, particularly when it comes to balancing the risks of ischaemia and bleeding. We aim to review the evidence for currently available antithrombotic treatments and provide a practical algorithm to aid the decision-making process.
Subject(s)
Acute Coronary Syndrome/drug therapy , Coronary Artery Disease/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Purinergic P2Y Receptor Antagonists/therapeutic use , Secondary Prevention/methods , Aged , Algorithms , Aspirin/administration & dosage , Cardiovascular Diseases/prevention & control , Decision Making , Female , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Myocardial Infarction/prevention & control , Myocardial Ischemia/drug therapy , Risk , Rivaroxaban/administration & dosage , Stroke/prevention & control , Ticagrelor/administration & dosageABSTRACT
Higher aspirin doses may be inferior in ticagrelor-treated acute coronary syndrome (ACS) patients and reducing bleeding risk whilst maintaining antithrombotic benefits could improve outcomes. We characterized the pharmacodynamics of a novel dual-antiplatelet-therapy regimen consisting of very-low-dose twice-daily (BD) aspirin with standard-dose ticagrelor. A total of 20 ticagrelor-treated ACS patients entered a randomized crossover to take aspirin 20 mg BD (12-hourly) during one 14-day period and 75 mg once-daily (OD) in the other. After 14 days of treatment, serum thromboxane (TX)B2 and light-transmittance aggregometry were assessed pre- and 2 h post-morning-dose, bleeding time was measured post-dose, and TXA2 and prostacyclin stable metabolites were measured in urine collected 2 h post-morning-dose. Data are expressed as mean ± SD. After 14 days treatment, serum TXB2 levels were significantly greater 2 h post-dosing with aspirin 20 mg BD vs. 75 mg OD (3.0 ± 3.6 ng/mL vs. 0.8 ± 1.9 ng/mL; p = 0.018) whereas pre-dosing levels were not significantly different (3.5 ± 4.1 ng/mL vs. 2.5 ± 3.1 ng/mL, p = 0.23). 1-mmol/L arachidonic acid-induced platelet aggregation was similarly inhibited by both regimens pre-dose (8.5 ± 14.3% vs. 5.1 ± 3.6%, p = 0.24) and post-dose (8.7 ± 14.2% vs. 6.6 ± 5.3%; p = 0.41). Post-dose bleeding time was shorter with 20 mg BD (680 ± 306 s vs. 834 ± 386 s, p = 0.02). Urinary prostacyclin and TX metabolite excretion were not significantly different. In conclusion, compared to aspirin 75 mg OD, aspirin 20 mg BD provided consistent inhibition of platelet TXA2 release and aggregation, and improved post-dose hemostasis, in ticagrelor-treated ACS patients. Further studies are warranted to assess whether this regimen improves the balance of clinical efficacy and safety.
Subject(s)
Acute Coronary Syndrome/drug therapy , Aspirin/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Aspirin/pharmacology , Female , Hemostasis , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/pharmacologyABSTRACT
BACKGROUND: Ticagrelor has superior efficacy to clopidogrel in the management of acute coronary syndromes but has not been assessed in patients undergoing percutaneous coronary intervention for stable coronary artery disease. We compared the pharmacodynamic effects of ticagrelor and clopidogrel in this stable population. METHODS: One hundred eighty aspirin-treated stable coronary artery disease patients, who were planned to undergo elective percutaneous coronary intervention in a single center, were randomized 1:1:1 to either a standard clopidogrel regimen or 1 of 2 regimens of ticagrelor, either 90 mg (T90) or 60 mg twice daily (T60), both with a 180 mg loading dose. Cellular adenosine uptake was assessed, at the time of the procedure and pre- and postdose at 1 month, by adding adenosine 1 µmol/L to aliquots of anticoagulated whole blood and mixing with a stop solution at 0, 15, 30, and 60 seconds, then measuring residual plasma adenosine concentration by high-performance liquid chromatography. Systemic plasma adenosine concentration and platelet reactivity were assessed at the same timepoints. High-sensitivity troponin T was measured pre- and 18 to 24 hours postpercutaneous coronary intervention. RESULTS: One hundred seventy-four patients underwent an invasive procedure, of whom 162 received percutaneous coronary intervention (mean age 65 years, 18% female, 21% with diabetes mellitus). No effect on in vitro adenosine uptake was seen postdose at 1 month for either ticagrelor dose compared with clopidogrel (residual adenosine at 15 seconds, mean±SD: clopidogrel 0.274±0.101 µmol/L; T90 0.278±0.134 µmol/L; T60 0.288±0.149 µmol/L; P=0.37). Similarly, no effect of ticagrelor on in vitro adenosine uptake was seen at other timepoints, nor was plasma adenosine concentration affected (all P>0.1). Both maintenance doses of ticagrelor achieved more potent and consistent platelet inhibition than clopidogrel (VerifyNow P2Y12 reaction units, 1 month, mean±SD: predose, T60: 62±47, T90: 40±38, clopidogrel 181±44; postdose, T60: 34±30, T90: 24±21, clopidogrel 159±57; all P<0.0001 for ticagrelor versus clopidogrel). High platelet reactivity was markedly less with both T60 and T90 compared with clopidogrel (VerifyNow P2Y12 reaction units>208, 1 month postdose: 0%, 0%, and 21%, respectively). Median (interquartile range) high-sensitivity troponin T increased 16.9 (6.5-46.9) ng/L for clopidogrel, 22.4 (5.5-53.8) ng/L for T60, and 17.7 (8.1-43.5) ng/L for T90 (P=0.95). There was a trend toward less dyspnea with T60 versus T90 (7.1% versus 19.0%; P=0.09). CONCLUSIONS: Maintenance therapy with T60 or T90 had no detectable effect on cellular adenosine uptake at 1 month, nor was there any effect on systemic plasma adenosine levels. Both regimens of ticagrelor achieved greater and more consistent platelet inhibition than clopidogrel but did not appear to affect troponin release after percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02327624.
ABSTRACT
Delayed onset of action of oral P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2-3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y12 inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y12 inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y12 inhibition.
Subject(s)
Anticoagulants/administration & dosage , Blood Coagulation/drug effects , Coronary Thrombosis/prevention & control , Enoxaparin/administration & dosage , Fibrinolytic Agents/administration & dosage , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction/therapy , Aged , Analgesics, Opioid/administration & dosage , Anticoagulants/adverse effects , Coronary Thrombosis/blood , Coronary Thrombosis/etiology , Drug Administration Schedule , Drug Monitoring/methods , England , Enoxaparin/adverse effects , Female , Fibrinolytic Agents/adverse effects , Humans , Infusions, Intravenous , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Pilot Projects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Function Tests , Purinergic P2Y Receptor Antagonists/administration & dosage , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/diagnosis , Stents , Thrombelastography , Time Factors , Treatment OutcomeABSTRACT
Aims: To determine whether fibrin clot properties are associated with clinical outcomes following acute coronary syndrome (ACS). Methods and results: Plasma samples were collected at hospital discharge from 4354 ACS patients randomized to clopidogrel or ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. A validated turbidimetric assay was employed to study plasma clot lysis time and maximum turbidity (a measure of clot density). One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were estimated using Cox proportional hazards models. After adjusting for CV risk factors, each 50% increase in lysis time was associated with CV death/spontaneous MI [HR 1.17, 95% confidence interval (CI) 1.05-1.31; P < 0.01] and CV death alone (HR 1.36, 95% CI 1.17-1.59; P < 0.001). Similarly, each 50% increase in maximum turbidity was associated with increased risk of CV death (HR 1.24, 95% CI 1.03-1.50; P = 0.024). After adjustment for other prognostic biomarkers (leukocyte count, high-sensitivity C-reactive protein, high-sensitivity troponin T, cystatin C, N-terminal pro B-type natriuretic peptide, and growth differentiation factor-15), the association with CV death remained significant for lysis time (HR 1.2, 95% CI 1.01-1.42; P = 0.042) but not for maximum turbidity. These associations were consistent regardless of randomized antiplatelet treatment (all interaction P > 0.05). Neither lysis time nor maximum turbidity was associated with major bleeding events. Conclusion: Fibrin clots that are resistant to lysis independently predict adverse outcome in ACS patients. Novel therapies targeting fibrin clot properties might be a new avenue for improving prognosis in patients with ACS.
Subject(s)
Acute Coronary Syndrome/blood , Acute Coronary Syndrome/drug therapy , Blood Coagulation , Clopidogrel/therapeutic use , Fibrin/metabolism , Platelet Aggregation Inhibitors/therapeutic use , Ticagrelor/therapeutic use , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/mortality , Aged , Double-Blind Method , Female , Fibrin Clot Lysis Time , Hemorrhage/etiology , Humans , Male , Middle Aged , Myocardial Infarction/etiology , Treatment OutcomeSubject(s)
Myocardial Infarction , Thrombosis , Anticoagulants , Fibrinolytic Agents , Humans , Platelet Aggregation InhibitorsABSTRACT
Platelet P2Y12 receptor inhibitors are crucial in the treatment of patients with acute coronary syndrome or undergoing percutaneous coronary intervention. Ticagrelor is a reversibly binding, potent oral P2Y12 inhibitor that also is a weak inhibitor of the equilibrative nucleoside transporter-1 pathway for cellular adenosine uptake. It is hypothesized that ticagrelor has clinically relevant "off-target" effects, independent of its effect on platelet aggregation and thrombosis. This review considers the pleiotropic effects of ticagrelor and some of the possible mechanisms related to these effects.
Subject(s)
Acute Coronary Syndrome/surgery , Adenosine/analogs & derivatives , Percutaneous Coronary Intervention , Platelet Aggregation/drug effects , Postoperative Complications/prevention & control , Adenosine/administration & dosage , Humans , Injections, Intravenous , Postoperative Complications/blood , Purinergic P2Y Receptor Antagonists/administration & dosage , TicagrelorSubject(s)
Anticoagulants/pharmacology , Blood Platelets/drug effects , Blood Platelets/metabolism , Citric Acid/pharmacology , Hirudins/pharmacology , Platelet Function Tests/standards , Receptors, Purinergic P2Y12/metabolism , Humans , Platelet Function Tests/instrumentation , Platelet Function Tests/methodsABSTRACT
AIMS: Stent thrombosis (ST) is an infrequent but potentially fatal complication of PCI. The reported incidence of ST varies from 0-5%, due to differences in definition of ST, inclusion/exclusion criteria, and the type of stent and dual antiplatelet therapy used. We aimed to examine the incidence of ST and associated risk factors in this "real-world, all-comers" study. METHODS AND RESULTS: All patients undergoing PCI at South Yorkshire Cardiothoracic Centre (UK) between 2007 and 2010 were included, with no exclusion criteria. ST cases were divided into definite and probable ST, according to the ARC criteria. Univariate predictors were identified using Student's t-test and chi-square test, and entered into a Cox proportional hazards model to identify factors independently associated with ST. For 5,833 PCI patients followed up for two years, the incidence of definite and probable ST together was 1.9% (n=109); of these 73% were early, 11% late and 16% very late ST. Cardiogenic shock, ST-elevation myocardial infarction (STEMI), lack of dual antiplatelet treatment, diabetes mellitus, stent length and stent diameter were the independent predictors of ST. CONCLUSIONS: The incidence of definite/probable ST in this "real-world" registry is 1.9%. Cardiogenic shock, often excluded in clinical trials, is the strongest independent predictor of ST.
Subject(s)
Coronary Artery Disease/therapy , Coronary Thrombosis/epidemiology , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Stents , Aged , Chi-Square Distribution , Coronary Artery Disease/epidemiology , Diabetes Mellitus/epidemiology , Drug Therapy, Combination , England/epidemiology , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/epidemiology , Myocardial Infarction/therapy , Platelet Aggregation Inhibitors/therapeutic use , Proportional Hazards Models , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Shock, Cardiogenic/epidemiology , Shock, Cardiogenic/therapy , Time Factors , Treatment OutcomeABSTRACT
VerifyNow (VN) P2Y12 is a point-of-care assay used to assess response to P2Y12 inhibitors. Sodium citrate (citrate) is the standard anticoagulant used for this assay but requires a pre-incubation period. Hirudin is an alternative anticoagulant for platelet function studies that maintains physiological divalent cation levels. We investigated whether hirudin anticoagulation might allow more rapid testing of P2Y12 inhibition at the time of percutaneous coronary intervention (PCI). Blood was collected from the arterial sheath of aspirin-treated patients undergoing elective, urgent or emergency coronary angiography±PCI and aliquots were anticoagulated with either citrate or hirudin. For each anticoagulant, VN P2Y12 was performed both immediately and after 20 minutes. A total of 98 patients were included in this study following pre-treatment with clopidogrel (n=88), prasugrel (n=6) or no P2Y12 inhibitor (n=4). PRU with hirudin immediately (PRU_H_Imm) and PRU with citrate 20 minutes post sampling (PRU_C_20) were very strongly correlated (R=0.95) though PRU_H_Imm tended to be lower than PRU_C_20 so that optimal correlation was estimated by the equation PRU_H_Imm=0.95xPRU_C_20 (p<0.001). Bland-Altman plots showed good agreement between PRU_H_Imm and (0.95xPRU_C_20). Platelet reactivity was more stable over the studied time course with hirudin as compared to citrate. We therefore conclude that VN P2Y12 with hirudin anticoagulation can be performed more rapidly and results are strongly correlated with delayed citrate measurements. Further studies are warranted to assess the utility of this method for improving clinical outcomes in patients undergoing PCI.
Subject(s)
Anticoagulants/pharmacology , Citrates/pharmacology , Hematologic Tests/methods , Hirudins/pharmacology , Receptors, Purinergic P2Y12/metabolism , Acute Coronary Syndrome/blood , Aged , Antithrombins/pharmacology , Area Under Curve , Cations , Clopidogrel , Coronary Angiography/methods , Female , Humans , Male , Middle Aged , Myocardial Infarction/blood , Piperazines/pharmacology , Platelet Function Tests/methods , Prasugrel Hydrochloride , Receptors, Purinergic P2Y12/analysis , Sodium Citrate , Thiophenes/pharmacology , Ticlopidine/analogs & derivatives , Ticlopidine/pharmacology , Treatment OutcomeABSTRACT
Coronary heart disease is the leading cause of death worldwide. In the United States, approximately 1 of every 6 deaths in 2007 was caused by coronary heart disease. Clinical presentation in the acute setting is mostly due to atherosclerotic plaque rupture leading to flow limitation in the affected vessel, and myocardial ischemia and infarction. ST-segment elevation myocardial infarction is usually associated with complete occlusion of the coronary artery and carries the worst prognosis in terms of in-hospital mortality. Despite various advances in treatment options, including percutaneous coronary intervention, ischemic heart disease still carries a significant morbidity and mortality. In this article, we aim to provide a summary of a few key advances in the management of ST-segment elevation myocardial infarction.