Trigger pci clinical trial

Patients triaged to the selective invasive strategy undergo coronary angiography only in case of hemodynamic or electrical instability, or a positive ischemia detection test. With the latest trials focusing mainly on patients undergoing invasive management, less data is available on conservatively managed patients. However a substudy from PLATO in ACS patients intended for non-invasive management showed that the benefits of ticagrelor over clopidogrel are consistent, and with a greater absolute benefit with those from the overall PLATO results [ 49 ].

This indicates that ticagrelor can be recommended unless there are contra-indications to this agent. Regardless of the intended treatment strategy in NSTE-ACS, a large proportion of the patients do not undergo revascularization during initial hospitalization.

Regarding ticagrelor, the abovementioned PLATO substudy in ACS patients intended for a non-invasive management showed a consistent benefit of ticagrelor regardless of revascularization. After diagnostic coronary angiography, the majority of PCI procedures ultimately result in stent placement.

The current European guidelines for myocardial revascularization recommend a clopidogrel loading dose of mg administered at least 6 h before the procedure class I, level c [ 2 ]. A mg loading dose may be preferred if given within 6 hours. If no intervention is planned after coronary angiography, clopidogrel can be stopped. In patients with a high thrombotic risk diabetics, patients after recurrent MI, after stent thrombosis, complex lesions such as left main stenting, or in life threatening situations should an occlusion occur or patients with a high on treatment platelet reactivity, clopidogrel might not optimally protect against thrombotic complications.

However, the role of currently available platelet reactivity assays are unclear as the predictive accuracy of platelet function tests for ischemic outcomes is only modest [ 51 ]. This point was made clear in the aforementioned GRAVITAS trial, showing a higher clopidogrel dosing in patients with a high residual platelet activity did not reduce ischemic outcomes.

Although these trials question the use of routine platelet testing in elective PCI, it must first be mentioned that it has been shown that the predictive accuracy of platelet function tests for ischemic outcomes is only modest. Moreover, no test is able to identify patients at high risk for bleeding. Second, no data is available in the abovementioned patients at high risk for ischemic events, including comparisons between prasugrel and ticagrelor with clopidogrel.

Third, although genotyping might assist in identifying patients with a low response to clopidogrel, CYP2C19 polymorphisms explain around 5. No data is currently available regarding ticagrelor, prasugrel, or a high dose clopidogrel after platelet function testing in patients at high risk for ischemic events. Diabetic patients, especially those with an ACS, are at a high risk for recurrent ischemic events.

This can partly be attributed to increased platelet reactivity [ 53 ]. Total major bleeding events were similar, but non-CABG related major bleeding events were numerically more frequent with ticagrelor.

When comparing prasugrel with clopidogrel in diabetic patients, a lower number of ischemic and similar bleeding events were observed [ 55 ]. Possible explanations for the similar bleeding rates remain speculative, but have been ascribe by investigators as possibly due to higher body weight or greater baseline platelet reactivity among diabetics, or simply the play of chance. The latter explanation is supported by the similar relative increase in the combination of major or minor bleeding among diabetics and nondiabetics and the higher major bleeding rate among diabetics compared with nondiabetics on clopidogrel.

These findings were not expected if related to platelet reactivity only. Moreover, there was no significant interaction regarding the main outcome. A high risk subgroup for bleeding events, often excluded from major clinical trials, are patients with an impaired renal function. The extent of renal dysfunction is related to cardiovascular outcomes, as illustrated in patients with renal dysfunction who presented with a MI [ 56 ].

Importantly, the initial dose of an antithrombotic drug does not add to the risk of bleeding in cases of renal dysfunction [ 2 ]. In contrast, repeated dosing results in accumulation of drugs and its associated increased bleeding risk.

Dose reductions could potentially mitigate the accumulation of drugs. Regarding clopidogrel, no information is available about dose reductions in patients with renal dysfunction. Ticagrelor is dosed twice daily which requires good adherence to medical therapy to ensure a reduction in risk of ischemic events, although this might also be true for the other medication required once daily.

Treatment with any of the more potent P2Y12 inhibitors results in higher risk for spontaneous bleeding events, accumulating over time which should be considered in frail patients. In patients with ACS, in which an invasive management is planned, the presence of shock, vomiting or sedation might prevent oral intake of P2Y12 inhibitors.

In these patients, intravenous cangrelor might prove to be an alternative for the oral agents. However, cangrelor is currently not approved for clinical practice. Patients treated with elinogrel, a reversible and competitive P2Yreceptor antagonist which requires no metabolic activation, had greater inhibition of platelet aggregation than those treated with clopidogrel.

At days, there was no difference in major bleeding, minor bleeding, or bleeding requiring medical attention among those treated with elinogrel and those treated with clopidogrel. Currently, a phase III trial is planned. Despite the improvement in clinical outcomes with the new P2Y12 inhibitors, remaining questions are the possibility to switch drugs, different doses, duration of therapy, optimal time of initiation in NSTE-ACS , and cost-effectiveness. Regarding the duration of therapy, current clinical practice guidelines recommend month treatment with dual antiplatelet therapy in the setting of ACS.

However, the optimal duration after PCI and the extent to which dual antiplatelet therapy confers benefit against ischemic events including stent thrombosis beyond 12 months is not known. The DAPT study is currently enrolling patients to assess the impact of 30 versus 12 months of dual antiplatelet therapy in patients undergoing PCI with stent placement [ 60 ]. Cost-effectiveness of the novel agents ticagrelor and prasugrel have been recently described.

From the US healthcare perspective, treatment with prasugrel versus clopidogrel for a median of The lower costs were mainly due to a reduction in the costs of repeat PCIs. Regarding the cost per quality-adjusted life year gained, ticagrelor was highly cost-effective applying conventional thresholds of cost-effectiveness. All other authors have no disclosures. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author s and source are credited.

National Center for Biotechnology Information , U. Journal of Thrombosis and Thrombolysis. J Thromb Thrombolysis. Published online Dec Kuijt , 1 Robbert J. James 2, 3. Wichert J. Robbert J. Stefan K. Author information Copyright and License information Disclaimer. James, Email: es. Corresponding author. This article has been cited by other articles in PMC.

Abstract Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Introduction Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Pharmacology of P2Y12 inhibitors An essential part in the platelet activation process is the interaction of ADP with the platelet P2Y12 receptor [ 9 ].

Pharmacological limitations of clopidogrel Despite proven clinical efficacy of clopidogrel in patients with an ACS or after PCI, either as monotherapy or in combination with aspirin, pharmacological limitations of clopidogrel prevent this medication from always being fully effective [ 12 ].

Pharmacology of prasugrel Prasugrel is a third generation thienopyridine. Pharmacology of the direct-acting P2Y12 inhibitors ticagrelor and cangrelor Ticagrelor is a compound that directly and reversibly binds to and inhibits the P2Y12 receptor at a site distinct from the ADP binding site [ 11 ]. Clinical trials Prasugrel The more effective platelet inhibition with the new P2Y12 inhibitors potentially results in a reduction of ischemic events and, the downside, more bleeding events. Open in a separate window.

Clinical practice The choice of drug, initiation, and duration of P2Y12 inhibition depend on the clinical setting urgent or elective intervention and patient-related factors such as the ischemic risk, bleeding risk and other baseline clinical characteristics.

Other clinical considerations in the choice of P2Y12 inhibition Diabetic patients, especially those with an ACS, are at a high risk for recurrent ischemic events. Conclusions and remaining questions New P2Y12 inhibitors have decreased ischemic events after PCI compared with clopidogrel [ 58 ]. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author s and source are credited.

References 1. Jennings LK. Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost. Guidelines for percutaneous coronary interventions. Eur Heart J. Clinical aspects of platelet inhibitors and thrombus formation. Circ Res. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium.

Addition of clopidogrel to aspirin in 45, patients with acute myocardial infarction: randomised placebo-controlled trial. Conclusions: Switching from clopidogrel to prasugrel in patients with HTPR afforded effective platelet inhibition. Trial registration: ClinicalTrials. Published by Elsevier Inc. Study Description. FDA Resources. Arms and Interventions. Outcome Measures. The endpoint in this measure is a combination of all-cause death or MI. Eligibility Criteria.

Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Key Inclusion Criteria: Have coronary artery disease and clinical indication for percutaneous coronary intervention PCI with implantation of at least one drug-eluting stent and where percutaneous coronary intervention of all treated lesions is successful. Have been given standard-of-care clopidogrel mg loading dose between 24 hours before and at the time of PCI. Contacts and Locations.

Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials. Wuppertal, Germany, More Information.

Publications automatically indexed to this study by ClinicalTrials. J Am Coll Cardiol. Epub Apr