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Endothelial dysfunction is an important predictor - and a determinant - of adverse clinical outcome. Endothelial function is impaired by coronary artery stenting, a stud from our group has shown that it can be improved by platelet inhibition using clopidogrel. However, clopidogrel unresponsiveness is a known problem, and it has been show that the endothelial effects of clopidogrel tend to wane upon prolonged treatment. Whether a more effective anti-platelet therapy is able to prevent/improve not only thrombotic events but also endothelial dysfunction, with potential positive impact on clinical outcome in patients undergoing coronary artery stenting, is an important hypothesis that needs to be further investigated. To date, evidence regarding "ancillary" (non-platelet-dependent) effects of antiaggregant drugs is very limited. For instance, while their antiplatelet effects, and their beneficial effects in patients with acute coronary syndromes, have been clearly demonstrated in multicentric trials, it remains to be shown whether these drugs also protect endothelial function. Interestingly, some authors suggest that the mortality benefit observed in the PLATO study is at least in part independent of direct antiplatelet effects. No study, to date, has tested the effects of prasugrel and/or ticagrelor on endothelial function. With the present trial, the investigators plan to test the effect of clopidogrel, prasugrel and ticagrelor on endothelial function before and up to 4 weeks after coronary artery stenting. This study will provide important pathophysiologic insight on the relationship between platelet aggregation and endothelial function, two parameters that have been shown to influence patients' prognosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ticagrelor | Active Comparator | Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting |
|
| Clopidogrel | Active Comparator | Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting. |
|
| Prasugrel | Active Comparator | Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Coronary stenting | Procedure | All patients will receive a drug eluting stent as clinically indicated. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in FMD | The primary endpoint is the change in flow-mediated dilation (FMD) (comparison before treatment versus after treatment and stenting) in the three study groups. The mean FMD across the three measurements (1 day, 1 week, 1 month) performed after coronary artery stenting will be compared to the FMD value before drug administration and stenting. | baseline and 1 month |
| Measure | Description | Time Frame |
|---|---|---|
| FMD 2 hours after loading dose | Change in FMD 2 hours after the administration of the study drug | baseline and 2 hours after loading dose |
| L-FMC at 2 hours after the loading dose | change in L-FMC at two hours after the loading dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Munzel, MD Prof. | University Medical Center Mainz | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 2 Medical Clinic | Mainz | 55131 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34966798 | Derived | Schnorbus B, Jurk K, Lackner KJ, Welk C, Munzel T, Gori T. Effects of Clopidogrel, Prasugrel and Ticagrelor on Microvascular Function and Platelet Reactivity in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Stenting. A Randomized, Blinded, Parallel Group Trial. Front Cardiovasc Med. 2021 Dec 13;8:780605. doi: 10.3389/fcvm.2021.780605. eCollection 2021. | |
| 24801283 |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000077486 | Ticagrelor |
| D000077144 | Clopidogrel |
| D000068799 | Prasugrel Hydrochloride |
| ID | Term |
|---|---|
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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| Ticagrelor | Drug | Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting |
|
| Clopidogrel | Drug | Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting. |
|
| Prasugrel | Drug | Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting |
|
| baseline and 2 hours |
| L-FMC 1 month after loading dose | change in flow-mediated constriction (L-FMC) (comparison before treatment versus after treatment and stenting) in the three study groups. The mean L-FMC across the three measurements (1 day, 1 week, 1 month) performed after coronary artery stenting will be compared to the value before drug administration and stenting | baseline and 1 day after stenting |
| Safety and tolerability | Number of patients with adverse events. | from baseline to 1 month after enrollment |
| Derived |
| Schnorbus B, Daiber A, Jurk K, Warnke S, Konig J, Krahn U, Lackner K, Munzel T, Gori T. Effects of clopidogrel, prasugrel and ticagrelor on endothelial function, inflammatory and oxidative stress parameters and platelet function in patients undergoing coronary artery stenting for an acute coronary syndrome. A randomised, prospective, controlled study. BMJ Open. 2014 May 6;4(5):e005268. doi: 10.1136/bmjopen-2014-005268. |
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D010879 | Piperazines |