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Postconditioning with Lactate-enriched Blood for Cardioprotection in ST-segment Elevation Myocardial Infarction
Published on: May 28, 2019
Ticagrelor enhances the cardioprotective effects of ischemic preconditioning in stable patients undergoing
Domenico D'Amario1,2, Mattia Galli3, Attilio Restivo4
1Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
Insights
Ticagrelor enhances ischemic preconditioning cardioprotection in stable patients undergoing percutaneous coronary intervention (PCI) compared to clopidogrel. This suggests ticagrelor offers greater protection against cardiac injury during PCI procedures.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Ticagrelor improves outcomes in acute coronary syndromes and shows cardioprotective effects in animal models.
- Investigated potential cardioprotective effects of ticagrelor versus clopidogrel in stable patients undergoing percutaneous coronary intervention (PCI).
Purpose of the Study:
- To compare the cardioprotective effects of ticagrelor and clopidogrel in stable patients undergoing PCI.
- To assess if ticagrelor enhances ischemic preconditioning (IPC) more effectively than clopidogrel.
Main Methods:
- Prospective Randomized Open Blinded End-points (PROBE) trial in stable coronary artery disease (CAD) patients undergoing fractional flow reserve-guided PCI.
- Used ST-segment elevation on intracoronary electrocardiogram (IC-ECG) during balloon inflations as a marker for IPC-induced cardioprotection.
- Primary endpoint was the change in ST-segment elevation (ΔST) during sequential balloon inflations.
Main Results:
- Ticagrelor significantly increased ΔST-segment elevation compared to clopidogrel (P < 0.0001).
- Ticagrelor use was associated with a lower angina score during PCI.
- Increased adenosine serum concentrations were observed with ticagrelor, but no difference in coronary microvascular resistance was found.
Conclusions:
- Ticagrelor enhances the cardioprotective effects of IPC in stable CAD patients undergoing PCI compared to clopidogrel.
- Further research is needed to fully understand the mechanisms of ticagrelor's cardioprotective effects in humans.
Background:
Ticagrelor improves clinical outcomes in patients with acute coronary syndromes compared with clopidogrel. Ticagrelor also inhibits cell uptake of adenosine and has been associated with cardioprotective effects in animal models. We sought to investigate the potential cardioprotective effects of ticagrelor, as compared with clopidogrel, in stable patients undergoing percutaneous coronary intervention (PCI).
Methods And Results:
This was a Prospective Randomized Open Blinded End-points (PROBE) trial enrolling stable patients with coronary artery disease (CAD) requiring fractional flow reserve-guided PCI of intermediate epicardial coronary lesions. ST-segment elevation at intracoronary electrocardiogram (IC-ECG) during a two-step sequential coronary balloon inflations in the reference vessel during PCI was used as an indirect marker of cardioprotection induced by ischemic preconditioning (IPC). The primary endpoint of the study was the comparison of the delta (Δ) (difference) ST-segment elevation measured by IC-ECG during two-step sequential coronary balloon inflations.
Results:
Fifty-three patients were randomized to either clopidogrel or ticagrelor. The study was stopped earlier because the primary endpoint was met at a pre-specified interim analysis. ΔST-segment elevation was significantly higher in ticagrelor as compared to clopidogrel arms (P < 0.0001). Ticagrelor was associated with lower angina score during coronary balloon inflations. There was no difference in coronary microvascular resistance between groups. Adenosine serum concentrations were increased in patients treated with ticagrelor as compared to those treated with clopidogrel.
Conclusions:
Ticagrelor enhances the cardioprotective effects of IPC compared with clopidogrel in stable patients with CAD undergoing PCI. Further studies are warranted to fully elucidate the mechanisms through which ticagrelor may exert cardioprotective effects in humans.
Clinical Trial Registration:
http://www.clinicaltrials.gov. Unique Identifier: NCT02701140.
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