De-Escalation of Antiplatelet Treatment in Patients with Myocardial Infarction Who Underwent Percutaneous Coronary Intervention: A Review of the Current Literature
Abstract
:1. Introduction
2. De-Escalation of Antithrombotic Therapy
3. Unguided De-Escalation
4. Platelet Function Testing-Guided De-Escalation
5. Genotype-Guided De-Escalation
6. Summary
7. How to De-Escalate Antiplatelet Therapy
8. Conclusions and Future Perspective
Author Contributions
Funding
Conflicts of Interest
References
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Table Header | TOPIC | TROPICAL-ACS | POPular Genetics |
---|---|---|---|
Study Size | n = 646 | n = 2610 | n = 2488 |
Population | ACS + PCI (40% STEMI) | (N)STEMI + PCI (55% STEMI) | STEMI + primary PCI (100% STEMI) |
Timing of De-Escalation | 1 Month After ACS | 7 Days After Discharge | 1–3 Days After Primary PCI |
Method of De-Escalation | Unguided | PFT-Guided | Genotype-Guided |
Study Design | Single-Center, Randomized, Open-Label Trial of Unguided De-Escalation Vs. Standard Treatment | Randomized, Open-Label, Non-Inferiority Trial Of PFT-Guided De-Escalation Vs. Standard Treatment | Randomized, Open-Label, Non-Inferiority Trial of Genotype-Guided De-Escalation Vs. Standard Treatment |
Control Arm | Ticagrelor/Prasugrel for 12 Months | Prasugrel for 12 Months | Ticagrelor/Prasugrel for 12 Months |
Experimental Arm | 1 Month of Ticagrelor/Prasugrel Followed By 11 Months of Clopidogrel | PFT-Guided De-Escalation With 1 Week Prasugrel Followed By 1 Week Clopidogrel, Then Depending on PFT Results Clopidogrel Or Prasugrel From Day 14 To 12 Months | CYP2C19 Genotyping Immediately After Primary PCI. Non-Carriers of loF Alleles Switched to Clopidogrel As Soon As Possible, Carriers Continued Ticagrelor/Prasugrel for 12 Months |
Primary Endpoint | 1-Yr Incidence of Cardiovascular Death, Unplanned Hospitalization Leading to Urgent Coronary Revascularization, Stroke or BARC ≥ 2 Bleeding | 1-Yr Incidence of Cardiovascular Death, Myocardial Infarction, Stroke or BARC ≥ 2 Bleeding | 1-Yr Incidence of All-Cause Death, Myocardial Infarction, Definite Stent Thrombosis, Stroke or PLATO Major Bleeding |
Key Safety Endpoint | BARC ≥2 Bleeding | BARC ≥2 Bleeding | PLATO Major and Minor Bleeding |
Key Findings | Primary Net Clinical Benefit Endpoint (13.4% In De-Escalation Vs. 26.3% In Control Group; P < 0.01; HR: 0.48, 95% CI: 0.34–0.68 Thrombotic Event Rates Of 9.3% In De-Escalation Vs. 11.5% In Control Group; P = 0.36 Bleeding Event Rates Of 4.0% In De-Escalation Vs. 14.9% In Control Group; HR 0.30, 95% CI: 0.18–0.50; P < 0.01 | Primary Net Clinical Benefit Endpoint (7.3% In De-Escalation Vs. 9.0% In Control Group; Pnoninf <0.001; HR: 0.81, 95% CI: 0.62–1.06 Thrombotic Event Rates Of 2.5% In De-Escalation Vs. 3.2% In Control Group; HR 0.77, 95% CI: 0.48–1.21; Pnoninf = 0.01 Bleeding Event Rates Of 4.9% In De-Escalation Vs. 6.1% In Control Group; HR 0.83, 95% CI: 0.59–1.13; P = 0.23 | Primary Net Clinical Benefit Endpoint (5.1% In De-Escalation Vs. 5.9% In Control Group; Pnoninf <0.001; HR: 0.87, 95% CI: 0.62–1.21 Thrombotic Event Rates Of 2.7% In De-Escalation Vs. 3.3% In Control Group; HR 0.83, 95% CI: 0.53–1.31 Bleeding Event Rates Of 9.8% In De-Escalation Vs. 12.5% In Control Group; HR 0.78, 95% CI: 0.61–0.98; P = 0.04 |
Funding | Investigator Initiated Trial. Funded by Hôpitaux De La Timone | Investigator Initiated Trial Funded by Roche Diagnostics. Eli Lilly & Daiichi Sankyo Company Supported Prasugrel Purchase and Drug Delivery | Investigator Initiated Trial. Funded by Netherlands Organization for Health Research and Development. Spartan Bioscience Provided Genotyping Equipment for Free |
Prior Major Bleeding |
---|
Anemia |
Clinically Significant Bleeding on Potent P2Y12 Inhibitors |
High Bleeding Risk Defined by Bleeding Risk Scores |
Socio-Economic Factors Favoring the Lower Costs of Clopidogrel |
Side Effects on Prasugrel And Ticagrelor, Especially Dyspnea on Ticagrelor |
Need for Triple Treatment Due to New Onset Atrial Fibrillation or Left Ventricular Thrombus After Myocardial Infarction |
Table Header | Platelet Function Testing | Genotyping |
---|---|---|
Availability of Different Assays | Yes | Yes |
Availability of Point-Of-Care Systems | Yes | Yes |
Inter-Assay Variability | Yes | No |
Variability of Results Over Time | Yes | No |
Association with Thrombotic Events | Yes | Yes |
Association with Bleeding Events | Yes | Yes |
Availability of Clinical Trial Data on Guided Therapy | Yes | Yes |
Feasibility in Clinical Practice | Yes | Yes |
Results Influenced by Extra Patient Factors | Yes | No |
Direct Measure of Response to Therapy | Yes | No |
Assessment of Influence of Both Genetic and Non-Genetic Factors on Platelet Function | Yes | No |
Need to Be Performed While on Treatment | Yes | No |
Modified and Adapted with Permission from Sibbing Et Al. [30] |
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Claassens, D.M.; Sibbing, D. De-Escalation of Antiplatelet Treatment in Patients with Myocardial Infarction Who Underwent Percutaneous Coronary Intervention: A Review of the Current Literature. J. Clin. Med. 2020, 9, 2983. https://doi.org/10.3390/jcm9092983
Claassens DM, Sibbing D. De-Escalation of Antiplatelet Treatment in Patients with Myocardial Infarction Who Underwent Percutaneous Coronary Intervention: A Review of the Current Literature. Journal of Clinical Medicine. 2020; 9(9):2983. https://doi.org/10.3390/jcm9092983
Chicago/Turabian StyleClaassens, Daniel MF, and Dirk Sibbing. 2020. "De-Escalation of Antiplatelet Treatment in Patients with Myocardial Infarction Who Underwent Percutaneous Coronary Intervention: A Review of the Current Literature" Journal of Clinical Medicine 9, no. 9: 2983. https://doi.org/10.3390/jcm9092983