Sandbox:DN
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]
Overview
Dual antiplatelet therapy (or DAPT) refers to the combination of aspirin and a P2Y12 receptor antagonist. DAPT is approved for SIHD and interventions for ACS, such as stent placement following PCI or CABG. The duration of treatment with DAPT for each of these categories differs and guidelines for treatment have been updated in the 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease. Much of the studies done on DAPT compared the use of different types of P2Y12 receptor antagonists, the dosage of drugs, as well as the duration of treatment. The current consensus is that the use of DAPT is associated with decreased risk of stent thrombosis, MI and stroke. However, the benefits of treatment should be weighed against the increased risk of major bleeding in certain patient populations.
Types and Dosage of Drugs
Aspirin
Aspirin 81 mg once daily (range 75-100 mg) is used in all patients with SIHD, stent placement following PCI or CABG. The use of aspirin should be continued indefinitely.
P2Y12 Inhibitors
There are several P2Y12 inhibitors currently on the market and they are given in the following doses:
- Clopidogrel: 75 mg once daily
- Ticagrelor: 90 mg once daily
- Prasugrel: 10 mg once daily
The drug of choice and duration of treatment depends on the medical condition and current recommendations.
Recommendations
The 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease includes recommendations for ACS treated with medical therapy and/or PCI, ACS treated with CABG, as well as stable ischemic heart disease[1]:
- Unstable Angina/ NSTEMI Treated with Medical Therapy Alone
- STEMI Treated with Medical Therapy Alone
- Following PCI
- CABG for NSTEMI
- CABG for STEMI
- Stable Ischemic Heart Disease
The use of DAPT in Stroke
The 2014 AHA/ASA Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack included the following updated recommendations for the use of DAPT in stroke patients[2]:
| Class IIb |
| "1. The combination of aspirin and clopidogrel might be considered for initiation within 24 hours of a minor ischemic stroke or TIA and for continuation for 21 days (Level of Evidence: B)" |
| "2. For patients with a history of ischemic stroke or TIA, AF, and CAD, the usefulness of adding antiplatelet therapy to VKA therapy is uncertain for purposes of reducing the risk of ischemic cardiovascular and cerebrovascular events (Level of Evidence: C). Unstable angina and coronary artery stenting represent special circumstances in which management may warrant DAPT/VKA therapy." |
The DAPT score
The DAPT score is a risk score derived from the DAPT Trial. It has been designed as a helpful tool for the continuation of dual antiplatelet therapy following PCI and the insertion of a drug-eluting stent (DES). A low DAPT score is associated with a higher risk of bleeding and a smaller reduction in ischemia. On the other hand, a high DAPT score translates into a greater reduction in ischemia, with a smaller risk of bleeding. The cut-off point has been set at the value of 2, such that a score of ≥2 is associated with a favorable benefit-to-risk ratio for prolonged DAPT, while a score of less than 2 is associated with an unfavorable benefit-to-risk ratio.[3]
| Variable | Points |
|---|---|
| Age ≥75 years | -2 |
| Age 65 to less than 75 years | -1 |
| Age less than 65 years | 0 |
| Current cigarette smoker | 1 |
| Diabetes Mellitus | 1 |
| MI at presentation | 1 |
| Prior PCI or prior MI | 1 |
| Prior PCI or prior MI | 1 |
| Stent diameter less than 3mm | 1 |
| Paclitaxel-eluting stent | 1 |
| CHF or LVEF less than 30% | 2 |
| Saphenous vein graft PCI | 2 |
The DAPT trial
The DAPT trial published in 2014 compared the duration of DAPT following DES implantation. The study compared the standard 12 month therapy versus 30 months of DAPT. Results showed decreased risk of stent thrombosis, MI and stroke with prolonged DAPT. However, those benefits were counterbalanced by an increased risk of major bleeding. Patients with a DAPT score of ≥2 can be considered for prolonged therapy.[3] In addition, it has been suggested that patients with a complex PCI might benefit from extended duration of DAPT therapy, as those patients are more likely to undergo revascularization or suffer from stent thrombosis. A complex PCI is a procedure with one or more of the following angiographic findings[4]:
- 3 vessels treated
- ≥3 stents implanted
- Bifurcation with 2 stents implanted
- Total stent length of more than 60mm
- Chronic total occlusion as target lesion
The PEGASUS-TIMI 54 Trial
The PEGASUS-TIMI 54 Trial published in 2015 looked at the long-term use of ticagrelor in addition to aspirin for 1-3 years following an acute coronary syndrome. The study compared the use of placebo versus ticagrelor at 60 and 90mg doses. While the use of ticagrelor at either dose was superior to placebo in the primary efficacy end-point, which was a composite of MI, stroke and cardiovascular death, it was associated a higher primary safety end point, which was major bleeding. Comparing 60mg to 90mg of ticagrelor, the 60mg dosage offered a better safety profile and fewer side effects of bleeding, dyspnea and attacks of gout. However, the results were not statistically significant.[5]
References
- ↑ Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC, Halperin JL, Levine GN, Al-Khatib SM, Birtcher KK, Bozkurt B, Brindis RG, Cigarroa JE, Curtis LH, Fleisher LA, Gentile F, Gidding S, Hlatky MA, Ikonomidis JS, Joglar JA, Pressler SJ, Wijeysundera DN (2016). "2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines". J. Thorac. Cardiovasc. Surg. 152 (5): 1243–1275. doi:10.1016/j.jtcvs.2016.07.044. PMID 27751237.
- ↑ Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA (2014). "Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association". Stroke. 45 (7): 2160–236. doi:10.1161/STR.0000000000000024. PMID 24788967.
- ↑ 3.0 3.1 Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR, Krucoff MW, Hermiller J, Dauerman HL, Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Ver Lee P, Rinaldi MJ, Massaro JM (2014). "Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents". N. Engl. J. Med. 371 (23): 2155–66. doi:10.1056/NEJMoa1409312. PMC 4481318. PMID 25399658.
- ↑ Giustino G, Chieffo A, Palmerini T, Valgimigli M, Feres F, Abizaid A, Costa RA, Hong MK, Kim BK, Jang Y, Kim HS, Park KW, Gilard M, Morice MC, Sawaya F, Sardella G, Genereux P, Redfors B, Leon MB, Bhatt DL, Stone GW, Colombo A (2016). "Efficacy and Safety of Dual Antiplatelet Therapy After Complex PCI". J. Am. Coll. Cardiol. 68 (17): 1851–1864. doi:10.1016/j.jacc.2016.07.760. PMID 27595509.
- ↑ Bonaca MP, Braunwald E, Sabatine MS (2015). "Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction". N. Engl. J. Med. 373 (13): 1274–5. doi:10.1056/NEJMc1508692. PMID 26398078.