March 2020 Issue
ISSN 2689-291X
ISSN 2689-291X
TICO: Is One Year Of DAPT Absolutely Necessary In ACS?
Abstract
Physicians often have to face the dilemma of balancing the risk of stent thrombosis versus the risk of major bleeding in patients who have suffered acute coronary syndrome (ACS) within less than one year. The ACC/AHA 2016 Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease [1] gives a Class I recommendation of one year of dual antiplatelet therapy (DAPT) after ACS, with a weaker Class IIb recommendation for discontinuation of DAPT after 6 months in patient who are at high risk of bleeding. With the advent of novel antiplatelet agents and newer generation stents, there seemed to be a need to retest the optimal period for DAPT in the setting of ACS. Last year, the TWILIGHT trial presented at TCT 2019 [2] demonstrated that among high risk coronary artery disease patients, discontinuing aspirin after 3 months of DAPT with ticagrelor following percutaneous coronary intervention (PCI) did not increase risk of death/MI/stroke, while lowering rate of bleeding events.
At the Virtual ACC Scientific Sessions in March 2020, the TICO trial [3] further confirmed that ticagrelor monotherapy after 3 months of DAPT was effective at preventing ischemia with a considerably lower rate of bleeding events. The following is a summary of the TICO trial, which compared ticagrelor monotherapy after 3 months of DAPT (ticagrelor mono) with standard DAPT (DAPT) for 12 months after PCI for ACS.
The TICO Study design:
Results:
Primary outcomes of net adverse clinical events (NACE): A composite of TIMI major bleed, major adverse cardiac events (death/MI/stent thrombosis) and cerebrovascular events:
3.9% ticagrelor mono; 5.9% DAPT.
Secondary outcomes:
Major bleed: 1.7% ticagrelor mono; 3% DAPT.
Stent thrombosis at 12 months: 0.4% ticagrelor mono; 0.3% in DAPT.
Discussion:
Among patients with ACS who received sirolimus-eluting stent, ticagrelor monotherapy after 3 months of standard DAPT was as effective at preventing subsequent ischemic events as the standard 12 months of DAPT therapy, with a lower bleeding risk. The TICO trial further confirmed the findings of the TWILIGHT trial that following 3 months of DAPT, aspirin may be safely discontinued without an increase in cardiac events.
Clinical Implication:
DAPT has been associated with a well established increased bleeding risk, which has been variably classified in different clinical trials [4]. However, the major aim of studies has been to balance the risk of stent thrombosis with the risk of bleeding, both of which could lead to fatal events [5]. Guidelines may have been based on older clinical trials involving patients treated with first generation stents and when clopidogrel was predominantly used in DAPT [6]. Based on current trials, it is time to consider revising the guideline recommendations for the duration of DAPT following intervention for ACS.
References
Authors:
Landai Nguyen, D.O.
Cardiology Fellow
University of South Alabama
Mobile, AL
Tien Nguyen
Visiting Student
University of South Alabama
Mobile, AL
Bassam Omar, M.D., Ph.D.
Professor of Cardiology
University of South Alabama
Mobile, AL
Physicians often have to face the dilemma of balancing the risk of stent thrombosis versus the risk of major bleeding in patients who have suffered acute coronary syndrome (ACS) within less than one year. The ACC/AHA 2016 Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease [1] gives a Class I recommendation of one year of dual antiplatelet therapy (DAPT) after ACS, with a weaker Class IIb recommendation for discontinuation of DAPT after 6 months in patient who are at high risk of bleeding. With the advent of novel antiplatelet agents and newer generation stents, there seemed to be a need to retest the optimal period for DAPT in the setting of ACS. Last year, the TWILIGHT trial presented at TCT 2019 [2] demonstrated that among high risk coronary artery disease patients, discontinuing aspirin after 3 months of DAPT with ticagrelor following percutaneous coronary intervention (PCI) did not increase risk of death/MI/stroke, while lowering rate of bleeding events.
At the Virtual ACC Scientific Sessions in March 2020, the TICO trial [3] further confirmed that ticagrelor monotherapy after 3 months of DAPT was effective at preventing ischemia with a considerably lower rate of bleeding events. The following is a summary of the TICO trial, which compared ticagrelor monotherapy after 3 months of DAPT (ticagrelor mono) with standard DAPT (DAPT) for 12 months after PCI for ACS.
The TICO Study design:
- Randomized, parallel, open labeled study
- Conducted at 38 Korean centers
- Enrolled 3056 patients who had undergone PCI for ACS
- Patients were followed for 12 months
- ACS post PCI with sirolimus-eluting stent
- 29% unstable angina
- 35% non ST elevation myocardial infarction
- 36% ST elevation myocardial infarction
- Age > 19 years. Mean age was 61 years
- Females: 21%
- Diabetes: 27%
- Age > 80 years
- Increased bleeding risk (Need for oral anticoagulants, hepatic dysfunction)
- Current or potential pregnancy
- Bradycardia
Results:
Primary outcomes of net adverse clinical events (NACE): A composite of TIMI major bleed, major adverse cardiac events (death/MI/stent thrombosis) and cerebrovascular events:
3.9% ticagrelor mono; 5.9% DAPT.
Secondary outcomes:
Major bleed: 1.7% ticagrelor mono; 3% DAPT.
Stent thrombosis at 12 months: 0.4% ticagrelor mono; 0.3% in DAPT.
Discussion:
Among patients with ACS who received sirolimus-eluting stent, ticagrelor monotherapy after 3 months of standard DAPT was as effective at preventing subsequent ischemic events as the standard 12 months of DAPT therapy, with a lower bleeding risk. The TICO trial further confirmed the findings of the TWILIGHT trial that following 3 months of DAPT, aspirin may be safely discontinued without an increase in cardiac events.
Clinical Implication:
DAPT has been associated with a well established increased bleeding risk, which has been variably classified in different clinical trials [4]. However, the major aim of studies has been to balance the risk of stent thrombosis with the risk of bleeding, both of which could lead to fatal events [5]. Guidelines may have been based on older clinical trials involving patients treated with first generation stents and when clopidogrel was predominantly used in DAPT [6]. Based on current trials, it is time to consider revising the guideline recommendations for the duration of DAPT following intervention for ACS.
References
- Levine GN, Bates ER, Bittl JA, et al. 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 Am Coll Cardiol. 2016 Sep 6;68(10):1082-115.
- Mehran R, Baber U, Sharma SK, et al. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019 Nov 21;381(21):2032-2042.
- Kim C, Hong SJ, Shin DH, et al. Randomized evaluation of ticagrelor monotherapy after 3-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with new-generation sirolimus-eluting stents: TICO trial rationale and design. Am Heart J. 2019 Jun;212:45-52.
- Urban P, Mehran R, Colleran R, et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J. 2019 Aug 14;40(31):2632-2653.
- Garg P, Galper BZ, Cohen DJ, et al. Balancing the risks of bleeding and stent thrombosis: a decision analytic model to compare durations of dual antiplatelet therapy after drug-eluting stents. Am Heart J. 2015 Feb;169(2):222-233.e5
- Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001 Aug 18;358(9281):527-33.
Authors:
Landai Nguyen, D.O.
Cardiology Fellow
University of South Alabama
Mobile, AL
Tien Nguyen
Visiting Student
University of South Alabama
Mobile, AL
Bassam Omar, M.D., Ph.D.
Professor of Cardiology
University of South Alabama
Mobile, AL