Benefit-risk profile of extended dual antiplatelet therapy beyond 1 year in patients with high risk of ischemic or bleeding events after PCI

Platelets ◽  
2020 ◽  
pp. 1-9
Author(s):  
Hao-Yu Wang ◽  
Run-Lin Gao ◽  
Bo Xu ◽  
Yue-Jin Yang ◽  
Dong Yin ◽  
...  
Keyword(s):  
High Risk ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Risk Profile ◽  
Bleeding Events

TWILIGHT: A Randomized Trial of Ticagrelor Monotherapy Versus Ticagrelor Plus Aspirin Beginning at 3 Months in High-risk Patients Undergoing Percutaneous Coronary Intervention

2020 ◽  
Vol 14 ◽  
Author(s):  
Johny Nicolas ◽  
Usman Baber ◽  
Roxana Mehran
Keyword(s):  
Percutaneous Coronary Intervention ◽  
High Risk ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Coronary Intervention ◽  
Bleeding Events ◽  
High Risk Patients ◽  
Risk Of Death ◽  
Percutaneous Coronary ◽  
Risk Patients

A P2Y12 inhibitor-based monotherapy after a short period of dual antiplatelet therapy is emerging as a plausible strategy to decrease bleeding events in high-risk patients receiving dual antiplatelet therapy after percutaneous coronary intervention. Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT), a randomized double-blind trial, tested this approach by dropping aspirin at 3 months and continuing with ticagrelor monotherapy for an additional 12 months. The study enrolled 9,006 patients, of whom 7,119 who tolerated 3 months of dual antiplatelet therapy were randomized after 3 months into two arms: ticagrelor plus placebo and ticagrelor plus aspirin. The primary endpoint of interest, Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, occurred less frequently in the experimental arm (HR 0.56; 95% CI [0.45–0.68]; p<0.001), whereas the secondary endpoint of ischemic events was similar between the two arms (HR 0.99; 95% CI [0.78–1.25]). Transition from dual antiplatelet therapy consisting of ticagrelor plus aspirin to ticagrelor-based monotherapy in high-risk patients at 3 months after percutaneous coronary intervention resulted in a lower risk of bleeding events without an increase in risk of death, MI, or stroke.

Benefits and risks of longer-than-1-year dual antiplatelet therapy in TWLIGHT-like patients with high risk of ischemic or bleeding events after drug-eluting stents implantation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H.Y Wang ◽  
K.F Dou ◽  
B Xu ◽  
R.L Gao ◽  
A Kirtane
Keyword(s):  
High Risk ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Target Lesion ◽  
Funding Source ◽  
Medical Sciences ◽  
Bleeding Events ◽  
Index Procedure ◽  
Drug Eluting

Abstract Background Dual-antiplatelet therapy (DAPT) exceeding 1 year may increase a bleeding risk despite reducing the risk of ischemic events. The benefits and harms of prolonging DAPT with aspirin and clopidogrel beyond 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for TWLIGHT-like patients with high-risk for bleeding or an ischemic event remain unknown. Method Between January 2013 and December 2013, all consecutive patients undergoing PCI were prospectively included in the China Fuwai PCI Registry. We evaluated 7521 patients who were at high risk for ischemic or hemorrhagic complications and were events free (no death, myocardial infarction [MI], stroke, stent thrombosis [ST], any revascularization, or major bleeding) at 1 year after the index procedure. Subjects were divided into 2 groups: DAPT&gt;1-year group (n=5252) and DAPT≤1-year group (n=2269). Patients at high-risk for ischemic or bleeding events were defined as having at least one additional clinical feature and one angiographic feature according to TWILIGHT trial criteria. The clinical criteria for high risk were age≥65 years, female sex, troponin-positive ACS, established vascular disease, diabetes mellitus that was being treated with medication, and CKD. Angiographic criteria included multivessel coronary artery disease, total stent lengthd≥30 mm, a thrombotic target lesion, a bifurcation lesion treated with two stents, an obstructive left main or proximal left anterior descending lesion, and a calcified target lesion treated with atherectomy. The primary outcome was major adverse cardiac and cerebrovascular events [MACCE] (a composite of all-cause death, MI, or stroke). Results During a median follow-up of 30 months after the index procedure, DAPT&gt;1-year was associated with a reduction in risk for MACCE compared with DAPT≤1-year (1.5% vs. 3.8%; adjusted hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.27–0.50; P&lt;0.001) after multivariable adjustment. This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of BARC type 2, 3 or 5 bleeding was statistically similar between the 2 groups (1.0% vs. 1.1%; adjusted HR: 0.81; 95% CI: 0.50–1.30; P=0.373). After propensity score matching, incidence of MACCE was still lower in the DAPT&gt;1-year group than the DAPT≤1-year group (1.6% versus 4.5%; HR, 0.34; 95% CI, 0.22–0.52; P&lt;0.001) and the rates of BARC type 2, 3 or 5 bleeding was not different between the 2 groups (1.1% versus 0.9%; adjusted HR, 1.12; 95% CI, 0.57–2.18; P=0.744). In subgroup analysis, the treatment effect of prolonged DAPT was consistent across subgroups regardless of ACS, DAPT score, or type of used DES. Conclusions DAPT continuation with aspirin and clopidogrel beyond 1-year after DES implantation resulted in a significantly lower rate of MACCE, with no higher risk of clinically relevant bleeding in TWLIGHT-like patients who were at high-risk for ischemic or bleeding events. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Natural Science Foundation of China

scholarly journals Thrombotic vs. Bleeding Events of Interruption of Dual Antiplatelet Therapy within 12 Months among Patients with Stent-Driven High Ischemic Risk Definition following PCI

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Hao-Yu Wang ◽  
Bo Xu ◽  
Chen-Xi Song ◽  
Chang-Dong Guan ◽  
Li-Hua Xie ◽  
...  
Keyword(s):  
High Risk ◽  
Propensity Score ◽  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Cox Regression ◽  
Major Adverse Cardiovascular Events ◽  
Bleeding Events ◽  
Risk Criteria ◽  
Clinical Events

Background. There is a paucity of real-world data regarding the clinical impact of dual antiplatelet therapy (DAPT) interruption (temporary or permanent) among patients at high ischemic risk. The aim of this study was to assess the risk of cardiovascular events after interruption of DAPT in high-risk PCI population. Methods. This study used data from the Fuwai PCI registry, a large, prospective cohort of consecutive patients who underwent PCI. We assessed 3,931 patients with at least 1 high ischemic risk criteria of stent-related recurrent ischemic events proposed in the 2017 ESC guidelines for focused update on DAPT who were free of major cardiac events in the first 12 months. The primary ischemic endpoint was 30-month major adverse cardiac and cerebrovascular events, and the key safety endpoints were BARC class 2, 3, or 5 bleeding and net adverse clinical events. Results. DAPT interruption within 12 months occurred in 1,122 patients (28.5%), most of which were due to bleeding events or patients’ noncompliance to treatment. A multivariate Cox regression model, propensity score (PS) matching, and inverse probability of treatment weighting (IPTW) based on the propensity score demonstrated that DAPT interruption significantly increased the risk of primary ischemic endpoint compared with prolonged DAPT (3.9% vs. 2.2%; Cox-adjusted hazard ratio (HR): 1.840; 95% confidence interval (CI): 1.247 to 2.716; PS matching-HR: 2.049 [1.236–3.399]; IPTW-adjusted HR: 1.843 [1.250–2.717]). This difference was driven mainly by all-cause death (1.8% vs. 0.7%) and MI (1.3% vs. 0.5%). Furthermore, the rate of net adverse clinical events (4.9% vs. 3.2%; Cox-adjusted HR: 1.581 [1.128–2.216]; PS matching-HR: 1.639 [1.075–2.499]; IPTW-adjusted HR: 1.554 [1.110–2.177]) was also higher in patients with DAPT interruption (≤12 months), whereas no significant differences between groups were observed in terms of BARC 2, 3, or 5 bleeding. These findings were consistent across various stent-driven high-ischemic risk subsets with respect to the primary ischemic endpoints, with a greater magnitude of harm among patients with diffuse multivessel diabetic coronary artery disease. Conclusions. In patients undergoing high-risk PCI, interruption of DAPT in the first 12 months occurred infrequently and was associated with a significantly higher adjusted risk of major adverse cardiovascular events and net adverse clinical events. 2017 ESC stent-driven high ischemic risk criteria may help clinicians to discriminate patient selection in the use of long-term DAPT when the ischemic risk certainly overcomes the bleeding one.

Benefit-risk profile of longer-than-1-year dual antiplatelet therapy in TWLIGHT-like patients with high risk of ischemic or bleeding events after drug-eluting stents implantation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H.Y Wang ◽  
R Gao ◽  
B.O Xu ◽  
K Dou ◽  
A Kirtane
Keyword(s):  
High Risk ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Target Lesion ◽  
Clinical Feature ◽  
Funding Source ◽  
Bleeding Events ◽  
Index Procedure ◽  
Drug Eluting

Abstract Background Dual-antiplatelet therapy (DAPT) exceeding 1 year may increase a bleeding risk despite reducing the risk of ischemic events. The benefits and harms of prolonging DAPT with aspirin and clopidogrel beyond 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for TWLIGHT-like patients with high-risk for bleeding or an ischemic event remain unknown. Method Between January 2013 and December 2013, all consecutive patients undergoing PCI were prospectively included in the Fuwai PCI Registry. We evaluated 7521 patients who were at high risk for ischemic or hemorrhagic complications and were events free (no death, myocardial infarction [MI], stroke, stent thrombosis [ST], any revascularization, or major bleeding) at 1 year after the index procedure. Subjects were divided into 2 groups: DAPT &gt;1-year group (n=5252) and DAPT ≤1-year group (n=2269). Patients at high-risk for ischemic or bleeding events were defined as having at least one additional clinical feature and one angiographic feature according to TWILIGHT trial criteria. The clinical criteria for high risk were age ≥65 years, female sex, troponin-positive ACS, established vascular disease, diabetes mellitus that was being treated with medication, and CKD. Angiographic criteria included multivessel coronary artery disease, total stent length ≥30 mm, a thrombotic target lesion, a bifurcation lesion treated with two stents, an obstructive left main or proximal left anterior descending lesion, and a calcified target lesion treated with atherectomy. The primary outcome was major adverse cardiac and cerebrovascular events [MACCE] (a composite of all-cause death, MI, or stroke). Results During a median follow-up of 30 months after the index procedure, DAPT &gt;1-year was associated with a reduction in risk for MACCE compared with DAPT ≤1-year (1.5% vs. 3.8%; adjusted hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.27–0.50; P&lt;0.001) after multivariable adjustment. This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of BARC type 2, 3 or 5 bleeding was statistically similar between the 2 groups (1.0% vs. 1.1%; adjusted HR: 0.81; 95% CI: 0.50–1.30; P=0.373). After propensity score matching, incidence of MACCE was still lower in the DAPT &gt;1-year group than the DAPT ≤1-year group (1.6% versus 4.5%; HR, 0.34; 95% CI, 0.22–0.52; P&lt;0.001) and the rates of BARC type 2, 3 or 5 bleeding was not different between the 2 groups (1.1% versus 0.9%; adjusted HR, 1.12; 95% CI, 0.57–2.18; P=0.744). In subgroup analysis, the treatment effect of prolonged DAPT was consistent across subgroups regardless of ACS, DAPT score, or type of used DES. Conclusions DAPT continuation with aspirin and clopidogrel beyond 1-year after DES implantation resulted in a significantly lower rate of MACCE, with no higher risk of clinically relevant bleeding in TWLIGHT-like patients who were at high-risk for ischemic or bleeding events. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China

scholarly journals Impact of on-clopidogrel platelet reactivity on incidence of peri-interventional bleeding in patients undergoing transcatheter aortic valve implantation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Kille ◽  
T Nuehrenberg ◽  
J Hromek ◽  
C.M Valina ◽  
D Trenk ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
High Risk ◽  
Aortic Valve ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Bleeding Events ◽  
Transcatheter Aortic Valve ◽  
Aortic Valve Implantation ◽  
Valve Implantation

Abstract Background Transcatheter aortic valve implantation (TAVI) has become clinical routine for patients at intermediate to high risk for surgical aortic valve replacement. The optimal antithrombotic strategy following TAVI is still not well defined. Antithrombotic treatment is administered to prevent hypo-attenuated leaflet thickening, valve thrombosis, or ischemic stroke. However, most of these patients are also at high risk for bleeding. Current guidelines recommend dual antiplatelet therapy although the clinical evidence is limited. Methods This analysis enrolled patients undergoing TAVI from 11/2013 until 04/2018. Patients were either on long-term dual antiplatelet therapy with clopidogrel and aspirin or received a loading dose 300 to 600mg of clopidogrel and 400mg aspirin before TAVI. Platelet reactivity was determined by multi-electrode impedance aggregometry after stimulation with arachidonic acid and adenosine diphosphate (ADP) before TAVI as well as at day 1 and 5 thereafter. Peri-interventional bleeding was assessed up to 5 days following TAVI and coded according to BARC-classification. Results The present analysis included 484 patients (median age 83 [79–86] years; female sex 54.5%). There were 199 (41.1%) patients with a bleeding event. Most frequent were BARC 2 bleedings in 117 (24.2%) cases followed by BARC 1 (6.0%), BARC 3b in 25 (5.2%) and BARC 3a in 22 (4.5%) cases. On-clopidogrel platelet reactivity tested after stimulation with ADP was significantly lower in patients with bleeding events as compared to patients without bleeding (Figure). No differences were observed in arachidonic acid-induced platelet reactivity as marker for aspirin-efficacy between both groups over time. Multivariate logistic regression analysis identified on-clopidogrel platelet reactivity and use of oral anticoagulation as strongest independent predictors for bleeding events. Conclusion On-clopidogrel platelet reactivity is an independent predictor for peri-interventional bleeding in patients undergoing TAVI. Taken together with previous data indicating no association of on-clopidogrel platelet reactivity with peri-interventional ischemic events, the present data question the need for a strong peri-interventional dual antiplatelet therapy in patients undergoing TAVI. Funding Acknowledgement Type of funding source: None

Abstract 297: Dual Antiplatelet Therapy versus Triple Therapy with Anticoagulant Following Percutaneous Coronary Intervention in High Risk Patients Requiring Long-Term Anticoagulation: A Meta-Analysis

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Hemang B Panchal ◽  
Tejaskumar Shah ◽  
Mukesh Singh ◽  
Sandeep Khosla ◽  
Vijay Ramu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
High Risk ◽  
Triple Therapy ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Bleeding Events ◽  
High Risk Patients ◽  
Risk Patients

Background: Dual antiplatelet therapy with aspirin and clopidogrel is the cornerstone of treatment to prevent major adverse cardiovascular events (MACE) in patients following percutaneous coronary intervention (PCI). In high-risk patients requiring long-term anticoagulant, the current literatures have controversial results in preventing MACE and bleeding events with the use of triple therapy with aspirin, clopidogrel and warfarin compared to dual antiplatelet therapy following PCI. The purpose of this meta-analysis was to compare the safety and efficacy of triple therapy with dual therapy following PCI in high-risk patients requiring long term anticoagulation. Methods: A literature search identified 4 prospective and 4 retrospective studies with total of 2439 patients requiring long term anticoagulation undergoing PCI. End points measured were bleeding events, deaths, ischemic stroke, myocardial infarction, stent thrombosis and MACE. The odds ratios (OR) with 95% confidence intervals (CI) were computed and two sided alpha error <0.05 considered as a level of significance. Results: In contrast to dual antiplatelet therapy, patients on triple therapy with anticoagulant had significantly lower stent thrombosis (OR: 0.45, CI: 0.21-0.94, p=0.03) and ischemic stroke (OR: 0.30, CI: 0.16-0.56, p<0.001) (Fig 1 - Zone A is dual therapy group, zone B is triple therapy group). No significant difference was found between two groups in overall bleeding events (OR: 1.57, CI: 0.87-2.85, p=0.14), major bleeding events(OR:1.21, CI: 0.57-2.59, p=0.62), deaths (OR:0.89, CI: 0.5-1.58, p=0.69), myocardial infarction (OR:1.31, CI: 0.85-2.02, p=0.22) and MACE (OR:0.61, CI:0.20-1.82, p=0.37). Conclusions: Our meta-analysis suggests that the triple therapy with anticoagulant does not increase bleeding compared to dual antiplatelet therapy. Moreover, triple therapy decreases stent thrombosis and ischemic stroke following PCI in patients requiring long-term anticoagulants. Our study did not show any difference in mortality between two groups. Triple therapy may be a favorable strategy following PCI in high-risk patients requiring long-term anticoagulation. The randomized control clinical trials are needed for further evaluation of long-term outcomes.

scholarly journals Benefit and Harm of Extended Dual Antiplatelet Therapy After PCI in high-risk TWILIGHT-like patients with acute coronary syndrome

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
HY Wang ◽  
R Zhang ◽  
ZX Cai ◽  
KF Dou
Keyword(s):  
Acute Coronary Syndrome ◽  
High Risk ◽  
Antiplatelet Therapy ◽  
Cardiovascular Death ◽  
Secondary Outcome ◽  
Short Term ◽  
Bleeding Events ◽  
Coronary Syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent emphasis on reduced duration and/or intensity of antiplatelet therapy following PCI irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients. This study sought to investigate the benefits and risks of extended-term (&gt;12-month) DAPT as compared with short-term DAPT in high-risk "TWILIGHT-like" ACS patients undergoing PCI. Methods All consecutive patients fulfilling the "TWILIGHT-like" criteria undergoing PCI from January 2013 to December 2013 were identified from the prospective Fuwai PCI Registry. High-risk "TWILIGHT-like" patients were defined by at least 1 clinical and 1 angiographic feature based on TWILIGHT trial selection criteria. The present analysis evaluated 4,875 high-risk "TWILIGHT-like" patients with ACS who were event-free at 12 months after PCI. The primary outcome was the composite of all-cause death, myocardial infarction (MI), or stroke at 30 months while BARC type 2, 3, or 5 bleeding was key secondary outcome. Results Extended DAPT compared with shorter DAPT reduced the composite outcome of all-cause death, MI, or stroke by 63% (1.5% vs. 3.8%; HRadj: 0.374, 95% CI: 0.256 to 0.548; HRmatched: 0.361, 95% CI: 0.221-0.590). The HR for cardiovascular death was 0.049 (0.007 to 0.362) and that for MI 0.45 (0.153 to 1.320) and definite/probable stent thrombosis 0.296 (0.080-1.095) in propensity-matched analyses. Rates of BARC type 2, 3, or 5 bleeding (0.9% vs. 1.3%; HRadj: 0.668 [0.379 to 1.178]; HRmatched: 0.721 [0.369-1.410]) did not differ significantly in patients treated with DAPT &gt; 12-month or DAPT ≤ 12-month. The effect of long-term DAPT on primary and key secondary outcome across the proportion of ACS patients with 1-3, 4-5, or 6-9 risk factors showed a consistent manner (Pinteraction &gt; 0.05). Conclusion Among high-risk "TWILIGHT-like" patients with ACS after PCI, long-term DAPT reduced ischemic events without increasing clinically meaningful bleeding events as compared with short-term DAPT, suggesting that extended DAPT might be considered in the treatment of ACS patients who present with a particularly higher risk for thrombotic complications. Abstract Figure.

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