Bleeding Risk of Dual Antiplatelet Therapy after Minor Stroke or TIA

Abstract Background Diabetes is a known risk factor for a first or recurrent cardiovascular event, however, its association with an increased risk of bleeding is controversial. To date, no study has explored the prognostic weight of insulin therapy in the setting of ACS. Purpose To investigate the differential role of insulin versus no insulin therapy on ischemic and bleeding risks in patients with diabetes and ACS. Methods START-ANTIPLATELET is a prospective, real-world multicenter registry including consecutive patients admitted for ACS. For the purpose of this analysis, patients were stratified according to diabetes status and insulin therapy. We compared 1-year rates of major adverse cardiovascular events, a composite of cardiovascular death, myocardial infarction and stroke, and of any bleeding, according to diabetes status (no diabetes, diabetes not on insulin therapy, diabetes on insulin therapy). In addition, we evaluated the net clinical benefit of dual antiplatelet therapy with the newer P2Y12 inhibitors (ticagrelor or prasugrel) vs dual antiplatelet therapy with clopidogrel according to diabetes status. Results In an overall population of 907 patients, 198 had diabetes, 10.6% of whom were on insulin. From non-diabetic patients to diabetic patients not on insulin and diabetic patients on insulin there was a stepwise decrease of MACE-free survival (log-rank p 0.039) with incidence of events at 1 year being 3.8%, 6.8% (adjusted p vs no diabetes 0.49) and 12.5% (adjusted p vs no diabetes 0.047), respectively (Figure, panel A). The rates of any bleeding were higher in patients on insulin (20.8% vs 8.8% in those without diabetes and 5.8% in diabetic patients not receiving insulin; log-rank p 0.028; Figure, panel B). Multivariable analysis demonstrated an almost 5-fold increase of any bleeding in diabetic patients with vs without insulin (OR 4.98, 95% CI 1.46–16.92; p=0.010). In the overall population, the incidence of the net composite endpoint including MACE or major bleeding with the use of ticagrelor/prasugrel on top of aspirin was significantly lower compared to use of clopidogrel (4.7% vs 8.4%; OR 0.54, 95% CI 0.30–0.94, p=0.031). This net clinical benefit in patients receiving a newer P2Y12 inhibitor was regardless of the diabetes status (p for interaction 0.48). Conclusions In this cohort of ACS patients, the presence of diabetes stratified by insulin therapy was associated with a graded increase in the 1-year rates of MACE. Conversely, insulin therapy significantly contributed to the overall increase of bleeding risk in diabetes. Funding Acknowledgement Type of funding source: None

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Comparison of outcome of patients with acute minor ischaemic stroke treated with intravenous t-PA, DAPT or aspirin

Stroke and Vascular Neurology ◽

10.1136/svn-2019-000319 ◽

2020 ◽

pp. svn-2019-000319

Author(s):

Peng Wang ◽

Mengyuan Zhou ◽

Yuesong Pan ◽

Xia Meng ◽

Xingquan Zhao ◽

...

Keyword(s):

Functional Outcome ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

National Institutes Of Health ◽

Minor Stroke ◽

Post Hoc Analysis ◽

Intravenous Tissue Plasminogen Activator ◽

Tissue Plasminogen ◽

Ischemic Attack ◽

Post Hoc

BackgroundWhether to treat minor stroke with intravenous tissue plasminogen activator (t-PA) treatment or antiplatelet therapy is a dilemma. Our study aimed to explore whether intravenous t-PA treatment, dual antiplatelet therapy (DAPT) and aspirin have different efficacies on outcomes in patients with minor stroke.MethodsA post hoc analysis of patients with acute minor stroke treated with intravenous t-PA within 4.5 hours from a nationwide multicentric electronic medical record and patients with acute minor stroke treated with DAPT and aspirin from the Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack Database. Minor stroke was defined by a score of 0–3 on the National Institutes of Health Stroke Scale at randomisation. Favourable functional outcome (defined as modified Rankin Scale (mRS) score of 0–1 or 0–2 at 3 months).ResultsCompared with those treated with intravenous t-PA, no significant association with 3-month favourable functional outcome (defined as mRS score of 0–1) was found neither in patients treated with aspirin (87.8% vs 89.4%; OR, 0.83; 95% CI, 0.46 to 1.50; p=0.53) nor those treated with DAPT (87.4% vs 89.4%; OR, 0.84; 95% CI, 0.46 to 1.52; p=0.56). Similar results were observed for the favourable functional outcome defined as mRS score of 0–2 at 3 months.ConclusionsIn our study, no significant advantage of intravenous t-PA over DAPT or aspirin was found. Due to insufficient sample size, our study is probably unable to draw such a conclusion that that intravenous t-PA was superior or non-superior to DAPT.

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Abstract 104: Disability After Minor Stroke and TIA in the POINT Trial

Stroke ◽

10.1161/str.51.suppl_1.104 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Brett L Cucchiara ◽

Jordan Elm ◽

J Donald Easton ◽

Shelagh Coutts ◽

Joshua Willey ◽

...

Keyword(s):

Ischemic Stroke ◽

Adverse Events ◽

Antiplatelet Therapy ◽

Primary Outcome ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Primary Outcome Measure ◽

Minor Stroke ◽

Serious Adverse Events ◽

Index Event

Background and Purpose: To assess the effect of combination antiplatelet therapy with aspirin and clopidogrel versus aspirin alone on disability following TIA or minor stroke and to identify factors associated with disability. Methods: The POINT trial randomized patients with TIA or minor stroke (NIHSS≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, MI, or vascular death. We performed a post-hoc exploratory analysis to examine the effect of treatment on overall disability (defined as mRS>1) at 90 days as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results: At 90 days, 188/1964 (9.6%) of patients enrolled with TIA and 471/2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% vs. 14.3%, OR 0.97, 95%CI 0.82-1.14, p=0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% vs. 4.0%, OR 0.73, 95%CI 0.53-1.01, p=0.06), and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% vs. 7.4%, OR 0.78, 95% CI 0.62-0.99, p=0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% vs. 6.0%, OR 0.74 95% CI 0.57-0.96, p=0.02). In multivariate analysis of patients enrolled with TIA, disability was significantly associated with age, subsequent ischemic stroke, serious adverse events, and major bleeding. In patients enrolled with stroke, disability was associated with female sex, hypertension, diabetes, NIHSS score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events. Conclusions: In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, dual antiplatelet therapy might reduce stroke-related disability.

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Revacept, a Novel Inhibitor of Platelet Adhesion, in Patients Undergoing Elective PCI—Design and Rationale of the Randomized ISAR-PLASTER Trial

Thrombosis and Haemostasis ◽

10.1055/s-0039-1692423 ◽

2019 ◽

Vol 119 (09) ◽

pp. 1539-1545 ◽

Cited By ~ 11

Author(s):

Stefanie Schüpke ◽

Ralph Hein-Rothweiler ◽

Katharina Mayer ◽

Marion Janisch ◽

Dirk Sibbing ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Phase Ii ◽

Platelet Adhesion ◽

Dual Antiplatelet Therapy ◽

Troponin T ◽

Stable Coronary Artery Disease ◽

Academic Research ◽

Bleeding Risk ◽

Double Blind ◽

Glycoprotein Vi

AbstractDespite dual antiplatelet therapy patients undergoing percutaneous coronary intervention (PCI) continue to experience periprocedural ischemic events. In addition, all currently used antithrombotic drugs increase the bleeding risk. Thus, there is an unmet clinical need for antithrombotic strategies with improved efficacy and no increase in bleeding. Revacept is a novel, lesion-directed antithrombotic drug that does not interfere with the function of circulating platelets. This dimeric fusion protein of the extracellular domain of glycoprotein VI (the major platelet collagen receptor) and the human Fc-fragment inhibits collagen-mediated platelet adhesion and subsequent aggregation at the site of vascular injury. The randomized, double-blinded, phase II ISAR-PLASTER trial is based on extensive preclinical evaluation of Revacept and a favorable first-in-man trial. A total of 332 patients with stable coronary artery disease undergoing elective PCI will be randomized to either Revacept 160 mg, Revacept 80 mg, or placebo administered as single intravenous infusion directly before the intervention, on top of standard dual antiplatelet therapy and either heparin or bivalirudin, based on local practice and current guidelines. The primary endpoint is the composite of death or myocardial injury (defined as increase in high sensitivity troponin T ≥ 5 times the upper limit of normal) at 48 hours. The safety endpoint is bleeding of class 2 or higher according to the Bleeding Academic Research Consortium at 30 days. This phase II randomized, double blind trial will assess for the first time the efficacy and safety of Revacept—a lesion-directed inhibitor of platelet adhesion—in patients undergoing elective PCI.

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Mo1276 – No Differences in Gi Bleeding Risk Between Clopidogrel-, Ticagrelor- Or Prasugrel- Based Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Gastroenterology ◽

10.1016/s0016-5085(19)38791-8 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-743

Author(s):

Viviana Laredo ◽

Sandra Garcia ◽

Nuria Saura ◽

Maria Hernandez Ainsa ◽

Patricia Carrera ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Bleeding Risk ◽

Coronary Intervention ◽

Gi Bleeding ◽

Percutaneous Coronary

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Lp-PLA2 and dual antiplatelet agents in intracranial arterial stenosis

Neurology ◽

10.1212/wnl.0000000000008733 ◽

2019 ◽

Vol 94 (2) ◽

pp. e181-e189 ◽

Cited By ~ 1

Author(s):

Ming Yang ◽

Anxin Wang ◽

Jiejie Li ◽

Xingquan Zhao ◽

Liping Liu ◽

...

Keyword(s):

High Risk ◽

Antiplatelet Therapy ◽

Proportional Hazards ◽

Dual Antiplatelet Therapy ◽

Cox Proportional Hazards ◽

Arterial Stenosis ◽

Minor Stroke ◽

Activity Levels ◽

Intracranial Arterial Stenosis ◽

Vascular Events

ObjectiveTo evaluate the interaction effect of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity on the efficacy and safety of dual/single antiplatelet therapy in patients with and without intracranial arterial stenosis (ICAS) by the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events trial.MethodsPatients with both MRI analysis and Lp-PLA2 testing results were included in the current subanalysis. The interaction of Lp-PLA2 activity with the effects of dual and single antiplatelet therapy were analyzed through Cox proportional hazards regressions model.ResultsAmong the 797 patients, the mean age was 63.1 ± 10.8 years, 518 (65%) were men, 356 (44.7%) had ICAS, and 441 (55.3%) did not. There were significantly more patients with elevated Lp-PLA2 activity in the ICAS group than in the non-ICAS group (43.8% vs 35.4%, p = 0.02). There was significant interaction between Lp-PLA2 activity levels and the 2 antiplatelet therapies for prevention of stroke recurrences and combined vascular events even after adjustment for confounding factors exclusively for patients with ICAS (p = 0.017, 0.017, respectively), but not for those without (p = 0.332, 0.674, respectively). Compared with aspirin alone, dual antiplatelet therapy significantly reduced the risk of stroke recurrences and combined vascular events (adjusted hazard ratio 0.33 [0.12–0.89], p = 0.028; 0.33 [0.12–0.89], p = 0.028, respectively) for patients with ICAS and nonelevated Lp-PLA2 activity.ConclusionsPresence of both ICAS and nonelevated Lp-PLA2 activity may predict better response to dual antiplatelet therapy in prevention of recurrent strokes and combined vascular events for patients with minor stroke or high-risk TIA.Clinicaltrials.gov identifierNCT00979589.

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