Dual Antiplatelet Therapy For Prevention Research Articles

Native Sinus Hemodynamics and Thrombosis in Transcatheter Heart Valve: Effect of Implant Depth and Coronary Flow.

This study aimed to investigate the hemodynamic and anatomic factors associated with sinus thrombosis following transcatheter aortic valve replacement (TAVR), integrating invivo patient data analysis and invitro experiments. Postprocedural, 4-dimensional, multiphase computed tomography data from 211 patients enrolled in the ADAPT-TAVR (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement) study were analyzed. The prevalence of native sinus thrombosis was examined in relation to valve type, implant depth, and anatomic features. Invitro experiments used particle image velocimetry to observe changes in sinus flow based on the transcatheter heart valves (23-mm SAPIEN3, Edwards Lifesciences; and 29-mm CoreValve, Medtronic) height and coronary artery flow. Native sinus thrombosis was more common in self-expanding valves (39.1% versus 14.9%, P=0.004). In per-cusp analysis of invivo patient data, adjusted transcatheter heart valve implant depth (odds ratio, 1.2 [95% CI, 1.1-1.3]; P<0.001), noncoronary sinus of Valsalva (odds ratio, 4.0 [95% CI, 2.0-7.8]; P<0.001), sinus inflow diameter (odds ratio, 0.8 [95% CI, 0.6-0.9]; P=0.008), and implanted valve size (odds ratio, 0.8 [95% CI, 0.7-1.0]; P=0.025) were significant factors associated with native sinus thrombosis. In the invitro experiments, CoreValve showed noticeable flow stasis compared with SAPIEN3. High-positioned SAPIEN3 was linked to reduced velocity within the native sinus of Valsalva. Coronary artery flow led to higher sinus velocity and improved particle washout, reducing sinus thrombosis risk. This study provides insights into the relationship between transcatheter heart valve deployment and native sinus thrombosis, emphasizing the role of anatomic factors in relation to the risk of sinus thrombosis.

Frequency, Predictors, and Clinical Impact of Valvular and Perivalvular Thrombus After Transcatheter Aortic Valve Replacement

BackgroundSubclinical aortic valve complex (valvular and perivalvular) thrombus is not rare after transcatheter aortic valve replacement (TAVR). The risk factors and clinical implications of these findings remain uncertain. ObjectivesThis study sought to evaluate the frequency, predictors, and clinical outcome of aortic valve complex thrombus after TAVR. MethodsIn the ADAPT-TAVR (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement) trial comparing edoxaban vs dual antiplatelet therapy in TAVR patients without an indication for chronic anticoagulation, the frequency of valvular (subclinical leaflet thrombus) and perivalvular (supravalvular, subvalvular, and sinus of Valsalva) thrombus was evaluated by 4-dimensional computed tomography at 6 months. The association of these phenomena with new cerebral thromboembolism on brain magnetic resonance imaging, neurologic and neurocognitive dysfunction, and clinical outcomes was assessed. ResultsAmong 211 patients with 6-month computed tomography evaluations, 91 patients (43.1%) had thrombus at any aortic valve complex, 30 (14.2%) patients had leaflet thrombus, and 78 (37.0%) patients had perivalvular thrombus. A small maximum diameter of the stent at the valve level and low body surface area were independent predictors of aortic valve complex and perivalvular thrombus, and decreased renal function was an independent predictor of leaflet thrombus. No significant differences were observed in new cerebral lesions, neurologic or neurocognitive functions, or clinical outcomes among patients with or without valvular or perivalvular thrombus. ConclusionsSubclinical aortic valve complex (valvular and perivalvular) thrombus was common in patients who had undergone successful TAVR. However, these imaging phenomena were not associated with new cerebral thromboembolism, neurologic or neurocognitive dysfunction, or adverse clinical outcomes. (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement [ADAPT-TAVR]; NCT03284827)

Impact of leaflet thrombosis on valve haemodynamic status after transcatheter aortic valve replacement

ObjectivesThe effect of subclinical leaflet thrombosis, characterised by hypoattenuated leaflet thickening (HALT), on the valve haemodynamic function and durability of the bioprosthetic valve, is not yet determined. We determined the...

Dual Antiplatelet Versus Single Antiplatelet in Post– Transcatheter Aortic Valve Implantation/Transcatheter Aortic Valve Replacement for Stroke Prevention: A Systematic Review and Meta-analysis

BACKGROUND: There is ambiguity on antiplatelet therapy for post–transcatheter aortic valve replacement (TAVR) patients for stroke prevention, but dual antiplatelet therapy (DAPT) is routinely started despite lack of data on effectiveness and bleeding safety of DAPT versus single antiplatelet therapy (SAPT). This study aims to determine the effectiveness of DAPT versus SAPT in stroke prevention and assess bleeding safety. METHODS: A systematic search was done for randomized clinical trials involving DAPT and SAPT in patients who underwent TAVR. The primary outcome was stroke after 1 year of either DAPT and SAPT and life-threatening bleeding. Secondary end points included all-cause mortality. Trials were identified through systematic searches on the following databases (November 2019): Cochrane, MEDLINE, and Google Scholar and ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform. Risk ratio was used for dichotomous outcomes. Heterogeneity among the studies for the meta-analysis was detected using a χ2 test (0.01 level of significance). Risk-of-bias assessment was done. RESULTS: There is a lower incidence of stroke in patients on DAPT, but with a higher incidence of life-threatening bleeding and major bleeding. There is also a lower incidence of all-cause mortality in SAPT. The statistical power of this meta-analysis is low due to small population size. CONCLUSION: Single antiplatelet therapy is comparable to DAPT in preventing stroke with the added benefit of a lower incidence of life-threatening and major bleeding and a lower incidence of all-cause mortality. KEYWORDS: antiplatelet therapy, bleeding, dual antiplatelet therapy, single antiplatelet therapy, mortality, myocardial infarction, stroke, transcatheter aortic valve replacement, transcatheter aortic valve implantation

Rationale and design of the ADAPT-TAVR trial: a randomised comparison of edoxaban and dual antiplatelet therapy for prevention of leaflet thrombosis and cerebral embolisation after transcatheter aortic valve replacement

IntroductionOptimal antithrombotic strategy following transcatheter aortic valve replacement (TAVR) is still unknown. We hypothesised that the direct factor Xa inhibitor edoxaban can potentially prevent subclinical leaflet thrombosis and cerebral embolisation...

Lp-PLA2 and dual antiplatelet agents in intracranial arterial stenosis.

To 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. Patients 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. Among 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. Presence 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. NCT00979589.

Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54.

PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup. This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21162 patients with prior MI (1-3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15-1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68-0.99) and with prior stenting (HR 0.85, 95% CI 0.75-0.96; P for interaction = 0.76). Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting. NCT01225562.

Short-term vs Long-term Dual Antiplatelet Therapy for Prevention of Delayed Thromboembolic Events after Stent-Assisted Coiling of Intracranial Aneurysm: A Randomized Clinical Trial

Short-term vs Long-term Dual Antiplatelet Therapy for Prevention of Delayed Thromboembolic Events after Stent-Assisted Coiling of Intracranial Aneurysm: A Randomized Clinical Trial

Dual antiplatelet therapy for prevention of recurrent ischemic events.

The advantages of dual antiplatelet therapy over monotherapy in preventing recurrent ischemic events are examined. Atherosclerosis is an insidious systemic process involving multiple vascular beds, including the cerebral, coronary, and peripheral arteries. Atherosclerotic plaque rupture is one of the inciting events in the progression of platelet activation, aggregation, and thrombus formation. Patients with any clinical manifestation of atherosclerosis are vulnerable to others in different vascular beds since the disease develops throughout the vasculature, and different vascular events have common predisposing risk factors. Ischemic coronary heart disease and cerebrovascular disease are two of the three most frequent causes of death in the United States. The efficacy of aspirin in the secondary prevention of myocardial infarction (MI) and stroke has been demonstrated in numerous trials. While dipyridamole has not been linked with a greater odds reduction than aspirin in the development of MI, stroke, and vascular death, ticlopidine and clopidogrel have been associated with a greater reduction in the development of acute MI, stroke, and vascular death than aspirin. Clinical trials evaluating the efficacy and safety of combination antiplatelet therapy in the prevention of recurrent ischemic events are ongoing. The rationale for using a combination of two mechanistically different antiplatelet agents is supported by ex vivo and clinical studies. Inhibition of platelet aggregation and thrombus formation is enhanced with dual antiplatelet therapy. Combination antiplatelet regimens with different mechanisms of action to inhibit multiple sites in the thrombotic pathway may further improve long-term clinical outcomes. Dual antiplatelet therapy may have advantages over monotherapy in the prevention of recurrent ischemic events.