Transcatheter aortic valve replacement (TAVR) introduction to the clinical practice revolutionized the interventional cardiology ,it is a valuable option for a non –operable patient with sever aortic stenosis or high risk population however ,TAVR is associated with a risk of cerebral embolization and ischemic vascular events and possible neurological impairment the estimate of these complication is vary but it have been reported early and late after the procedure moreover the reported incidence of bleeding associated with TAVI is relatively high . with this given incident of complication required adequate antithrombotic therapy during and following procedure ,however despite the current guidelines recommendation the optimal antithrombotic is not very well established . Introduction:Sever Aortic Stenosis (AS) is a major cause of mortality and morbidity in elderly duo to a bimodal age distribution ,degenerative calcification of Tricuspid valve is the major cause of AS in the population ,unlike the younger patient etiology which is : bicuspid valve calcification or rheumatic heart disease . 1The Burden of the disease is high with a prevalence of 3.
4% 2. With the progressive nature of the disease and the increased severity of the symptoms made the surgery the gold standard for symptomatic AS patients ,however up to 30% of cases are considered too high risk for classical valve replacement surgery and remain untreated and experiencing poor prognosis . Fortunately , with the introduction of TAVR its offer a valuable option for the inoperable or at high risk of surgery patients3. . the annual eligible candidate for this procedure expected to be 27,000 in 19 European countries and North America according to recent meta-analysis and modeling study2,TAVI is associated with a high risk of stroke ,transient ischemic stroke ,Atrial Fibrillation and myocardial infarction and the long term outcome associated with bleeding complication mainly duo to the use of Dual antiplatlets therapy (DAPT) which raise the need to find the optimal regimen of antithrombotic to avoid the early cerebrovascular complication ,provide optimum stroke prevention and avoid the bleeding as a long term outcome . This article will review the current recommendation of antithrombotic during and following TAVI and the recent evidence and advancement in this unique procedure.
TAVI Versus SAVR :Although there are cumulative data suggesting superior survival and symptomatic outcomes for inoperable patients who undergo TAVI versus medical palliation4,5 The available data on TAVI versus AVR showed that major adverse outcomes such as mortality and stroke appeared to be similar between the two treatment modalities. Evidence on the outcomes of TAVI compared with AVR in the current literature is limited by inconsistent patient selection criteria, heterogeneous definitions of clinical endpoints and relatively short follow-up periods. two meta-analysis have been conducted that include TAVR and SAVR studies in their evaluation . one meta-analysis compared TAVR to AVR combining the results from two randomized controlled trials and 11 observational reports comparing TAVI with AVR in patients with severe aortic stenosis6. Interestingly, selected studies identified no significant differences in mortality and stroke between the two treatment groups. However, vascular complications, permanent pacemaker insertion and significant aortic regurgitation were relatively common after TAVI, and significantly more frequent than after conventional AVR.
Conversely, major bleeding was more likely to occur after surgical AVR than TAVI. The second meta-analysis of seventeen studies in (n=4,659) comparing TAVR (n=2,267) and SAVR ( n2,392) was conducted to determine the differences in postprocedural mortality and major adverse cardiovascular and cerebrovascular events between the two attack, and major bleeding interventions . 7 End points were baseline logistic European System for Cardiac Operative Risk Evaluation score, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke,transient ischemic events. There was no significant difference in cardiovascular mortality (p[0. 54) as well as the incidence of myocardial infarction (p[0.
59), stroke (p[0. 36), and transient ischemic attack (p [ 0. 85) at averages of 86, 72, 66, and 89 weeks, respectively Similar to the previous meta-analysis ,TAVI WAS noninferior to SAVR for postprocedural myocardial infarctions and cerebrovascular events but it was superior to SAVR for major bleeding complications. therfore TAVR should be considered in selected high risk elderly patients and the use of TAVR for eligible surgical candidate should be considered within the boundaries of clinical trials duo to the importan;t cerebrovascular and cardiovascular debilitating adverse events which is a significant predictor of mortality the suggested predisposing factors for the occurrence of stroke are a newly onset of atrial fibrillation and a higher-grade mitral valve insufficiency8,9. Moreover, the antithrombotic regimen appear to play a major role in prevention of those fatal complications.
10 however , it is unclear what is the optimal antithrombotic regimen to provide protection for early and late thrombotic events in patients who undergoing to TAVR11 in the absence of randomized control trials and lack of evidence base recommendation from the international societies who based their recommendation on observational studies 12Antithrombotic Prior TAVR:Up to our knowledge there is no specific recommendation for antithrombotic prior TAVR ,however ,few recent study suggested bridging with unfractionated heparin For those who required anticoagulation therapy before TAVR (e. g. mechanic mitral valve),,13,14,15Recent study evaluated the early and long term bleeding complications after TAVR suggest to avoid pre-treatment with clopidogrel in patient with advanced age, BMI, and a history of anemia who have increased the risk for early bleeding and suggested Vitamin K natagonists with clopidogrel seems to be thesafest therapy in the early post-TAVI period13. Antithrombotic During TAVR :Anticoagulants :The current expert consensus document of ACCF/AATS/SCAI/STS on transcatheter aortic valve replacement guidelines recommended unfractionated heparin to be started prior ti insertion of the artrtial sheath with a target activated clotting time (ACT ) greater than 250-300 second16 similar to the target ACT in PARTNER trials following a 5,000 IU bolus of unfractionated heparin followed by additional boluses to maintain the target 17,18 . this ACT target was extrapolated from the other cardiovascular invasive procedure targets to provide ischemic cerebrovascular protection following the perioperative period which required higher doses of heparin administrated during the procedure compared to dose given during Percutanouse interventions (PCI ) with a target of 220-250 second to prevent coronary thrombosis and myocardial infarction with acceptable risk of bleeding19,20 and this is one of the reasons to give intravenous Protamine at the end of procedure( 1 mg can neutralize nearly 100 units of UFH) 16,21,in addition to avoid the bleeding related to mechanical factors such as ( larger size of delivery catheter and minimize the access site bleeding events )This reversal may be affected by the short half life of protamine leading to rebound anticoagulation and prolonged the bleeding 22. Along with other side effects including hypotension and bradycardia which is related to the infusion rate of protamine and can be extended the impact of these side effect have been shown to increase the hospital mortality after invasive cardiovascular procedure and the influence of this drug induced adverse events on TAVR is not yet addressed20,23Another major side effect of heparin is thrombocytopenia (HIT ) the guidelines did not recommend any other anticoagulants to manage patient who have history or developed HIT ,however there is few reports suggest direct thrombin inhibitors for this patient population specifically , bivalirudin which has more predictable pharmacokinetic than unfractionated heparin and reduce the need for laboratory monitoring with lower incident of bleeding rate24 .
the disadvantage of Bivalirudin is that clinicians are less familiar with it and there is no study compared it to heparin in TAVR settings . The future Procedural anticoagulation trials should compare regimens that have complications (bivalirudin) compared with the current standard of care (heparin). Antiplatelet:The role of pre-operative antiplatelet in TAVI it is not fully understood nor studied therefore, the current guidelines did not suggest a specific recommendation in this regards. However in PARTNER trials and several survey studies a loading dose of aspirin 300 mg and clopidogrel of 300 mg was given. 14 the role of early administration of antiplatelet and if the early antithrombotic evens is a platelets events is not yet established and no prospective study evaluated it.
16,25Antithrombotic after TAVR :DAPTDAPT is the most widely used antithrombotic strategy after TAVR and the suggested durations is 3-6 months suggested by the international guidelines and interestingly these are not an evidence based recommendation and it was extrapolated from the ischemic events post PCI in order to reduce the risk of thrombosis and embolization however ,the pathology of thromboembolic events related to TAVI is unknown to provide the information about the optimal duration of DAPT . but the similarity between the mechanical pathobiology of the stent after PCI and bioprosthatic valve do exist since they both required neointimal tissue growth and endothiliazation which associated with higher stroke risk after 3 months of the implementation . therefore the the future direction of antithrombotic prevention will be as early as 24 hours after the procedure up to 3 months thereafter 21,26. although small sample size studies27 showed no difference in term of ischemic and bleeding events between aspirin alone or DAPT post TAVR which enable clinician to have a definite conclusion about the combination therapyshowed no differences in ischemic and bleeding definite conclusion about the role of combination therapy in addition an ongoing ARTE (Aspirin Versus Aspirin and Clopidogrel Following Transcatheter Aortic Valve Implantation)28 Pilot study compared the previous regimen to provide a solid Evidence to draw a conclusion for DAPT controversy regarding possible premature discontinuation of them in special patient populations such as elderly who have a high risk to cardiovascular events and tend to bled and the patient whom high on clopidogrel platelets activity and the potential alternative to replace clopidogrel especially in patient with increased risk of bleeding21,29 . Conclusion:TAVR is unique procedure and implementing optimal antithrombotic therapy during and after it is challenging. Several technical s limit its widespread use in elderly patients who have higher atherosclerotic plaque burden, severe calcification or peripheral vascular disease.
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