Acute Limb Ischemia and Role of DOAC.pptx

Acute Limb Ischemia

1. Acute Limb Ischemia Role of DOAC Dr. d r. Bagus Ari Pradnyana Dwi Sutanegara , Sp.JP(K), FIHA, FICA, FSCAI

2. Epidemiology The incidence of ALI is approximately 1.5 cases out of 10,000 people per year. Complications among ALI patients are high and despite early revascularization, 30-day mortality and amputation rates are between 10 and 15%. ALI patients experience increased in-hospital major adverse events including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function and respiratory complications.

3. BACKGROUND AND DEFINITION Acute Limb Ischemia (ALI) is defined as a sudden decrease in limb perfusion that threatens the viability of the limb Less than 14 days’ duration Symptoms develop over a period of hours to days Variable ischemic clinical manifestations Potential risk of limb loss Incidence 1.5 cases per 10,000 persons per year

4. Progression of Plaque toward rupture

5. Thrombus forms and extends into the lumen Adventitia Lipid core Thrombus Weissberg, 1999 Thrombus formation  Acute Limb Ischemia

6. Definition of Acute Limb Ischemia Sudden decrease of arterial limb perfusion causing threat to limb viability

7. Etiology of acute limb ischemia Acute arterial embolism : Acute traumatic ischemia: Of a relatively healthy arterial tree Acute arterial thrombosis : Of a previously diseased arterial tree

8. Pathophysiology Acute Embolic Ischemia Acute Thrombotic Ischemia An embolus suddenly occludes a relatively healthy arterial tree Atherosclerosis causes progressive narrowing of the arterial tree Stimulates development of collaterals Sluggish flow & rough surface will favor acute thrombosis It usually arrest at arterial bifurcation Aortic bifurcation Iliac bifurcation Femoral bifurcation Popliteal trifurcation An embolus can originate from the heart (MS with atrial fibrillation, MI with mural thrombus) or dilated diseased arteries (aortic aneurism)

9. CAUSES of ALI Thrombosis ( 50% of cases ) Atherosclerosis (native or bypass) Aneurysm Trauma Vasculitis Hypercoagulable states Embolism ( 30% of cases ) Uncommon causes : Arterial dissection Naidoo et al, 2013

10. It is important to differentiate between embolic & thrombotic ischemia: Naidoo et al, 2013

11. SOURCE EMBOLUS Spontaneous (80%) Cardiac source Arrhythmias, MI, prosthetic valve, endocarditis Non-Cardiac source Proximal Aneurysm, Paradoxical emboli Iatrogenic (20%) Angiographic manipulation Surgical manipulation

12. SITE of EMBOLUS

13. PRINCIPAL INVESTIGATION for DIAGNOSTIC Acute Limb Ischemia is a CLINICAL DIAGNOSIS If time allows, especially if atherosclerotic thrombosis is suggested, preoperative angiography is often wise

14. CLINICAL SIGN of ALI REMEMBER THE 6 P’S: PAIN PALLOR PULSELESNESS PERISHING COLD (POIKILOTHERMIA) PARASTHESIAS PARALYSIS

15. DIAGNOSTIC METHODS Palpation arteries (detect pulse, temperature and pallor ) Presence of flow with a Doppler instrument Duplex Ultrasonography Computed Tomographic Angiography Magnetic Resonance Angiography Contrast Angiography Kovacs et al, 2013

16. Diagnostic Approach for ALI

17. RUTHERFORD CLINICAL CLASSIFICATION of ALI Rutherford RB, et al.  Recommended standards for reports dealing with lower extremity ischemia: revised version . J Vasc Surg. 1997 Sep;26(3):517-38. Erratum in: J Vasc Surg 2001 Apr;33(4):805.

18. Management of Acute Limb Ischemia GOAL  to prevent thrombus propagation and worsening ischemia The standard therapy (except in cases of heparin antibodies) is unfractionated heparin intravenously . There is no clear superiority for thrombolysis versus surgery on 30 day limb salvage or mortality. Access to each is a major issue, as time is often critical. Surgery is used three- to five-fold more frequently than thrombolysis. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-society consensus for the management of peripheral arterial disease (TASC II). JVasc Surg 2007;45( suppl S):S5–S67.

19. Aboyans E, et al. 2017 ESC Guidelines on the diagnosis and treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). European Heart Journal 2018; 39: 763–821. doi:10.1093/ eurheartj /ehx095 Thrombolysis “Contraindication to thrombolysis” When thrombolysis reveals underlying localized arterial disease, catheter-based revascularization becomes an attractive option Endovascular techniques Percutaneous aspiration thrombectomy (PAT) Percutaneous mechanical thrombectomy (PMT) Percutaneous catheter directed thrombolytic therapy

20. Contraindications to thrombolysis ABSOLUTE RELATIVE MINOR 1. Established cerebrovascular event (excluding TIA within previous 2 months) 1. Cardiopulmonary resuscitation within previous 10 days 1. Hepatic failure, particularly those with coagulopathy 2. Active bleeding diathesis 2. Major nonvascular surgery or trauma within previous 10 days 2. Bacterial endocarditis 3. Recent gastrointestinal bleeding (within previous 10 days) 3. Uncontrolled hypertension (systolic >180 mmHg or diastolic >110 mmHg) 3. Pregnancy 4. Neurosurgery (intracranial, spinal) within previous 3 months 4. Puncture of noncompressible vessel 4. Active diabetic proliferative retinopathy 5. Intracranial trauma within previous 3 months 5. Intracranial tumor 6. Recent eye surgery Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-society consensus for the management of peripheral arterial disease (TASC II). JVasc Surg 2007;45( suppl S):S5–S67.

21. SURGICAL MANAGEMENT Modalities include surgical thrombectomy, embolectomy bypass and/or arterial repair, and amputation Strategy will depend on the presence of a neurological deficit, ischaemia duration, its localization, comorbidities, type of conduit (artery or graft) and therapy-related risks and out- comes. Endovascular therapy is often preferred, especially in patients with severe comorbidities to reduce mortality Hybrid operation of endovascular and surgical is possible Lower extremity four compartment fasciotomies should be performed in patients with long-lasting ischemia to prevent a post-reperfusion compartment syndrome.

22. DOAC in ALI Direct oral anticoagulants (DOACs) induce anticoagulation via blocking the activity of coagulation factors Xa (rivaroxaban and apixaban) and IIa (dabigatran) DOACs induce anticoagulation via inhibiting the activity of FXa and FIIa via binding to the activation site.

23. DOAC in ALI Even though the use of DOAC have been increasing lately, there are still limited data on the use of DOAC in arterial thrombosis disease . Several studies have conducted regarding the benefit of DOAC in Acute Limb Ischemia In a Meta-Analysis of a total of 44 563 patients from three RCTs, patients randomly assigned to DOACs had a nonsignificant decreased risk for life-threatening limb ischemia (RR, 0.57; 95% CI, 0.26‐1.2). In the analysis between agents, rivaroxaban significantly lowered the risk of life-threatening limb ischemia compared to warfarin (RR, 0.23; 95% CI, 0.064–0.82), and other DOACs . 1 In a peripheral vascular registry of 9682 patients following limb revascularization, the use of DOACs (n = 619 patients) were reported to be associated with a shorter length of stay , and a trend toward lower transfusion compared to patients receiving vitamin K antagonists (n = 1379). However, these data are observational in nature and subject to confounding and thus cannot be considered conclusive. 2 Future observational studies and/or RCTs of full‐dose DOACs in patients in whom full‐dose anticoagulation are required to fully characterize their efficacy and safety profiles. De Haro J, Bleda S, Varela C, Canibano C, Acin F. Meta‐analysis and adjusted indirect comparison of direct oral anticoagulants in prevention of acute limb ischemia in patients with atrial fibrillation. Curr Med Res Opin . 2016;32(6):1167‐1173 Obi AT, Barnes GD, Wakefield TW et al. Practical diagnosis and treatment of suspected venous thromboembolism during COVID‐19 pandemic. J Vasc Surg Venous Lymphat Disord . 2020;8(4):526‐534.

24. CONCLUSION: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use. Circulation . 2021;144:1831–1841. DOI: 10.1161/CIRCULATIONAHA.121.055146 December 7, 2021

25. CONCLUSION: Rivaroxaban added to aspirin or dual antiplatelet therapy after LER for peripheral artery disease reduces ischemic risk and increases major bleeding without an increased risk of intracranial or fatal bleeding . These benefits are consistent in those treated with endovascular and surgical approaches with significant benefits for major adverse limb events. These data support the use of rivaroxaban in addition to aspirin or dual antiplatelet therapy after endovascular intervention for symptomatic peripheral artery disease. Circulation . 2023;148:1919–1928. DOI: 10.1161/CIRCULATIONAHA.122.063806 December 12, 2023

26. CONCLUSION In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone. (Funded by Bayer and Janssen Pharmaceuticals; VOYAGER PAD ClinicalTrials.gov number, NCT02504216.) N Engl J Med 2020;382:1994-2004. DOI: 10.1056/NEJMoa2000052

27. Conclusion: patients with acute upper limb ischemia undergoing thrombembolectomy that were followed by Vascular Surgery/ Cardiology/ Internal Medicine after discharge were correctly long-term anticoagulated. There was also a correlation among NOACs prescription at discharge and long-term NOACs medication. Finally, long-term correct anticoagulation was related with a lower recurrence rate of acute limb ischemia. Silva, Joana Cruz et al. Analysis of Long-term Oral Anticoagulation and Relation to Recurrence of Acute Limb Ischemia After Urgent Upper Limb Embolectomy: A 5-year Evaluation. European Journal of Vascular and Endovascular Surgery, Volume 58, Issue 6, e817

28. TAKE HOME MESSAGE Acute Limb Ischemia is commonly caused by either embolism or thrombosis Remember the 6P of ALI Treatment options are thrombolysis, endovascular, surgical, or hybrid procedure For patients treated with DOAC, the lowest dose in approved studies for stroke prevention should be applied when combined with antiplatelet therapy

29. Terima Kasih This Photo by Unknown Author is licensed under CC BY-SA-NC