Management of Acute Coronary Syndrome in Patients With Liver Cirrhosis

Taha Ahmed; Alla Y. Grigorian; Adrian W. Messerli

Am J Cardiovasc Drugs. 2022;22(1):55-67.

Diagnosis of ACS in LC

ACS is a time-dependent medical emergency; it requires prompt recognition and risk stratification to ensure rapid institution of appropriate management. Cardiac biomarkers should be measured as soon as ACS is suspected and serial electrocardiograms (ECGs) performed concurrently. The spectrum of ACS encompasses one of the following three entities: STEMI, NSTEMI, and unstable angina. STEMI is characterized by the complete occlusion of the lumen, with resultant symptoms of myocardial ischemia accompanied by a persistent elevation of the ST segment on the ECG and the subsequent release of biomarkers of myocardial necrosis. It remains a medical emergency, where rapid revascularization, either by fibrinolytic administration or mechanical intervention, is mandated. An NSTEMI may be caused by partial or complete occlusion of a coronary artery, demand ischemia, or coronary vasospasm; it is defined by ischemic ECG changes and elevated cardiac biomarkers. Unstable angina is caused by a non-occlusive coronary thrombus formation, which allows for dynamic ischemic ECG changes, but not necessarily biomarker elevations. All patients who suffer from an ACS are candidates for several cardio-protective medications. The diagnostic gold standard is invasive coronary angiography, a minimally invasive procedure serving diagnostic and therapeutic purposes, although the procedure may not be indicated in every patient.^[15]

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Abstract and Introduction
Literature Search
Etiology and Pathophysiology of ACS in LC
Diagnosis of ACS in LC
Management Overview of ACS in LC
Conclusions and Future Directions
References
Sidebar

Table 1. Child–Pugh classification of severity of cirrhosis
Measure	1 point	2 points	3 points
Total bilirubin, mg/dL	< 2	2–3	> 3
Serum albumin, g/dL	> 3.5	2.8–3.5	< 2.8
INR	< 1.7	1.7–2.3	> 2.3
Ascites	None	Slight	Mod/severe
Encephalopathy	None	Grade I–II	Grade III–IV

Child–Pugh class A (mild cirrhosis): 5–6 points; Child–Pugh class B (moderate cirrhosis): 7–9 points; Child–Pugh class C (severe/decompensated cirrhosis): 10–15 points
INR international normalized ratio, Mod moderate

Table 2. Antithrombotic drugs registered for clinical use and recommended for treatment of ACS in LC patients as per the most current recommendations. Their potential benefits, harms, and reversal agents in patients with LC are shown
Agent	Benefits in LC	Harms in LC	Reversal options
Antiplatelet agents
Aspirin	Low cost, prevent progression of liver fibrosis and hepatocarcinogenesis and improve survival in LC	GI bleeding risk, concern regarding potentiating acute renal failure, hyponatremia, and/or diuretic resistance	Minor: desmopressin 0.3 mcg/kg one-time dose Major: platelet transfusion—consider one pheresis unit (RCT showed worsened outcomes in ICH)
Clopidogrel (Plavix®)	Unaltered pharmacokinetics in Child Pugh A, B, and C LC	Variable response due to drug interactions, increased bleeding risk, need to stop at least 1 week prior to LT	Minor: desmopressin 0.3 mcg/kg one-time dose Major: platelet transfusion—consider two units if life- or brain-threatening bleeding
Prasugrel (Effient®)	No hepatic activation or clearance; hence, consistent inhibition of platelet function in LC	Bleeding risk	Minor: desmopressin 0.3 mcg/kg one-time dose Major: platelet transfusion—consider two units
Ticagrelor (Brilinta®)	Undergoes hepatic clearance by CYP3A4, CYP3A5	Bleeding risk	Minor: desmopressin 0.3 mcg/kg × 1 Major: platelet transfusion—consider two units if life- or brain-threatening bleeding
Abciximab (Reopro®)	No data on utility	Bleeding risk	Major: platelet transfusion
Eptifibatide (Integrilin®)	No data on utility	Bleeding risk, profound thrombocytopenia in LC (case reports)	Minor: desmopressin 0.3 mcg/kg × 1 Major bleeding reversal: platelet transfusion + infusion of 10 units of cryoprecipitate
Tirofiban (Aggrastat®)	No data on utility	Bleeding risk	Minor: desmopressin 0.3 mcg/kg × 1 Major bleeding reversal: platelet transfusions plus infusion of 10 units of cryoprecipitate
Statins	Retard the progression of hepatic fibrosis and prevent hepatic decompensation with a potential to reduce mortality in LC	Concern for worsening liver injury and rhabdomyolysis	–
Heparin and heparin-like agents
UFH	Low cost, reversible with protamine	Risk of HIT, low antithrombin, hence, aPTT monitoring may underestimate the levels in LC, IV mode of administration	Time since last heparin dose	Dose of protamine
			< 30 min	1 U/100 U of heparin
			30–60 min	0.5–0.75 U/100 U of heparin
			60–120 min	0.375–0.5 U/100 U of heparin
			> 120 min	0.25–0.375 U/100 U of heparin
LMWH	Reduced risk of HIT, subcutaneous route of administration	Preferred anticoagulant in LC; however, antithrombin dependence, unreliable anti-Xa monitoring, partial reversal with protamine, accumulation in low CrCl states	Infusion rate should not exceed 5 mg/min; maximum dose is 50 mg per dose
			Major bleeding: protamine (works just as well with LMWH as UFH)
			Within 4 h of dose of LMWH	1 mg of protamine for each 1 g of LMWH or 100 U of dalteparin and tinzaparin
			Within 4 h of dose of LMWH	Repeat one-half dose of protamine in 4 h
			4–8 h after dose of LMWH	Give 0.5 mg for each 1mg of enoxaparin or 100U of dalteparin and tinzaparin
Fondaparinux (Arixtra®)	Further reduced risk of HIT compared to heparins, synthetic drug	Antithrombin dependence, unreliable anti-Xa monitoring, no established reversal agent, and accumulation in low CrCl states	Major bleeding: protamine ineffective—Kcentra (4-factor PCC) 50 U/kg may be of use
Thrombolytic therapy	None	Increased bleeding risk	Immediate infusions equivalent to 6–8 U of platelets (or one platelet pheresis product), 2 U of plasma, and 10 U of cryoprecipitate. No value in infusing antifibrinolytic agents

Minor bleeding: Any clinically overt sign of hemorrhage (including imaging) that is associated with a < 5 g/dL decrease in the hemoglobin concentration or < 15% decrease in the hematocrit felt by the clinician to be related to anticoagulation. Major bleeding: Intracranial hemorrhage or a > 5 g/dL decrease in the hemoglobin concentration or a > 15% absolute decrease in the hematocrit resulting in a hemodynamic compromise or compression of a vital structure and felt by the clinician to be related to anticoagulation
ACS acute coronary syndromes, aPTT activated partial thromboplastin time, CrCl creatinine clearance, GI gastrointestinal, HIT heparin-induced thrombocytopenia, ICH intracranial hemorrhage, IV intravenous, LC liver cirrhosis, LMWH low-molecular-weight heparin, LT liver transplant, PCC prothrombin complex concentrate, RCT randomized controlled trial, UFH unfractionated heparin