Abstract and Introduction
Abstract
Liver cirrhosis (LC) is becoming increasingly common among patients presenting with acute coronary syndromes (ACS) and is associated with significant cardiovascular morbidity and mortality. Management of such patients is complicated by LC related complications. Literature is scarce on the safety of antithrombotic regimens and invasive strategies for ACS in patients with LC, especially those undergoing liver transplant evaluation. Recently there has been evidence that cirrhosis is an independent risk factor for adverse outcomes in ACS. As patients with LC are generally excluded from large randomized trials, definitive guidelines for the management of ACS in this particular cohort are lacking. Many antithrombotic drugs require either hepatic activation or clearance; hence, an accurate assessment of hepatic function is required prior to initiation and dose adjustment. Despite a demonstrated survival benefit of optimal medical therapy and invasive revascularization techniques in LC patients with ACS, both strategies are currently underutilized in this population. This review aims to present currently available data and provide a practical, clinically oriented approach for the management of ACS in LC. Randomized clinical trials in LC patients with ACS are the need of the hour to further refine their management for favorable outcomes.
Introduction
While there has been considerable focus on the cardiomyopathy associated with liver cirrhosis (LC), a significant number of LC patients present with acute coronary syndromes (ACS). Cardiovascular disease constitutes one of the main causes of morbidity and mortality in patients with LC.[1] Indeed, cardiovascular risk is higher in liver disease (20%) than in the general population (12%), and cardiovascular disease is the foremost cause of morbidity and mortality in patients with LC.[2] Initial hypotheses promoted a protective effect of cirrhosis against the development of atherosclerosis and resultant coronary artery disease (CAD). Proposed etiologies for the “cardio-protective effect” of LC included an elevated level of estrogen, impairment in hepatic cholesterol synthesis, and/or peripheral vasodilation with a decreased systemic blood pressure.[3,4] Autopsy studies in the latter half of the twentieth century supported the contention, showing a lower prevalence of atherosclerosis and myocardial infarction (MI) in patients with LC.[5,6] However, more recent evidence has refuted much of this, and epidemiologic studies of patients with LC have noted a CAD prevalence of up to 28%, similar to if not greater than the prevalence of CAD in the general population.[2,7] The risk is especially high in patients with decompensated cirrhosis complicated by ascites.[7] Moreover, the presence of CAD in LC is independently related to diabetes, increasing age and alcohol etiology.[2] This is especially relevant for patients with non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD), where even precirrhotic stages have high incidence of CAD.[8,9] Importantly, the presence of CAD of any degree of severity is associated with an increased rate of post-transplant major adverse cardiac events in liver transplant recipients[10] (Figure 1).
Figure 1.
Timeline of understanding of atherosclerotic cardiovascular disease risk in LC. ACS acute coronary syndromes, BP blood pressure, CAD coronary artery disease, LC liver cirrhosis, MI myocardial infarction, NASH non-alcoholic steatohepatitis, PAD peripheral arterial disease
It is generally believed that LC patients have high bleeding risk due to the common coexistence of thrombocytopenia, coagulopathy, and risk of bleeding due to variceal rupture or portal hypertensive gastropathy/enteropathy. Very likely, these commonly expressed convictions potentially keep many patients with LC from receiving necessary percutaneous coronary intervention (PCI). To add to the confusion, there exist no societal guidelines to guide clinical judgment, since LC patients are underrepresented in clinical trials.
As the number of patients with NASH cirrhosis continues to increase, patients with cirrhosis have an increasing number of comorbidities for cardiovascular disease such as obesity and diabetes. Nearly a third of patients with decompensated/Child–Pugh class C LC undergoing liver transplant evaluation have CAD. Regrettably, the diagnosis of CAD often puts these patients at prohibitive risk; in fact, at least one in 12 liver transplant candidates are rejected based upon cardiac disease.[11]