Work

Statins for the prevention of cirrhosis complications: An American emulation of the StatLiver Trial

Year: 2024

Type: article

Abstract: To the editor, Statins are hypothesized to prevent the progression of liver disease.1–6 StatLiver is a recently completed randomized trial from Europe that did not show an improvement in outcomes.7 This trial, however, closed early and missed its enrollment target.8 We conducted a trial emulation of StatLiver with the intention of examining a larger sample to evaluate the effect of atorvastatin in a nationally representative database of adult Americans with cirrhosis with Medicare insurance from 2008 to 2020. We used a new user design with a landmark of a new outpatient diagnosis of cirrhosis. All patients were followed from 90 days after cirrhosis diagnosis to the primary endpoint of StatLiver, which was death or transplantation. Liver-related hospitalizations were defined as hospitalization with decompensation: ascites (diagnosis code or paracentesis), spontaneous bacterial peritonitis, hepatorenal syndrome, TIPS, HE, or variceal bleeding. After applying StatLiver inclusion and exclusion criteria, we found 200 new users of atorvastatin and 52,345 nonusers, which were matched using inverse probability of treatment weighting using the variables shown in Table 1. Overall, 11.5% of the atrovastatin users and 14.0% of the nonusers were hospitalized (p = 0.31). Atorvastatin was associated with an incidence rate ratio for hospitalizations per person-year of 0.69, 95% CI (0.34–1.40). Decompensations occurred in 20% and 22% of patients, respectively (p = 0.89), with an subdistribution hazard ratio of 0.85, 95% CI (0.46–1.56) for atorvastatin. Death occurred in 13.5% of atorvastatin users and 12.5% of nonusers, with an subdistribution hazard ratio of 1.12, 95% CI (0.69–2.02) (Table 2). We conducted our study with a larger population of 400 subjects to maximize the data available for the intended 18 months. In contrast, StatLiver examined the outcomes of 78 subjects for a shortened 180 days. In StatLiver, 8% and 5% died in the atorvastatin and placebo arms within 180 days, respectively; 31.5% and 32.5% were hospitalized, respectively. In contrast, fewer patients in our study were hospitalized or died within 18 months. Although the StatLiver randomized patients with portal hypertension as determined invasively, we lacked such data. Although this is the greatest limitation of our emulation framework, portal pressures are not routinely measured in clinical practice. At the same time, the majority of enrollees in the StatLiver group had ascites, while 1 in 4 patients in our emulated study had ascites. However, the number of patients with ascites receiving atorvastatin in our emulation outnumbered the subjects in each arm of the StatLiver. Our trial emulation appears to confirm the findings of the StatLiver. Namely, atorvastatin did not improve the risk of hospitalization or decompensation in patients with cirrhosis. Our trial emulation extends the results of the StatLiver by providing data reflecting its intended duration and using a larger-than-expected sample size. TABLE 1 - Population Atorvastatin No statins p Demographics n 200 200 Median age (SD) 67.5 (8.1) 66.5 (9.8) 0.24 Race % White (n) 69.5 (139) 68.0 (136) 0.80 % Black (n) 18.0 (36) 20.5 (41) 0.80 % Other (n) 12.5 (25) 11.5 (23) 0.80 % Male (n) 61.0 (122) 63.0 (126) 0.76 % Urban (n) 62.0 (124) 60.5 (121) 0.83 Region % Midwest (n) 14.5 (29) 13.0 (26) 0.82 % Northeast (n) 23.5 (47) 22.5 (45) 0.82 % South (n) 38.0 (76) 43.5 (87) 0.82 % West (n) 22.5 (45) 19.0 (38) 0.82 % Other (n) 1.5 (3) 2.0 (4) 0.82 % Medicaid (n) 24.5% (49) 19.5 (39) 0.29 Hepatic decompensations % Ascites (n) 23.0 (46) 24.5 (49) 0.90 % HE (n) 13.0 (26) 14.0 (28) 0.89 Etiology of liver disease % Alcoholic (n) 18.0 (36) 19.5 (39) 0.94 % Viral/autoimmune/biliary (n) 30.0 (60) 29.5 (59) 0.94 % Neither (n) 52.0 (104) 51.0 (102) 0.94 Medical history % Fibrates (n) 10.5 (21) 11.5 (23) 0.87 % Insulin use (n) 29.5 (59) 30.5 (61) 0.91 % Hypertension medication (n) 63.0 (126) 66.5 (133) 0.53 % Hypertension diagnosis (n) 89.5 (179) 91.5 (183) 0.61 % Beta-blockers (n) 44.5 (89) 43.0 (86) 0.84 % Chronic heart failure (n) 47.0 (94) 45.5 (91) 0.85 % Myocardial infarction (n) 35.5 (71) 32.0 (64) 0.51 % Peripheral vascular disease (n) 39.0 (78) 43.0 (86) 0.48 % Cardiovascular disease (n) 34.5 (69) 37.5 (75) 0.61 % Hyperlipidemia (n) 71.0 (142) 71.5 (143) 1.00 % COPD (n) 46.0 (92) 43.5 (87) 0.70 % Chronic kidney disease (n) 18.5 (37) 20.5 (41) 0.71 % Diabetes (n) 23.0 (46) 24.0 (48) 0.90 % Gastroenterology consult (n) 33.5 (67) 32.0 (64) 0.83 TABLE 2 - Outcomes Outcome Atorvastatin (n = 200) No statins (n = 200) p Hospitalization % (n) 11.5 (23) 14.0 (28) 0.31 Time to first hospitalization (IQR) 184 (71,342) 134 (48,225) Hospitalization per person-year 0.24 0.27 Death % (n) 13.5 (27) 12.5 (25) 0.89 Time to event, d (IQR) 174 (72–299) 146 (74–357) Any decompensation % (n) 20.0 (40) 22.0 (44) 0.90 Time to event, d (IQR) 168 (45–296) 139 (29–285) HE % (n) 6.0 (12) 6.0 (12) 1.00 Time to event, d (IQR) 173 (56–361) 140 (36–289) Variceal bleeding % (n) 2.0 (4) 1.5 (3) 1.00 Time to event, d (IQR) 150 (38–305) 133 (26–305) Ascites % (n) 14.0 (28) 14.0 (28) 1.00 Time to event, d (IQR) 183 (45–309) 49 (18–152)

Source: Hepatology Communications

DOI: 10.1097/hc9.0000000000000530

Authors: Elliot B. Tapper, Zhe Zhao, James Henderson

Institutions: University of Michigan, Michigan Medicine

Language: English

Topic: Liver Disease and Transplantation

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,700