Study results showed that while treatment with Ocaliva for nonalcoholic steatohepatitis led to an increase in LDL cholesterol at 12 weeks, levels reverted to baseline 24 weeks after discontinuation.
Mohammad S . Siddiqui, MD, from the Virginia Commonwealth University, and colleagues used patient data from the FLINT trial to evaluate the impact of Ocaliva (obeticholic acid or OCA, Pfizer) on atherogenic lipoproteins.
“The findings from the FLINT trial have served a major impetus for concomitant use of statin therapy and a priori guidelines with medications targeting the bile acid pathway for treatment of NAFLD,” Siddiqui and colleagues wrote.
The baseline lipid panel of LDL-C, HDL-C, total cholesterol and triglyceride along with the distribution of total, large, medium and small very LDL (VLDL) particles were similar between patients who received OCA (n = 99) and those who received placebo (n = 97).
At 12 weeks, the baseline adjusted mean difference was higher in the treated group than the placebo group for total cholesterol (206 vs. 182 mg/dL; P < .0001) and LDL-C (135 vs. 107 mg/dL; P < .0001), and lower for HDL-C (39.3 vs. 43.3 mg/dL; P < .0001).
At 72 weeks, the treated group also had higher total serum cholesterol (196 vs. 181 mg/dL; P = .0009) and LDL-C (120 vs. 103 mg/dL; P < .0001) compared with controls, but both decreased after treatment discontinuation and were similar to placebo at 96 weeks.
The researchers also found that the initially lower levels of HDL-C at 72 weeks in the treatment group (42.5 vs. 44.7 mg/dL; P = .01) became similar to the placebo group after treatment discontinuation.
The treatment group had lower large VLDL concentration (6.8 vs. 8.9 nmol/L; P = .002) and increased small VLDL particle concentration (33.9 vs. 28 nmol/L; P = .02) compared with controls at 12 weeks. However, these differences were no longer significant at 72 weeks or 96 weeks.
Although 14 patients in the treatment group developed an adverse event related to cardiovascular disease during the trial, the researchers found no significant differences between those who did and did not develop CVD adverse events in baseline-adjusted changes in any lipoprotein particle.
Siddiqui and colleagues noted in the limitations of the study that the data showed correlative relationships, but they were unable to explore the key mechanisms responsible for the dyslipidemia associated with OCA use.
“Co-administration of statin therapy with [farnesoid x receptor (FXR)] agonist may potentially blunt the increases in lipoprotein sub-particles associated with FXR agonism, however, this strategy requires further validation,” they concluded. – by Talitha Bennett
Disclosures: Siddiqui reports he is an advisory board member of Pfizer. Please see the full study for all other authors’ relevant financial disclosures.