Comparison of pleiotropic effects of statins vs fibrates on laboratory parameters in patients with dyslipidemia

Abstract

Differences in the mechanism of action and potential pleiotropic effects between statins and fibrates would potentially drive a different effect on various laboratory parameters, but this remains controversial because of a paucity of reports comparing them. Therefore, the aim of this study was to compare the effects of statins and fibrates on laboratory parameters in Japanese patients in routine clinical practice. This retrospective cohort study included patients with dyslipidemia who had been newly treated with statin or fibrate monotherapy between January 2005 and December 2017. Patients were randomly matched into two sets of pairs by sex, age, and baseline triglyceride (TG) or low-density lipoprotein (LDL) cholesterol level. The 830 patients in TG-matched pairs (415 fibrate users and 415 matched statin users) and 1172 patients in LDL cholesterol-matched pairs (586 fibrate users and 586 matched statin users) were included in this study. Generalized estimating equations were used to estimate the effects of the drugs on serum creatinine level, estimated glomerular filtration rate (eGFR), urea nitrogen, hemoglobin A 1c , aspartate aminotransferase, and alanine aminotransferase (ALT), in addition to LDL cholesterol and TG levels, and red blood cell (RBC) and platelet (PLT) counts, up to 12 months after the start of study drug administration. In TG-matched pairs, the increases in creatinine and urea nitrogen levels ( P = .010 and P < .001, respectively) and the decreases in eGFR, ALT level and RBC count ( P < .001, P = .003, and P = .014, respectively) were greater in fibrate users than in statin users. The decrease in PLT count was greater in statin users than in fibrate users ( P < .001). The mean changes in aspartate aminotransferase and hemoglobin A 1c levels were not significantly different between statin users and fibrate users. In LDL cholesterol-matched pairs, the differences in changes of all laboratory parameter levels between statin users and fibrate users were similar to those in TG-matched pairs. We demonstrate here that fibrates have a greater effect of increasing creatinine and urea nitrogen levels and of reducing eGFR, ALT level, and RBC count than statins, and that the lowering effect on PLT count is greater with statins than with fibrates.

Identifying Antidepressants Less Likely to Cause Hyponatremia: Triangulation of Retrospective Cohort, Disproportionality, and Pharmacodynamic Studies

“…Prescriptions are coded using the Japanese drug coding system, which is mapped to the Anatomical Therapeutic Chemical (ATC) classification. Several epidemiological studies have been previously published evaluating the effects of various drugs on laboratory parameters using NUSM’s CDW 17–20 . The experimental protocol was approved by the Ethical Committee of NUSM (approval number: P21‐01‐0), and the study was conducted in compliance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects of the Ministry of Education, Culture, Sports, Science, and Technology and the Ministry of Health, Labour, and Welfare, Japan.…”

Differential effect of statin use on coagulation markers: an active comparative analysis in the NEO study

“…Besides, in a cohort of Japanese subjects who were LDL-cholesterol matched at baseline and were treated either with statins or fibrates, the overall mean LDL cholesterol level was lower by 27.3 mg/dl in statin users than in fibrate users ( P < 0.001) [ 49 ]. Furthermore, a meta-analysis of fourteen studies revealed that statin use significantly reduced VTE risk (OR, 0.81; 95% CI, 0.66–0.99, random-effect model), while the use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23–2.02), and niacin did not change the risk of VTE [ 50 ].…”

Pharmacotherapeutics for dyslipidemia management

“…Fibrates, such as fenofi brate and gemfibrozil, are a group of lipid-lowering agents with the primary targets of lowering plasma TG and increasing HDL levels. 22,23 A Cochrane Review and metaanalysis examining six trials with a combined total of 16,135 individuals of all ages noted that, in comparison with patients on placebo, patients who underwent fi brate therapy saw a 16% reduction in risk for a combined outcome of CV death, non-fatal MI, or nonfatal stroke and a 21% reduction in the risk of a combined outcome of nonfatal MI or coronary heart disease death. 24 However, the Cochrane Review points out that "low-quality evidence suggests that fi brates have no eff ect on overall mortality or non-CVD mortality."…”