Adverse events following statin–fenofibrate therapy versus statin alone: A meta‐analysis of randomized controlled trials

Abstract

The combination of fenofibrate with statins is a beneficial therapeutic option for patients with mixed dyslipidaemia, but concerns about adverse events (AEs) make physicians reluctant to use this combination therapy. Medline, Embase and the Cochrane Library were searched to identify 13 randomized controlled trials, involving 7712 patients, of statin-fenofibrate therapy versus statin alone for review. There were significant decreases in low-density lipoprotein-cholesterol, triglycerides and total cholesterol and increases in high-density lipoprotein-cholesterol in patients receiving combination therapy compared with statin therapy alone. The incidence of aminotransferase elevations in the fenofibrate-statin therapy group was significantly higher than in the statin monotherapy group (odds ratio (OR), 1.66; 95% confidence interval (CI) 1.17-2.37; P < 0.05). The incidence of elevated creatine kinase levels (OR 0.88; 95% CI 0.63-1.23; P > 0.05), muscle-associated AEs (OR 0.98; 95% CI 0.88-1.09; P > 0.05) and withdrawals attributed to liver and muscle dysfunction did not differ significantly between the two groups. The efficacy of fenofibrate + standard-dose statin and incidence of AEs in the fenofibrate + standard-dose statin group were almost identical to those in the fenofibrate-statin group. In conclusion, combination therapy improves the blood lipid profile of patients. Fenofibrate-statin combination therapy appears to be as well tolerated as statin monotherapy. Physicians should consider fenofibrate-statin combination therapy in patients but monitor aminotransferase levels to avoid hepatic complications.

Role of selective peroxisome proliferator‐activated receptor modulators in managing cardiometabolic disease: tale of a roller‐coaster

“…In the ACCORD study, combination therapy with fenofibrate and simvastatin was associated with a greater effect on TG (−22% vs. −9% for combination therapy vs. statin monotherapy, respectively), HDL‐C (+8% vs. +6%) and TC (−13% vs. −12%) but not LDL‐C . The ACCORD results are consistent with the findings of a recent meta‐analysis showing a greater effect of statin‐fibrate combination therapy compared with statin monotherapy on all major components of the plasma lipid profile (TG, HDL‐C, LDL‐C and TC) .…”

“…Reassuringly, fenofibrate was found to exert renoprotective effects by reducing albuminuria and slowing glomerular filtration rate (GFR) loss in type 2 diabetic patients [80]. The results of two meta-analyses of randomized controlled trials also showed that the combination of fibrates and statins is as well tolerated as statin monotherapy [75,102]. As referred to earlier, fibrates have been shown to increase serum creatinine levels, but this increase does not apparently reflect nephrotoxicity nor is associated with any adverse renal outcome [84].…”

Tendon rupture associated with concomitant simvastatin and gemfibrozil use: Biological and pharmacokinetic implications

“…Fenofibrate appears to be safer than gemfibrozil because renal excretion of statins appears to be significantly inhibited by gemfibrozil but not by fenofibrate . Meta‐analyses of randomized trials have found no increase in muscle or tendon‐related adverse events in patients taking fenofibrate plus a statin compared with a statin alone . Studies have also failed to show an increase in the incidence of myopathy or tendinopathy in patients with combined hyperlipidemia who were prescribed pravastatin plus gemfibrozil …”

“…15,16 Metaanalyses of randomized trials have found no increase in muscle or tendon-related adverse events in patients taking fenofibrate plus a statin compared with a statin alone. 17,18 Studies have also failed to show an increase in the incidence of myopathy or tendinopathy in patients with combined hyperlipidemia who were prescribed pravastatin plus gemfibrozil. 19 Although myopathy and myositis are common adverse outcomes, tendon rupture remains a seldom reported entity of statin-gemfibrozil combination use.…”

The Effect of Intraoperative N-Acetylcysteine on Hepatocellular Injury During Laparoscopic Bariatric Surgery. A Randomised Controlled Trial

“…Eleven (58 %) of patients completing the study were taking cholesterol-lowering medications, including various statins and fenofibrate. These drugs are known to cause liver dysfunction [37], although it should be noted that all patients had normal liver function at baseline.…”