Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials

Abstract

Objective To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates. Methods Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic. Results We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94–5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80–1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95–1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36–0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08–0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03–1.99, I2 = 44%; seven studies, n = 5225; low certainty). Conclusions The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.

Prevalence of and Factors Associated With the Prescription of Fibrates Among Patients Receiving Lipid-Lowering Drugs in Germany

“…A systematic review and meta-analysis of 19 head-to-head randomized controlled trials showed that, although there was no significant difference between statin monotherapy and fibrate monotherapy for cardiovascular mortality or major cardiovascular events, adverse events were less frequent with statins than with fibrates. 23 Interestingly, another meta-analysis of 9 studies revealed that kidney-related adverse events (ie, events corresponding to a >50% increase in baseline creatinine exceeding the upper limit of normal) were significantly more common in patients receiving statin-fibrate dual therapy than in those receiving fibrate monotherapy. 24 In view of these findings, general practitioners may be reluctant to treat patients with fibrates and may prefer to prescribe these medications to patients with statin intolerances.…”

Guía de práctica clínica mexicana para el diagnóstico y tratamiento de las dislipidemias y enfermedad cardiovascular aterosclerótica

“…Una RS publicada por Sahekbar et al 125 reportó que el fenofibrato disminuyó los niveles de ApoC3 (DMP: –4.78 mg/dl; IC 95%: –6.95 a –2.61) en 10 estudios clínicos (477 participantes). Una RS publicada por Blais et al 126 en 2021 tuvo como objetivo evaluar la eficacia de los fibratos en comparación con las estatinas como monoterapias para disminuir la mortalidad y los eventos cardiovasculares. Los autores incluyeron 19 estudios clínicos, sin embargo, los tiempos de seguimiento fueron muy cortos (desde 10 semanas a dos años) y los resultados del metaanálisis no mostraron diferencias en la mortalidad cardiovascular (RM: 2.35; IC 95%: 0.94-5.86), eventos cardiovasculares (RM: 1.15; IC 95%: 0.80-1.65).…”

“…La frecuencia de eventos adversos fue menor en el grupo tratado con estatinas (RM: 0.57; IC 95%: 0.36-0.91). Debido a que los estudios fueron diseñados para evaluar eficacia para modificar el perfil de lípidos, no fue posible evaluar el impacto en desenlaces cardiovasculares y mortalidad 126 .…”

The Role of PPAR Alpha in the Modulation of Innate Immunity

“…Pharmacological PPARα agonists, such as fibrates, are clinically used to normalize blood lipid profile, particularly to lower concentrations of cholesterol and low-density lipoprotein fractions [ 47 ]. Fenofibrate and gemfibrozil are the most widely prescribed drugs from a fibrate group, and they are generally very well tolerated [ 48 ]. Nevertheless, some adverse effects have been reported in patients chronically taking fibrates, with myopathy and rhabdomyolysis being the most common problems [ 49 ].…”