Effects of Statins Withdrawal on Cardiovascular Events in Chronic Hemodialysis Patients: A Randomized, Triple-blind, Placebo-controlled trial (ESC-HD trial)
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Abstract
Background: The leading cause of death in patients with end stage kidney disease on maintenance hemodialysis (ESKD-D) is a cardiovascular (CV) disease. Efficacy of statins therapy has been proven in non-dialysis patients, but recent guidelines recommend not to initiate statins in ESKD-D patients due to uncertain benefit. However, the clinical outcomes of statins withdrawal in ESKD-D patients previously taken the medications have not been explored.
Method: This is a single-center, prospective, triple-blind, randomized, placebo-controlled trial conducted in ESKD-D patients in Vajira Hospital. The patients were allocated into the statins-withdrawal group, in which the statins were replaced with placebo, and the simvastatin group, in which 20 milligrams per day of simvastatin was prescribed. All participants were followed up for six months with safety interim analysis at 1st and 3rd month. The primary endpoint is the incidence of CV event. The secondary endpoints include serum lipid profile, high-sensitivity C-reactive protein (hs-CRP), high-sensitivity cardiac troponin-T (hs-cTnT), and all-cause mortality.
Results: Fortyone participants were included in the study and allocated into the statins-withdrawal group (n = 19) and the simvastatin group (n = 22). One participant was withdrawn from the study. At 6th month, the incidence of CV events was 1.56 and 1.30 per 100 person-months in the statins-withdrawal and the simvastatin group, respectively, which was not statistically different by the Log-rank analysis (p-value=0.834). Total cholesterol and low-density lipoprotein were significantly higher in the statins-withdrawal group at 3rd and 6th months. No difference in hs-CRP and hs-cTnT between groups was detected. No serious adverse events such as hepatitis, rhabdomyolysis, hemorrhagic stroke, or death was reported throughout the study period.
Conclusion: Statins withdrawal in ESKD-D patients significantly increases serum cholesterol level without increasing CV events in the intermediate term. No serious adverse event was reported with simvastatin prescription.
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