The effect of hydroxychloroquine on cholesterol metabolism in statin treated patients after myocardial infarction

• Published in: Atherosclerosis plus Vol. 53; pp. 26 - 32
• Main Authors: Ulander, Lotta, Simonen, Piia, Tolppanen, Heli, Hartman, Otto, Rissanen, Tuomas T., Eklund, Kari K., Kalaoja, Marita, Kurkela, Mika, Neuvonen, Mikko, Niemi, Mikko, Backman, Janne T., Gylling, Helena, Sinisalo, Juha
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2023; Elsevier
• Subjects: Cholesterol metabolism; Full Length; Hydroxychloroquine; Myocardial infarction; Non-ST-Elevation myocardial infarction; ST-Elevation myocardial infarction; Myocardial infarction; Hydroxychloroquine; ST-Elevation myocardial infarction; Cholesterol metabolism; Non-ST-Elevation myocardial infarction
• ISSN: 2667-0895; 2667-0909; 2667-0895
• DOI: 10.1016/j.athplu.2023.06.003

To evaluate the effect of hydroxychloroquine (HCQ) on serum and lipoprotein lipids and serum biomarkers of cholesterol synthesis and absorption in myocardial infarction patients with a high-dose statin.
Myocardial infarction patients (n = 59) with a constant statin dose were randomized to receive hydroxychloroquine 300 mg (n = 31) or placebo (n = 28) daily for six months and followed up for one year.
Statin reduced total-c (−26 ± 22% in hydroxychloroquine and −28 ± 19% in placebo group, P = 0.931), LDL-c (−38 ± 26% vs. −44 ± 23%, respectively, P = 0.299), and cholesterol synthesis biomarkers zymostenol, desmosterol, and lathosterol ratios from baseline to one year (e.g., serum lathosterol ratio −17 ± 45% vs. −15 ± 41%, respectively, P < 0.001 for both, P = 0.623 between groups). Compensatorily, cholesterol absorption increased during the intervention (e.g., serum campesterol ratio 125 ± 90% vs. 113 ± 72%, respectively, P < 0.001 for both, P = 0.488 between groups). Hydroxychloroquine did not affect cholesterol concentrations or cholesterol absorption. It prevented the statin-induced increase in cholesterol precursor, desmosterol ratio, from six months to one year in the hydroxychloroquine group (P = 0.007 at one year compared to placebo).
Combined with a high-dose statin, hydroxychloroquine had no additional effect on serum cholesterol concentration or cholesterol absorption. However, the findings suggest that hydroxychloroquine interferes with lanosterol synthesis, and thereafter, it temporarily interferes with the cholesterol synthesis pathway, best seen in halting the increase of the desmosterol ratio.
Trial Registration ClinicalTrials.gov Identifier: NCT02648464.
HCQ = hydroxychloroquine, mo/mos = month/months, yr = year. [Display omitted]
•Myocardial infarction patients received HCQ or placebo for six months (72).•HCQ had no additive effect on serum cholesterols with concomitant high-dose statin (85).•HCQ affected the metabolism of cholesterol synthesis biomarkers, ex. desmosterol (83).•An increase in desmosterol ratio was prevented by HCQ (55).•The finding suggests that HCQ interferes with cholesterol synthesis (69).