Variants Near CETP, MTTP and BUD13-ZPR1-APOA5 may be Nominally Associated with Poor Statin Response Among Filipinos

Hepatic enzyme elevation is low (< 3%) in large statin trials. Elevations are reversible after dose reduction or statin withdrawal. Very rare cases of hepatitis have been reported. No data are available how predisposing risk factors /diseases might influence hepatic statin response. Among the patients suffering from hepatic side effects during statin therapy 896 (477 m, 419 f; aged 31–76 years) admitted with (one or more) elevated hepatic enzyme, anamnestic data on hepatitis A, B, C, hepatic steatosis, alcohol abuse, hepatobiliary problems, abnormal enzymes (GOT, GPT, γGT) were assessed. The prevalence (% vs. % statin use in Austria) was for lovastatin n= 4; 0,2 (0,7), fluvastatin n = 111; 12,4 (14,0), simvastatin n = 297; 33,1 (34,8), pravastatin n = 82; 9,2 (11,8), rosuvastatin n = 69; 7,9 (1,5), atorvastatin n = 333; 37,2 (37,2). Only 41 patients (4,27%) had concomitant muscle complaints (21 cramps, 16 aches, 3 stiffness, 1 weakness), 12 (1,33%) CK elevation, 261 (29,13%) elevated isoprostane 8epiPGF 2α . Those with muscle complaints had normal CK levels and vice versa. Pretherapeutic findings (more than one possible) were hepatitis A 326 (36,4% !!), hepatitis B 7 (0,8%), hepatitis C 3 (0,3%), hepatic steatosis 141 (15,7%), alcohol abuse 104 (11,6%) and /or hepatobiliary problems 17 (1,9%). Abnormal enzymes GOT 116 (12,9%), GPT 113 (12,6%), γGT 147 (16,4%) persisted for < 1 week. Patients after hepatitis A had significantly (p < 0,001) higher transaminases as compared to the other patients. Withdrawal of the respective statin normalized transaminases within 4 weeks in 129 patients (14,4%), in only 7 elevation persisted for a longer period (up to 7 months). After 1 year all were in the normal range. Transaminase levels due to steatosis hepatis even sometimes showed improvement after statin therapy (mean: −12,7% GOT; −14,1 GPT; −16,0 γGT). Reexposure to another statin compound after a 4 weeks drug free interval caused recurrence of side effects in 87 patients (49 with earlier hepatitis A = 56,3%). Hepatitis A seems to represent a high risk for abnormal liver function response on statin therapy and reexposure to other compounds of this family. The combination of abnormal hepatic response with muscle complaints is very rare.

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Abstract 16278: Discordant Lipid Phenotype and Other Determinants of Statin Response in the Pravastatin Inflammation/crp Evaluation (PRINCE) Trial

Circulation ◽

10.1161/circ.142.suppl_3.16278 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Oluremi N Ajala ◽

Olga Demler ◽

Yanyan Liu ◽

Paul M Ridker ◽

Robert J Glynn ◽

...

Keyword(s):

Moderate Intensity ◽

Forward Selection ◽

Cvd Risk ◽

Double Blind ◽

Apo B ◽

Lipid Phenotype ◽

Validation Of Models ◽

Baseline Levels ◽

Hs Crp ◽

Statin Response

Introduction: Wide variability in LDL-C change is observed with statins, yet determinants of statin response are uncertain. Methods: Participants were selected from the primary prevention cohort of the Pravastatin Inflammation/CRP Evaluation double-blind trial that randomized participants to pravastatin 40 mg/d or placebo over 24 weeks. Baseline and 24-week levels of LDL-C and 15 other biomarkers were measured in 495 participants. We defined optimal statin response as >=30% LDL-C reduction and suboptimal response as <30% reduction. Sub-optimal hs-CRP response was defined as >=median (14%) decline in hs-CRP from baseline to 24 weeks and non-response as no decrease or an increase in hs-CRP. χ 2 , t-tests and ANOVA were used to compare variables across optimal statin response (N=166) and suboptimal response (N=287). Multivariable logistic regression models evaluated associations of determinants of statin response. Forward selection identified variables that associated with response. Xgboost was used to train and validate the models using 2/3 and 1/3 of the data respectively. Results: Significant determinants of optimal statin response included older age, and higher baseline levels of LDL-C and triglyceride-rich lipoproteins. By contrast, female sex, alcohol intake >=1 drink/day, diabetes, higher baseline levels of apo B and lipoprotein(a) were associated with decreased response, as was hs-CRP non-response (Table). Race, baseline hs-CRP and sub-optimal hs-CRP response, smoking, HDL-C and BMI had no significant effect on statin LDL-C response. Training and validation of models predicted suboptimal LDL-C response with an AUC of 0.71. Similarly, training and validation of models using Xgboost yielded an AUC of 0.85. Conclusion: This study identified discordant lipid phenotype and other determinants of moderate-intensity statin response and suggests other pathways of CVD risk beyond those addressed by statin treatment that require further investigation.

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