Statin-associated muscle symptoms and SLCO1B1 rs4149056 genotype in patients with familial hypercholesterolemia.
Patients with familial hypercholesterolemia (FH) may be at increased risk for statin-associated muscle symptoms because they require long-term treatment with high-intensity statin therapy. We sought to determine (1) whether other predisposing factors, including the well-known genetic variant associated with statin-associated muscle symptoms-solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of statin-associated muscle symptoms in FH patients, and (2) the natural history and management for FH patients with statin-associated muscle symptoms.



We queried electronic records (2004-2014) of 278 genetically screened FH patients (113 men, 165 women; mean [SD] pretreatment low-density lipoprotein cholesterol [LDL-C] 259 [72] mg/dL) recruited from lipid clinics in the Dallas, TX, area from 2004 to 2014. Statin-associated muscle symptoms were defined as muscle symptoms arising while taking a statin and interrupting therapy.



The risk of muscle symptoms was associated with age (odds ratio 1.6 [95% CI 1.2-2.2]), body mass index in non-African Americans (0.90 [0.83-0.97]), and hypertension (0.4 [0.2-0.9]). Simvastatin was the most commonly used statin, and it was the statin most associated with muscle symptoms. Among FH patients with muscle symptoms, 41% (n = 40) reestablished statin therapy ("eventually tolerant") and 29% (n = 28) never reestablished statin therapy ("never tolerant"). Rosuvastatin (43%) and pravastatin (30%) were the most common eventually tolerated statins, and eventually tolerant patients achieved lower treated LDL-C levels (eventually tolerant 127 vs never tolerant 192 mg/dL, P < .001). Never tolerant patients also developed muscle symptoms on nonstatins (16% vs 50%, P = .003). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients (TT) and 49 heterozygotes (TC). SLCO1B1 genotype was not associated with the risk of statin-associated muscle symptoms (odds ratio 1.40 [95% CI 0.74-2.64]).



Age, not SLCO1B1 rs4149056 genotype, was the strongest risk factor for statin-associated muscle symptoms in FH patients. After developing muscle symptoms, many patients reestablished statin therapy and achieved significant LDL-C reductions. Overall, 10% of all FH patients had statin-associated muscle symptoms and never reestablished statin therapy. Such patients developed muscle symptoms even on nonstatin lipid-lowering drugs and continued to have elevations in LDL-C. Further insight is needed into the relationship between FH and statin-associated muscle symptoms so all FH patients can be adequately treated.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
Htet
H
Khine
Department of Pharmacotherapy, University of North Texas System College of Pharmacy, Fort Worth, TX.
Wei Cheng
WC
Yuet
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX; Department of Clinical Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX.
Beverley
B
Adams-Huet
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX; Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: Zahid.Ahmad@utsouthwestern.edu.
Zahid
Z
Ahmad
D000367:Age Factors; D015992:Body Mass Index; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D006973:Hypertension / Q000453:epidemiology; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D063806:Myalgia / Q000139:chemically induced / Q000235:genetics*; D016017:Odds Ratio; D017035:Pravastatin / Q000009:adverse effects / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium / Q000009:adverse effects / Q000627:therapeutic use; D019821:Simvastatin / Q000009:adverse effects
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; C503999:SLCO1B1 protein, human; D000068718:Rosuvastatin Calcium; D019821:Simvastatin; D017035:Pravastatin