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Therapeutic efficacy and safety of PCSK9-monoclonal antibodies on familial hypercholesterolemia and statin-intolerant patients: A meta-analysis of 15 randomized controlled trials.

ABSTRACT: Proprotein convertase subtilisin/kexin9 monoclonal antibodies (PCSK9-mAb) have been studied intensively to identify their effect in lowering levels of low density lipoprotein cholesterol (LDL-C). However, the applicable target of PCSK9-mAbs remains inconclusive so far. Therefore, this first meta-analysis was carried out to clarify the therapeutic efficacy and safety of PCSK9-mAbs on the potential patients: familial hypercholesterolemia and statin-intolerant patients. All randomized controlled trials that met the search terms were retrieved in multiple databases. Efficacy outcomes included parameter changes from baseline in LDL-C and other lipid levels. Therapeutic safety were evaluated by rates of common adverse events. A total of 15 studies encompassing 4,288 patients with at least 8 weeks duration were selected. Overall, the therapeutic efficacy was achieved with significant reduction in LDL-C, TC, TG, Lp(a), Apo-B versus placebo. The decline in familial hypercholesterolemia patients (-53.28%, 95% CI: -59.88 to -46.68%) was even more obvious than that in statin-intolerant patients (-34.95%, 95% CI: -41.46 to -28.45%). No obvious safety difference was found out in the rates of common and serious adverse events. To conclude, PCSK9-mAb contributes to the decreased level of LDL-C and other lipids in familial hypercholesterolemia and statin-intolerant patients with satisfactory safety and tolerability.

SUBMITTER: Qian LJ

PROVIDER: S-EPMC5428249 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Therapeutic efficacy and safety of PCSK9-monoclonal antibodies on familial hypercholesterolemia and statin-intolerant patients: A meta-analysis of 15 randomized controlled trials.

Qian Li Jun LJ Gao Yao Y Zhang Yan Mei YM Chu Ming M Yao Jing J Xu Di D

Scientific reports 20170322 1

Proprotein convertase subtilisin/kexin9 monoclonal antibodies (PCSK9-mAb) have been studied intensively to identify their effect in lowering levels of low density lipoprotein cholesterol (LDL-C). However, the applicable target of PCSK9-mAbs remains inconclusive so far. Therefore, this first meta-analysis was carried out to clarify the therapeutic efficacy and safety of PCSK9-mAbs on the potential patients: familial hypercholesterolemia and statin-intolerant patients. All randomized controlled tr ...[more]

PMID: 28331223

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Project description:UnlabelledPatients 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.MethodsWe 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.ResultsThe 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]).ConclusionAge, 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.

Dataset Information

Therapeutic efficacy and safety of PCSK9-monoclonal antibodies on familial hypercholesterolemia and statin-intolerant patients: A meta-analysis of 15 randomized controlled trials.

Publications

Therapeutic efficacy and safety of PCSK9-monoclonal antibodies on familial hypercholesterolemia and statin-intolerant patients: A meta-analysis of 15 randomized controlled trials.

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