Comparative efficacy and safety of lipid-lowering agents in patients with hypercholesterolemia

Zhao, Zonglei; Du, Shisuo; Shen, Shuxin; Luo, Ping; Ding, Shoukun; Wang, Guanggong; Wang, Lixia

doi:10.1097/md.0000000000014400

Cited by 37 publications

(37 citation statements)

References 57 publications

(65 reference statements)

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“…27 In a recent frequentist network meta-analysis (which essentially illustrates the probability of events by testing significance with P value, CI; in contrast to the Bayesian model which uses subjective prior knowledge for statistical inference), the researchers concluded that statins were associated with an increase of incident diabetes while PCSK9i and ezetimibe were not. 19…”

Section: Ezetimibementioning

confidence: 99%

“…17 Moreover, there are few metaanalyses regarding ezetimibe in conjunction with statins on whether it may cause incident diabetes. [18][19] In this study, we conducted a systematic review and meta-analysis of large, double-blinded, randomized controlled trials involving PCSK9i and ezetimibe to evaluate their risk of causing newonset diabetes mellitus. In particular, we analyzed trials that had at least a 52-week usage of medications, of which a few large statin trials used this criterion to assess for longer-term impact of medication use.…”

Section: Introductionmentioning

confidence: 99%

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Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials

Chiu

Pratt

Feinn

et al. 2020

J Cardiovasc Pharmacol Ther

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Background: Previous meta-analyses have shown that statins may cause incident diabetes. This article reviews randomized controlled trials using proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) or ezetimibe on the risk of new-onset diabetes. Methods: Eight trials involving PCSK9i and 3 trials of ezetimibe were selected for review. PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were thoroughly searched for relevant trials. Inclusion criteria included at least 100 patients per treatment arm, follow-up of at least 52 weeks, and at least double-blinded study design. Exclusion criteria included patients with previously diagnosed diabetes, nonrandomized, placebo-controlled, open-label, and crossover trials. The primary outcome was the number of incident diabetes cases. A random effects model was used. Heterogeneity in effect sizes was measured with I 2 parameter and the Q statistic was used to test for excessive between-study heterogeneity. Results: A total of 52 214 participants for the PCSK9i and a total of 20 084 for the ezetimibe meta-analyses were included. Participants randomized to PCSK9i did not differ from the control patients in diabetes incidence (risk ratio [RR] = 0.99, P = .87, 95% CI = 0.92-1.07). Participants randomized to ezetimibe did not differ from the control patients in diabetes incidence (RR = 1.05, P = .37, 95% CI = 0.95-1.15). Discussion: The use of PCSK9i and ezetimibe does not appear to impact the risk of incident diabetes mellitus when added to guideline-directed medical therapy.

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Section: Ezetimibementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials

Chiu

Pratt

Feinn

et al. 2020

J Cardiovasc Pharmacol Ther

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“…Within our cohort in general practice, the current prescription rate for PCSK-9 inhibitors is 0.37% and it would thus need to increase more than 10-fold to achieve LDL-C targets in these patients at high or very high CV risk. Given the current prices of PCSK-9 inhibitors and the small additional benefits in terms of absolute risk reductions, the implementation of such a recommendation may be contested from a cost-efficiency perspective [ 21 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

The Impact of the 2019 European Guideline for Cardiovascular Risk Management: A Cross-Sectional Study in General Practice

Meier

Rachamin

Rosemann

et al. 2020

JCM

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The aim of this study was to assess the impact of the 2019 published European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline on cardiovascular (CV) risk management compared with its predecessor from 2016 in a cohort in general practice. We performed a cross-sectional retrospective study with data from electronic medical records. The study cohort included 103,351 patients with known CV risk. We assessed changes in CV risk classification and low-density lipoprotein cholesterol (LDL-C) target values, the impact on LDL-C achievement rates, and the current lipid-lowering treatments. Under the 2019 ESC guideline, CV risk categories changed in 27.5% of patients, LDL-C target levels decreased in 71.4% of patients, and LDL-C target achievement rate dropped from 31.1% to 16.5%. Among non-achievers according to the 2019 guideline, 52.2% lacked lipid-lowering drugs entirely, and 41.5% had conventional drugs at a submaximal intensity. Of patients in the high-risk and very high-risk categories, at least 5% failed to achieve the LDL-C target level despite treatment at maximal intensity with conventional lipid-lowering drugs, making them eligible for PCSK-9 inhibitors. In conclusion, the 2019 ESC/EAS guideline lowered LDL-C target values for the majority of patients in general practice and halved LDL-C target achievement rates. There is still a large undeveloped potential to lower CV risk by introducing conventional lipid-lowering drugs, particularly in patients at high or very high CV risk. A substantial proportion of the patients can only achieve their LDL-C targets using PCSK-9 inhibitors, which would currently require an at least 10-fold increase in prescribing of these drugs.

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“…Phenotype information related to diabetes status was collected by each case-control or cohort study, as previously described in Flannick et al Additionally, we defined prediabetes as any individual with HbA1c ≥ 5.7%, fasting blood glucose ≥ 100 mg/dL, or oral glucose tolerance test (OGTT) 2 hour blood glucose ≥ 140 mg/dL. In individuals who were reported to be on lipid-lowering medication, serum LDL cholesterol and triglyceride levels were adjusted for statin use based on previous studies estimating the impact 53,54 : we divided LDL by 0.7 and triglycerides by 0.85 as has been previously been implemented 55 . Self-reported ancestry was used, as this was previously shown to correlate well with principal component analysis (PCA) defined ancestry and specific exceptions were dropped from analyses 18 .…”

Section: General Study Characteristics Are Provided In Supplementary mentioning

confidence: 99%

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Goodrich

Singer-Berk

Son

et al. 2020

Preprint

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Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier will develop the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we applied clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias displayed effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers averaged below 60% in both studies for all conditions except monogenic diabetes. We assessed additional epidemiologic and genetic factors contributing to risk prediction, demonstrating that inclusion of common polygenic variation significantly improved biomarker estimation for two monogenic dyslipidemias.

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Comparative efficacy and safety of lipid-lowering agents in patients with hypercholesterolemia

Abstract: Supplemental Digital Content is available in the text

Cited by 37 publications

References 57 publications

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials

The Impact of the 2019 European Guideline for Cardiovascular Risk Management: A Cross-Sectional Study in General Practice

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

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