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Cardiovascular Disease Risk Assessment & LDL-C Goal

Very high-risk patients with ASCVD are defined as having multiple major ASCVD events or one major ASCVD event and multiple other risk factors such as smoking, hypertension, diabetes, or persistent elevated LDL-C to name a few.1 While unclear exactly how many patients are considered very high-risk, separate studies show a range of 26-58% of ASCVD patients may be classified as very high-risk.2-3 The most recent ACC/AHA guideline recommends optimizing LDL-C management in very high-risk ASCVD patients with high-intensity statin therapy or maximally tolerated statin therapy.1 The guidelines further recommend using an LDL-C threshold of 70 mg/dL (1.8 mmol/L) in very high-risk ASCVD patients when considering the addition of nonstatins to statin therapy.1





  • What percentage of your own secondary prevention patients would you classify as being very high-risk?

  • Of those very high-risk patients, what percentage would you estimate are at goal utilizing statins alone?

  • Do you feel that 70 mg/dL LDL-C is low enough to prevent additional ASCVD events or do you target even lower? Should ACC/AHA LDL-C guidelines be adjusted to provide an LDL-C goal ≤55 mg/dL, similar to ESC4?



 



References:




  1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019; 73(24):3168-3209

  2. Sajja A, Li HF, Spinelli KJ, et al. A simplified approach to identification of risk status in patients with atherosclerotic cardiovascular disease. American Journal of Preventive Cardiology 2021; (7): 100187

  3. Colantonio LD, Shannon ED, Orroth KK, et al. Ischemic Event Rates in Very-High-Risk Adults. Journal of the American College of Cardiology, 2019; 74(20): 2496-2507

  4. Mach F, Baigent C, Catapano A, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). 2020; 41(1): 111–188


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  • 4yr
    approximately 50% of my pts are considered high risk, LDL goal for my pts with diabetes is <50, approximately 50% of my pts will reach the goal with statin monotherapy, Show More
  • 4yr
    There are only a few patients who have their first ASCVD event in the absence of multiple risk factors -- I think perhaps only about 20%; meaning that virtually all Show More

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Hyperlipidemia patients carrying LDLR splicing mutation c.1187-2A>G respond favorably to rosuvastatin and PCSK9 inhibitor evolocumab - Molecular Genetics and Genomics

Hyperlipidemia patients carrying LDLR splicing mutation c.1187-2A>G respond favorably to rosuvastatin and PCSK9 inhibitor evolocumab - Molecular Genetics and Genomics

Source : https://link.springer.com/article/10.1007/s00438-022-01892-4

Mutations in the LDL receptor gene LDLR cause familial hypercholesterolemia (FH); however, the pharmacogenomics of specific LDLR mutations remains poorly understood. The goals of this study were to identify the...



Conclusion/Relevance: These results suggest that combined treatment with rosuvastatin (but not lovastatin or ezetimibe) and evolocumab can control LDL-C to meet the LDL-C treatment goal for patients with LDLR splicing mutation c.1187-2A>G.

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Efficacy and Safety of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors as Adjuvant Treatments for Patients with Hypercholesterolemia Treated with Statin: A Systematic Review and Network Meta-analysis

Efficacy and Safety of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors as Adjuvant Treatments for Patients with Hypercholesterolemia Treated with Statin: A Systematic Review and Network Meta-analysis

Source : https://www.frontiersin.org/articles/10.3389/fphar.2022.832614/full

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent LDL-C lowering agents. However, few head-to-head studies evaluated the efficacy on the lowering in other atherogenic apolipoproteins and safety...



Conclusion: PCSK9 inhibitors showed a significant effect on the reduction in LDL-C, ApoB, and Lp(a) levels in statin-treated patients. Evolocumab 140 mg Q2W showed significantly larger degrees of LDL-C, ApoB, and Lp(a) reduction.

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4yr
Acute Effect of Evolocumab on Lipoprotein(a) Level and Inflammation in Patients with Coronary Artery Disease - PubMed

Acute Effect of Evolocumab on Lipoprotein(a) Level and Inflammation in Patients with Coronary Artery Disease - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/35448076/

doi: 10.3390/jcdd9040101. 1 Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul 02447, Korea. 2 Department of Medicine, Graduate School of Medicine, Kyung Hee...



Conclusions: One-time PCSK9 inhibitor treatment may be effective in lowering Lp(a) levels in Korean patients in the short term.

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4yr
PCSK9 inhibition protects against myocardial ischemia-reperfusion injury via suppressing autophagy

PCSK9 inhibition protects against myocardial ischemia-reperfusion injury via suppressing autophagy

Source : https://www.sciencedirect.com/science/article/abs/pii/S0026286222000619?via=ihub

the expression levels of PCSK9 and autophagy markers rose in a proportional ratio with increasing reperfusion time, peaking at 1 day of reperfusion and thereafter decreased. Meanwhile, we believe that...



Conclusion/Relevance: These results suggest that combined treatment with rosuvastatin (but not lovastatin or ezetimibe) and evolocumab can control LDL-C to meet the LDL-C treatment goal for patients with LDLR splicing mutation c.1187-2A>G.

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