PCSK9 inhibitors: clinical evidence and implementation

@article{Sabatine2018PCSK9IC,
  title={PCSK9 inhibitors: clinical evidence and implementation},
  author={Marc S. Sabatine},
  journal={Nature Reviews Cardiology},
  year={2018},
  volume={16},
  pages={155-165}
}
  • M. Sabatine
  • Published 12 November 2018
  • Biology, Medicine
  • Nature Reviews Cardiology
The gene encoding PCSK9 was first identified and linked to the phenotype of familial hypercholesterolaemia approximately 15 years ago. Soon after, studies uncovered the role of PCSK9 in the regulation of LDL-receptor recycling and identified loss-of-function variants of PCSK9 that were associated with low circulating levels of LDL cholesterol (LDL-C) and a reduced risk of coronary artery disease. With amazing rapidity, monoclonal antibodies against PCSK9 were developed and studied in large… 

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Practical guide for the use of PCSK9 inhibitors in Portugal.

  • R. Fontes-CarvalhoPedro Marques Silva J. Morais
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    Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology
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PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD)

The role of PCSK9 in lipid homeostasis was elucidated, the effect ofPCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniques that focused on PCSK 9 were summarized.
...

References

SHOWING 1-10 OF 93 REFERENCES

Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes.

Variants in PCSK9 had approximately the same effect as variants in HMGCR on the risk of cardiovascular events and diabetes per unit decrease in the LDL cholesterol level and the increased risk of diabetes was limited to persons with impaired fasting glucose levels for both scores and was lower in magnitude than the protective effect against cardiovascular events.

Cardiovascular Efficacy and Safety of Bococizumab in High‐Risk Patients

In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococzumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower‐risk patients but did have a significant benefit in the Trial involving higher‐risk Patients.

Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease.

Using PCSK9 inhibitor use in patients with heterozygous FH or ASCVD did not meet generally acceptable incremental cost-effectiveness thresholds and was estimated to increase US health care costs substantially, compared with initiating statins in all statin-tolerant individuals who are not currently using statins.

Inflammatory and Cholesterol Risk in the FOURIER Trial

The efficacy of evolocumab stratified by baseline high-sensitivity C-reactive protein (hsCRP) and the importance of inflammatory and residual cholesterol risk across the range of on-treatment LDL-C concentrations were explored.

Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

In this trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events.

Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.

Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels and there was evidence of a reduction in the rate of cardiovascular events.
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