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• Currently, near about half of the adults (48.1%) with elevated LDL-C is
getting treatment. Less than one-third (29.5%) of the population with high
LDL-C is under control;
Primary Prevention
40- 75 years
• PCSK9 gene mutation is the third commonest cause of FH, after LDL-R or apolipoprotein B
(ApoB) genes mutation.
• The loss-of-function mutation of PCSK9 gene exhibited mitigation of CVD risk by 88% in the
black population
WHY PCSK9 INHIBITORS HAVE GREAT POTENTIAL?
Evolocumab Placebo
Endpoint (N=13,784) (N=13,780) HR (95% CI)
3-yr Kaplan-Meier rate
CV death, MI, or stroke 7.9 9.9 0.80 (0.73-0.88)
Cardiovascular death 2.5 2.4 1.05 (0.88-1.25)
Death due to acute MI 0.26 0.32 0.84 (0.49-1.42)
Death due to stroke 0.29 0.30 0.94 (0.58-1.54)
Other CV death 1.9 1.8 1.10 (0.90-1.35)
MI 4.4 6.3 0.73 (0.65-0.82)
Stroke 2.2 2.6 0.79 (0.66-0.95)
BRIEF DESCRIPTION OF PCSK9 INHIBITORS
• PCSK9 inhibitor in mice study had reduced atherosclerosis lesion size, monocyte and
T-cell recruitment, smooth muscle cells proliferation, collagen, and macrophage content,
thus improving plaque morphology in mice and reduced antiinflamatory.
• The PCSK9 level is also higher in patients on peritoneal dialysis and nephrotic
syndrome in comparison to hemodialysis or renal transplant patients
• According Sattar et al. revealed that PCSK9 inhibitor markedly decreases atherogenic
lipoproteins in diabetic patients and results are similar as seen in nondiabetic patients.
• According Koren et al. PCSK9 inhibitor does not reduce the cholesterol normalized level
of vitamin E, ACTH, and gonadal hormones despise lowering LDL-C level.
• PCSK9 effect beyond LDL receptor degradation in the liver is largely unknown.
PCSK9 is expressed by extrahepatic tissues such as intestine, pancreas, kidney, smooth
vascular cells, endothelial cells, goblet cells, and brain.
• The most common adverse events occurring in alirocumab treated patients were
gastrointestinal disorders, infections and infestations, musculoskeletal disorders, and
skin and subcutaneous tissue disorders
CONCLUSION AND FUTURE DIRECTION
• PCSK9 inhibitors pave the path of achieving an extremely lowplasma level of LDL-C
and have shown to reduce lifetime risk for CVD events and reduced all causes of
mortality including cardiovascular mortality with less adverse effects like myopathy and
hepatotoxicity
THANK YOU