Safety Low LDL-C Levels, Nocebo Effects, Guidelines for Side Effects.pptx

Safety

1. How Low Should You Go? Is Very Low LDL-C Safe ? Reference : Giugliano , R. P., Pedersen, T. R., Park, J. G., De Ferrari, G. M., Gaciong , Z., Češka , R., Tóth , K., Gouni ‐Berthold, I., López‐Miranda, J., Schiele, F., Mach, F., Ott, B. R., Kanevsky , E., Pineda, A. L., Somaratne , R., Wasserman, S. M., Keech, A., Sever, P., & Sabatine , M. S. (2017). Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab : a prespecified secondary analysis of the FOURIER trial. The Lancet, 390(10106), 1962–1971. https://doi.org/10.1016/s0140-6736(17)32290-0 Newman, C. B., Preiss, D., Tobert , J. A., Jacobson, T. A., Page, R. L., Goldstein, L. B., Chin, C., Tannock , L. R., Miller, M., Raghuveer, G., Duell , P. B., Brinton, E. A., Pollak, A. W., Braun, L. T., Welty, F. K., & Biology, V. (2019). Statin safety and associated adverse events: A scientific statement from the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biology, 39(2). https://doi.org/10.1161/atv.0000000000000073 Cui, Y., Zong , H., Yan, H., & Zhang, Y. (2014). The Effect of Statins on Erectile Dysfunction: A Systematic Review and Meta‐Analysis. The Journal of Sexual Medicine, 11(6), 1367–1375. https://doi.org/10.1111/jsm.12497 Hsia, J., MacFadyen, J., Monyak , J. T., & Ridker , P. M. (2011). Cardiovascular Event Reduction and Adverse Events Among Subjects Attaining Low-Density Lipoprotein Cholesterol <50 mg/dl With Rosuvastatin. Journal of the American College of Cardiology, 57(16), 1666–1675. https://doi.org/10.1016/j.jacc.2010.09.082 Blom , D., Djedjos , C. S., Monsalvo , M. L., Bridges, I., Wasserman, S. M., Scott, R., & Roth, E. M. (2015). Effects of evolocumab on vitamin E and steroid hormone levels. Circulation Research, 117(8), 731–741. https://doi.org/10.1161/circresaha.115.307071

2. LDL-C levels <25 or <15 mg/dl on alirocumab were not associated with an increase in overall treatment-emergent adverse event rates or neurocognitive events , although cataract incidence appeared to be increased in the group achieving LDL-C levels <25 mg/dl ODYSSEY TRIAL Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab

3. Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment

4. 28,000 patients found that 3 in 10 stopped taking their statins because they presumed the aches and pains they were experiencing were due to the drug. The result: 8.5% suffered a heart attack or stroke within just four years, compared to 7.6% who continued taking the drugs Cardiovascular Outcomes and Mortality Associated With Discontinuing Statins in Older Patients Receiving Polypharmacy Sune Fallgaard Nielsen, et al 2016

5. Mach F, et al . Eur Heart J . 2019;00:1–18 CK, creatine kinase; FH, familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9; ULN, upper limit of normal 2019 ESC/EAS Guidelines: Algorithm for the treatment of muscular symptoms during statin treatment Consider if statin-attributed muscle symptoms favour statin continuation/re-initiation Symptomatic and CK <4 X ULN CK ≥4 X ULN Rhabdomyolysis 2–4 weeks washout of statin 6 weeks washout of statin until normalisation of CK and symptoms Symptoms persist: Statin re-challenge Check for other causes of muscular symptoms Symptoms improve: second statin at usual or starting dose Low-dose third efficacious (potent) statin Efficacious statin with alternate day or once/twice weekly dosing regimen Symptoms re-occur Low-dose third efficacious (potent) statin Efficacious statin with alternate day or once/twice weekly dosing regimen AIM: Achieve LDL-C goal with maximally tolerated dose of statin Add ezetimibe Add a PCSK9 inhibitor I/A recommendation for secondary prevention patients (very high risk) I/C recommendation for primary prevention FH patients with another major risk factor (very high risk) IIb/C recommendation for primary prevention in individuals at very high risk (but without FH) Consider adding bile acid sequestrant • IIb/C recommendation

6. 2019 ESC/EAS GUIDELINES: SUMMARY OF RECOMMENDATIONS FOR MONITORING LIPIDS AND ENZYMES IN PATIENTS ON LIPID-LOWERING THERAPY Mach F, et al . Eur Heart J . 2019;00:1–18

7. Step-by-step diagnosis and management of the nocebo/ drucebo effect in statin-associated muscle symptoms patients: a position paper from theInternational Lipid Expert Panel (ILEP) Penson, Peter E et al. Journal of cachexia, sarcopenia and muscle  vol. 13,3 (2022): 1596-1622. doi:10.1002/jcsm.12960

8. Penson, Peter E et al. Journal of cachexia, sarcopenia and muscle  vol. 13,3 (2022): 1596-1622. doi:10.1002/jcsm.12960