How much should LDL cholesterol be lowered in secondary prevention? Clinical efficacy and safety in the era of PCSK9 inhibitors

• Published in: Progress in cardiovascular diseases Vol. 67; pp. 65 - 74
• Main Authors: Cybulska, Barbara, Kłosiewicz-Latoszek, Longina, Penson, Peter E., Nabavi, Seyed Mohammad, Lavie, Carl J., Banach, Maciej
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2021
• Subjects: Cardiovascular; High risk patients; LDL cholesterol; Lipids; PCSK9 inihbitors; Safety; Statins; Apo; PAV; LDL-C; FOURIER; GLAGOV; MTTP; ACTH; Lipids; PCSK9; HR; EBBINGHOUS; HMGCR; HoFH; PCSK9 inihbitors; CARE; IMPROVE-IT; MRFIT; PROVE IT TIMI 22; IDL; HDL; ARIC; VLDL; VH-IVUS; Safety; TNT; MI; Statins; TGs; OR; MR; CK; PRECISE IVUS; SRB1; REVEAL; TC; CVD; ACS; RCTs; High risk patients; LDL cholesterol; CHD; apolipoprotein; myocardial infarction; Evaluating PCSK9 BINDING antiBody Influence oN coGnitive HeAlth in High Cardiovascular Risk Subjects study; Multiple Risk Factor Intervention Trial; odds ratio; randomized controlled trials; virtual histology intravascular ultrasound; adrenocorticotropic hormone; total cholesterol; Randomized EValuation of the Effects of Anacetrapib Throuth Lipid-modification study; Atherosclerosis Risk In Communities; Mendelian Randomization; hydroxymethylglutaryl-coenzyme A reductase; Further Cardiovascular Outcomes Research with PCSK9 inhibiton in Subiects with Elevated Risk; Global Assessment of Plaque reGRession With PCSK9 antibOdy as Measured by intraVascular Ultrasound study; homozygous familial hypercholesterolaemia; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22; microsomal TG transfer protein; low-density lipoprotein cholesterol; IMProved Reduction of Outcomes: Vytorin Efficacy International Trial; scavenger receptors class B type 1; very-low-density lipoprotein; acute coronary syndrome; Treating to New Targets study; creatine kinase; intermediate-density lipoproteins; Cholesterol and Recurrent Events study; cardiovascular disease; proprotein convertase subtilisin/kexin type 9; Plaque Regression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular Ultrasound study; high-density lipoproteins; triglycerides; percent atheroma volume; hazard ratio; coronary heart disease
• ISSN: 0033-0620; 1532-8643; 1873-1740
• DOI: 10.1016/j.pcad.2020.12.008

There is a strong evidence that more marked lowering of low-density lipoprotein cholesterol (LDL-C) leads to progressively lower risk of cardiovascular disease (CVD) events. The evidence on validity of this hypothesis comes from epidemiological, genetic and clinical studies. The hypothesis “the lower the better” has been recently strongly supported by the results of secondary prevention trials with PCSK9 inhibitors. The combination of PCSK9 inhibitors and statins has resulted in achieving extremely low LDL-C levels with additional reduction of CVD events in secondary prevention. However, despite large clinical benefits, the safety of aggressive LDL-C lowering should be always taken into consideration, and there is still an ongoing discussion on whether very low LDL-C might result in some non-CVD adverse events. However, based on the available knowledge, so far the serious adverse events associated with achieving of very low LDL-C levels or intensive drug therapy have not been noted. These positive clinical effects were reflected in current ESC/EAS Guidelines (2019) for dyslipidaemia management. The experts strongly recommended the LDL-C lowering to levels that have been achieved in trials of PCSK9 inhibitors. In this state of the art review, we aimed to finally justify the critical need for LDL-C reduction to very low levels in secondary prevention patients in order to be as low as possible, as early as possible, and preferably lifelong.