PCSK9 inhibitors--past, present and future.
Lowering low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular disease (CVD) morbidity and mortality. Statins are the treatment of choice for lowering LDL-C but a considerable number of patients treated with statins are unable to achieve LDL-C target values and many are statin-intolerant. New LDL-C-lowering drugs--antibodies to PCSK9 (alirocumab, evolocumab and bococizumab)--have been developed and are being tested in large clinical trials. They further reduce LDL-C above maximally tolerated statin therapy by up to > 70%; they also reduce Lp(a), non-HDL-C, apolipoprotein-B, and modestly increase HDL-C. These drugs are well tolerated and even patients who achieved very low LDL-C ≤ 0.65 mmol/l (∼ 25 mg/dl) did not have any significant adverse effects. Treatment with PCSK9 inhibitors resulted in LDL-C target values in 70-90% of patients according to the guidelines. However, although PCSK9 inhibitors seem to be the most promising emerging therapeutic option for LDL-C lowering today, outcome data with endpoints on their effects are still lacking. Another important open question is their long-term safety. Their use in statin-intolerant patients also raises questions, as the criteria for statin-intolerance are neither clear nor generally accepted. The presumed high cost of PCSK9 inhibitors might be an obstacle for their broader use.
a University Hospital Centre Zagreb, School of Medicine University of Zagreb, Department of Internal Medicine , Kispaticeva 12, Zagreb, Croatia +385 1 237 6041 ; +385 1 238 8623 ; zreiner@kbc-zagreb.hr.
Željko
Ž
Reiner
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D017410:Practice Guidelines as Topic; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C000598888:bococizumab; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab; C571059:alirocumab
PCSK9 inhibitors; alirocumab; bococizumab; cardiovascular disease prevention; evolocumab; low-density lipoprotein-cholesterol; statins