title: Efficacy, safety, Low density lipoprotein cholesterol lowering, and calculated 10-year cardiovascular risk reduction of alirocumab and evolocumab in addition to maximal tolerated cholesterol lowering therapy: a post-commercialization study.
abstract: BACKGROUND
  Efficacy and safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO) have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated cholesterol lowering therapy, we assessed efficacy and safety of ALI and EVO.
  
  
  METHODS
  Post-commercially, we started 25 patients on ALI 75 mg, 15 on ALI 150 mg, and 32 on EVO 140 mg bi-weekly added to entry LDLC lowering regimen, with follow-up for a median 24 weeks. History, physical exam, demographics, and adverse event data were collected. Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed on ALI and EVO.
  
  
  RESULTS
  Of 72 patients, 25 had HeFH only, 25 CVD only, 22 had both, median age was 65 years, 63% females, 38% males, 86% Caucasian, 11% African-Americans, 17% diabetics, 63% on anti-hypertensives, and 7% smokers. At entry, 30 (42%) were on a statin and 42 (58%) could not tolerate any statins. At 24-weeks, median LDLC decreased on ALI 75 mg from 117 to 62 mg/dL (-54%), on ALI 150 mg from 175 to 57 mg/dL (-63%), and on EVO 140 mg from 165 to 69 mg/dL (-63%), p <0.0001 for all. Absolute and percent LDLC reduction did not differ (p >.05) between ALI 150 and EVO 140 mg, but were less on ALI 75 mg vs ALI 150 mg and EVO 140 mg (p <.05). Percent reductions in 10-year CVD risks by AHA and NIH calculators, respectively were ALI 75 mg -22 and -44%, ALI 150 mg -31 and -50%, and EVO 140 mg -29 and -56%, p ≤.002 for all. The three most common adverse events included flu-like myositis 10%, respiratory tract symptoms 8%, and injection site reaction 6%.
  
  
  CONCLUSIONS
  In patients with HeFH and/or CVD, LDLC was lowered by 63% on EVO and ALI 150 mg, and 54% on ALI 75 mg. Adverse events were minimal and tolerable. ALI and EVO represent paradigm shifts in LDLC lowering. Long term, post-commercial safety and efficacy remain to be determined.
authors.affiliation: Graduate Medical Education Department, Jewish Hospital of Cincinnati, Cincinnati, Ohio, USA. prshah06@gmail.com.
authors.forename: Parth
authors.initials: P
authors.lastname: Shah
authors.affiliation: Graduate Medical Education Department, Jewish Hospital of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Glueck
authors.affiliation: Graduate Medical Education Department, Jewish Hospital of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Naila
authors.initials: N
authors.lastname: Goldenberg
authors.affiliation: The Jewish Hospital Internal Medicine Residency Program, 4777 E Galbraith Rd, Cincinnati, Ohio, 45236, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Min
authors.affiliation: The Jewish Hospital Internal Medicine Residency Program, 4777 E Galbraith Rd, Cincinnati, Ohio, 45236, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Mahida
authors.affiliation: The Jewish Hospital Internal Medicine Residency Program, 4777 E Galbraith Rd, Cincinnati, Ohio, 45236, USA.
authors.forename: Ilana
authors.initials: I
authors.lastname: Schlam
authors.affiliation: The Jewish Hospital Internal Medicine Residency Program, 4777 E Galbraith Rd, Cincinnati, Ohio, 45236, USA.
authors.forename: Matan
authors.initials: M
authors.lastname: Rothschild
authors.affiliation: The Jewish Hospital Internal Medicine Residency Program, 4777 E Galbraith Rd, Cincinnati, Ohio, 45236, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Huda
authors.affiliation: Graduate Medical Education Department, Jewish Hospital of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000633:toxicity; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C577155:evolocumab; C571059:alirocumab
keywords: Alirocumab; Cardiovascular risk; Efficacy; Evolocumab; Hypercholesterolemia; Low-density lipoprotein; PCSK9 Inhibitor; Safety