Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus.

Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE

Original Publication: London : BioMed Central, [2002-

PCSK9 Inhibitors*; Anticholesteremic Agents/*therapeutic use ; Cardiovascular Diseases/*prevention & control ; Cholesterol, LDL/*blood ; Diabetes Mellitus, Type 2/*drug therapy ; Dyslipidemias/*drug therapy ; Serine Proteinase Inhibitors/*therapeutic use; Aged ; Anticholesteremic Agents/adverse effects ; Biomarkers/blood ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/diagnosis ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/diagnosis ; Dyslipidemias/blood ; Dyslipidemias/diagnosis ; Female ; Glycated Hemoglobin/metabolism ; Heart Disease Risk Factors ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Assessment ; Serine Proteinase Inhibitors/adverse effects ; Tertiary Care Centers ; Time Factors ; Treatment Outcome

Background: The lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of individuals with high cardiovascular risk. As real-world data are still scarce, specifically in patients with type 2 diabetes (T2D), the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care.
Methods: A retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (alirocumab or evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels as well as subsequent cardiovascular events were assessed over an observation period of 18 months.
Results: We identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. 26.2% of the population had a concomitant diabetes diagnosis. Intolerance to statins (83.1%), ezetimibe (44.7%) or both agents (42.6%) was reported frequently. Three months after initiation of PCSK9 inhibitor therapy, 61.2% of the patients achieved LDL-C levels < 70 mg/dl, and 44.1% LDL-C levels < 55 mg/dl. The median LDL-C was lowered from 141 mg/dl at baseline, to 60 mg/dl after 3 months and 66 mg/dl after 12 months indicating a reduction of LDL-C as follows: 57.5% after 3 months and 53.6% after 12 months. After 3 months of observation, target achievement of LDL-C was higher in patients with T2D compared to non-diabetes patients; < 55 mg/dl: 51% vs. 41.5%; < 70 mg/dl 69.4 vs. 58.5%. After 12 months even more pronounced target LDL achievement in T2D was demonstrated < 55 mg/dl: 58.8% vs. 30.1%; < 70 mg/dl 70.6 vs. 49.6%. Patients with insufficiently controlled T2D (HbA1c > 54 mmol/mol) had a higher reduction in LDL-C but still were more likely to subsequent cardiovascular events.
Conclusions: Significant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. The percentage of patients with T2D meeting recommended LDL-C targets was higher than in those without T2D. Still some patients did not achieve LDL-C levels as recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.

Diabetes Obes Metab. 2019 Apr;21(4):903-908. (PMID: 30485622)
J Am Heart Assoc. 2019 May 7;8(9):e011246. (PMID: 31020929)
Diabetologia. 2020 Feb;63(2):221-228. (PMID: 31853556)
Curr Med Res Opin. 2020 Sep;36(9):1419-1425. (PMID: 32568565)
N Engl J Med. 2015 Nov 26;373(22):2117-28. (PMID: 26378978)
N Engl J Med. 2017 May 4;376(18):1713-1722. (PMID: 28304224)
Cardiovasc Diabetol. 2019 Oct 31;18(1):144. (PMID: 31672148)
Lancet. 2019 Jul 13;394(10193):121-130. (PMID: 31189511)
Diabetes Obes Metab. 2017 Jul;19(7):989-996. (PMID: 28206704)
Eur Heart J. 2017 Aug 21;38(32):2459-2472. (PMID: 28444290)
Cochrane Database Syst Rev. 2017 Apr 28;4:CD011748. (PMID: 28453187)
Lancet. 2015 Jan 24;385(9965):331-40. (PMID: 25282519)
Lancet Diabetes Endocrinol. 2017 Dec;5(12):941-950. (PMID: 28927706)
N Engl J Med. 2017 Nov 23;377(21):2099. (PMID: 29166232)
Eur Heart J. 2010 Dec;31(23):2844-53. (PMID: 20965889)
Eur Heart J. 2018 Jul 14;39(27):2526-2539. (PMID: 29718253)
Atherosclerosis. 2018 Mar;270:205-210. (PMID: 29254691)
N Engl J Med. 2014 May 8;370(19):1809-19. (PMID: 24678979)
Cardiovasc Diabetol. 2013;12 Suppl 1:S3. (PMID: 23819776)
Cardiovasc Diabetol. 2020 Dec 10;19(1):209. (PMID: 33302966)
Lancet Diabetes Endocrinol. 2017 Apr;5(4):280-290. (PMID: 28215937)
Cardiovasc Diabetol. 2021 Feb 13;20(1):45. (PMID: 33581713)
JAMA. 2014 May 14;311(18):1870-82. (PMID: 24825642)
Diabetes Obes Metab. 2018 Jun;20(6):1479-1489. (PMID: 29436756)
Lancet. 2005 Oct 8;366(9493):1267-78. (PMID: 16214597)
Eur Heart J. 2015 Nov 14;36(43):2996-3003. (PMID: 26330422)
Am Heart J. 2015 Jun;169(6):906-915.e13. (PMID: 26027630)
N Engl J Med. 2018 Nov 29;379(22):2097-2107. (PMID: 30403574)
Diabetologia. 2019 Jun;62(6):948-958. (PMID: 30953107)
Lancet Diabetes Endocrinol. 2019 Aug;7(8):618-628. (PMID: 31272931)
N Engl J Med. 2019 May 9;380(19):1881-1882. (PMID: 31067395)
Trends Endocrinol Metab. 2018 Jun;29(6):420-434. (PMID: 29665987)
Cardiovasc Diabetol. 2020 Oct 6;19(1):167. (PMID: 33023603)
N Engl J Med. 2016 Jul 28;375(4):311-22. (PMID: 27295427)
Cardiovasc Diabetol. 2019 Oct 22;18(1):139. (PMID: 31640795)
Cardiovasc Ther. 2018 Oct;36(5):e12439. (PMID: 29863817)
Eur Heart J. 2020 Jan 1;41(1):111-188. (PMID: 31504418)
Diabet Med. 2018 Dec;35(12):1742-1751. (PMID: 30183102)
Eur Heart J. 2021 Jan 20;42(3):243-252. (PMID: 33367526)
Diabetes Obes Metab. 2017 Jan;19(1):98-107. (PMID: 27619750)
N Engl J Med. 2020 Jan 16;382(3):244-255. (PMID: 31893580)
Cardiol J. 2018;25(1):32-41. (PMID: 29168543)
Lancet Diabetes Endocrinol. 2017 Feb;5(2):97-105. (PMID: 27908689)

Keywords: Lipid lowering therapy; PCSK9 inhibitor therapy; Real world data

0 (Anticholesteremic Agents)
0 (Biomarkers)
0 (Cholesterol, LDL)
0 (Glycated Hemoglobin A)
0 (PCSK9 Inhibitors)
0 (Serine Proteinase Inhibitors)
0 (hemoglobin A1c protein, human)
EC 3.4.21.- (PCSK9 protein, human)

Date Created: 20210425 Date Completed: 20211101 Latest Revision: 20221207

20240829

PMC8070307

10.1186/s12933-021-01283-w

33894772