Meta-analysis of clinical outcomes of PCSK9 modulators in patients with established ASCVD
© 2021 Pharmacotherapy Publications, Inc..
The advent of monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) ushered in a new era of dyslipidemia pharmacotherapy. The first two antibodies targeting PCSK9 (evolocumab, alirocumab) approved by the United States Food and Drug Administration (FDA) provided significant and sustained reductions in atherogenic lipids and a reduced risk of atherosclerotic cardiovascular disease (ASCVD) events. More recently, phase 3 trials of inclisiran-a small interfering RNA-based agent targeting PCSK9-reported similar lipid-lowering effects and preliminary evidence of ASCVD risk reduction, although significant questions remain regarding the extent of benefits across cardiovascular outcomes. We conducted a systematic review and meta-analysis (random-effects model) of the available data on lipid lowering, incidence of atherosclerotic cardiovascular disease (ASCVD) events, and safety of pharmacologic agents targeting PCSK9. A significant and consistent reduction in low-density lipoprotein cholesterol (LDL-C) was observed across all agents (-51% [95% confidence interval {CI}: -61%, -41%]). Despite the impressive reduction in LDL-C, the individual effects on mortality, cardiovascular death, myocardial infarction (MI), and stroke remained nonsignificant. However, a consistent reduction was observed in the composite outcomes of MI, stroke, and cardiovascular death [relative risk {RR} (95% CI): 0.80 (0.73-0.87)] and MI, stroke, unstable angina (requiring revascularization), and cardiovascular death [RR (95% CI): 0.85 (0.74-0.97)]. In terms of safety outcomes, there was no significant difference in severe adverse events, new onset diabetes, neurocognitive disorders, or myalgia. Meanwhile, injection site reaction was more frequent in patients receiving these agents compared to placebo [RR 2.11 (95% CI): 1.26-3.54]. These findings suggest a class effect for favorable lipid changes and a low risk of serious adverse events among pharmacologic agents targeting PCSK9. Although there is compelling evidence that PCSK9-targeting agents reduce the risk of some cardiovascular outcomes, adequately powered studies with longer follow-up may be needed to fully characterize the magnitude of benefits across the cardiovascular spectrum.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
|---|---|
| Enthalten in: |
Pharmacotherapy - 41(2021), 12 vom: 01. Dez., Seite 1009-1023 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Talasaz, Azita H [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Atherosclerotic cardiovascular disease |
|---|
| Anmerkungen: |
Date Completed 08.02.2022 Date Revised 08.02.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/phar.2635 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM331977559 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM331977559 | ||
| 003 | DE-627 | ||
| 005 | 20231225214648.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/phar.2635 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1106.xml |
| 035 | |a (DE-627)NLM331977559 | ||
| 035 | |a (NLM)34657313 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Talasaz, Azita H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Meta-analysis of clinical outcomes of PCSK9 modulators in patients with established ASCVD |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.02.2022 | ||
| 500 | |a Date Revised 08.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 Pharmacotherapy Publications, Inc. | ||
| 520 | |a The advent of monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) ushered in a new era of dyslipidemia pharmacotherapy. The first two antibodies targeting PCSK9 (evolocumab, alirocumab) approved by the United States Food and Drug Administration (FDA) provided significant and sustained reductions in atherogenic lipids and a reduced risk of atherosclerotic cardiovascular disease (ASCVD) events. More recently, phase 3 trials of inclisiran-a small interfering RNA-based agent targeting PCSK9-reported similar lipid-lowering effects and preliminary evidence of ASCVD risk reduction, although significant questions remain regarding the extent of benefits across cardiovascular outcomes. We conducted a systematic review and meta-analysis (random-effects model) of the available data on lipid lowering, incidence of atherosclerotic cardiovascular disease (ASCVD) events, and safety of pharmacologic agents targeting PCSK9. A significant and consistent reduction in low-density lipoprotein cholesterol (LDL-C) was observed across all agents (-51% [95% confidence interval {CI}: -61%, -41%]). Despite the impressive reduction in LDL-C, the individual effects on mortality, cardiovascular death, myocardial infarction (MI), and stroke remained nonsignificant. However, a consistent reduction was observed in the composite outcomes of MI, stroke, and cardiovascular death [relative risk {RR} (95% CI): 0.80 (0.73-0.87)] and MI, stroke, unstable angina (requiring revascularization), and cardiovascular death [RR (95% CI): 0.85 (0.74-0.97)]. In terms of safety outcomes, there was no significant difference in severe adverse events, new onset diabetes, neurocognitive disorders, or myalgia. Meanwhile, injection site reaction was more frequent in patients receiving these agents compared to placebo [RR 2.11 (95% CI): 1.26-3.54]. These findings suggest a class effect for favorable lipid changes and a low risk of serious adverse events among pharmacologic agents targeting PCSK9. Although there is compelling evidence that PCSK9-targeting agents reduce the risk of some cardiovascular outcomes, adequately powered studies with longer follow-up may be needed to fully characterize the magnitude of benefits across the cardiovascular spectrum | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Systematic Review | |
| 650 | 4 | |a PCSK9 | |
| 650 | 4 | |a atherosclerotic cardiovascular disease | |
| 650 | 4 | |a dyslipidemia | |
| 650 | 4 | |a meta-analysis | |
| 650 | 7 | |a PCSK9 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 650 | 7 | |a Proprotein Convertase 9 |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 700 | 1 | |a Ho, Ai-Chen Jane |e verfasserin |4 aut | |
| 700 | 1 | |a Bhatty, Fawzia |e verfasserin |4 aut | |
| 700 | 1 | |a Koenig, Rachel A |e verfasserin |4 aut | |
| 700 | 1 | |a Dixon, Dave L |e verfasserin |4 aut | |
| 700 | 1 | |a Baker, William L |e verfasserin |4 aut | |
| 700 | 1 | |a Van Tassell, Benjamin W |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmacotherapy |d 1983 |g 41(2021), 12 vom: 01. Dez., Seite 1009-1023 |w (DE-627)NLM012960926 |x 1875-9114 |7 nnns |
| 773 | 1 | 8 | |g volume:41 |g year:2021 |g number:12 |g day:01 |g month:12 |g pages:1009-1023 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/phar.2635 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 41 |j 2021 |e 12 |b 01 |c 12 |h 1009-1023 | ||