Effect of proprotein convertase subtilisin/kexin type 9 inhibition on cancer events: A pooled, post hoc, competing risk analysis of alirocumab clinical trials.
Cancer Med
; 12(16): 16859-16868, 2023 08.
Article
em En
| MEDLINE
| ID: mdl-37458138
ABSTRACT
OBJECTIVE:
Assess the risk of new and worsening cancer events among participants who received the lipid-lowering therapy alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor.DESIGN:
Pooled post hoc analysis.SETTING:
Six phase 3 or phase 4 placebo-controlled randomised trials with alirocumab.PARTICIPANTS:
A total of 24,070 patients from the safety population with complete dosing data (alirocumab, n = 12,533; placebo, n = 11,537). INTERVENTION Alirocumab 75 mg, alirocumab 150 mg, alirocumab 75 mg increasing to 150 mg if low-density lipoprotein cholesterol <50 mg/dL not achieved, or placebo, all every 2 weeks. All participants received background high-intensity or maximum-tolerated statin therapy. OUTCOMES ANDMEASURES:
The first new or worsening incident cancer events were assessed during the treatment-emergent adverse event period. Four outcomes were evaluated any-neoplasm, malignant neoplasms, broad definition of hormone-sensitive cancers, and stricter definition of hormone-sensitive cancers. Sub-distribution hazard ratios and 95% confidence intervals (CIs) were estimated using a competing risk framework, with death as a competing risk.RESULTS:
Considering both treatment arms in aggregate, 969 (4.03%), 779 (3.24%), 178 (0.74%) and 167 (0.69%) patients developed any neoplasm, malignant neoplasms, broad definition of hormone-sensitive cancer and strict definition of hormone-sensitive cancer events, respectively. There was no significant difference in the risk of having any neoplasm in the alirocumab versus the placebo group (sub-distribution hazards ratio [95% CI], 0.93 [0.82-1.1]; p = 0.28). A nominally lower risk of having any neoplasms with alirocumab was observed among subjects aged ≥64 years (sub-distribution hazards ratio 0.83; 95% CI, 0.70-0.99).CONCLUSIONS:
Intensive low-density lipoprotein cholesterol lowering with a proprotein convertase subtilisin/kexin type 9 inhibitor combined with statin does not appear to increase the risk of new or worsening cancer events.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de PCSK9
/
Anticorpos Monoclonais
/
Neoplasias
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Med
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos