A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients
BACKGROUND: Dyslipidaemia is a crucial risk factor for cardiovascular morbidity and mortality. A short interfering RNA called inclisiran diminishes circulating levels of PCSK9 and LDL-C by hindering PCSK9 translation in the liver.
METHODS: RCTs were electronically searched on PubMed, Cochrane Central, and Clinicaltrials.gov to assess the safety and efficacy of inclisiran. Cochrane Review Manager 5 was used to conduct the pooled analysis. Risk of bias was assessed and GRADE pro-GDT was utilized, respectively, to estimate the methodological quality and overall quality of evidence.
RESULTS: Of 218 records screened, four studies were included with 2203 participants in inclisiran and 1949 participants in the placebo group. Inclisiran was related to non-significant elevated risk of total adverse events[RR = 1.05(0.98,1.12), p = 0.16; I2 = 53%], non-serious adverse events[RR = 1.09(0.97,1.22),p = 0.15;I2 = 61%] and all-cause mortality[RR = 1.01(0.60,1.70),p = 0.97;I2 = 0%] whereas a lower risk of serious adverse events[RR = 0.94(0.70,1.25),p = 0.67;I2 = 73%], cardiac disorders [RR = 0.87(0.66,1.15),p = 0.33;I2 = 42%] and Major adverse cardiovascular events(MACE)[RR = 0.79(0.62,1.00),p = 0.05; I2 = 0%] as compared to placebo. Inclisiran was also linked to a substantial decline in the percentage of LDL-C, PCSK9, total cholesterol, and Apo B.
CONCLUSION: The pooled analysis of the existing evidence shows that inclisiran showed reduced risk of MACE along with excellent efficacy in managing dyslipidemia.
CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT03399370, NCT03397121, NCT03400800, and NCT02597127.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Expert opinion on drug safety - 23(2024), 2 vom: 01. Feb., Seite 187-198 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dutta, Siddhartha [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.02.2024 Date Revised 23.02.2024 published: Print-Electronic ClinicalTrials.gov: NCT02597127, NCT03397121, NCT03399370, NCT03400800 Citation Status MEDLINE |
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| doi: |
10.1080/14740338.2023.2293201 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365542326 |
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| 245 | 1 | 2 | |a A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients |
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| 500 | |a ClinicalTrials.gov: NCT02597127, NCT03397121, NCT03399370, NCT03400800 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Dyslipidaemia is a crucial risk factor for cardiovascular morbidity and mortality. A short interfering RNA called inclisiran diminishes circulating levels of PCSK9 and LDL-C by hindering PCSK9 translation in the liver | ||
| 520 | |a METHODS: RCTs were electronically searched on PubMed, Cochrane Central, and Clinicaltrials.gov to assess the safety and efficacy of inclisiran. Cochrane Review Manager 5 was used to conduct the pooled analysis. Risk of bias was assessed and GRADE pro-GDT was utilized, respectively, to estimate the methodological quality and overall quality of evidence | ||
| 520 | |a RESULTS: Of 218 records screened, four studies were included with 2203 participants in inclisiran and 1949 participants in the placebo group. Inclisiran was related to non-significant elevated risk of total adverse events[RR = 1.05(0.98,1.12), p = 0.16; I2 = 53%], non-serious adverse events[RR = 1.09(0.97,1.22),p = 0.15;I2 = 61%] and all-cause mortality[RR = 1.01(0.60,1.70),p = 0.97;I2 = 0%] whereas a lower risk of serious adverse events[RR = 0.94(0.70,1.25),p = 0.67;I2 = 73%], cardiac disorders [RR = 0.87(0.66,1.15),p = 0.33;I2 = 42%] and Major adverse cardiovascular events(MACE)[RR = 0.79(0.62,1.00),p = 0.05; I2 = 0%] as compared to placebo. Inclisiran was also linked to a substantial decline in the percentage of LDL-C, PCSK9, total cholesterol, and Apo B | ||
| 520 | |a CONCLUSION: The pooled analysis of the existing evidence shows that inclisiran showed reduced risk of MACE along with excellent efficacy in managing dyslipidemia | ||
| 520 | |a CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT03399370, NCT03397121, NCT03400800, and NCT02597127 | ||
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| 700 | 1 | |a Piparva, Kiran |e verfasserin |4 aut | |
| 700 | 1 | |a Katoch, Chandan Dev Singh |e verfasserin |4 aut | |
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