PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis
Khan SU, Yedlapati SH, Lone AN, Hao Q, Guyatt G, Delvaux N, Bekkering GET, Vandvik PO, Riaz IB, Li S, Aertgeerts B, Rodondi N
BMJ (Clinical research ed.) · 94 citas
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Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación no declarada
Publicación
- Publicado
- 2022-05-04 · BMJ · vol. 377 · pág. e069116
- Citado
- 148 citas · más que el 99% de estudios similares · 8.8× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 41 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Acute Myocardial Infarction Research · Cancer, Lipids, and Metabolism
- Palabras clave
- PCSK9 inhibitors, ezetimibe, statin therapy, statin intolerance, cardiovascular risk reduction, myocardial infarction, stroke, all-cause mortality, cardiovascular mortality, hypercholesterolemia, LDL cholesterol lowering, minimal important difference, cardiovascular disease prevention, combination lipid-lowering therapy, LDL cholesterol targets
- MeSH
- humans, cardiovascular diseases, myocardial infarction, anticholesteremic agents, hydroxymethylglutaryl-coa reductase inhibitors, risk factors, adult, stroke, ezetimibe, proprotein convertase 9, heart disease risk factors, pcsk9 inhibitors
12 autores
- Safi Ullah Khan🇺🇸 · autor de correspondenciaHouston Methodist
- Siva Harsha Yedlapati🇺🇸Erie County Medical Center
- Ahmad Naeem Lone🇺🇸Guthrie Robert Packer Hospital
- Qiukui Hao🇨🇳🇨🇦Sichuan University; West China Hospital of Sichuan University; McMaster University
- Gordon Henry Guyatt🇨🇦McMaster University
- Nicolas Delvaux🇧🇪KU Leuven
- Geertruida Elsiena Bekkering🇧🇪KU Leuven
- Per Olav Vandvik🇳🇴University of Oslo
- Irbaz Bin Riaz🇺🇸Mayo Clinic; Harvard University; Mayo Clinic Hospital; Mass General Brigham
- Sheyu Li🇨🇳Sichuan University; West China Hospital of Sichuan University
- Bert Aertgeerts🇧🇪KU Leuven
- Nicolas Rodondi🇨🇭University of Bern; University Hospital of Bern
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objective
To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant.
Design
Network meta-analysis.
Data sources
Medline, EMBASE, and Cochrane Library up to 31 December 2020.
Eligibility criteria for selecting studies
Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months.
Main outcome measures
We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke.
Results
We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke.
Conclusions
Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk.
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