Prevention & lipidsSecondary analysis
The Effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition on the Risk of Venous Thromboembolism
- Secondary analysis of the FOURIER randomised trial
- post hoc analysis
- meta-analysis with ODYSSEY OUTCOMES
- exploratory genetic analysis
Authors' conclusion
PCSK9 inhibition significantly reduces the risk of VTE. Lp(a) reduction may be an important mediator of this effect
Study context
- Population
- FOURIER trial participants
- Comparison
- Evolocumab vs placebo
- Primary endpoint
- VTE (DVT or PE)
Primary result
VTE
Hazard ratio
0.71
95% CI 0.50–1.00
P = 0.05
Evolocumab vs placebo (PCSK9 inhibition)
HR 0.71 (95% CI 0.50–1.00); P = 0.05
As reported in the abstract
Further findings
Venous thromboembolism (VTE) by time period
| Comparison | HR (95% CI) | P value | |
|---|---|---|---|
| Evolocumab · 1st year | 0.96 (0.57–1.62) | ||
| Evolocumab · beyond 1 year | 0.54 (0.33–0.88) | P = 0.014 | |
| 0.20.5125Hazard ratio (log scale) |
VTE, meta-analysis of FOURIER and ODYSSEY OUTCOMES
| Comparison | HR (95% CI) | P value | |
|---|---|---|---|
| PCSK9 inhibition · 31% relative risk reduction | 0.69 (0.53–0.90) | P = 0.007 | |
| 0.512Hazard ratio (log scale) |
VTE by baseline Lp(a) (subgroup)
| Comparison | HR (95% CI) | P value | |
|---|---|---|---|
| Evolocumab · higher baseline Lp(a); Lp(a) reduced by 33 nmol/L | 0.52 (0.30–0.89) | P = 0.017 | |
| 0.20.5125Hazard ratio (log scale) |
- VTE by baseline Lp(a) (subgroup) — Lp(a) as continuous variable: significant interaction with VTE risk reduction
- Pinteraction=0.04
- VTE by baseline Lp(a) (subgroup): Pinteraction 0.087 for HR
- VTE by baseline Lp(a) (subgroup): Pheterogeneity 0.037 for absolute risk reduction
VTE by baseline Lp(a) (subgroup)
- Lower baseline Lp(a): Lp(a) reduced by only 7 nmol/L, no effect on VTE risk
- No relation between baseline LDL-C and magnitude of VTE risk reduction
VTE by polygenic risk score (subgroup)
- Greater relative VTE reduction with high genetic risk
- P for interaction = 0.04
- Greater absolute VTE reduction with high genetic risk
- P for heterogeneity = 0.009
- High genetic risk: >2-fold increased VTE risk
- exploratory genetic analysis
Original publication
The Effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition on the Risk of Venous Thromboembolism. Circulation. Published 29 March 2020. doi:10.1161/circulationaha.120.046397
Summarised from the published abstract; every number is checked against it