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Published on: August 28, 2018
Sex Differences in Cardiovascular Outcomes and Cholesterol-Lowering Efficacy of PCSK9 Inhibitors: Systematic Review
Frederick Berro Rivera1, Sung Whoy Cha2, John Paul Aparece3
1Department of Medicine, Lincoln Medical Center, Bronx, New York, USA.
Insights
Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein cholesterol (LDL-C) and major adverse cardiovascular events (MACE) in both men and women. While MACE reduction is similar, men experience greater LDL-C lowering with PCSK9i treatment.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets are frequently unmet, particularly in women.
- Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) offer further LDL-C reduction and cardiovascular risk mitigation.
- Understanding sex-based differences in PCSK9i efficacy is crucial for optimizing treatment.
Purpose of the Study:
- To evaluate sex-specific differences in the efficacy of PCSK9 inhibitors for LDL-C reduction.
- To assess sex-specific differences in the reduction of major adverse cardiovascular events (MACE) with PCSK9 inhibitor use.
- To compare the efficacy of different types of PCSK9 inhibitors between sexes.
Main Methods:
- A systematic literature search was conducted for randomized controlled trials comparing PCSK9 inhibitors with placebo up to October 17, 2022.
- Outcomes included LDL-C reduction and MACE incidence, with analyses stratified by patient sex and PCSK9 inhibitor type.
- Data from 16 trials involving 54,996 adults (27.5% female) were analyzed.
Main Results:
- PCSK9 inhibitors significantly reduced MACE in both women (HR: 0.86) and men (HR: 0.85), with no significant sex difference observed.
- Significant LDL-C reductions were achieved in both sexes at 12 and 24 weeks.
- Males showed a statistically significant greater reduction in LDL-C compared to females at both 12 weeks (MD: -4.55) and 24 weeks (MD: -7.11).
Conclusions:
- PCSK9 inhibitors demonstrate significant efficacy in reducing both LDL-C and MACE in both male and female patients.
- While MACE reduction is comparable between sexes, males exhibit a more pronounced LDL-C lowering effect.
- The findings support the equitable use of PCSK9 inhibitors across all eligible patients, irrespective of sex.
Background:
Guideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i) monoclonal antibodies can help further reduce LDL-C and major adverse cardiovascular events (MACE) although differences in efficacy by sex and type are less understood.
Objectives:
The authors sought to determine if there are differences in the efficacy of LDL-C lowering and reduction in the risk of MACE by sex and type of PCSK9i.
Methods:
A comprehensive literature search was done through October 17, 2022, for published trials comparing PCSK9i vs control. Outcomes assessed were LDL-C reduction and incidence of MACE following the use of PCSK9i vs placebo, stratified by sex and type of PCSK9i used.
Results:
We identified 16 trials with 54,996 adults, and 15,143 (27.5%) of them were female. PCSK9i significantly reduced MACE compared to placebo in both women (HR: 0.86, 95% CI: 0.74-0.97, P < 0.001) and men (HR: 0.85, 95% CI: 0.79-0.91, P < 0.001) with no significant sex difference (MD -0.01, 95% CI: -0.14 to -0.13, P = 0.930). PCSK9i also significantly reduced LDL-C levels in both sexes at 12 weeks (females: MD -62.57, 95% CI: -70.24 to -54.91, P < 0.001; males: MD -66.19, 95% CI: -72.03 to -60.34, P < 0.001) and 24 weeks (females: MD -47.52, 95% CI: -52.94 to -42.09, P < 0.001; males: MD -54.07, 95% CI: -59.46 to -48.68, P < 0.001). Significant sex difference was seen in the LDL reduction of PCSK9i for both 12 weeks (males vs females: MD -4.55, 95% CI: -7.34 to -1.75, P < 0.01) and 24 weeks (males vs females: MD -7.11, 95% CI: -9.99 to -4.23, P < 0.001).
Conclusions:
The use of PCSK9i results in significant LDL-C and MACE reduction in both males and females. While there is no significant sex difference in MACE reduction, LDL-C reduction is greater in males than in females. Our data support the equal use of PCSK9i in all eligible patients, regardless of sex.
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