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Time to benefit of intensive lipid lowering therapy in individuals with cardiovascular disease
Linjie Li1, Chuanyi Huang1, Wennan Liu1
1Department of Cardiology, Tianjin Medical University General Hospital, Heping District, Tianjin, China (Drs L. Li, Huang, Liu, J. Li, Geru, Chen, Jiang, Fang, Y. Li, Yang, and Zhou).
Insights
Intensive lipid-lowering therapy, including statins, PCSK9 inhibitors, and ezetimibe, shows varying times to benefit for cardiovascular events. Personalized treatment is key for optimizing major adverse cardiovascular event (MACE) reduction in patients with established cardiovascular disease (CVD).
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- The clinical benefit timing of intensive lipid-lowering therapy for major adverse cardiovascular events (MACE) in established cardiovascular disease (CVD) is not well-defined.
- This is especially true considering the introduction of novel medications like proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and ezetimibe after 2010.
Purpose of the Study:
- To determine the time to benefit (TTB) associated with intensive lipid-lowering therapies.
- To compare TTB across different therapeutic regimens and historical periods.
Main Methods:
- A systematic review of randomized controlled trials (RCTs) investigating intensive lipid-lowering therapy was conducted.
- Individual participant data were reconstructed to fit Weibull survival curves and estimate TTB for predefined absolute risk reduction thresholds.
- The primary outcome assessed was MACE.
Main Results:
- Seven RCTs involving 92,180 participants were analyzed, with an average age between 58.2 and 63.6 years.
- An overall TTB of 19.6 months was required to prevent one MACE per 100 patients.
- Before 2010, high-intensity statin therapy required a TTB of 15.2 months; post-2010, PCSK9i-based therapy had a TTB of 17.7 months, and ezetimibe-based therapy required 47.3 months.
Conclusions:
- Contemporary intensive lipid-lowering strategies require significant time to demonstrate clinical benefit in reducing MACE.
- PCSK9i-based therapy shows a relatively rapid TTB (17.7 months), while ezetimibe-based therapy has a longer TTB (47.3 months).
- These findings underscore the importance of personalized treatment approaches based on individual patient risk and chosen therapeutic regimen.
Background:
The timing of the clinical benefit of intensive lipid-lowering therapy in reducing major adverse cardiovascular events (MACE) in individuals with established cardiovascular disease (CVD), both before and after the advent of novel medications (proprotein convertase subtilisin/kexin type 9 inhibitor [PCSK9i] and ezetimibe) in 2010, is unclear.
Objective:
To evaluate the time to benefit (TTB) from intensive lipid-lowering therapy.
Methods:
The investigators systematically searched for randomized controlled trials evaluating intensive lipid-lowering therapy. The primary outcome was MACE. Utilizing reconstructed individual participant data, Weibull survival curves were fitted to estimate the TTB for specific absolute risk reduction thresholds (0.002, 0.005, and 0.01).
Results:
Seven trials randomizing 92,180 adults aged between 58.2 and 63.6 years were identified. A TTB of 19.6 months (95% CI: 12.3-31.4) of intensive lipid-lowering was needed to prevent 1 MACE per 100 patients. Before 2010, when statin was the only option, a TTB for high-intensity statin therapy of 15.2 months (95% CI: 6.52-35.5) was needed. After 2010, the TTB for PCSK9i-based, ezetimibe-based intensive lipid-lowering on a background of statin therapy was 17.7 (95% CI: 12.2-25.6) and 47.3 (95% CI: 20.4-110) months, respectively.
Conclusion:
In contemporary practice, to prevent 1 MACE in 100 individuals with established CVD, a TTB of 17.7 and 47.3 months was needed for PCSK9i-based and ezetimibe-based intensive lipid-lowering therapy on a background of statin therapy, respectively. The observed variations across different drug regimens highlight the need for a personalized approach to treatment decisions.
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