Large interpersonal variation in estimated benefit from PCSK9 inhibition in CAD patients
Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease
Introduction and methods
Patients with coronary artery disease (CAD) are at high risk for recurrent CV events, particularly if they have high LDL-c levels, despite high-dose statin therapy .
The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial showed that the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab attenuate the LDL-c-induced residual CV risk. It is, however, not clear which patients should be treated with this effective but costly therapy [2,3].
This study evaluated the individual benefit of PCSK9 inhibition in patients with stable CAD on high-dose statin therapy. The individual benefit was estimated from a lifetime perspective and expressed in terms of gain in life expectancy free of (recurrent) stroke or MI, in patients originating from the Treating to New Targets (TNT) trial [4,5].
The measures of individual benefit from PCSK9 inhibition in addition to high dose statins was estimated based on:
- individual relative risk reduction, derived from large clinical trial data  and dependent on an individual’s LDL-c level
- individual CV disease prognosis, based on two competing risk models [7,8] that were derived from patient data in the TNT trial
- The study population (N=4853) was characterized by a high interpersonal variation in estimated benefit from PCSK9 inhibition.
- The median estimated lifetime benefit from initiating PCSK9 inhibition was 5 months (IQR: 2–8) and ranged from <6 months in 61% of the patients to >12 months in 10% of the patients.
- Patients aged 40–60 years with a high risk factor burden had the highest estimated benefit, particularly if LDL-c levels were >1.8 mmol/L (>70 mg/dL).
The potential incremental benefit of PCSK9 inhibition varies a lot among patients with stable CAD on high-dose statin treatment, ranging from a few months to more than a year gain in life expectancy free of recurrent stroke or MI. Highest benefit is expected in younger patients with a high risk factor burden and high LDL-c levels. Individualized estimated treatment benefit may contribute to targeted treatment and shared decision making on whether or not initiating PCSK9 inhibition in statin-treated patients with stable CAD.