Prof JC Kaski, St George's, University of London, UK

Despite the beneficial effect of statin treatment on cardiovascular risk reduction in patients with coronary artery disease (CAD) there is a residual risk of major adverse cardiovascular events, ie, myocardial infarction (MI), stroke and cardiovascular death, that needs to be addressed in clinical practice. (1) It has been argued that this residual risk is at least in part associated with LDL-cholesterol levels (1). The availability of new lipid lowering agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which have been shown in recent studies (2) to markedly reduce LDL-cholesterol levels even in patients receiving optimal dose of statins, has given the possibility of testing this hypothesis.

A recent study by Lotte Kaasenbrood et al. in Heart (3) -aimed at estimating the individual benefit of PCSK9 inhibition in CAD patients already treated with high-dose statin- showed that an estimation of the effectiveness of PCSK9 inhibition for individual patients can be extrapolated from the expected lipid lowering effect obtained through PCSK9 inhibition (50%–60%) and the robust relationship between LDL-C reduction and cardiovascular events reported in the literature. As described by the authors, “individual lifetime benefit was estimated in months gain free of stroke or MI until age 80 years. Predictions were based on two competing risk models developed in data from 4853 patients with CAD originating from the atorvastatin 80 mg arm of the Treating to New Targets (TNT) trial.” They accounted for individual LDL-C levels, assuming 50% LDL-C reduction by PCSK9 inhibition and 21% cardiovascular risk reduction per mmol/L (39 mg/dL) LDL-C lowering.

The main findings of the study were: 1. Estimated individual gain was <6 months in 61% of the patients, 6–12 months in 28% and ≥12 months in 10% of the patients. 2. The highest estimated benefit was observed in patients aged 40–60 years, particularly if LDL-C levels were >1.8 mmol/L (>70 mg/dL); 3. Estimated benefit was ≤5 months in patients ≥70 years of age, in particular if LDL-C and other risk factors levels were low.

These findings are of interest given the great expectation generated by the availability of these relatively new powerful lipid lowering agents. As expected, the potential incremental benefit of PCSK9 inhibition was shown to vary greatly among patients receiving high-dose statin treatment. Indeed, life expectancy free of stroke or MI ranged from just a few months to more than a year in the study. Another important determinant of outcome was age, with most of the benefit achieved in middle-aged patients (40–60 years) with relatively high levels of LDL-C and other risk factors compared with older patients. Of course we need to await further results from prospective trials and cost-economics studies to know the true magnitude of the benefit and cost related to the use of PCSK-9 inhibitors in clinical practice. The Kaasenbrood et al study, however, shows that individualised estimated treatment benefit –as proposed by the authors- may contribute to “targeted treatment and shared decision making on whether or not initiating PCSK9 inhibition in statin-treated patients with stable CAD”. This is important as no ‘blanket’ treatment appears to be anticipated by the conclusions reached by the authors.


  1. Mora S, Wenger NK, Demicco DA, et al. Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study. Circulation 2012;125:1979–87
  2. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713-22
  3. Kaasenbrood L, Ray KK, Boekholdt SM, et al. Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease. Heart Published Online First: 05 April 2018. doi: 10.1136/heartjnl-2017-312510
  4. original research article: