Optimal implementation of the 2019 ESC/EAS dyslipidaemia guidelines in patients with and without atherosclerotic cardiovascular disease across Europe: a simulation based on the DA VINCI study

Abstract

Background: The impact of the stepwise implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) treatment algorithm on low-density lipoprotein cholesterol (LDL-C) goal attainment was simulated in patients from the DA VINCI study.

Methods: Monte Carlo simulation was used to evaluate treatment optimisation scenarios, based on a patient's risk category: statin intensification (step 1), addition of ezetimibe (step 2), and addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (step 3). Residual cardiovascular risk and predicted relative and absolute risk reduction (RRR and ARR) in cardiovascular events were assessed.

Findings: In DA VINCI, 2482 patients did not achieve their 2019 ESC/EAS LDL-C goals and were included in the simulation. In patients without atherosclerotic cardiovascular disease (ASCVD) (n = 962), 27.0% (n = 259) and 57.0% (n = 548) are likely to achieve their LDL-C goals at step 1 and step 2, respectively. Of those at very high risk without ASCVD (n = 74), 88.1% (n = 65) are likely to achieve their LDL-C goals at step 3. In patients with ASCVD (n = 1520), 12.0% (n = 183), 42.1% (n = 641) and 93.2% (n = 1416) are likely to achieve their LDL-C goals at steps 1, 2 and 3, respectively. In patients with and without ASCVD, treatment optimisation may result in mean simulated RRR of 24.0% and 17.7%, respectively, and ARR of 8.1% and 2.6%, respectively.

Interpretation: Most patients at high cardiovascular risk are unlikely to achieve LDL-C goals through statin optimisation and ezetimibe, and will require a PCSK9 inhibitor, leading to greater reduction in cardiovascular risk.

Funding: Amgen.

Keywords: Atherosclerotic cardiovascular disease; Cardiovascular risk; ESC/EAS guidelines; LDL-C; Lipid-lowering.

Fig. 1

Treatment optimisation simulation. ^aUptitration of statins for patients not already receiving the highest available dose of their currently prescribed statin and not already receiving ezetimibe. The black horizontal arrows signify the patients who already are receiving high intensity statin at step 1 or those already receiving ezetimibe at step 2. These patients do not require further optimisation of their statin therapy (step 1) or addition of ezetimibe (step 2). ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9.

Fig. 2

Proportion of patients receiving optimised treatment at each step in the simulation: step 1, intensification of statin therapy (a); step 2, addition of ezetimibe (b); and step 3, addition of a PCSK9 inhibitor (c). ^aRecurrent ASCVD was defined as patients who experience at least two cardiovascular events within 2 years. ^bEzetimibe includes patients on ezetimibe monotherapy or ezetimibe and statin therapy. ^cPCSK9 inhibitor combination includes patients on any PCSK9 inhibitor therapy, including those who were initially on ezetimibe only, or on ezetimibe in combination with any statin therapy. ASCVD, atherosclerotic cardiovascular disease; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor.

Fig. 3

Simulation of LDL-C goal attainment through optimal implementation of the 2019 ESC/EAS dyslipidaemia guidelines^a in patients without ASCVD (a) and patients with ASCVD (b). ^aA full overview of the LDL-C goals in the 2019 ESC/EAS dyslipidaemia guidelines is detailed in Mach F et al. Eur Heart J. 2020; 41:111–188. ^bUptitration of statins for patients not already on the highest available dose of the currently prescribed statin and not already on ezetimibe. ^cAccording to the 2019 ESC/EAS guidelines, PCSK9 inhibitors are only recommended for patients at very high risk. ^dRecurrent ASCVD was defined as patients who experience at least two cardiovascular events within 2 years. Error bars show standard deviation. NA has been added to total column of patients without ASCVD, as only those at very high CV risk were eligible for a PCSK9 inhibitor per the treatment guidelines. Given that the intention of the analysis was to model the implementation of the ESC/EAS guidelines, the proportion of patients who were receiving PCSK9 inhibitors and achieved their LDL-C goals with low, moderate or high CV risk was not evaluated. ASCVD, atherosclerotic cardiovascular disease; EAS, European Atherosclerosis Society; ESC, European Society of Cardiology; LDL-C, low-density lipoprotein cholesterol; NA, not applicable; PCSK9, proprotein convertase subtilisin/kexin type 9.

Fig. 4

Simulated risk reduction following treatment optimisation in patients without ASCVD (SCORE) (a) and patients with ASCVD (REACH) (b). Data are shown as mean (SD). ^aRecurrent ASCVD was defined as patients who experience at least two cardiovascular events within 2 years. ASCVD, atherosclerotic cardiovascular disease; NA, not applicable; REACH, reduction of atherothrombosis for continued health; SCORE, systematic coronary risk evaluation SD, standard deviation.