Cardiovascular diseases (CVD) are the leading cause of death worldwide, accounting for 18.6 million deaths globally in 2019.1 In Spain, CVD are responsible for approximately 115000 deaths yearly, which represents 26.5% of total deaths.2 The major component of CVD is atherosclerotic cardiovascular disease (ASCVD), which refers to coronary heart disease, cerebrovascular disease, and peripheral artery disease.3 In turn, patients with established ASCVD are considered to be at very high cardiovascular risk.4

Despite that multiple cardiovascular risk factors have been described,5,6 it has been demonstrated that elevated levels of low-density lipoprotein cholesterol (LDL-C) have a causal role in ASCVD.7,8 In this context, the scientific evidence available suggests that decreasing LDL-C should be a primary target in the treatment of dyslipidaemia.9 In fact, the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)4 recommend reducing LDL-C levels ≥ 50% from baseline, with a goal of < 55mg/dL (< 1.4mmol/L) for patients with very high cardiovascular risk.4

Despite the number of lipid-lowering therapies (LLT) available to meet this goal,10,11 most patients do not achieve the recommended LDL-C levels,12–14 which could be due to therapeutic inertia, lack of perceived risk, or low patient adherence to treatment, among other causes.14–16

In patient-centred care, patients and clinicians discuss the best therapeutic option with patients’ preferences and concerns in mind. This shared-decision making process has demonstrated a better conflict resolution, adherence to treatment, and health outcomes.17 However, therapeutic decision-making has become a more complex process, especially in multidisciplinary teams.

In this context, preference studies are of relevance as they allow to gather information on the value that participants assign to different attributes of a given medical intervention.18 The most commonly used method to study patients’ and healthcare professionals’ (HCP) health preferences is the discrete choice experiment (DCE), in which participants are asked to choose between 2 or more alternatives (scenarios) where at least one attribute is systematically varied.19,20

Studies aiming at assessing patients’ and HCP preferences in the field of ASCVD LLT are scarce. Thus, considering all the above, the main goal of this study was to identify the preferences of patients with very high cardiovascular risk and HCP for the attributes related to LLT in Spain. We also aimed to describe the sociodemographic and clinical characteristics of patients and HCP and to evaluate the association between patients’ preferences and their adherence to treatment.

The results obtained in our study regarding treatment preferences were similar for patients and HCP, as both preferred a treatment able to reduce cardiovascular events and LDL-C to the recommended levels. Similar results were also reported by a recent publication evaluating the adherence of physicians to ESC/EAS guidelines, with most of the participants selecting reducing LDL-C levels followed by cardiovascular risk reduction as the primary target of a LLT.13 Although direct comparisons with our results cannot be established, the results of this study emphasize that reduction of cardiovascular risk and LDL-C levels are the 2 most important attributes of a LLT for HCP when selecting the most appropriate therapy. This is likely due to the established association of LDL-C reduction and the reduction in the occurrence of major adverse cardiovascular events.4,23,24

Regarding the estimated RI for each attribute, patients considered prevention of cardiovascular problems (26.8%), LDL-C reduction (26.8%), and treatment safety (24.0%) almost equally important. HCP equally had a strong preference for the prevention of cardiovascular problems (estimated RI: 37.7%) and LDL-C reduction (estimated RI: 31.6%). However, noteworthy discrepancies were observed between HCP and patients concerning the third most important attribute. While HCP identified route and frequency of administration as the third priority (10.9%), patients placed greater importance on safety. This difference could be explained as given the HCP experience managing LLT, where safety represent no longer a concern for them, and low treatment adherence is a major issue for LLT. Patients prioritization of treatment safety might be probably due to the different perceptions patients have about health status or medication compared with HCP25 or the uncertainty some patients have about the safety of LLT such as statins.26 Similar discrepancies regarding treatment preferences between patients and HCP have been already described in several fields,27,28 with patients giving more importance to risk and side effects than HCP.29 A review on this matter reported that HCP consider more important those attributes related to structure and outcomes care than patients.30 Our results are in line with these findings; HCP estimated a higher RI for the efficacy attributes, while treatment safety was more important for patients than for HCP.

One of the main findings of our study is the difference observed in the preferred route and frequency of administration. HCP preferred a subcutaneous injection administered by an HCP once every 6 months to oral treatment, probably as it ensures treatment effect for those 6 months. Additionally, HCP administering the treatment twice per year could reinforce to patients the importance of being compliant with therapies, resulting in an improved adherence and persistence to other LLTs. Thus, representing an opportunity for overcoming the challenge of a low adherence rate to LLT.31,32 In this regard, a previous study showed that patients adherent to a low-intensity LLT presented lower risk of cardiovascular events compared with nonadherent patients receiving a high-intensity LLT.33 The mentioned route is also significantly preferred over a self-administered injection twice per month. The results reported by HCP are slightly different from those obtained for patients, who equally preferred a subcutaneous injection administered by an HCP once every 6 months and an oral daily treatment over a self-administered injection twice per month. This suggests that patients prioritize comfort of the administration, understood as oral administration or an injection as widely spaced in time as possible, a preference that has also been documented in previous studies conducted in other disease areas.34,35

On the other hand, patients preferred to collect the medication in their primary care centre, followed by the street pharmacy, while HCP preferred that patients collected the medication at the street pharmacy in first place, followed by the primary care centre. Both considered collecting the medication at the hospital as the least preferred option. This could be explained as HCP might consider that collecting the medication at the usual street pharmacy could increase the adherence to the treatment, while patients, especially older patients, could feel more confident collecting it from their trusted primary care physician. In this regard, it could be hypothesised that the option of collecting the medication at a primary care centre was the least preferred by HCP, as this could increase the already high workload of primary care.

Finally, it is worth mentioning that, overall, we did not find statistically significant differences in patients’ and HCP preferences regarding their sociodemographic or clinical variables. However, we cannot rule out that patients LDL-C levels could influence their preferences as approximately a third of them did not report these data. In addition, no statistically significant differences were observed regarding patients’ adherence to treatment. However, it should be noted that information on adherence was provided by participating patients and their responses could have been influenced by the effect of memory.

For physicians, understanding patients’ perceptions and preferences might help during the treatment shared decision-making process.27,30 Thus, we believe that the study provides added value by considering patients’ preferences, which are key to this process. In addition, the information obtained in the present study can help better understand the strategies that could be implemented to improve patient-HCP relationship and collaboration in the management of patients with established ASCVD.

This study has some limitations. All estimated preferences and RI depended on the attributes and levels selected to define the scenarios, which were related to the available treatments and their effects and the pathologies they cover. Thus, other attributes such as treatment costs were not considered. The inclusion of other criteria that placed more emphasis on variables perceived by patients (e.g. quality of life, satisfaction) could potentially offer other more striking results and differences between patients and HCP. The sample size was not large enough to show differences between subgroups. These results should be taken as a first approximation to the estimation of these preferences and therefore, further studies are necessary to expand these results. On the other hand, it is possible that participating patients were better informed than the general population, as they were recruited by a patients’ association. This factor might also account for the high adherence observed, given that such individuals are likely to be more aware of their condition and committed to strict treatment compliance. Despite the stated limitations, a high number of patients and experienced HCP from 6 different specialties participated in the study, being representative of the situation of the management of LLT in patients with established ASCVD.

In conclusion, treatment efficacy preventing cardiovascular events and reducing LDL-C levels were the most important attributes for HCP and patients. Furthermore, HCP showed their preference for a subcutaneous injection administered by an HCP once every 6 months to a self-administered treatment while patients equally preferred oral or a subcutaneous injection administered by HCP once every 6 months over a self-administered injection twice a month. Patients valued treatment safety, preferring frequent side effects not altering their daily life activities. Overall, the results of the present study can contribute to improve decision-making in the management of ASCVD.

This study of the Research Agency of the Spanish Cardiology Society was funded by Novartis.

The study was approved by the Ethics Committee of the Arnau de Vilanova Hospital in Valencia and conducted in accordance with the principles of the Declaration of Helsinki. Patients who accepted the conditions of the study gave their consent to participate in the study. A cross-sectional, non-interventional design was employed for analysis and consecutive sampling was carried out on 33 males and 17 females. A total of 89 HCP participated in the study, 51 males and 38 females.

No artificial intelligence was employed.

R. Fernández Olmo, J. Parrondo, L. Martín Mitjana, S. Reimondez-Troitiño, and J. Cosín-Sales: conceptualization, methodology, investigation, original draft writing, review and editing.. A.B. Álvarez Hermida, M. Castellanos Rodrigo, J.F. Gómez Cerezo, M.J. Igual Guaita, S.J. Jansen Chaparro, and J.C. Obaya Rebollar: investigation, writing – review and editing.

R. Fernández Olmo has received honoraria from Amarin, Amgen, AstraZeneca, Daiichi-Sankyo, Novartis, Novo Nordisk, Pfizer, Sanofi, and Servier. M. Castellanos Rodrigo has received honoraria as a speaker from Ferrer, Daiichi-Sankyo and BMS-Pfizer, and has participated in advisory services for BMS, Daiichi-Sankyo, Novartis, and Pfizer. J.F. Gómez Cerezo has received fees as a speaker from Amgen SA, Daiichi-Sankyo, Menarini, Novartis, and Sanofi. M.J. Igual Guaita has received honoraria for advisory services from Novartis. S.J. Jansen Chaparro has received honoraria as a speaker and for advisory services from Amgen, AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, and Sanofi-Aventis. J.C. Obaya Rebollar has received fees as a speaker from AstraZeneca, Boehringer-Ingelheim, Esteve, Lilly, Novartis, Novo Nordisk, and Sanofi. J. Cosín-Sales has received conference fees from Almirall, Amgen, Daiichi-Sankyo, Ferrer, MSD, Mylan, Novartis, Organon, Rovi, and Sanofi; has participated in advisory services for Almirall, Amgen, MSD, Novartis, and Sanofi; and has received research grants from Amgen, Daiichi-Sankyo, Ferrer, MSD, and Sanofi. J. Parrondo, L. Martín Mitjana, and S. Reimóndez-Troitiño are employees at Novartis. A.B. Álvarez Hermida has nothing to declare.

Data are available from the corresponding author upon reasonable request complying with the corresponding data protection laws.