The systematic implementation approach was effective at introducing dapagliflozin in an outpatient heart failure clinic. The approach could identify eligible patients within the hospital’s catchment area according to prespecified objective criteria, which shows its feasibility in real-world settings. Despite performing the implementation of dapagliflozin in a specialist clinic with efforts to simplify the systematic approach, not all patients who fulfilled the eligibility criteria received the information letter or were assessed for dapagliflozin. This accentuates that education or time for the threating physician is often insufficient in ordinary care settings, which motivates the need for a systematic approach to implement novel medications. By using the limited resources of healthcare and focus the implementation of novel treatments to the intended patients, the more cost-effective the implementation will be.

The systematic approach shows that it is possible to manage an implementation process by using objective criteria, based on national guidelines or clinical study criteria. The systematic approach can be used to both speed up or take a more cautious implementation strategy. For example, if the safety profile of the novel medication is uncertain in real-world settings, it is possible to conduct more strict criteria in the first round of implementation. This would identify eligible patients that are highly representative of the population included in clinical trials, where the strongest evidence is shown. However, for a treatment like dapagliflozin the safety profile is not a problem since the substance has been approved and used without any major safety concern in real-world diabetes mellitus type 2 (T2DM) populations for several years [23, 24]. Now when dapagliflozin is approved for a wide range of patients (including T2DM, heart failure and chronic kidney disease), the financial burden rises. At this stage, the systematic approach can be used to prioritize which patients should receive treatment with dapagliflozin based on budget allocations.

The systematic implementation approach was developed to introduce sacubitril-valsartan in the same clinical setting as the current study. In addition, the first two steps of the approach have been used to assess the real-world eligibility of sacubitril-valsartan, SGLT2 inhibitors, and faricimab before market authorization for budget planning [17,18,19]. In the sacubitril-valsartan study, the eligibility assessment was based on the strict main criteria from the PARADIGM-HF trial resulting in few eligible patients in the real-world population compared to the SGLT2 inhibitors and faricimab studies. This shows the consequence when clinical trials apply strict criteria, which in turn diminishes the external validity of the evidence since old and frail patients are rarely included in clinical trials.

To apply an implementation process across all patients in a clinic can be difficult [25]. In the current study, it became evident that not all physicians choose to send their patients the information letter. We attempted to simplify the approach by allowing this possibility for physicians who already had a scheduled appointment with eligible patients at the outpatient clinic. Consequently, many patients did not receive the information letter beforehand, depriving them of the opportunity to consider the option independently before their cardiologist appointment. In our earlier research, patients expressed appreciation for receiving the information letter in advance, as it allowed them time to consider the new treatment on their own terms before their scheduled appointment [16]. Furthermore, medical record data is not always complete, there can be some additional patients that received the letter even though it was not documented.

We also learned that even though all physicians at the outpatient clinic were involved in the systematic implementation approach with dapagliflozin, the knowledge of the drug may not be entirely spread since not all identified patients were assessed for dapagliflozin eligibility. Additionally, as the systematic approach was not the standard implementation procedure at the clinic, an initial increased workload could be observed to assess patients’ eligibility based on medical records and to assess and initiate dapagliflozin to patients not already listed at the clinic. This may suggest that the process can work more efficiently if the work is concentrated on a smaller team of interested physicians, nurses, and pharmacists.

The majority of the patients were followed-up within 3 and at 12 months after initiation of dapagliflozin (81% and 90%, respectively), which is an expected result in real-world settings. Since there was no documented follow-up for the remaining patients, it was not feasible to analyse the reasons behind the lack of follow-up in these cases. This information would be valuable to investigate further prior to the implementation of the next novel medication in the clinic.

Regarding safety outcomes, dapagliflozin was well tolerated in our population with few reported adverse events and 87% persistence on treatment after 12 months. Seven patients discontinued dapagliflozin due to various adverse events. The findings align with the outcomes of the phase III trials DAPA-HF and DELIVER [20, 26], suggesting that the safety characteristics observed with dapagliflozin could be applicable to our heart failure cohort.

Dapagliflozin has shown to be effective both in clinical trials and real-world populations [20, 26,27,28,29]. In our small real-world cohort, only one-fifth of the individuals experienced a heart failure hospitalization during the first year after dapagliflozin initiation. Despite the substantial amount of missing data on changes in NYHA class and self-reported well-being, the high proportion of individuals with unchanged NYHA class and well-being suggests disease stabilization. Given the progressive nature of heart failure, this stabilization, along with the low number of hospitalizations, is considered a beneficial outcome.

This study has several limitations. This was an observational study based on medical record data which may not be completely documented for all included individuals. We could have missed eligible patients who met the dapagliflozin criteria but with missing parameters in their medical records, resulting in exclusion. Furthermore, missing data can also have resulted in an underestimation of the number of individuals receiving the information letter or being followed-up after initiation.

The current study was not an explicit implementation study since we performed the primary selection of step 2 in the Håkansson et al. paper long time in advance. The gap between steps 2 and 3 was mainly caused by awaiting regulatory approval for dapagliflozin in heart failure. Approximately 14 months later, the rest of the systematic implementation approach was continued with step 3 and forward. This resulted in many excluded individuals (n = 161) in steps 3 and 4 due to lost eligibility in the meantime. It is possible that we missed to treat some individuals that were eligible 14 months earlier but due to disease progress later had deceased or were too ill to still fulfil eligibility. For future use of the systematic approach, a more continuous process would be recommended.

At the 12-month follow-up, nearly one-third of the individuals were monitored at their primary care centres. Unfortunately, we did not have access to the primary care medical records, resulting in missing data, particularly for the variables NYHA class and self-reported well-being. These variables are also influenced by various factors such as disease progression, comorbidities, and other heart failure medications in addition to dapagliflozin. Therefore, the effect outcomes should be interpreted with caution.

The single-centre study design reduces generalizability to other settings. However, we have applied the systematic approach in both other heart failure treatments and other diseases, such as ophthalmology, which indicates that the approach is flexible and can be adapted to other settings as well.

Previous and current studies have demonstrated that the systematic implementation approach is applicable across various settings and adaptable to different medical treatments. However, further research is warranted to assess the cost-effectiveness of this approach in clinical practice. Additionally, exploring the systematic approach across a broader range of diagnoses and medications would be of interest. The core principle remains consistent: screening and identifying suitable patients based on predefined objective criteria to optimize the utilization of healthcare resources.