NAERINGSPH-Nærings-phd

Heart failure (HF) is a clinical syndrome with symptoms and signs of congestion due to deteriorated pump function. HF is a global pandemic affecting 1-2% of adults. Even though medical innovations have improved the prognosis over the past decades, mortality remains high and exceeds most forms of cancers. Renin-angiotensin system inhibitors (RASi) (angiotensin-converting enzyme inhibitors [ACEI] or angiotensin-II receptor blockers [ARB]), beta-blockers (BB), and mineralocorticoid receptor blockers (MRA) have been the cornerstones of the treatment of HF with reduced ejection fraction for several years. After two decades without novel pharmacological breakthroughs, the angiotensin receptor-neprilysin inhibitor (ARNI) was recommended as a replacement for ACEI in selected patients in the 2016 ESC HF Guidelines. In 2021, the Guidelines introduced a simplified treatment algorithm and a fourth novel treatment class, the sodium-glucose co-transporter 2 inhibitors. Several critical knowledge gaps regarding the Norwegian HF population were identified when new pharmacological therapy for HF was introduced in 2016. Data on the Norwegian HF population were scarce, and incidence, prevalence, and mortality were unknown. Despite available pharmacotherapy, knowledge of real-world drug implementation was lacking. Besides the clinical and scientific relevance, the data are valuable for healthcare system decision-makers to prioritise and allocate resources. For example, the data may reduce uncertainty in cost-effectiveness and budget impact analyses. The three studies of this thesis are historical cohort studies based on data from Norwegian nationwide health registries, allowing for research on large and unselected patient populations with long-term follow-up. We used data from The Norwegian Prescription Database (NorPD) and the Norwegian Patient Registry (NPR) to study HF incidence, prevalence, mortality, and treatment compliance in Norway. Moreover, we addressed an important pitfall called lookback bias when using longitudinal patient data to isolate incident from prevalent HF cases. In Paper I, we estimated incidence rates, prevalence, and mortality of HF in Norway from 2013-2016. The study population consisted of 54,542 patients in the NorPD with a mean age of 72. We found that the prevalence increased during the study period, while the incidence rate was stable, and survival improved. Age-adjusted incidence, prevalence, and mortality were higher in men than women. In Paper II, we investigated how different approaches in lookback periods affect estimates of HF incidence from 2008-2018. Furthermore, we estimated incidence rates and prevalence from 2014 to 2018. In this study of 187,297 patients with HF in the NPR, we found that the incidence rates were more inflated with a shorter lookback period. Too short a lookback period also led to misleading conclusions of decreasing incidence rates. The longer the lookback period, the better; however, compromises are necessary due to limitations in the available number of calendar years. We proposed that six years of lookback was sufficient to estimate HF incidence based on calculated overestimation, HF mortality and morbidity. Secondly, age- and sex-standardised incidence rates and prevalence of HF in 2018 were 5.04 per 1000 person-years and 2.51%, respectively. We found that both incidence rates and prevalence increased from 2014 to 2018. In Paper III, we studied compliance with HF pharmacotherapy in 54,899 patients aged 18-80 during 2014-2020. We found low drug compliance with RASi, BB, and MRA. Of the 61% and 16% of patients that initiated treatment with dual and triple HF therapy, 42% and 5% were considered adherent the first year following drug initiation. Approximately half the patient population discontinued treatment with either RASi or BB within two years. This thesis has closed knowledge gaps on HF occurrence and treatment compliance in patients with HF in Norway. The results highlight that the HF prevalence in Norway will continue to increase mainly due to the ageing of the population. Decision-makers must act and address the increasing HF prevalence. Systematic efforts are needed to improve adherence and persistence to HF pharmacotherapy in clinical practice.

Forskningsresultatene har bidratt til å tette kunnskapshull på forskningsfeltet. I tillegg til klinisk relevans er et godt datagrunnlag viktig for beslutningstakere i helsevesenet ved prioritering og fordeling av ressurser. Endrede demografiske forutsetninger med en aldrende befolkning, et økende prispress og økte legemiddelkostnader ved medisinske innovasjoner i helsevesenet setter press på norske helsemyndigheter der prioritering står høyt på dagsordenen. Eksempelvis er kravet til dokumentasjon av aktuelle pasientpopulasjoner i helseøkonomiske metodevurderinger økende. Resultatene kan bidra til å redusere usikkerhet i beregning av kostnadseffektivitet og budsjettkonsekvenser av å innføre et nytt legemiddel. Bruk av registerdata i forskning er økende i Norge. Dette prosjektet har økt bedriftens kompetanse på anvendelse av registerdata. Den generelle metodiske kompetansen som opparbeides gjennom et doktorgradsprogram har stor verdi for et selskap som driver med kommersialisering av legemidler, både med tanke på å vise sykdomsbyrde samt å sikre tilgang til nye, innovative legemidler på det norske markedet. Spesifikt har prosjektet økt bedriftens kompetanse innenfor hjertesvikt i den norske populasjonen, og dannet grunnlag for diskusjoner med helsemyndigheter i blant annet refusjonsprosesser. Kunnskapen som genereres kan benyttes til å vise omfanget av hjertesvikt i Norge, og vil også kunne brukes i kommersiell sammenheng. Ved å la prosjektet inngå i et doktorgradsprosjekt er Novartis frigitt ressurser til å utnytte potensialet som ligger i disse dataene ved at resultatene blir publisert. Grunnet kompleksitet i metodene og forutsetningene som anvendes, vil prosjektet sikkerstille at bedriften øker sin kompetanse for å sikkerstille høyt faglig nivå. Metoden vil kunne adapteres til å benyttes for andre terapiområder, for å bidra til at usikkerhet rundt pasientpopulasjoner reduseres og man potensielt kan sikre raskere tilgang til nye og innovative legemidler i fremtiden. Overordnet vil Novartis kunne øke sitt konkurransefortrinn i bransjen og være en attraktiv arbeidsgiver for å tiltrekkes og beholde kompetent arbeidskraft.

In order to assess and understand the burden of heart failure, it is important to identify the broad patient population. The aim of this project is therefore to characterize the adult heart failure population in Norway with respect to prevalence and incidence, current treatment patterns, medical resource utilization and health-related costs, utilizing Norwegian registry data. The results would provide information that could help improving the future treatment of heart failure patients, and could also uncover a clinical unmet need in the treatment of heart failure in Norway.