Heart failure is caused by the heart not working properly: it fails to empty or fill correctly. The symptoms of the disease include breathlessness, tiredness and ankle swelling. More serious symptoms from heart failure or associated diseases can result in the affected individuals being admitted to hospital. Previous studies have shown that the more heart failure hospital visits a patient has, the more likely it is that they will die. There are different types of heart failure: they differ by the amount of blood that is pumped through the heart. Those that have less blood pumped through the heart are treated effectively at present, but those that have higher amounts of blood pumped are more difficult to treat. A recent drug produced by Novartis ("sacrubitril/valsartan") can potentially reduce heart failure hospital visits and risk of death for both types of heart failure. This study will take a similar approach to previous studies looking into the relationship between heart failure hospital visits and death, but this time in a UK population and for the two different types of heart failure. This will help Novartis understand how the new drug may benefit heart failure patients in the UK.
Objectives:
Heart failure (HF) is a leading cause of hospitalization among older adults. It is associated with a large burden of disease for the individual and with high morbidity and mortality post diagnosis. Previous studies have suggested that recurrent hospitalizations is a strong predictor of mortality. The main objective of this study is to quantify the association between recurrent HF hospitalizations and cardiovascular (CV) death in the overall HF population and in patients with different ejection fraction (EF) phenotypes. The two types of EF phenotypes are HF with "reduced" EF (HFrEF) and HF with "preserved" EF (HFrEF). Other objectives are similar to the main objective and include: quantifying the association between recurrent HF hospitalizations and (i) all cause death and (ii) CV death in a hospital setting for the overall HF population and EF phenotype; quantifying the association between recurrent HF hospitalizations with all-cause or CV death in patients with comorbidities of interest; and trying to find predictors of mortality. We wish to leverage the Clinical Practice Research Datalink (CPRD) linked to national hospital episode statistics (HES) and mortality statistics (ONS) in order to quantify these associations for the UK population. The results from this study will help illustrate the potential benefits for a promising new Novartis HF drug in the UK population.
Methods:
Descriptive statistics will characterise the demographic and clinical characteristics of the patients at their first hospitalization. Cox proportional hazards regression will quantify the relationship between recurrent hospitalizations and mortality. Time to event (hospitalization and death) will be displayed using Kaplan-Meier graphs with comparisons calculated by the log-rank test. Negative binomial regression will be used to establish potential predictors of mortality using baseline demographic and clinical characteristics.
Study design:
This is a cohort study of patients aged >18. Patients with a HF diagnosis in the primary care database will be used to find patients in HES with HF in-patient admissions. Patients will be used for the analysis that are admitted for HF in the in-patient setting from 2010 to 2014 (inclusive) and without admissions for HF in the four years previous. Follow-up will be until study end, death or transfer out of practice.
Primary:
Unadjusted and adjusted relative cardiovascular (CV) mortality rates for 1, 2, 3, ?4 HF hospitalizations after the index HF hospitalization compared to patients without recurrent heart failure hospitalizations (for all HF patients and HF phenotype subgroups);
Endpoints for Secondary Objectives 1, 2 and 3:
Unadjusted and adjusted CV and all-cause relative mortality rates for 1, 2, 3, ?4 HF hospitalizations after the index HF hospitalization compared to patients without recurrent heart failure hospitalizations (for all heart failure patients, stratified by HF phenotype and specific comorbidities);
Unadjusted and adjusted CV and all-cause relative mortality rates for 1, 2, 3, ?4 HF hospitalizations after the index HF hospitalization compared to patients without recurrent heart failure hospitalizations for all HF patients controlling for HF phenotype;
Time to CV death from index hospitalization and from 1st, 2nd, 3rd and 4th recurrent hospitalization;
Time to all cause death from index hospitalization and from 1st, 2nd, 3rd and 4th recurrent hospitalization;
Time to 1st, 2nd, 3rd and 4th recurrent hospitalization from index hospitalization;
Time to immediate next recurrent hospitalization from the previous recurrent hospitalization (1st to 2nd, 2nd to 3rdand 3rd to 4th);
Endpoint for Secondary Objective 4:
Unadjusted and adjusted relative in-hospital CV mortality rates for 1, 2, 3, ?4 HF hospitalization after the index HF hospitalization compared to patients without recurrent heart failure hospitalizations;
Time to in-hospital CV death from index hospitalization and from 1st, 2nd, 3rd and 4th hospitalization;
Proportion of patients discharged alive for the 1st, 2nd, 3rd, and ?4th HF hospitalizations;
Endpoint for Secondary Objective 5:
Variables predictive of mortality and recurrent hospitalizations;
Baseline patient characteristics as available from the data source associated with all-cause and CV mortality and HF hospitalizations.
Raquel Lahoz - Chief Investigator - NOVARTIS
Ailis Fagan - Corresponding Applicant - NOVARTIS
Ann Barber - Collaborator - Not from an Organisation
Clare Proudfoot - Collaborator - Novartis Pharma AG ( Switzerland )
Martin McSharry - Collaborator - Optum
Philippe Ferber - Collaborator - Novartis Pharma AG ( Switzerland )
Rachel Studer - Collaborator - Novartis Pharma AG ( Switzerland )
Sibasish Saha - Collaborator - Novartis Pharma AG ( Switzerland )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation