Heart failure (HF) is a clinical syndrome defined by the presence of typical symptoms and signs that develop due to an abnormality in cardiac structure or function. Outcome is similar to that of some cancers but has vastly improved in recent years due to advances in medical therapy.
Fluid retention (venous congestion) is the root cause of most HF symptoms, and is the most common reason for hospitalisation amongst patients with HF. Loop diuretics cause increased salt and water loss from the kidneys and are the cornerstone of treatment of venous congestion but are commonly prescribed to patients without a diagnosis of HF. The reasons behind this and the consequences for the patient are unclear.
An audit of practice at a General Practice in East Yorkshire suggested that 1 in 4 patients who are prescribed a loop diuretic without a diagnosis of HF either die or are admitted to hospital with HF symptoms during 2 years’ follow up. It is possible that many patients who are prescribed loop diuretics without a diagnosis of HF have undiagnosed HF as the cause of their symptoms.
Our project will use anonymised data collected from General Practices across the UK to assess the links between the use of loop diuretics in patients without a diagnosis of HF and HF-related outcomes. If the results of our pilot study are replicated on a national scale it would provide a strong case for discouraging the use of loop diuretics without investigating for the possibility of underlying HF.
Loop diuretics are one of the most commonly prescribed medications in primary care. However, there are few indications for loop diuretics other than the treatment of venous congestion in patients with heart failure (HF).
A pilot study at a single General Practice in East Yorkshire found that of 94 patients who were taking loop diuretic without a diagnostic code for HF in their electronic record, 13% were diagnosed with HF, and 25% died or were hospitalised with HF during 2 years’ follow up. It is possible that a proportion of these patients had undiagnosed HF as the cause of their symptoms. Furthermore, use of loop diuretics may mask symptoms of congestion without treating the underlying disease; thus delaying diagnosis and worsening outcome. Whether these results are generalisable is unknown.
Our project will use data from the CPRD to investigate the link between loop diuretic prescription and HF-related events in two separate cohort comparisons. Firstly (analysis A), between patients prescribed loop diuretic without a diagnostic code for HF in their electronic record (study population) and patients with a diagnostic code for HF (control group 1), propensity matched for age, sex and co-morbidities. Secondly (analysis B), between the study population and patients with risk factors for HF propensity matched for age, sex and co-morbidities (control group 2). Using independent samples T-test and hazard regressions, we will compare the number of consultations with HF symptoms, the number of new HF diagnoses (analysis B), the number of cause specific hospitalisations and the number of cause specific deaths. We will also compare the time to each event using Cox regression adjusted for important co-variables such as age. Hospital Episode Statistics Admitted Patient Care (HES APC) will be used to determine hospitalisations and Office of National Statistics death registration data will be used to determine deaths.
All outcomes assessed at yearly intervals over a five year period.
Primary Outcomes
Number of first hospitalisations with heart failure in any diagnostic position; number of recurrent hospitalisations with heart failure; number of all-cause deaths; time to first hospitalisation with heart failure in any diagnostic position; time to all-cause death; number of new heart failure diagnoses (analysis B); time to heart failure diagnosis (analysis B).
Secondary Outcomes
Number of consultations with breathlessness, fatigue, ankle swelling, or any combination of symptoms; number of patients undergoing natriuretic peptide testing; number of patients undergoing echocardiography; number of patients referred to outpatient cardiology services; number of new prescriptions of loop diuretics (amongst patients in control group 2); number of cause-specific hospitalisations; time to any hospitalisation; number of cardiovascular deaths; time to cardiovascular death.
Joe Cuthbert - Chief Investigator - University Of Hull
Joe Cuthbert - Corresponding Applicant - University Of Hull
Ahmet Fuat - Collaborator - Durham University
Andrew Clark - Collaborator - University Of Hull
Ireneous Soyiri - Collaborator - University Of Hull
John Turgoose - Collaborator - University Of Hull
Judith Cohen - Collaborator - University Of Hull
HES Admitted Patient Care;ONS Death Registration Data