Heart failure is one of the most prevalent long-term conditions, which arises as a complication of several other cardiac conditions—the most common being ischaemic heart disease. Over 900 000 people are living with heart failure in the UK (British Heart Foundation, 2019) and it is a condition that can have a tremendous impact on a person's quality of life. While most common in older people, heart failure can occur at any age, and tends to gradually worsen over time. It often co-exists with depression, and can manifest in symptoms of breathlessness, tiredness and swelling of the ankles and legs (NHS, 2018; Sharap and McCowat, 2019).
Current treatment
Alongside important lifestyle changes, first-line treatment for heart failure is an angiotensin-converting enzyme (ACE) inhibitor and a beta blocker licensed for heart failure in people with reduced ejection fraction (National Institute for Health and Care Excellence (NICE), 2018). If ACE inhibitors are unsuitable or not tolerated, the other main pharmacological treatments for heart failure currently include: angiotensin receptor blockers (ARBs), beta blockers as mentioned, mineralocorticoid receptor antagonists, diuretics, ivabradine, sacubitril valsartan, hydralazine with nitrate and digoxin (NHS, 2018). Some people with heart failure may also have devices implanted such as a pacemaker or an implantable cardioverter defibrillator (ICD) (NHS, 2018).
Polypharmacy is a growing challenge and careful attention to drug interactions, adverse reactions and prescription errors is required (Rushton and Kadam, 2011). Guidelines suggest combination prescribing of evidence-based medicines to improve both symptoms and patient prognosis. Further to this, clinicians caring for patients with heart failure are managing not only the heart failure itself, but causative factors and comorbidities, potentially and very likely increasing the extent of pharmacological management (Rushton and Kadam, 2011). Patients may therefore be taking two or three different medications.
However, research into more novel treatments is taking place all the time. Some recent studies shine a light on the possible direction of the evolution of drugs for heart failure care.
Research: novel drugs to reduce risk
Studies have investigated and demonstrated the efficacy of relatively new glucose-lowering drugs used in the treatment of type-2 diabetes for cardiovascular outcomes.
Randomised placebo-controlled trials have been conducted over the last few years in patients with type-2 diabetes with a history of cardiovascular disease or otherwise deemed high risk for cardiovascular disease, and shown a reduction in the risk of hard cardiovascular endpoints with the use of drugs such as canagliflozin, dapagliflozin, and empagliflozin (Zinman et al, 2015; Neal et al, 2017; Wiviott et al, 2019).
A more recent meta-analysis of these studies concluded that such sodium glucose cotransporter 2 (SGLT2) inhibitors reduced major adverse cardiovascular events such as stroke, myocardial infarction and cardiovascular death, as well as hospital admission for heart failure (Zelniker et al, 2019).
Against this backdrop, and in an effort to take these findings beyond the confines of controlled trials, researchers have now published a cohort study in the British Medical Journal using data from nationwide registers in Denmark, Norway and Sweden, investigating the cardiovascular effectiveness of SGLT2 inhibitors in routine clinical practice (Pasternak et al, 2019).
From April 2013 to December 2016, 20 983 new Scandinavian users of the SGLT2 inhibitor drugs (either initiating treatment or who had no use of the drug in the last 2 years), aged 35-84 were compared with the same number of new users of dipeptidyl peptidase 4 (DPP4) inhibitors, and matched by age, sex, cardiovascular history and propensity score (Pasternak et al, 2019). The mean age of the participants was 61 years, with 60% being men, 19% having a history of major cardiovascular disease and 6% having a history of heart failure (Pasternak et al, 2019).
The authors note that the primary outcomes were major cardiovascular events (defined by the authors as a composite of myocardial infarction, stroke, and cardiovascular death) and heart failure (defined as hospital admission for heart failure or death due to heart failure), while secondary outcomes consisted of the individual components of the cardiovascular composite and any-cause death (Pasternak et al, 2019). Interestingly, the authors also included supplementary outcomes, analysing two serious adverse event outcomes of current concern with SGLT2 inhibitors: lower limb amputation and diabetic ketoacidosis (Pasternak et al, 2019).
Findings indicate that over the median follow-up of 1.4 years, risk of heart failure was 34% lower in patients taking the SGLT2 inhibitors than in those taking the DPP4 inhibitors. The drugs were also associated with a 20% reduction in all-cause mortality. However, in terms of the risk of major cardiovascular events, there was no difference between groups, which was in contrast with the findings of the meta-analysis by Zelniker et al (2019).
Regarding supplementary outcomes, the study showed a two-fold increased risk of diabetic ketoacidosis, but inconclusive results for lower limb amputation. These findings support existing research showing both the increased risk of diabetic ketoacidosis and ambiguity surrounding the potential adverse event of lower limb amputation (Pasternak et al, 2019).
Conclusion
There continues to be encouraging development regarding current and future treatments for heart failure. However, it remains a long-term condition that typically becomes progressively worse and for which there is no ultimate cure, except in cases where it has a treatable cause such as damaged heart valves.
Treatments currently tend to control symptoms, and can even slow down the progression of the condition; but heart failure can have a tremendous impact on a person's quality of life. In addition to the evolving options for pharmacological management of heart failure, non-pharmacological approaches in care such as lifestyle changes in the form of a healthy diet, exercise and emotional support, cannot be underestimated.
Cardiac rehabilitation plays an important role in these aspects and community prescribers are well placed to refer and signpost patients to local services and to provide information and encouragement to promote the uptake of these services, while also keeping abreast of current and emerging treatments.