The prevalence of heart failure (HF) continues to rise, driven by an ageing population, increasing rates of obesity and diabetes, and better survival in patients with cardiovascular disease.1 While HF is associated with substantial morbidity and mortality, a number of treatments have been shown to improve outcomes in large-scale randomised controlled trials (RCT), including pharmacological inhibition of the renin-angiotensin system (with or without neprilysin inhibition), betablockers, mineralocorticoid receptor antagonists, sinus node inhibition, cardiac resynchronisation therapy with biventricular pacing, implantable cardioverter defibrillators and multidisciplinary models of care. [2][3][4] In order to realise the benefits of these treatments, however, we need to consider how patients were selected for these RCT and how the treatments were delivered.The adoption of innovative models of care and the delivery of device therapies can be particularly challenging, given that they are highly dependent on the individual operators and rely on substantial infrastructure and staffing support. At first glance, it would appear that the administration of pharmacological therapies for HF should be relatively straightforward, but such therapies are also highly dependent on the individual prescribers, rely on substantial infrastructure and staffing support, and involve real complexities around medication persistence and patient adherence.In this review, we will discuss medication titration in HF and consider whether or not it is too complex in the real-world setting.We conducted a literature search in November and December 2016 using PubMed. Keywords included 'heart failure', which was used in combination with 'medication' or 'therapy' and 'titration' or 'up-titration', 'dose' or 'target dose'. We also searched reference lists of relevant primary studies and systematic reviews. We used no language or date restrictions. All types of study design were included where medication titration was a primary endpoint.
Clinical Trials Evaluating Medications in Heart FailureLarge-scale randomised controlled trials (RCTs) have demonstrated that angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers and mineralocorticoid receptor antagonists all improve clinical outcomes in patients with HF associated with a reduced left ventricular ejection fraction (HFrEF).
5-12Indeed, such studies suggest that the combination of an ACEI, betablocker and mineralocorticoid receptor antagonist should translate to a 60-70 % relative risk reduction in all-cause mortality. 13 Nevertheless, it is likely that the balance between benefit and harm varies according to patient age, disease severity, associated comorbidities and approaches to monitoring and medication titration. An example of the impact of comorbidities was demonstrated by an individual patient data meta-analysis of the beta-blocker RCTs, in which the benefits were only observed in patients in sinus rhythm, there was no reduction in hospitalisation or...