Main findings
In this review of heart failure RCTs, we found a relatively broad range of potentially patient-relevant outcomes addressing mortality, hospitalization, and outcomes in the Bangma health domains. This finding is promising and may demonstrate an awareness of the importance of a variety of outcomes that are desirable for patients. However, none of the trials reported goal attainment in accordance with patients’ individual preferences. Whereas all-cause mortality and hospitalization were more frequently measured than their disease-specific counterparts, the majority of patient-reported outcomes measured were still based on disease-specific instruments. Almost two-thirds of the trials studied outcomes in at least one of the four domains of health (i.e. functional domain, domain of signs and symptoms, psychological domain, or social domain): of these, signs and symptoms were by far the most investigated, and functioning and the psychological and social domains were the least investigated. Remarkably, non-drug trials used other patient-relevant outcomes than signs and symptoms about twice as often than drug trials.
Although many of the trials applied QoL instruments that cover most or all domains to some extent, the aggregation of different domains in a sum score hampers a differentiated conclusion to inform medical decision-making. Nevertheless, it has been argued that QoL measures should be used more often in heart failure trials [
15,
16] in order to incorporate outcomes that are relevant to patients, in addition to mortality and hospital admission. However, Gill et al. [
17] argue that QoL measures do not include patients’ opinions and reactions and therefore do not aim at the correct target; this conclusion was confirmed by Dunderdale et al. [
18]. Most of the QoL instruments are not patient-centred and restrict the patient’s choice by imposing standard models of QoL and preselected domains on the individual. Furthermore, QoL instruments have mainly been developed and validated in younger populations and tend to be phrased mainly in relation to physical function, thus underestimating QoL in older persons whose physical function is likely to be not as good as that of younger people [
19]. QoL of older people (e.g. most patients with chronic heart failure) is considered a multidimensional construct that includes objective indicators and subjective evaluations related to developmental processes of growth, maintenance, and resilience, as well as management of loss, which have not been adopted by the QoL instruments used in the RCTs included in this review [
20].
In the reviewed trials, important specific outcomes (e.g. dyspnoea, oedema and fatigue) were mainly evaluated by the QoL questionnaires used; however, this method of evaluating heart failure outcomes is reported to be inadequate [
21]. In addition, pain is generally not included in heart failure-specific QoL measures, as it is not a symptom caused by heart failure. Nevertheless, pain is very common in heart failure patients due to the high prevalence of (painful) comorbidities [
22]. Another disadvantage of (in particular) disease-specific QoL instruments is that the questions relate to the disease under study, in this case heart failure. For example, a question about depressive feelings links these feelings to heart failure: ‘
Did your heart failure prevent you from living as you wanted during the past month (4 weeks) by making you feel depressed?’ In this way, general feelings of depression unrelated to heart failure might be missed [
23].
To the best of our knowledge, this is the first study to classify outcomes into patient-relevant domains of health. We used the Bangma criteria that provide a holistic framework that has been used and validated in rehabilitation medicine. The Bangma model [
13] is designed to support problem-based care as opposed to disease-oriented care and lists all clinically relevant problem areas of the patient: activities of daily living, signs and symptoms, psychological, social, and communicative domains. This model is similar to the composite measure recommended by the National Institute on Aging to monitor the health of older people with multiple chronic conditions [
5].
Strengths and limitations
We used Pubmed to select a systematic sample of RCTs over a certain period of time that included patients with heart failure and multiple diseases. Some RCTs might have been missed by not searching other databases such as Embase or Web of Science. However, our aim was not to conduct an exhaustive overview of RCTs including heart failure patients, but rather to capture a large sample of such studies. A strength of our study is that all selection and data extraction was conducted by two reviewers independently, which reduces the risk of bias.
In this review, although the attention paid to more patient-relevant outcomes is promising, this finding may be influenced by the choice of the primary condition. We chose heart failure as it is a common condition in older patients with multimorbidity. The association between heart failure and multimorbidity was reported more than a decade ago [
14], and therefore, recent heart failure guidelines address multimorbidity more often than the guidelines for other diseases [
24]. For these reasons, our results may be overly optimistic when applied to other chronic diseases where the debate about multimorbidity is still relatively young and may not have influenced the choice of outcomes in research.
Conclusion and implications
Although an encouragingly high proportion of heart failure trials report patient-relevant outcomes, patients’ individual goal attainments were universally absent from all the trials included in this review. In practice, clinicians negotiate clinical management with their patients usually taking their individual preferences into account. However, in research we are still far from giving individual goals a priority. Some research groups have developed patient-reported outcomes that include patients’ goals [
25‐
28]. However, their feasibility and completeness, especially for research purposes, is still suboptimal [
29]. To make progress in patient-centred care, more studies are needed to further develop these outcomes, examine their merits and pitfalls, and intensify their use in research. Patients need to be centrally involved in the design, development, and testing of such goal-orientated outcome research methods.