Smartphones, Barbershops, and Pharmacists to Improve Adherence to Drug Treatment in Chronic Cardiovascular Conditions: The End Justifies all the Means

This article refers to ‘PHARMacy-based interdisciplinary program for patients with Chronic Heart Failure (PHARM-CHF): rationale and design of a randomized controlled trial, and results of the pilot study’ by U. Laufs et al., published in this issue on pages 1350–1359. The outcome of ambulatory patients with chronic heart failure, specifically those with reduced ejection fraction, substantially improved over the last decades due to the widespread introduction of several pharmacological and non-pharmacological treatments that were clearly demonstrated by controlled clinical trials to be able to reduce mortality and hospitalizations for worsening heart failure.1, 2 As a consequence, these treatments have been included in the current international guidelines with a strong recommendation for their use in patients with this clinical condition.3, 4 Despite these remarkable achievements, admissions for heart failure remain the most frequent cause of hospitalization in subjects aged more than 65 years, determining not only a poor quality of life but also very high costs for the different national health systems.5 Despite the clear reduction observed in the last few years in different countries, 1-year all-cause mortality is still occurring in approximately 6–8% of ambulatory patients with heart failure. Further research testing new hypotheses of intervention is obviously very welcome, but appropriate application of what we already have in our hands is mandatory, also considering that the majority of life-saving pharmacological treatments are out-of-patent and, for this reason, relatively inexpensive. Therefore, adherence of doctors and patients to the recommended treatments for heart failure is a public health issue to be tackled in a vigorous and effective way, just as for other chronic cardiovascular conditions for which effective treatments are available, such as arterial hypertension or secondary prevention strategies after an athero-thrombotic event. Actually, some estimates of non-adherence are close to 50%,5, 6 and non-adherence either in terms of prescription and correct dosage of recommended drugs has been shown to be associated with worse outcomes in patients with heart failure.7-9 Several interventions to improve drug adherence have been developed and formally evaluated, some of them specifically in patients with heart failure. These interventions were mainly based on doctor and/or patient education but also on the use of mobile technology.10 In this issue of the Journal, the paper by Laufs et al.11 enters in this area of research proposing a randomized clinical trial testing whether an interdisciplinary pharmacy-based intervention might safely improve medication adherence, determining a potential favourable impact on the clinical endpoint of days lost due to unplanned cardiovascular hospitalizations or death. Based on a pilot experience, the design of this study seems to be sufficiently rigorous to answer the question about the potential role of a pharmacist-based intervention in improving drug adherence. However, the dimension of the study cannot allow a reliable evaluation of the effects of the proposed intervention on patients' outcomes. Similarly, previous studies did not reliably answer the question about the real effective role of pharmacist-based interventions due to methodological flaws, specifically inadequate sample sizes, or very short periods of follow-up.12 Recently, different approaches to increase drug adherence with the aim at improving outcomes of patients with chronic cardiovascular conditions have been tested and published. Worthy of note for the originality of the approach is the cluster trial that tested a pharmacist-led intervention in the setting of US barbershops (in which barbers encouraged patients to have meetings inside the barbershops with specialty-trained pharmacists) vs. a control approach (in which barbers just encouraged lifestyle modification and doctor appointments).13 Patients eligible for the study were black hypertensive patients. The primary outcome was the reduction of systolic blood pressure at 6 months. The health promotion provided by barbers resulted in a large blood pressure reduction when coupled with medication management in barbershops by specialty-trained pharmacists. Considering that black people with arterial hypertension have generally multiple risk factors for cardiovascular disease, the mean reduction in systolic blood pressure achieved in the trial (21.6 mmHg less with the active intervention compared with blood pressure levels measured in the control group) might, very likely, correspond to a relevant reduction of the high rates of hypertension-related disabilities and death. Almost in the same period, another trial on hypertensive patients has been conducted with less impressive results.14 This trial, named MedISAFE-BP, evaluated the association of medication adherence with blood pressure control testing a ‘stand-alone’ smartphone app vs. a control arm based on no specific interventions among patients with insufficiently controlled hypertension. The smartphone app provided systematic alerts to remind patients when it was time for them to take medications, generated weekly adherence reports, and facilitated optional peer support. The authors found a significant improvement in adherence to blood pressure-lowering medications but, disappointingly, no differences in systolic blood pressure reduction were observed between the intervention and control groups. Due to these neutral results, the benefit of this and other stand-alone mobile health interventions on clinical outcomes remains to be established. As a general comment related to the study of Laufs et al.11 but also to the majority of studies conducted in the field of adherence improvement, it is worth noticing that the sample sizes calculated for these trials were generally too small to provide definite and reliable answers in terms of efficacy on patients' outcomes. Differently from studies testing new drugs or devices that generally include thousands of patients, trials evaluating strategies to improve medication adherence are based on few hundred subjects showing reliable results just on the modification of adherence level but providing, in the majority of cases, inconclusive results with respect to the harder endpoints such as the reduction of clinical events, which should be the natural consequence of improved drug adherence. In this context, the implementation of these studies within large-scale registries such as those based on electronic health records could allow a more reliable comparative evaluation of the different approaches aimed to improve adherence to recommended treatments for chronic cardiovascular clinical conditions, such as heart failure. The methodology of ‘registry trials’ for evaluating medication adherence might be the most efficient approach, reducing complexity and costs of studies.15 Similarly to other chronic cardiovascular conditions, today treatment of heart failure with reduced ejection fraction includes several evidence-based drug therapies, which have proven by well conducted, controlled studies to be effective in improving outcomes of patients with this clinical condition. The widespread introduction of these treatments in routine clinical practice should be associated with a measurable beneficial effect on real populations of patients with heart failure, specifically those with a reduced ejection fraction. Adherence of doctors and patients to drug treatments recommended by current guidelines seems to be still insufficient and needs to be optimized in the future. All the means to achieve this goal are justified and seem to work quite efficiently but just in terms of higher levels of drug adherence. To convincingly close the circle, studies evaluating the different approaches based either on high technologies or educational projects at lower costs, conducted even in non-conventional settings (the barbershop initiative is a good, original example), should be undertaken to assess whether better adherence may also translate into better patients' outcomes. This kind of studies are surely more difficult to be financially supported than those on drugs or devices; for this reason, the simpler and less costly approach to conduct them in the context of a ‘registry trial’ seems to be the most attractive hypothesis.15 Conflict of interest: A.P.M. has no conflict of interest to disclose with respect to the present manuscript. Outside the present work, A.P.M. received honoraria for participation in committees of studies sponsored by Bayer, Novartis and Fresenius.