Evaluation of Adherence Should Become an Integral Part of Assessment of Patients With Apparently Treatment-Resistant Hypertension.

Renal Denervation: An Eye Opener Since the publication of the first Symplicity studies in 2009 to 2010, renal sympathetic denervation gained acceptance as a novel treatment of drug-resistant hypertension. The latter has been defined as a blood pressure (BP) >140/90 mm Hg, despite appropriate lifestyle measures plus a diuretic and 2 other antihypertensive drugs belonging to different classes at adequate doses. According to the US definition, patients with controlled BP on ≥4 antihypertensive drugs are also considered as resistant hypertensives. However, a substantial proportion of patients with apparently resistant hypertension are in fact poorly adherents to drug treatment. The highly variable BP response to renal denervation (RDN) prompted to a more rigorous evaluation of eligible patients, with the goal to exclude false resistant hypertension, because of poor adherence to drug treatment. In particular, several publications documented a high proportion of low drug adherence in patients with apparently resistant hypertension (23%–66%), using witnessed drug intake or plasma/urine drug determinations (Figure 1). Furthermore, RDN studies shed the light on the dynamic character of drug adherence. Inclusion in RDN trials may influence drug adherence in various, unpredictable directions. In some patients, close follow-up and massive attention devoted to them may lead to improved adherence to lifestyle measures and drug treatment, particularly in the RDN arm (Hawthorne effect). Other patients may stop their medications after RDN according to their perception that the intervention cured their hypertension. On the other hand, patients from the control group may have not taken their medications properly to keep their BP high, in the hope that this will make them eligible for crossover to the RDN group. Overall, RDN trials confirm (1) that poor drug adherence is a frequent cause of apparently resistant and difficulttotreat hypertension, (2) that drug adherence is a dynamic phenomenon influenced by complex psychosocial determinants and cannot be captured by any single assessment, (3) and that changes in drug adherence are a major potential confounder in trials assessing new treatment modalities of resistant hypertension. Although the prevalence of resistant hypertension has been estimated to be 10% to 30%, it may decrease to <2% when patients with low drug adherence estimated by pharmacy refill are excluded. Furthermore, even in those patients with truly resistant hypertension, the benefits of antihypertensive treatment are predominantly present in patients with acceptable (>80%) baseline drug adherence, in terms of both BP control and regression of target organ damage. Therefore, from a public health and pharmacoeconomic perspective, diagnosis and management of poor drug adherence in patients with apparently resistant hypertension is a priority. Identification of poorly adherent patients among those with apparently resistant hypertension will avoid unnecessary and potentially harmful treatment intensification and allow implementation of strategies to improve drug adherence. This approach would be expected to result in a more costeffective allocation of health resources. Unfortunately, healthcare providers underestimate the size of the problem of poor