Treatment resistant hypertension in General Practice: prevalence, pseudo-resistance, and a feasibility study of prognosis
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Background. Both the American Heart Association (AHA) in 2008 and the UK National Institute for Health and Care Excellence (NICE) in 2011 suggest the need for further research into the management of treatment resistant hypertension (TRH). Apparent TRH is defined, by the AHA and European Society of Cardiology (ESC), as high blood pressure in patients taking three or more differing groups of anti-hypertensive medications (one of which must be a diuretic type medication) or patients who are taking four or more anti-hypertensive medications regardless of type and blood pressure level. The term apparent is used because some of this group will have true resistant hypertension, others undiagnosed secondary hypertension and more pseudo-resistant hypertension. A patient is pseudo-resistant when other factors, such as non-adherence to medications, inadequate drug dosing, lifestyle issues and white coat hypertension (WCH) are responsible for the seemingly poor blood pressure control. Before identifying patients with true TRH, ambulatory blood pressure measurement (ABPM) must be used to exclude WCH. Non-adherence to therapy, drug dosing and diet/lifestyle should also be examined. When these major features of pseudo-resistance have not yet been ruled out as a potential cause for the ongoing poor blood pressure control, the term apparent Treatment Resistant Hypertension (aTRH) must apply. Papers. 1. Prevalence of treatment-resistant hypertension after considering pseudo-resistance and morbidity: a cross-sectional study in Irish primary care. BJGP. 2018 Jun; 68(671):e394-e400. doi: 10.3399/bjgp18X696221. Epub 2018 May 8. 2. Prognosis of patients with apparent treatment resistant hypertension-a feasibility study. PilotFeasibilityStud.2018Jan30;4:43.doi:10.1186/s40814-018-0232-5.eCollection 2018. 3. Apparent treatment resistant hypertension in primary care: the feasibility and impact of urine toxicological analysis combined with ambulatory blood pressure monitoring Accepted for publication in BJGP in April 2019. Methodological Considerations. In Paper 1, the authors performed a cross sectional study of the prevalence of aTRH in general practice and followed the STROBE guidelines when reporting on this cohort. https://www.strobe-statement.org/index.php?id=strobe-home In Paper 2, the authors completed a feasibility study examining whether prognosis could be assessed, on persons with TRH, in general practice. We used a specific reporting guide provided by Biomed. https://pilotfeasibilitystudies.biomedcentral.com/submission-guidelines In Paper 3, patients were invited to attend their own general practices for ABPM to rule out WCH and to provide a urine sample for toxicological analysis, to assess for drug adherence. Drug assays were analysed utilizing a similar methodology to that of Jung et al. (2013). The NICE guidelines governing the use of ABPM in clinical care were applied. Results/Conclusions. In a meta-analysis examining the prevalence of non–adherence in aTRH, we estimate up to 30% of patients fail to take their prescribed medications (Supplementary Paper 1). Controversy remains regarding a ‘Gold Standard’ for the measurement of adherence. Possibly the best way to assess this is to use a combination of both direct (urine/blood toxicology, observed therapy) and indirect (questionnaire) methods when trying to ascertain estimates. Direct measures usually give much larger estimates for the prevalence of non-adherence than indirect, and a combination of both methods gives closest to the pooled estimate in the meta-analysis. Paper 1 shows that the prevalence of aTRH (10%) is not as large as previously described (10-30%). When pseudo-resistance is adequately examined, the prevalence of TRH falls to 3% of hypertensive patients. The examination of pseudo-resistance may be all that is required for managing TRH in the vast majority of cases. In paper 2, the authors found that it is feasible to do a prognosis study on a cohort of patients with TRH in general practice. Both the AHA and NICE recommend that further research is needed in TRH, especially on prognosis. We plan to follow the TRH cohort identified in Paper 1 for 5 years, and then assess prognosis in 2020. Limiting all loss to follow-up and the identification of a complete set of core outcomes for prognosis in TRH are vital to the success of any future study. In paper 3, the authors established that non-adherence when assessed via urine toxicological analysis suggests that most patients in primary care take their medications (74%), and that complete non-adherence to therapy is rare. WCH is also common in patients with TRH (28%). This combined approach of using ABPM to assess WCH and urine toxicological analysis to test adherence has never previously been performed in general practice. Such an approach may well yield savings for healthcare programs in the long run through maximizing blood pressure control in high risk populations and improving prognosis. Further research on how to incorporate routine urine toxicological analysis into individual patient consultations and its associated cost-effectiveness is now appropriate.