Manage uncontrolled hypertension as ‘treatment failure’ before labelling patients with resistant hypertension
We read with great interest the study on resistant hypertension by Sinnott et al., 2017. Uncontrolled hypertension (≥140/90 mm Hg) despite adherence to a prescribed drug regimen of three or more concurrent antihypertensive drugs which include a diuretic; or a four anti-hypertensive agents, non-diuretic based-regimen, is considered ‘resistant hypertension’.
Classical diagnostic reasoning suggests that ‘treatment failure’ should be considered if a diagnosis is made(e.g. hypertension) but the patient fails to respond to treatment (i.e. antihypertensive medication). We therefore recommend that the cohort of patients identified by Sinnott et al., 2017  should in fact be considered to have treatment failure. The management of treatment failure requires a systematic approach. Consider that perhaps:
1. The treatment is not reaching the circulation (concordance issues, malabsorption) or is ineffective (counterfeit medication)
2. The choice of treatment was suboptimal for a given patient (e.g. thiazide diuretic in a young Caucasian?)
3. The diagnosis is incorrect (pseudohypertension, faulty measurement, white coat hypertension etc.)
4. The patient has true resistant hypertension
We suspect that the true incidence of resistant hypertension is far lower than that suggested by Sinnott et al., 2017 . This is because compliance with antihypertensive medication is generally very poor. One meta-analysis reported that nearly 85% of patients with uncontrolled hypertension were not taking their medications. Sinnott et al., 2017  sought to detect compliance by assessing the collection of repeat prescriptions. However a prescription refill does not confirm that the patient is actually taking their medications. Even inspection of patient’s medications and pill counting at each clinic visit may not always reflect adherence. Inquiring about the side effects of medications, such as cough with ACE inhibitors or ankle swelling with calcium channel blockers can be helpful. However, these side-effects may in some instances be a consequence of the ‘nocebo’ effect.
Whilst measurement of serum levels of medications can provide definitive evidence of adherence these tests are rarely available outside the context of clinical trials. Clinical signs such as bradycardia (beta-blockers) or hypokalaemia (diuretics) are among the best tools to gauge adherence with antihypertensive medications that are currently available to jobbing clinicians.
In conclusion, we reiterate the importance of assessing for objective evidence of adherence and excluding other possible causes of treatment failure before labelling patients with resistant hypertension.
Rajkumar Rajendram,[1,2] Azra Mahmud 
 Consultant in Internal Medicine, Department of Medicine, King Abdulaziz Medical City, Riyadh, Ministry of the National Guard Health Affairs, Saudi Arabia
 Chairman, Medication Utilization & Process Evaluation Subcommittee, Medication Safety Program, Central Region, Ministry of the National Guard Health Affairs, Saudi Arabia
 Consultant in Adult Cardiology, Department of Cardiac Sciences, King Abdul Aziz Cardiac Center, King Abdulaziz Medical City, Riyadh, Ministry of the National Guard Health Affairs, Saudi Arabia
1 Sinnott SJ, Smeeth L, Williamson E, Douglas IJ. Trends for prevalence and incidence of resistant hypertension: population based cohort study in the UK 1995-2015. BMJ. 2017;358:j3984.
2 Mancia G, Fagard R, Narkiewicz K, et al. Task Force for the management of arterial hypertension of the European Society of Hypertension Task Force for the management of arterial hypertension of the European Society of Cardiology. 2013 ESH/ESC Guidelines for the Management of Arterial Hypertension. Blood Press. 2013;358:193-278.
3 Abegaz TM, Shehab A, Gebreyohannes EA, Bhagavathula AS, Elnour AA. Nonadherence to antihypertensive drugs: A systematic review and meta-analysis. Medicine (Baltimore). 2017;96:e5641.
Competing interests: No competing interests