Authors: Sian Jenkins, Thejashwini Mahadevaswamy, Hanad Osman, Pankaj Gupta
Categories: CME: Hypertension, Medication adherence, Apparent treatment-resistant hypertension, Chemical adherence testing, Learning objectives
Source: Clinical Medicine
Authors: Sian Jenkins, Thejashwini Mahadevaswamy, Hanad Osman, Pankaj Gupta
•Consider non adherence in patients on three or cardiovascular medications.•Clinician judgement alone is unreliable; —objective assessment is often required.•Normalise the Ask about adherence routinely.•Use appropriate tools to Check, including pharmacy data or biochemical testing where available.•Chat nonjudgmentally, focusing on understanding barriers and supporting behaviour change.
After reading this article, clinicians should be able 1.Recognise medication non-adherence as a major contributor to apparent treatment resistant hypertension.2.Apply a structured Ask–Check–Chat approach to routine clinical practice.3.Understand the role, strengths and limitations of chemical adherence testing (CAT).
‘Drugs don’t work in patients who don’t take them.’ — C. Everett Koop, US Surgeon General.
Medication non-adherence has been recognised for centuries. Hippocrates warned clinicians to ‘keep a watch on the faults of patients, which often make them lie about the taking of things prescribed’. Despite advances in pharmacology and healthcare systems, this problem remains largely unchanged. The World Health Organization highlighted non-adherence as a major global health challenge over 2 decades ago, and contemporary data continue to show that 30–50% of patients with long-term conditions do not take medications as prescribed.^1^^,^^2^
In hypertension, non-adherence has particularly serious consequences. It is associated with a doubling of cardiovascular risk and up to a fourfold increase in stroke risk,^2^ leading to avoidable morbidity, mortality and healthcare costs.
This article outlines a practical, clinician-focused approach to identifying and managing medication non-adherence in routine practice, with particular emphasis on aTRH, using a simple Ask, Check, Chat.
Resistant hypertension is defined as uncontrolled blood pressure despite treatment with three antihypertensive agents at maximally tolerated doses, one of which should be a diuretic.^3^ Before making this diagnosis, clinicians must exclude pseudoresistance. The two most common causes are white-coat hypertension and medication non-adherence.
The National Institute for Health and Care Excellence recommends that adherence is assessed before referral of patients with aTRH to specialist hypertension services. Studies consistently demonstrate that around one-third to one-half of patients labelled as having aTRH are at least partially non-adherent, and non-adherence increases in a near-linear fashion with the number of prescribed medications.^4^ For clinicians managing patients with apparent treatment-resistant hypertension (aTRH), failure to recognise non-adherence risks leads to unnecessary escalation of therapy, inappropriate investigations and referral for invasive procedures.
Despite its prevalence, non-adherence is infrequently discussed in consultations. A multinational survey of over 3,000 healthcare professionals working in primary care and community settings found that only around half routinely ask patients about adherence.^5^ Many clinicians report discomfort raising the issue, concern about damaging trust, or lack of training. Importantly, subjective clinician judgement performs no better than chance in identifying non-adherence.^6^
Patients, meanwhile, may not volunteer difficulties unless prompted. They may feel embarrassed, fear disapproval, or not recognise their behaviour as non-adherence – particularly when they take medication ‘most of the time’. This creates a mutual blind spot, where non-adherence remains hidden.
The first and most important step is to ask. Conversations about adherence should be routine, normalised and non-judgemental. Framing matters. Open with questions such ‘Many people find it difficult to take tablets every day. Does that ever happen to you?’
Such a framing helps reduce stigma and signal that honesty is welcome. Normalising difficulty makes it easier for patients to disclose problems, whether due to forgetfulness, side effects, beliefs or practical barriers. However, asking alone is often insufficient. Patients may overreport adherence, consciously or unconsciously. This leads to the second checking.
Assessing adherence should be viewed as a diagnostic exercise, akin to measuring renal function or performing ambulatory blood pressure monitoring, rather than a judgement of behaviour. Explaining this clearly to patients is crucial for maintaining trust. A range of methods exist,^6^ varying in objectivity and •Self-report questionnaires (eg Medication Adherence Report Scale) are simple but tend to overestimate adherence.•Pharmacy refill data can be useful where accessible (such as NHS Summary Care Records), but reflect past collection rather than current ingestion.•Pill counts are time-consuming and easily manipulated.•Objective biochemical testing, such as chemical adherence testing (CAT), provides direct evidence of recent medication ingestion.•Directly observed therapy – patients attend a day case unit and are observed taking their medications, with their blood pressure measured. This is resource intensive and may cause harm to the patient–doctor relationship and undermine trust.
CAT uses liquid chromatography–tandem mass spectrometry (LC-MS/MS),^7^ a technology widely employed in clinical toxicology, and is highly robust and reliable. A single spot urine/blood sample can detect the presence or absence of most commonly prescribed antihypertensive drugs. The test is highly sensitive, relatively inexpensive (approximately £30–40), and samples can be sent by standard post.
In the UK, this service is available through specialist centres such the National Centre for Adherence Testing (NCAT) at Leicester which receives samples from over 50 hypertension clinics across UK and at Birmingham Heartlands, and Manchester. The use of CAT in aRH has been given a Level1 recommendation by the European Societies of Cardiology and Hypertension and is also recommended by the British and Irish Hypertension Society.
This testing is best performed on the same day as the consultation and to minimise white-coat adherence, which is temporary improvement in medication taking around clinic visits; adherence testing should not occur predictably at every appointment. Verbal consent is obtained as for any other routine investigation, and results are reported in binary terms (detected/not detected).
Concerns are sometimes raised about pharmacokinetic variability or damage to the doctor–patient relationship. Observational data suggest that pharmacokinetic factors have minimal impact on interpretation, and qualitative studies demonstrate that when results are discussed sensitively, patient trust is not adversely affected.
Identifying non-adherence is only useful if followed by a meaningful conversation. Results should be discussed openly and without confrontation. A simple approach ‘Your test didn’t detect some of your medications. Taking tablets every day is hard for many people. Can we talk about what makes it difficult for you?’
This opens the door to understanding why non-adherence occurs. Broadly, this can be divided into unintentional and intentional non-adherence.
Unintentional non-adherence includes forgetfulness, complex regimens, travel, shift work, cost or misunderstanding instructions. Practical solutions include simplifying regimens, using combination tablets, linking doses to daily routines, or using reminder aids.
Intentional non-adherence reflects beliefs and fear of long-term harm, side effects, dependence or doubts about benefit, particularly in an asymptomatic condition like hypertension. Here, education and shared decision making are key. Explaining how medications work, what happens to them in the body, and the evidence for long-term benefit can address misconceptions.
Behaviour changes frameworks such as the COM-B model (Capability, Opportunity, and Motivation for Behaviour Change) provide a useful structure for these discussions and help tailor interventions to individual barriers.^8^
Importantly, non-adherence should be documented neutrally in the medical record (for example, ‘biochemical drug screen negative for prescribed antihypertensive’), ensuring that future clinicians consider adherence before escalating treatment.
Our observational study has demonstrated that identifying non-adherence using CAT, followed by structured discussion, is associated with the majority of patients becoming adherent on follow-up and had substantial reductions in blood pressure of ∼20 mmHg systolic without adding medications.^9^ Randomised trials in this area are challenging due to behaviour change induced by observation (the Hawthorne effect).
Medication non-adherence is not unique to hypertension and represents a cross-cutting challenge across multiple long-term conditions, particularly where symptoms are minimal and treatment escalation is common. CAT has therefore been applied beyond hypertension, notably in cardiometabolic diseases such as diabetes, heart failure, transient ischaemic attack and in patients on cardiovascular disease (CVD) medications with kidney disease, and patients with HIV on CVD.10, 11, 12, 13
Further, in research CAT has strengthened the internal validity of major trials, (such as PATHWAY2, ORBITA and RADIANCEHTN), by excluding non-adherence as a cause of non-response to treatment.
Medication adherence is everyone’s responsibility and needs to be diagnosed. A simple, structured approach can prevent unnecessary treatment escalation, improve blood pressure control and strengthen the clinician–patient relationship.
1.Summary over view Gupta P, Patel P, Horne R, Buchanan H, Williams B, Tomaszewski M. How to screen for non-adherence to antihypertensive therapy. Curr Hypertens Rep. 2016;18(12):89.2.Link to podcasts on https://www.eshonline.org/spotlights/esh-podcasts-on-adherence/3.NCAT https://www.uhleicester.nhs.uk/services/pathology/blood-sciences-chemical-pathology/#national-cen
Sian Jenkins: Conceptualization, Writing – original draft. Thejashwini Mahadevaswamy: Conceptualization, Writing – original draft. Hanad Osman: Writing – original draft. Pankaj Gupta: Conceptualization, Writing – original draft.
The authors declare the following financial interests/personal relationships which may be considered as potential competing Pankaj Gupta reports a relationship with Amgen Inc that speaking and lecture fees and travel reimbursement. Pankaj Gupta reports a relationship with Daiichi Sankyo that speaking and lecture fees and travel reimbursement. Pankaj Gupta reports a relationship with Servier Monde that speaking and lecture fees and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.