Objective measures of non-adherence in cardiometabolic diseases: a review focused on urine biochemical screening

Figures & data

Figure 1 Barriers to overcome for tackling non-adherence.

Notes: The four classes that contribute to non-adherence.¹⁷

Figure 2 Adherence rates of different drug classes of cardiovascular disease and type 2 diabetes mellitus.

Notes: Adherence rates determined through biochemical testing in 256 patients. Minimally adapted from Atheroscler Suppl, Gupta P, Mohamed AA, Patel P, et al, 34, High rates of non-adherence to antidiabetic, antihypertensive and lipid lowering treatment in patients with type 2 diabetes revealed liquid chromatography-tandem mass spectrometry (lc-ms/ms) urine analysis, e2, Copyright 2018,²⁰ with permission from Elsevier.
Abbreviations: ACE/ARBs, angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists; AD, antidiabetics; AH, antihypertensives; BB, beta blockers; CCB, calcium channel blockers; DI, diuretics.

Figure 3 Mortality risks of non-adherence to antihypertensives in cardiovascular disease.

Notes: Cohort sizes for good, intermediate, and poor adherences were N=12,647, N=10,846, and N=11,223, respectively. Data were adjusted using common clinical factors and patient identifiers, with bars indicating 95% CI. Data were adapted from Kim S, Shin DW, Yun JM, et al. Medication adherence and the risk of cardiovascular mortality and hospitalization among patients with newly prescribed antihypertensive medications. Hypertension. 2016;67:506–512.⁴⁴

Table 1 Diagnostic tools for adherence testing

Adherence diagnosis method	Subjective?	Objective?		Description of use	Strengths	Weaknesses
		Indirect?	Direct
Physician perception	✓	✘		Physician clinically judging patients’ adherence	Simple, quick, and non-invasive	Capacity of perception is poor
Patient self-report methods	✓	✘		Patient reporting their own adherence, usually through use of a validated questionnaire	Easy to administer and may find rationale for adherence	Potential to overreport or falsify adherence; can be intrusive for some patients
Reviewing pharmacy records	✘	✓	✘	Reviewing patient pharmacy visits to acquire medication	Provides data on prevalence of adherence behavior over time	Accuracy of results depends on accuracy of records
Pill counting	✘	✓	✘	Counting remaining pills after a set period	Can give information on non-adherence rates for a particular medication	Time consuming and can easily be manipulated by a patient
Electronic monitoring devices	✘	✓	✘	Devices, such as pill dispensers, which provide a record of use	Gives plentiful, continuous information (eg, dosing times and patterns)	Expensive; poorly integrates with the elderly; lack of mainstream multimedication monitoring systems
Directly observed therapy	✘	✘	✓	Continuous observation of patient by practitioner, in a clinical setting	Provides a confident yes/no adherence answer	Intrusive and potentially dangerous for non-adherent patients who ingest their previously avoided medications
Digital pills	✘	✘	✓	Pills that can record use, to a localized sensor, after ingestion	Provides precise time of ingestion data	Expensive and limited availability
Biochemical testing	✘	✘	✓	Detecting parent drug, drug metabolite, or biomarker in a patients’ bodily fluids	Finds definitive yes/no adherence snap shot	Labor intensive; current methods (screens) provide only data on most recent ingestion, methods are not widespread, and adherence may be skewed by drug pharmacokinetics

Notes: A comparison of adherence testing methods detailing strengths and weaknesses of either approach. Information sourced from Gupta et al.¹⁰

Table 2 National Centre for Adherence Drug Testing: current list of detectable urinary medications in the screen for non-adherence

Drug class	Medications
Angiotensin-converting enzyme inhibitors	Enalapril
	Lisinopril
	Perindopril
	Ramipril
	Trandolapril
Calcium channel blockers	Amlodipine
	Diltiazem
	Felodipine
	Lacidipine
	Lercanidipine
	Nicardipine
	Nifedipine
	Verapamil
Diuretics	Amiloride
	Bendroflumethiazide
	Bumetanide
	Eplerenone
	Furosemide
	Hydrochlorothiazide
	Indapamide
	Spironolactone
	Triamterene
Angiotensin II receptor antagonists	Candesartan
	Irbesartan
	Losartan
	Olmesartan
	Telmisartan
	Valsartan
Beta blockers	Atenolol
	Bisoprolol
	Carvedilol
	Labetalol
	Metoprolol
	Nebivolol
	Propranolol
Miscellaneous	Alfuzosin
	Clonidine
	Doxazosin
	Ivabradine
	Minoxidil
	Moxonidine
	Nicorandil
	Prazosin
	Ranolazine
Anticoagulant/antiplatelet drugs	Apixaban
	Clopidogrel
	Dabigatran
	Rivaroxaban
Antilipid drugs	Atorvastatin
	Rosuvastatin
Antidiabetic drugs	Metformin
Sulfonylureas	Glibenclamide
	Gliclazide
	Glimepiride
	Glipizide
Meglitinides	Nateglinide
	Repaglinide
Glitazones	Pioglitazone
Gliptins	Linagliptin
	Saxagliptin
	Sitagliptin
SGLT-2 inhibitors	Canagliflozin
	Dapagliflozin
	Empagliflozin

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GuptaPMohamedAAPatelPHigh rates of non-adherence to antidiabetic, antihypertensive and lipid lowering treatment in patients with type 2 diabetes revealed liquid chromatography-tandem mass spectrometry (lc-ms/ms) urine analysisAtheroscler Suppl201834e210.1016/j.atherosclerosissup.2018.07.021

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GuptaPPatelPHorneRBuchananHWilliamsBTomaszewskiMHow to screen for non-adherence to antihypertensive therapyCurr Hypertens Rep2016181810.1007/s11906-015-0615-426694820

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