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What to Do When You Find Your Patient Is Non-Adherent to Antihypertensive Therapy ?

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What to Do When You Find Your Patient Is Non-Adherent to Antihypertensive Therapy ? What to do when you find your patient is non-adherent to antihypertensive therapy ? Indranil Dasgupta Consultant in nephrology and hypertension Heartlands Hospital Birmingham Honorary Reader, University of Birmingham Conflict of interest • Received – Research grants: Medtronic and Daiichi Sankyo – Speaker fees: Sanofi, MSD, Pfeizer, GSK, Mitshubishi pharma, Otsuka, Agenda • Case studies • Size of the problem • Cost to the NHS • Detection • Factors responsible • Measures to improve adherence • Further research Case study 1 Case study 1 • 57 year old lady, FH of hypertension, BMI 38 • Mean BP in clinic: 171/92 mmHg • Mean daytime ABP: 147/84 mmHg • Current medications: – Amlodipine 10 mg once daily – Bisoprolol 2.5 mg once daily – Doxazosin MR 8 mg once daily – Furosemide 40 mg once daily – Indapamide 2.5 mg once daily – Losartan 100 mg once daily • Urine sent for antihypertenive drug assay Urine antihypertensive drug assay • She was advised to take amlodipine 5mg only and given life style advice especially to lose weight Case study 2 • 55 year old lady, teacher – Deputy Head of English • Recent clinic BP 175/104, 177/75, 222/114 • Known white coat effect, BMI 41 • Medication: – Losartan 100 mg once daily – Felodipine 20 mg once daily – Doxazosin 8 mg twice daily – Furosemide 60 mg once daily – Bisoprolol 7.5 mg once daily • Urine AHT assay requested She wouldn’t accept the result but since then her BP control has improved! Case study 3 • 41 year old man, engineer Rolls Royce • Referred a year ago for drop in GFR 64 to 23 • Losartan 150mg, felodipine 10mg, propranolol 100mg • Clinic BP 117/84 • Losartan stopped, felodipine increased to 20 mg • 1 month later BP 188/124, GFR 50 – Losartan restarted at 50 mg, propranolol changed to atenolol 25 mg • 6 weeks later BP 129/89 Case study 3 • Returned in 3 months – BP 98/72, tired, atenolol stopped, GFR>60 – Next appointment - BP 107/70 • Last week BP 145/103 – ‘getting side effects – tired, no appetite …..’ – ‘taking tablets as you suggested’ • Wife (accompanied first time) – – ‘also affecting sexual function but taking meds regularly’ • Urine assay requested Urine result – neither drug detected! Non-adherence to anti-hypertensive medication • Non-adherence encompasses – Non-persistence – not taken for ≥12 months – Non-compliance –medication taken <80% days • Non-concordance – failure of therapeutic agreement between the prescriber and patient – assumes the patient is involved in decision making • Common problem in chronic diseases Non-adherence is very common among hypertensives Database of 4783 patients on single dose treatment from 21 phase IV clinical trials Vrijens et al. BMJ 2008;336(7653):1114-7 Resistant Hypertension • Office BP ≥140/90 despite 3 antihypertensive agents in optimum doses, including a diuretic • Reported to be present in up to 30% of all hypertensives • True prevalence in the UK ≈ 10% Myat A et al. Resistant hypertension. BMJ 2012;345:e7473 Treatment resistant hypertension • Present • 50% of those with apparent resistance to antihypertensive drugs (after excluding white coat effect and secondary HT) are either completely or partially non-adherent to prescribed treatment 67 year old man on 5 drugs, BP 220/127 in clinic Supervised administration BP changes • 25 out of 50 patients truly resistant (24h SBP <5mmHg). • Remaining non-adherent (mean drop 19.5/9.4 mmHg) Tests of Adherence • Indirect methods – Patient interview – Pill counts, drug diary – Prescription refill query – Morisky medication adherence scale – 8 items – Medication Events Management System - bottle caps • Admission for supervised administration of medications and monitoring of BP. – Costly in regards to bed/ clinic usage and staff time, and inconvenient to patients. • Objective test – Therapeutic Drug Monitoring – blood or urine Benefits of Urine Screening • Use of a single assay can detect multiple drugs / metabolites – Ease of use – Low cost (<£20 per test) – Rapid test • Large volume of a non-invasive sample • Typically higher concentrations of drugs / metabolites than blood • Sampling time unimportant Downsides of Urine Screening • Difficult to say exactly when the patient took the drug – Positive = exposure • Complex metabolism of some drugs mean parent compound may not be present – Especially ACE-I • Difficult to get one method suitable for extraction and concentration of all drugs Examples 2013 2014 2015 • Highly sensitive LC-MS/MS assay for detection of antihypertensive medications • Small sample volume (50 µL), simple preparation and fast run time (10 min per sample) • Can detect 23 commonly used antihypertensive agents Positive Mode 25 μg/L 11, 12 13, 14 1. Atenolol 2. Moxonidine 3. Lisinopril 4. Metoprolol 5. Labetalol 6. Bisoprolol 7. Doxazosin 8. Enalapril 9. Perindopril 10. Diltiazem 11. Amlodipine 12. Ramipril 13. Verapamil 14. Indapimide 15. Irbesartan 16. Candesartan 9,10. 17. Losartan 18. Nifedipine 19. Carenone 20. Felodipine 17. 5. 6, 7, 8 1, 2. 4. 15,16 18. 3. 19. 20. National survey of hypertension specialists Through the British Hypertension Society • 82% response – 53 specialists from 29 centres • 42% - more than half of patients non-adherent • 38% - 26-50% non-adherent • 63% specialists do not routinely check adherence Hameed MA, Cappuccio F, Padmanabhan S and Dasgupta I Journal of Human Hypertension (2016) 30, 633–656; doi:10.1038/jhh.2016.60 Consequence of non-adherence • Higher CV events and mortality • Patients with resistant hypertension have a seven fold higher risk of CV events Daugherty SL, et al. Circulation. 2012; 125(13):1635–42 Minor BP reductions can make a difference • Meta-analysis of 61 prospective, observational studies • 1 million adults • 12.7 million person years 7% reduction in risk of ischaemic heart disease 2 mm Hg mortality decrease in mean SBP 10% reduction in risk of stroke mortality Adapted from Lewington S et al. Lancet 2002;360:1903-1913 Cost of non-adherence to the NHS • Health economic modeling taking into account event rates and cost of treatment • Expected annual cost per adherent hypertensive person is £573 • Non-adherent hypertensive patient £912/ year • Shifting all patients with hypertension to a position of complete adherence will save £390 million a year • A more realistic target of 80% of patients will save £100 million a year to the NHS Truman et al, Report of DH funded national project. 2010, Factors responsible for non-adherence Hameed, Dasgupta and Gill. BMJ 21 July 2016 How to deal with non-adherence? Open and frank discussion with the patient • Reason for non-concordance • Asymptomatic – unaware of risks • Harmful consequences of not taking medication • Using absolute numbers and visual aids – e.g. ‘2 mmHg higher BP increases risk of dying of stroke by 10% and of heart attack by 7%’ • Life style changes that may improve BP – Lowering salt intake by 4 g/day by 5/3 mmHg – 40 min 3-4 times a week aerobic exercise by 5/3 mmHg Visual representation of Qrisk2 score https://qrisk.org/ Discuss medication • How the patient is managing his or her drugs – In particular side effects of drugs, dosing frequency, and number of different drugs • Complicated dosing regimens are associated with lower adherence • Fewer daily doses, mono-therapy, and fewer changes in medication • May negotiate a reduction in the number of drugs aiming for a higher, more realistic BP target . Role of pharmacist • New Medicines Service – Based at the CCG – provides support for people with long-term conditions newly prescribed a medicine to help improve medicines adherence – focused on particular patient groups and conditions • Medicines Use Review – Consists of accredited pharmacists – undertake structured adherence-centred reviews – with patients on multiple medicines, particularly for long- term conditions • Single pill combination drugs are associated with improved adherence and BP control • Should be considered where patients are prescribed multiple antihypertensive drugs Empowering patients • Empowering patients to monitor their blood pressure at home and to manage their drugs improve BP control. • Tele-health interventions Motivational Interviewing • MI is beneficial in substance abuse (smoking, alcohol, drugs) and life style changes (diet, exercise). • It has also been shown to improve medication adherence. • Intrinsic motivation is targeted moving towards a position where the patient can initiate, pursue and achieve the required behaviour change MI in hypertension • One meta-analysis – 7 underpowered RCTs in primary care setting – MI had a significant effect on SBP after intervention and F/U • One open label RCT (n=395) – Multifaceted intervention including MI vs usual care – 7.2 mmHg reduction in SBP at 6 months – 21% higher adherence in intervention group • None of the studies looked at the benefit of MI in people with apparent drug resistance • Used indirect measure of adherence Ren Y, et al. Inter J Cardiology. 2014; 172(2):509-11. Stewart K, et al. J Clinical Pharmacy & Therapeutics. 2014; 39(5):527-34. Case study 4 • 70 year old man, retired engineer • Referred from another centre for renal denervation • Persistent high BP – day ABP 201/108 mmHg • Multiple drug intolerance: bendroflumethiazide, indapamide, furosemide, fosinopril, candesartan, aliskerin, amlodipine, nifedipine, diltiazem, verapamil, atenolol, nebivolol, labetalol, propranolol, doxazosin, spironolactone, moxonidine, hydralazine and methyldopa Multiple antihypertensive drug intolerance • A common cause non-adherence – difficult to deal with • Rule out white coat hypertension and secondary
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