Delving into Deprescription. Todd C. Lee MD MPH FRCPC Associate Professor of Medicine, McGill University With thanks to Dr. Emily G.

Transcription

1 Delving into Deprescription Todd C. Lee MD MPH FRCPC Associate Professor of Medicine, McGill University With thanks to Dr. Emily G. McDonald

2 Conflict of interest slide I don t think I have any conflicts of interest to declare But I have a software product in development to help physicians/patients deprescribe Sometimes I worry that pharma will take a contract out on me for my crusade for stopping medications (that s more of a confession)

3 Objectives Introduce the concept of deprescription and why it is important for your patients and for Canadians as a whole. Define the concepts of therapeutic and deprescribing cascades Provide an overview of the evidence in support of efforts to stop unnecessary or potentially harmful medications and point out specifically good examples of common drugs which would be appropriate to deprescribe. Give you resources you can turn to help you tackle these issues with your patients -- and, though it won't be an infomercial, perhaps empower you to set out to make this a regular part of your practice.

4 Polypharmacy: definition Five or more medications (40% of elderly) New terms on the horizon: extreme polypharmacy, mega-polypharmacy, polypharmacy+++ (I ve seen the residents write this in their admission note and it makes me so proud) 50% of our admitted elderly patients take 10 or more medications There are 10% of our patients on the ward who have more than 20 medications prescribed

5 What s the problem with too many pills? Many medications are: Potentially inappropriate (NEW TERM: PIMs or potentially inappropriate medications are those which have a high probability of risk exceeding benefit) BEERS criteria, STOPP criteria, Choosing Wisely lists Continued beyond their original indication (a classic example is aspirin and clopidogrel continued together beyond 12 months following a stent or an acute coronary syndrome) Associated with harm in the form of Adverse Drug Events (ADEs) Estimate 27,000 ER visits in Canada per year due to ADE

6 What s the problem with too many pills? Complex interactions We know the simple ones of Drug A with B; but what about 10 in combination? Complex side effects We know the side effects of Drug A or Drug B; but what about 10 in combination? Therapeutic cascades Difficulty prioritizing the important pills Adherence

7 Therapeutic Cascades When a drug is given to manage/treat the side effect of another drug Give me some examples!

8 Therapeutic Cascades When a drug is given to manage/treat the side effect of another drug Furosemide for calcium channel blocker induced edema Magnesium for proton pump inhibitor related hypomagnesemia Laxatives for iron associated constipation Beta-blockers for beta-agonist induced palpitations Nystatin for inhaled steroid induced thrush Codeine for ACE inhibitor cough --- I m not joking I ve seen it!

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10 Low value medications cost big bucks This says NOTHING about medications not on STOPP/BEERS which may also be inappropriate or low value

11 Defining deprescribing It is another relatively new term that first enters the research realm at most 5 years ago but certainly has been done It is the process of regular reassessment of medications for the purposes of discontinuing medications which are no longer considered necessary or are of low benefit compared to risk

12 Deprescribing It enters into the medical lexicon around Deprescribing has a wikipedia entry but it was not one of the 500 new words that were entered into the Oxford English Dictionary in 2016 (which included Oompa Loompa and Scrumdiddlyumptious) All this to say that children won t be asked to spell deprescribing at next year s spelling bee.

13 How would one consider deprescribing Low hanging fruit (PIMs) Higher hanging fruit (low benefit medications) Highest hanging fruit (medications which are no longer needed but once were)

14 PIMs Information on PIMs is expert-derived, freely available, widely publicized, and taught in medical school, medical residencies, and geriatrics/internal medicine training programs. BEERS criteria 2015, STOPP criteria, Choosing Wisely Canada There are many doctors who have a great command of this literature and who practice accordingly. There are others who know some of the basics but may forget some of the more complex or newer recommendations.

15 PIMs The care of the patient is highly dependent on being paired with a doctor who is more or less active in this area. Consider: Dr. B may frequently discuss with their patients stopping sedative-hypnotics to reduce the risk of falls. The patient chooses to continue them. Dr. A does not do this and continues the medications without reconsidering them. The patient has a hip fracture due to sedative-hypnotics

16 PIMs How to systematically address Interventions are needed that bring the overall level of knowledge on the issues of PIMs in the elderly to a more standardized level, to facilitate thinking about these issues through for example: computerized support evidence based solutions for helping patients stop these medications While we wait for many of these tools to be developed and deployed, we can still apply the concepts

17 Barbara Farrell- deprescribing research In 2013 Dr. Barbara Farrell (pharmd and assistant professor in the faculty of family medicine at the University of Ottawa) received a $ grant from the Ontario Ministry of Health and Long-term care to develop, implement and evaluate guidelines for deprescribing medications in primary and long-term care facilities CMAJ published a piece describing the goals of the grant Identified several classes of medications based on a modified Delphi approach

18 Table 2. Round One Ranking: Drug/drug classes identified by 70% of participants as probably or definitely useful. Farrell B, Tsang C, Raman-Wilms L, Irving H, Conklin J, et al. (2015) What Are Priorities for Deprescribing for Elderly Patients? Capturing the Voice of Practitioners: A Modified Delphi Process. PLoS ONE 10(4): e doi: /journal.pone

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20 The number needed to treat with a sedative-hypnotic for improved sleep is 13. The average improvement in sleep is 8 minutes of latency and 14 minutes more sleep Number needed to harm is 6. Use of benzodiazepines should be reserved for alcohol withdrawal symptoms/delirium tremens or severe generalized anxiety disorder unresponsive to other therapies. Prescribing or discontinuing sedative-hypnotics in hospital can have substantial impact on long-term use.

21 Harms of inpatient benzodiazepines and Z- drugs Falls in hospital Hip fracture Cognitive impairment on MMSE/MOCA Length of stay increased Death Particular risk of death in CHF and COPD patients

22 Hospitalization confers increased risk of new outpatient benzodiazepine in elderly (OR) 3.09; 95% CI, Benzodiazepines prescribed to (3.1%) patients within 7 days of discharge Nearly half of these became new chronic benzodiazepine users.

23 So what s the problem then? Lets just stop some drugs! WELL there are several Physicians hesitate to bring up the topic of deprescribing as it may make their patients uncomfortable by implying reduced life expectancy Stopping medications is a complicated process REF: Schuling BMC Fam Pract 2012

24 Barriers Addressing polypharmacy requires some knowledge of the barriers and challenges of deprescribing Up until recent years the concept of less is more as it applies to medications (and indeed most realms of medicine) has been relatively unfamiliar to patients, pharmacists and clinicians.

25 Barriers Prescriber barriers: The medication is prescribed by another physician (missing information) There is no evidence to guide deprescribing Ageism (an ADE is thought to represent a normal symptom of aging) eg. decreased appetite or energy, falling down, agitation or alterations in sleep Pressure to prescribe according to guidelines Concern that rocking the boat will cause a problem Limited knowledge of how to stop Time

26 Barriers-consumer Patient/family barriers: Feeling of abandonment Medications represent hope Fear of rocking boat

27 Guidance from hit lists Lists of potentially inappropriate medications exist (Beers criteria and the STOP/START criteria; Choosing Wisely Canada) The first two do not give guidance on how to implement the process they merely list drugs Applications online ex. MedStopper.com give tapering instructions but do not link stopping medications with patient s underlying conditions (addresses the issue of lack of knowledge of how to stop or fear of side effects)

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30 Addressing chronic medications What is the patient s prognosis? What was the INITIAL intention of the therapy? Is it being achieved? Is it still reasonable to attempt to achieve? What is the time until realizing benefits (or harms)?

31 Example Donepezil to slow progression of mild Alzheimer s in a patient living in the community autonomously or semi-autonomously vs. Donepezil which has not been stopped in a patient residing in a nursing home with advanced dementia and limited life expectancy What are the harms? (Cardiac conduction. Anorexia and weight loss. Diarrhea, nausea, vomiting. Worsening of BPH symptom.) REF: Tija Clinics in Geriatric Medicine 2012

32 Framework The medical indication The patient s preference Quality of life Contextual issues

33 A deprescribing protocol (1) ascertain all drugs the patient is currently taking and the reasons for each one (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention REF: Scott JAMA int med 2015

34 A deprescribing protocol (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects.

35 Has the medication already caused harm? Patients admitted to hospital with opioid overdose often leave the hospital on.

36 Similar considerations: What is the current indication for the drug? Is the patient actually taking the drug? Does the drug fit with the patient s circumstances? Does the likely benefit of the drug outweigh the potential harms?

37 Put the drug into one of two categories Disease or symptom control drug à controlling active disease or symptoms (anti-anginals, levothyroxine, heart failure medication etc ) Stopping these drugs may result in uncontrolled symptoms Preventive drug (statin, warfarin, bisphosphonates etc...) Stopping these drugs requires considering the absolute risks and benefits

38 Strategies Empower the patient Choosing wisely Canada what are the treatment options for my condition? What are the possible benefits and harms of each drug? What are reasonable grounds for discontinuing a medication?

39 Strategies Care provider should ask if any new symptoms at each visit Any problems taking your medications? Prediction tools and evidence tables if they exist Decision aids that estimate absolute risk of disease

40 CASES

41 Case 1 65 year old man admitted for weakness PMH: TIA in 2005 Atrial fibrillation since 2013 Diabetes Hypertension Meds: ASA Coumadin Omeprazole Sotalol Ramipril Pravastatin Hydrochlorothiazide Metformin Magnesium

42 Case 1 O/E: 140/80 HR 90 irregularly irregular, afebrile JVP ASA; no murmurs or extra sounds No edema Chest clear 4/5 power Brisk reflexes with clonus Positive Chvostek and Trousseau signs

43 LABS: Hemoglobin 135/WBC 9.5/Plt 340 AST/ALT normal A1c 9.5% TSH normal Na 135/ K+ 3.2/ Creatinine Normal Calcium total 1.6 Magnesium 0.15 CXR Normal ECG: Atrial fibrillation with adequate rate control and no ST-T changes PR 160 QRS 90 QTc 490

44 Introducing a counter-concept: The Deprescribing Cascade PRESCRIBING CASCADE Adding medications to deal with the side effects of other medications DEPRESCRIBING CASCADE Removing medications which are no longer necessary, which allows the removal of medications given to prevent/treat side effects of other medications

45 Taking the Ascent ASA and Coumadin together the ASA was for a remote TIA and the Coumadin for his atrial fibrillation. There is, in this patient, no compelling indication for both Markedly increases his risk of bleeding without significant benefit How common is this at MUHC: 40-50% (McDonald et.al,under review) If you stop the ASA, the indication for the proton pump inhibitor is no longer present (ASA + coumadin) and therefore without a history of complicated GI bleed the omeprazole can safely be stopped This is a good thing because it was likely the cause of the metabolic problem and we can also stop the magnesium soon

46 Can we cascade further? He is in atrial fibrillation (rate controlled) Why then is he still on sotalol for rhythm control (which has clearly failed) instead of a rate control agent? AFFIRM trial, RACE trial Sotolol HR 1.6 for death Am J Cardiol Sep 1;114(5): Sotolol + hypomagnesemia + hypokalemia = torsades de pointes Can thus change to alternative rate control agent (i.e. diltiazem, bisoprolol)

47 Net Result Adverse drug event recognized and offending medication stopped Potential ADE averted 3 fewer medications per day (a 33% reduction!)

48 Case of an adverse drug event 76 year old man who presents to the ER with a dizziness and an episode of syncope after passing bright red blood per rectum His hemoglobin is found to 45 g/l He has acute kidney injury with a creatinine of 200

49 Medications include: Metformin 850 mg po BI Nifedipine ER 60 mg po daily Quinine 200 mg po daily ISMN 60 mg po daily Asa 80 mg po daily Tamsulosin 0.4 mg po daily Simvastatin 40 mg po daily Pantoprazole 40 mg po daily Canagliflozin 300 po daily Amlodipine 2.5 mg po daily Azithromycine 250 mg po daily x 5 days Furosemide 80 mg po BID Clopidogrel 75 mg po daily Dutasteride 0.5 mg po daily

50 Additional information? Regarding metformin and canagliflozin Hemoglobin a1c History of hypoglycemia? Risks with canagliflozin? AKI, euglycemic DKA, genitourinary infections

51 Additional information Aspirin and clopidogrel Indication? Timing? DES in the right coronary artery 5 years ago (new risk calculators àdapt score calculator) REF: Mauri et al NEJM 2014 and Yeh et al JAMA 2016

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54 Never drugs? They exist in my world Some examples: Quinine (only 2 health canada advisories saying please stop using) Colace (it doesn t work, sorry) Meperidine and Codeine (seizures and unpredictable pharmacokinetics) Chloral hydrate (it was cool back in Victorian England)

55 Deprescribing cascade Had his clopidogrel been stopped the pantoprazole could have been stopped Other examples include patients who are on magnesium supplements and a proton pump inhibitor

56 ISMN Other drugs to consider stopping

57 ISMN Other drugs to consider stopping

58 Final remarks before we conclude Don t forget that some drugs need to be tapered before stopping them Some because of rebound symptoms Some because of adverse effects from stopping the drug which could prove dangerous Some because a tapering regiment may improve your chances of the drug not being restarted (classic example is sleeping pills; less thought of example is PPIs).

59 For excellent patient directed resources (Because counselling a patient about deprescribing is time-consuming) Choosing Wisely Canada The deprescribing network: has a series of really excellent deprescribing pamphlets

60 Designed and tested with patient stakeholders They use patient friendly language They are freely available online They are translated in french and english They are validated They exist for benzos, sedative hypnotics, antipsychotics, antihistamines, sulfonylureas and PPIs Future pamphlets for general deprescribing and for statins

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65 MedStopper Can enter drugs there; it tries to tell you risk:benefit and how one would stop for many drugs MedStopper McGill version 2.0 is the subject of a 1.8 million dollar 3 year CIHR funded RCT where it will combine patient comorbidities with recommendations and expanded ruleset

66 End on a quote rarely is it a good idea to substitute a big word, (like) deprescribe, when a small one, like stop, would do. But deprescribing is more than just stopping a therapy. It s more than just an action; it s a way of thinking, a mindset. It brings to the fore another important verb (and noun) need. The act of deprescribing offers an opportunity to inject care back into healthcare. Let s embrace the idea together. Please help me add the new verb to our language. Dr. John Mandrola from his editorial on deprescribing in 2014

67 Questions?