AGS Annual Meeting May 2010 Sponsored by the Polypharmacy Special Interest Group and the Pharmacists Section
No financial conflicts of interest Sponsored by the Polypharmacy Special Interest Group Thanks to Joe Hanlon, Sunny Linnebur, Shelley Grey
To understand evidence about medication discontinuation, and to identify gaps in the evidence base To appreciate ethical and legal issues in medication discontinuation To learn and apply a thoughtful approach to discontinuing medications To develop strategies for safely and effectively discontinuing medications
Concepts and approaches to medication discontinuation Holly Holmes, MD Asst. Professor, U. Texas MD Anderson Cancer Center The evidence base for medication discontinuation Kevin Bain, PharmD, MPH VP Clinical Support, excellerx, Inc, an Omnicare Co. Practical strategies for discontinuing medications Michael Steinman, MD Assoc. Professor of Medicine, UCSF & SFVAMC Point-counterpoint discussion Thomas Finucane, MD - Professor, Johns Hopkins University. Janice Feinberg, PharmD, JD - Research Director, American Society of Consultant Pharmacists Research and Education Foundation Ken Brummel-Smith, MD Professor, Florida State University Ronald Shorr, MD - Professor, U. Florida & North FL/South GA VA HCS Q&A
83 yo M with HTN, CAD, type II DM, CKD, OA. Generally well, independent in ADLs and IADLs. Mild dizziness, somewhat but not clearly positional. Says no problems with adherence. BP 138/65, HR 75. Formal orthostatics negative. Cr 1.5 (CrCl 30). A1c 7.2. HDL 36, LDL 80, Triglycerides WNL. Amlodipine 10 qd Lisinopril 40 qd Metoprolol 50 bid ISDN 5 tid HCTZ 25 qd Simvastatin 40 qhs Glipizide 10 bid APAP 650 qid prn MVI qd Vitamin D 400 IU qd Omeprazole 20 qd Should any drugs be discontinued? How?
Holly M. Holmes, MD UT MD Anderson Cancer Center
Medication List as of 5/14/10 amlodipine 10 mg daily multivitamin metoprolol 50 mg 2 a day hydrochlorothiazide 25 lisinopril 40 mg once glipizide 10 mg 2 a day vitamin D omeprazole 20 mg Tylenol Isosorbide 5 mg, 3 a day
Danger: 10 medications Indication to discontinue Adherence? Pulse is 95 Reaching target HbA1c? Should this patient be on an aspirin? a statin? Medication List as of 5/14/10 amlodipine 10 mg, 2 daily multivitamin metoprolol 50 mg 2 a day hydrochlorothiazide 25 lisinopril 40 mg once glipizide 10 mg 2 a day vitamin D omeprazole 20 mg Tylenol Isosorbide 5 mg, 3 a day dinitrate Should be q day Q day? levels checked? prn? Still needed? How often? Indication? Toxic dosing?
Bain KT, et al. JAGS 56:1946 1952, 2008.
Indication to Start Medication Benefit/ Risk Acceptable Communicate Monitor Bain KT, et al. JAGS 56:1946 1952, 2008.
Monitor Communicate Low Benefit or High Risk Indication to Stop Medication Bain KT, et al. JAGS 56:1946 1952, 2008.
Monitor Communicate Low Benefit or High Risk Indication to Stop Medication No longer needed Wasn t needed in the first place Diminished benefit Increased risk New interaction or contraindication As a TEST of whether it s needed Bain KT, et al. JAGS 56:1946 1952, 2008.
Monitor Communicate Low Benefit or High Risk Indication to Stop Medication Bain KT, et al. JAGS 56:1946 1952, 2008.
Holmes HM, et al. Arch Int Med 2006; 166: 605-9. % event-free Is the effect statistically and/or clinically significant? What is the benefit? TIME Is there a wide variation in time to benefit, or by subgroups?
LaRosa JC, et al. TNT trial. Am J Cardiol 2010;105:283 287.
Nowakowski, et al. J Clin Oncol 28:412-417.
Monitor Communicate Low Benefit or High Risk Indication to Stop Medication Statins for prevention? Benefit = nothing happens Comparing time to benefit with life expectancy Translating efficacy into effectiveness for the individual patient Harm with statins? Prevalence of myopathy 1.5-5% in RCTs Observational: 10% Real world? Bain KT, et al. JAGS 2008. Joy TR et al. Ann Intern Med. 2009;150:858-868. Shanahan RL, et al. Pharmacother 2005;25:345 351.
25 20 Mortality According to US Life Tables Top 25th Percentile 50th Percentile Lowest 25th Percentile Risk for Mortality in Frail Elders 15 10 5 0 70 75 80 85 90 Various ways to think about remaining life expectancy to compare to the time until benefit for a drug Walter LC, Covinsky KE. JAMA 2001; 285: 1750. Carey EC et al. JAGS 2008; 56:68 75.
Monitor Communicate Low Benefit or High Risk Indication to Stop Medication Why do you think the medication should be stopped? Why does the patient want to stop it (and are they even taking it)? How does this decision fit with Goals of care Treatment preferences Attitudes/behaviors Bain KT, et al. JAGS 2008.
Adherence to Statins 100 % Adherent 80 60 40 20 0 3 6 12 36 Time (months) Communicating benefits important when starting a med Patient aware of lower LDL more likely to adhere Lack of effect detectable by patient Reverse side of the coin for stopping? McGinnis B, et al. Ann Pharmacother 2007;41:1805-11.
Evaluate benefit and risk Population level: time until benefit (harm), effect size Individual level: likelihood of benefit (harm) in an individual patient Communicate with the patient Adherence, health behaviors Goals and preferences and relationship to med use Holmes HM, et al. Arch Int Med 2006; 166: 605-9.
Kevin T. Bain, PharmD, MPH Vice President for Clinical Support, excellerx, Inc., an Omnicare company
A clinically significant set of symptoms or signs caused by the removal of a drug. Graves T. Arch Intern Med. 1997
Physiological Exacerbation New Symptom
Alpha-antagonists ACE inhibitors Anticonvulsants Antidepressants Antiparkinson drugs Antipsychotics Baclofen Benzodiazepines Beta-blockers Corticosteroids Opioids Sedatives Bain KT. J Am Geriatr Soc. 2008
ACE inhibitors Antianginal drugs Anticonvulsants Antidepressants Antiparkinson drugs Beta-blockers Digoxin Diuretics H 2 blockers NSAIDs Statins Bain KT. J Am Geriatr Soc. 2008
Antiparkinson drugs Baclofen Corticosteroids Statins Bain KT. J Am Geriatr Soc. 2008
33% of patients have an ADWE Gerety MB. J Am Geriatr Soc. 1993 Graves T. Arch Intern Med. 1997
Multi-center, observational study 333 patients aged 70-84 years Followed for 5 years Ekbom T. J Intern Med. 1994
Remaining without antihypertensive treatment 40% at 1 year 20% at 5 years Outcomes Lower total mortality risk than the general population Lower risk of CV events than those treated Ekbom T. J Intern Med. 1994
Multi-center, prospective cohort study Part of a larger RCT 503 patients aged 65-84 years Those who remained normotensive for at least 2 weeks after withdrawal of all antihypertensives Followed for 12 months Nelson M. BMJ. 2002
Maintained normotension 36% Returned to hypertension 54% Half returned to hypertension within 70 days after withdrawal and half beyond 70 days Other 10% Nelson M. BMJ. 2002
BP control Lower pre-treatment, on-treatment, and post-treatment BP Nature of BP treatment Fewer antihypertensives Lower doses of antihypertensives 42% of patients remain normotensive Nelson M. Am J Hypertens. 2001
Discontinuing Psychotropics in the LTC Setting
Randomized, placebo-controlled, discontinuation study 102 dementia patients aged 67-100 years 51 patients continued antipsychotic 51 patients discontinued antipsychotic Followed for 12 months Ballard C. PLoS Med. 2008
Severe Impairment Battery (SIB) score No significant difference Neuropsychiatric Inventory (NPI) No significant difference A non-significant advantage for patients with NPI scores > 15 who continued neuroleptics Ballard C. PLoS Med. 2008
Michael Steinman, MD University of California, San Francisco San Francisco VA Medical Center
83 yo M with HTN, CAD, type II DM, CKD, OA. Dizzy BP 138/65, CrCl 30, A1c 7.2 Amlodipine 10 qd Lisinopril 40 qd Metoprolol 50 bid ISDN 5 tid HCTZ 25 qd Simvastatin 40 qhs Glipizide 10 bid APAP 650 qid prn MVI qd, Vitamin D 400 IU qd Omeprazole 20 qd Harms > benefits Any symptom in an older patient is a drug side effect until proven otherwise Minimal or no effectiveness No indication Patient not taking (and not priority to push adherence)
Condition Drug HTN Amlodipine Lisinopril ISDN HCTZ Metoprolol CAD Metoprolol (2) Simvastatin DM CKD Glipizide +/- Lisinopril (2) Harms > benefits Minimal or no effectiveness Not indicated Not adherent OA APAP MVI Omeprazole
When stop drug, goal is to avoid adverse drug withdrawal events ADWE = adverse event that results from withdrawing a medication Physiologic withdrawal Exacerbation of underlying condition
Occur when target organ has undergone lasting readjustment from previous steady state in response to drug Never abruptly discontinue opiates in long-term user Changes in receptor function and signaling -> withdrawal Never abruptly discontinue corticosteroids in long-term user HPA axis suppressed -> adrenal insufficiency Rules of thumb Any drug in which typically taper up dose over time probably should be tapered down Taper down at same rate as might taper up Bain, JAGS 2008
If exacerbation are going to occur, happen sooner or later Taper can blunt harms of exacerbation by testing the waters For example: Furosemide in heart failure -> taper down, monitor weight and symptoms Bain, JAGS 2008
Drug Physiological withdrawal Exacerbation of underlying symptoms Action SSRI Proton pump inhibitor Clonidine
Drug Physiological withdrawal Exacerbation of underlying symptoms Action SSRI Serotonin withdrawal syndrome Moderate Taper Proton pump inhibitor Clonidine
Drug Physiological withdrawal Exacerbation of underlying symptoms Action SSRI Serotonin withdrawal syndrome Moderate Taper Proton pump inhibitor No Mild Stop Clonidine
Drug Physiological withdrawal Exacerbation of underlying symptoms Action SSRI Serotonin withdrawal syndrome Moderate Taper Proton pump inhibitor No Mild Stop Clonidine Headache, HTN, palpitations Absent Taper
Analagous to monitoring for adverse drug events (ADEs) Most ADEs not preventable at time a drug is rx ed Decision to start drug was reasonable choice Monitoring can reduce morbidity of ADEs Lack of monitoring the most common error that results in ADEs 36% of preventable ADEs failure to monitor 37% of preventable ADEs failure to respond appropriately to patient symptoms or labs Gurwitz, JAMA 2003
When discontinue a drug, monitor for recurrence of symptoms and withdrawal reactions Literature on ADEs suggests approaches for best ways to monitor Active surveillance Educate and activate patients Schedule follow-up call or visit Nurse, pharmacist Schiff, JAMA 2009; Clapp Am J Health System Pharm 2008
Withdrawing drugs = abandonment Clearly explain reasons for discontination Establish trust If patient still resistant, prescriber right to discontinue particularly when harms > benefits Clear instructions Patients commonly misuse drugs -> mistakes in tapering Write out how to taper What to watch for Cross out on wallet medication list Bain, J Amer Geriatr Soc 2008
Multiple prescribers Physicians reluctant to discontinue medications prescribed by colleagues Multiple prescribers, multiple sites of care, transitions of care risk factors for unnecessary medication use 1/3 to 2/3 of patients started on PPIs during hospitalization for stress ulcer ppx continued after discharge ~1 unnecessary drug per patient PPIs, CNS medications, vitamins and minerals Tamblyn CMAJ 2003; Rahmner Ann Fam Med 2010 Steinman Arch Intern Med 2009; Doucette Clin Ther 2005
OK to discontinue, e.g. if harms > benefits or no indication Maintain communication with specialists
AGS Annual Meeting May 2010
83 yo M with HTN, CAD, type II DM, CKD, OA. Generally well, independent in ADLs and IADLs. Mild dizziness, somewhat but not clearly positional. Says no problems with adherence. BP 138/65, HR 75. Formal orthostatics negative. Cr 1.5 (CrCl 30). A1c 7.2. HDL 36, LDL 80, Triglycerides WNL. Amlodipine 10 qd Lisinopril 40 qd Metoprolol 50 bid ISDN 5 tid HCTZ 25 qd Simvastatin 40 qhs Glipizide 10 bid APAP 650 qid MVI qd Vitamin D 400 IU qd Omeprazole 20 qd
75 yo M with diabetic neuropathy, BPH Among other meds, takes amitriptyline 25 mg qhs Patient unsure that helping with neuropathic pain, but credits the drug with helping him sleep and reluctant to stop it. Denies current urinary symptoms (except 1x/night nocturia), dry mouth, cognitive impairment, constipation, orthostasis
87 yo F moderate dementia, COPD, Class 3 HF, CAD. Lived in LTCF for 6 mos. Prior to admission day-night reversal and calling out with risperidone. Tried discontinuing risperidone shortly after admission; behavioral symptoms so restarted. Uses 4WW. MMSE 10/30. Wt 120#, down 8# since admission Risperidone 1 mg qhs plus 1 mg qam prn (gets 2x/week) Donepezil 10 mg qd
72 yo M Stage IV NSC lung cancer referred to hospice from hospital No response to chemotherapy; goals comfort & symptom mgmt Severe COPD, CAD s/p MI, CHF, A fib frequent RVR, HTN, DM Morphine 5 mg liquid q 4 hours prn Lorazepam 1 mg tid prn Tiotropium, Fluticasone / Salmeterol (Advair) Warfarin, Aspirin 325 daily Cardevilol 12.5 bid, Lisinopril 40 bid, Furosemide 40 bid Atorvastatin 20 qhs Amiodarone 200 daily MVI daily