Potentially inappropriate prescribing medication Pr. Pierre Olivier LANG MD, MPH, PhD, PD2 pierre-olivier.lang@chuv.ch AGY 9ème colloque Jeudi 10 décembre 2015 Which tool using to improve medication appropriateness? Hôpital de la Porte Verte Versailles

My Objectives (1)To provide a critical review existing sets of explicit criteria (2)To provide arguments for considering STOPP/START (3)To show you that even the Bible is sometimes just a Tale

Heterogeneous group Older people Older people

Heterogeneous group often with MULTIPLE COMORBIDITIES Older people Older people for which they are prescribed MULTIPLE MEDICATIONS

Heterogeneous group often with MULTIPLE COMORBIDITIES GREATER RISK OF Older people DRUG-RELATED PROBLEMS ADVERSE DRUG EVENTS DRUG-DRUG INTERACTIONS DRUG-DISEASE(s) INTERACTIONS Older people DRUG-RELATED PROBLEMS GREATER RISK OF for which they are prescribed MULTIPLE MEDICATIONS

Heterogeneous group INAPPROPRIATE PRESCRIBING MAJOR CAUSE OF DRPs often with MULTIPLE COMORBIDITIES GREATER RISK OF Older people INAPPROPRIATE PRESCRIBING = MAJOR CAUSE OF DRPs DRUG-DRUG INTERACTIONS DRUG-DISEASE(s) INTERACTIONS Older people GREATER RISK OF for which they are prescribed MULTIPLE MEDICATIONS

Definition APPROPRIATE prescribing medication INAPPROPRIATE It encompasses the use of medicines clinically indicated at a right frequency and during the right period with acceptable risks of adverse drug-drug interactions with acceptable risks of adverse drug-disease(s) interactions It encompasses the use of medicines no clinically indicated at a higher frequency and/or longer periods than clinically indicated with high risks of adverse drug-drug interactions with high risks of adverse drug-disease interactions where adverse drug event outweighs the clinical benefit

Definition APPROPRIATE prescribing medication INAPPROPRIATE It encompasses the use of medicines clinically indicated at a right frequency and during the right period with acceptable risks of adverse drug-drug interactions with acceptable risks of adverse drug-disease(s) interactions It encompasses the use of medicines no clinically indicated at a higher frequency and/or longer periods than clinically indicated with high risks of adverse drug-drug interactions with high risks of adverse drug-disease interactions where adverse drug event outweighs the clinical benefit and prescribed with respect to patients’ life expectancy and disabilities and the UNDER-USE of medicines that are clinically indicated

Review of the literature is an effective way for limiting PIM and DRPs Systematic prescriptions review is an effective way for limiting PIM and DRPs Topinková E et al. Drugs Aging 2012 EXISTING TOOLS Beers’ criteria (1991 – USA) McLeod (1997 – CAN) Oborne (1997 – UK) ACOVE (1999 – USA) IPET (2000 - CAN) Rancourt (2004 – Quebec) Laroche (2006 – FR) Lindblad (2006 – SWE) Winit-Watiana (2008 – TH) STOPP/START (2008 – IR) NORGEP (2009 - NW) Priscus (2010 - GER) Minica (2012 - CRO) PIEA (2012 – AUS) BEER’s criteria = First well-organised list of common errors of prescribing O’Mahony D et al. Eur Geriatr Med 2010 Desnoyer A et al. (Submitted)

Review of the literature is an effective way for limiting PIM and DRPs Systematic prescriptions review is an effective way for limiting PIM and DRPs Topinková E et al. Drugs Aging 2012 EXISTING TOOLS Beers’ criteria (1991 – USA) McLeod (1997 – CAN) Oborne (1997 – UK) ACOVE (1999 – USA) IPET (2000 - CAN) Rancourt (2004 – Quebec) Laroche (2006 – FR) Lindblad (2006 – SWE) Winit-Watiana (2008 – TH) STOPP/START (2008 – IR) NORGEP (2009 - NW) Priscus (2010 - GER) Minica (2012 - CRO) PIEA (2012 – AUS) BEER’s criteria = First well-organised list of common errors of prescribing Several deficiencies militate against its widespread use in Europe 1/3 medications obsolete or no available in Europe Some drugs listed are not actually contra-indicated, according to up-to-date evidence Criteria do not included several important instances of potential inappropriate prescribing O’Mahony D et al. Eur Geriatr Med 2010 Desnoyer A et al. (Submitted)

Desnoyer A et al. (Submitted)

Desnoyer A et al. (Submitted)

Desnoyer A et al. Rev Med Intern (Submitted)

Desnoyer A et al. (Submitted)

Desnoyer A et al. (Submitted)

Desnoyer A et al. (Submitted) Chang CB, Chan DC. Drugs Aging 2010 – Comparison of published explicit criteria for PIM Desnoyer A et al. (Submitted)

O’Mahony D et al. Eur Geriatr Med 2010  STOPP/START criteria have practical clinical value: they improve medication appropriateness STOPP criteria associated with ADEs and they have additional didactic effects Medication Appropriateness Index (MAI) scores used as an outcomes measure to compare intervention group and controls O’Mahony D et al. Eur Geriatr Med 2010

FINALLY THE STOPP/START set of criteria Since the first iteration of STOPP/START.V1  More than 121 publications (PubMed.gov) >80 original research articles (various clinical scenarios) from 24 countries (and NOT EUROPEEN ONLY!)  STOPP criteria are associated with ADEs, unlike Beers 2003 criteria STOPP criteria, as an intervention applied at single time, improve medication appropriateness STOPP/START criteria as an intervention applied within 72h of admission reduce DRP (-10%) and average LoS by 3 days O’Mahony D et al. Age Ageing 2015 Perspectives for STOPP/START.V2  EU 7th FWP – SENATOR (www.senator-project.eu) Primary outcome = software efficacy on DRPs incidence Horizon 2020 – OPERAM (European project) Primary outcome = impact on hospital admission

By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel. J Am Geriatr Soc 2015; Oct 8. doi: 10.1111/jgs.13702. [Epub ahead of print]

Lang PO et al. Neurol Psychiatr Geriatr 2015;15:323-36

Lang PO et al. Neurol Psychiatr Geriatr 2015;15:323-36

Lang PO et al. Neurol Psychiatr Geriatr 2015;15:323-36

Benetos A et al. JAMA 2015

And just before to conclude AN IMPORTANT REMINDER STOPP/START criteria were never meant to replace clinical judgement that is based on high-level clinical knowledge and experience; rather they were intended as an aid to routine pharmacotherapy in old age. O’Mahony D et al. Eur Geriatr Med 2010

Mais comment ça marche en pratique ?

Médicaments à l’admission : Acénocoumarol selon INR Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour Digoxine 250 μg 1x /jour Furosémide 40 mg 1x /jour

? 34 START criteria 81 STOPP criteria 81 STOPP criteria Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl 34 START criteria 81 STOPP criteria ? Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour Digoxine 250 μg 1x /jour Furosémide 40 mg 1x /jour 81 STOPP criteria 34 START criteria

Médicaments à l’admission : Acénocoumarol selon INR Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour Digoxine 250 μg 1x /jour Furosémide 40 mg 1x /jour

Critères STOPP–B et C Critères START–A Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl Critères STOPP–B et C Critères START–A Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour Digoxine 250 μg 1x /jour Furosémide 40 mg 1x /jour

Critères STOPP–B et C Critères START–A Critères STOPP–H Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl Critères STOPP–B et C Critères START–A Critères STOPP–H Critères START–E Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour Digoxine 250 μg 1x /jour Furosémide 40 mg 1x /jour

Critères STOPP–B Critères STOPP–C Critères START–A Critères STOPP–H Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl Critères STOPP–B Critères STOPP–C Critères START–A Critères STOPP–H Critères START–E Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour Digoxine 250 μg 1x /jour Furosémide 40 mg 1x /jour

Critères STOPP–B Critères STOPP–C Critères START–A Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl Critères STOPP–B Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour Digoxine 250 μg 1x /jour Furosémide 40 mg 1x /jour Critères STOPP–C Critères START–A

Critères STOPP–B Critères STOPP–C Critères START–A Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl Critères STOPP–B Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour Digoxine 250 μg 1x /jour Furosémide 40 mg 1x /jour Critères STOPP–C Critères START–A

Médicaments à l’admission : Acénocoumarol selon INR Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour Digoxine 250 μg 1x /jour Furosémide 40 mg 1x /jour

Médicaments à l’admission : Acénocoumarol selon INR Cas clinique N°10   Femme de 71 ans Motifs d’admission : Insuffisance cardiaque congestive Dermo-hypodermite jambe droite Histoire personnelle : Infarctus du myocarde (2000) FA permanente Hypertension Insuffisance veineuse des membres inférieurs Fracture du col du fémur (1998 – AVP) Tension artérielle : 118/80 mmHg (TA <130/80 durant les 24ère heures)   ECG : FA, 60bpm Biochimie : Urée 13.8 mmol/l Créatinine 157 μmol/l (eGFR 40 ml/min) Sodium 129 mmol/l Potassium 3.8 mmol/l Tests hépatiques NORMAUX Cholestérol 3.2 mmol/l Hémoglobine : 13.2 g/dl Médicaments à l’admission : Acénocoumarol selon INR Bisoprolol 5mg 1x /jour Amiodarone 100 mg 1x /jour STOPP-A1 Digoxine 250 μg 1x /jour STOPP-E1 Furosémide 40 mg 1x /jour IEC START-A6 (IC, IDM) Statine START-A5 (IDM) Aspirine ? START-A3 mais aussi STOPP-C5 et C6

“YOUR DOGGY BAG”  STOPP/START criteria were never meant to replace clinical judgement.  STOPP/START were intended as an aid to routine pharmaceutical care.  STOPP/START with this aim, is a set of criteria: that captures the dual nature of IP in older people (PIM + PO) that is well designed (according to physiological systems) that is easy and quick to use (< 2 minutes) with a good inter-rater reliability (physician, pharmacist, …)  STOPP/START criteria have practical clinical value: they improve medication appropriateness they reduce DRPs and they have additional didactic effects  STOPP/START criteria definitely need APP for iPhone and Androids

I do thank them for their active and friendly collaboration Pr. Pierre Olivier LANG MD, MPH, PhD, PD2 pierre-olivier.lang@chuv.ch Louvain Drug Research Institute, Brussels Benoît BOLAND, Olivia DALLEUR Pharmacy department of HUG, Geneva Bertrand GUIGNARD, Nicole Vogt-Ferrier AGY 9ème colloque Jeudi 10 décembre 2015 Département de pharmacologie, Hôpital Robert Debré APHP, Paris André RIEUTOR, Aude DESNOYER Hôpital de la Porte Verte Versailles

I do thank you for your ATTENTION! Pr. Pierre Olivier LANG MD, MPH, PhD, PD2 I do thank you for your ATTENTION! pierre-olivier.lang@chuv.ch AGY 9ème colloque Jeudi 10 décembre 2015 Centre Hospitalier Universitaire Vaudois Rolex Learning Center - EPFL