Journal name: Clinical Interventions in Aging Article Designation: Original Research Year: 2019 Volume: 14 Clinical Interventions in Aging Dovepress Running head verso: Aguiar et al Running head recto: Aguiar et al open access to scientific and medical research DOI: 192252 Open Access Full Text Article ORIGINAL RESEARCH Identification of potentially inappropriate medications with risk of major adverse cardiac and cerebrovascular events among elderly patients in ambulatory setting and long-term care facilities This article was published in the following Dove Medical Press journal: Clinical Interventions in Aging João Pedro Aguiar1 Purpose: Cardiovascular diseases (CVDs) are extremely common among the elderly, but Luís Heitor Costa2 information on the use of potentially inappropriate medications (PIMs) with cardiovascular Filipa Alves da Costa3,4 risk is scarce. We aimed to determine the prevalence of PIMs with risk of cardiac and cere- Hubert GM Leufkens5 brovascular adverse events (CCVAEs), including major adverse cardiac and cerebrovascular Ana Paula Martins1 events (MACCE). Patients and methods: A cross-sectional study was performed using a convenience sample 1Research Institute for Medicines (iMED.ULisboa), Faculdade de from four long-term care facilities and one community pharmacy in Portugal. Patients were For personal use only. Farmácia, Universidade de Lisboa, included if they were aged 65 or older and presented at least one type of medication in their 2 Lisboa, Portugal; Serviço de medical and pharmacotherapeutic records from 2015 until December 2017. The main outcome Medicina Interna, Centro Hospitalar Psiquiátrico de Lisboa (CHPL), Lisboa, was defined as the presence of PIMs with risk of MACCE and was assessed by applying a Portugal; 3Centro de Investigação PIM-MACCE list that was developed from a previous study. All medications included in this Interdisciplinar Egas Moniz (CiiEM), list were assessed for their availability in Portugal. Instituto Universitário Egas Moniz (IUEM), Caparica, Portugal; 4Faculdade Results: A total of 680 patients were included. Of those, 428 (63%) were female with a mean de Farmácia, Universidade de Lisboa, age of 78.4±8.1 years. Four-hundred and four (59.4%) patients were taking medications asso- Lisboa, Portugal; 5Division of Pharmacoepidemiology and Clinical ciated with CCVAEs risk (mean =1.7±1.0 drugs/patient), including 264 patients (38.8%) who Pharmacology, Utrecht Institute for used drugs with MACCE risk (mean =1.4±0.8 drugs/patient). Fifty percent of patients with a Pharmaceutical Sciences, Utrecht previous history of CVD (n=521) were taking PIMs with risk of CCVAEs, including 30.0% University, Utrecht, the Netherlands with risk of MACCE. Our findings show that 50% of patients with previous history of CVD were taking Clinical Interventions in Aging downloaded from https://www.dovepress.com/ by 195.23.63.110 on 13-Nov-2019 Conclusion: drugs with risk of CCAVEs and 30% with risk of MACCE. More tailored tools for the manage- ment of drug therapy in elderly patients with CVD are of major importance in clinical practice. Keywords: patient safety, therapeutic uses, outcome process assessment (health care), cardio- vascular risk, NSAIDs, antipsychotics Introduction The elderly are usually fragile and more susceptible to drug-related problems as a result of multimorbidity, polypharmacy, and physiological changes that affect the Correspondence: João Pedro Aguiar 1 Research Institute for Medicines (iMED. pharmacokinetics and pharmacodynamics of drugs. Therefore, this population is more ULisboa), Faculdade de Farmácia prone to using medications that can be considered inappropriate. da Universidade de Lisboa, Avenida A potentially inappropriate medication (PIM) is any medication used by a patient Professor Gama Pinto, 1649-003 Lisboa, Portugal that could introduce a significant risk of an adverse drug reaction (ADR), in particular Tel +351 96 910 4137 when there is an equally or more effective alternative with lower risk available. Fax +351 21 794 6470 Email [email protected] In the elderly, ADRs can sometimes be difficult to recognize as they often present submit your manuscript | www.dovepress.com Clinical Interventions in Aging 2019:14 535–547 535 Dovepress © 2019 Aguiar et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you http://dx.doi.org/10.2147/CIA.S192252 hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Powered by TCPDF (www.tcpdf.org) 1 / 1 Aguiar et al Dovepress with unspecific symptoms (eg, falls, fatigue, and orthostatic of PIMs described addressing their association with the risk hypotension). ADRs are observed 2–3 times more often in the of cardiovascular adverse events.20 Some pharmacothera- elderly and account for 5%–17% of all hospital admissions.2 peutic groups have been established to be associated with A systematic review has found a mean prevalence of ADRs cardiovascular events such as nonsteroidal anti-inflammatory in the elderly of 11% (95% CI: 5.1%–16.8%) and a preva- drugs (NSAIDs), antipsychotics, selective calcium chan- lence of ADRs leading to hospitalization of 10% (95% CI: nel blockers, and dopaminergic agents. Unfortunately, the 7.2–12.8). These authors have also shown that increased prevalence of those PIMs in elderly patients is still unknown. comorbid complexity and increased number of medications The primary objective of this study was to assess the were significantly associated with an increased risk of ADRs.3 prevalence of PIMs with risk of MACCE in the elderly. We It is estimated that 30%–60% could be prevented.2 A recent then specifically aimed to study the prevalence of PIMs with study has shown that 45.1% (95% CI: 33.1%–57.2%) of the risk of cardiac and cerebrovascular adverse events (CCVAEs) ADRs leading to hospitalization were preventable.4 In the and to study the presence of these PIMs in patients with USA and Canada, the prevalence ranged between 14% and previous history of CVD. 37.0%;5 in Europe, the prevalence ranged between 23% and 43%.6 Differences found between both continents could be Materials and methods explained by different drug markets, different prescribing Study design patterns, and most importantly, by the tool used to measure A descriptive cross-sectional study was conducted, where a prevalence.7 convenience sample (based on geographic criteria) of citizens Several tools have been developed to guide prescrib- living in long-term care facilities (LTCFs) in the region of ing, to maximize the efficacy and safety of therapy, and to Lisboa e Vale do Tejo and the region of Alentejo and inde- minimize the consequences of using PIMs, including costs, pendently in their own home (ambulatory) in the region of hospitalizations, and mortality.8 The Beers criteria (Mark Lisboa e Vale do Tejo, Portugal were invited to participate. Beers, MD) was the first tool, developed in 1991, and last Citizens’ information (including drug use) was collected For personal use only. updated in 2019 by the American Geriatric Society.9,10 Since from two LTCFs in the region of Lisboa e Vale do Tejo and then, a considerable number of tools have been developed, two LTCFs in the other region of Alentejo. While, for indi- describing not only PIMs, but also drug–drug and drug– viduals who live independently in their own home, citizens’ disease interactions.3 Most of these tools are based on explicit information was collected from their community pharmacy. criteria, ie, are normally more drug- or disease-oriented and are developed based on literature review, expert opinions, Population and sample and consensus techniques.3 The study population (n=904) consisted of 224 residents Cardiovascular diseases ([CVDs] which also include and 680 patients from the community pharmacy and the cerebrovascular diseases) such as hypertension, coronary LTCF, respectively. In the LTCF, residents were eligible heart disease, congestive heart failure, stroke, and atrial fibril- if they were aged 65 or older and living in the facility until Clinical Interventions in Aging downloaded from https://www.dovepress.com/ by 195.23.63.110 on 13-Nov-2019 lation are prevalent among the elderly.11 They represent one 2017. In the community pharmacy, the study population was of the leading causes of death worldwide, with 17.7 million calculated based on the minimum legal number of inhabit- deaths registered in 2015 (31.0% of all-cause mortality).12,13 ants per pharmacy (3,500 inhabitants) and on the percentage In Europe, 3.9 million people (45.0% of all-cause mortality) of elderly living in the district of Cascais in 2016 (19.6%). have died from CVDs in 2016.13 Moreover, individuals were included if they were aged 65 Few studies have identified PIMs in patients with CVD. or older and had their medication history available in the A study conducted in a cardiology service showed that pharmacy database in 2017. We excluded patients if their 20% of hospitalized patients were previously exposed to a records were out of date, ie, if there were no sales in 2017. PIM in the ambulatory setting.14 However, information on PIMs associated with risk of cardiovascular adverse events, Outcomes’ definition and measurement especially with major adverse cardiac and cerebrovascular Our previous study focused on a systematic review of events (MACCE) for elderly is still scarce. Some of these 24 PIM-lists, where PIMs associated with CCVAEs and medications can increase the risk of cardiovascular events MACCE were identified (Table S1 shows the full list of those or even exacerbate underlying conditions.