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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleDisplayedQuote" id="dsq0005"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#8221;Drugs don&#8217;t work in patients who don&#8217;t take them&#46;&#8221;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">C&#46; Everett Koop&#44; MD&#44; US Surgeon General&#44; 1985</p></span></p><p id="par0010" class="elsevierStylePara elsevierViewall">Not many drugs in this century can claim to be &#8220;game changers&#8221; in disease management as is the case with direct oral anticoagulants &#40;DOACs&#41;&#46; Their introduction led to a true revolution in anticoagulation&#44; reaching a greater number of patients&#44; with a wide range of indications&#44; safer profile&#44; and more convenient use and dosage than that of vitamin K antagonists &#40;VKAs&#41;&#46; Recently&#44; epidemiological data have suggested that atrial fibrillation &#40;AF&#41; related strokes are decreasing as the uptake of DOACs is increasing&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> Yet&#44; for drugs to work they must be properly prescribed by physicians and patients must be compliant&#44; particularly in chronic diseases such as AF&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Adherence is defined as the extent to which patients can follow the recommendations for prescribed treatments&#46; It is particularly important in a therapy that relies on full compliance and adequate dosing for efficacy and safety in preventing thromboembolic events&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the article by Br&#237;zido et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a>&#44; using data from AF patients followed in a specialized cardiology outpatient clinic from 2016 to 2018&#44; a concerning scenario was depicted&#46; Half of the patients were considered non-adherent&#44; only one in three patients were fully adherent and nearly one in five changed DOACs during the study&#46; Likewise&#44; treatment for secondary prevention of thromboembolic events &#40;16&#37; of all patients&#41; had no impact on adherence&#46; As expected&#44; higher out of pocket costs&#44; bid posology and longer treatment duration were predictors of non-compliance&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">This was a cross-sectional&#44; retrospective analysis of a cohort of 264 patients with low bleeding risk &#40;median HASBLED score of 1&#41;&#44; followed by cardiologists at a high-volume tertiary center&#46; This is certainly a selected population&#44; 30&#37; of whom had vascular disease and 34&#37; were on antiplatelet therapy&#46; One can speculate that the setting may be more dismal outside cardiology outpatient clinics&#44; where patients are older&#44; have more comorbidities&#44; with a higher bleeding risk and more irregular follow-up&#46; Non-adherence was defined as medical refill adherence &#60;90&#37;&#44; a threshold considered appropriate given the nature of the intervention&#46; There are several ways to assess adherence&#44; but medical refill is probably one of the simplest and can be determined by any doctor at any time&#44; given precious information that can help to address barriers to compliance&#46; Therefore&#44; this study is an import call to action to doctors following AF patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Non-adherence comes at a cost&#46; A meta-analysis of over 500 studies on medication compliance revealed an average non-adherence rate of 25&#37;&#44; with variations according to disease&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> Good adherence has been associated with increased survival&#44; probably also due to the &#8220;healthy adherent effect&#8221; since patients compliant with placebo also have better survival&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> Adherence is&#44; in fact&#44; the reflection of several health-related factors&#44; comprising behavior changes toward a healthier lifestyle&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Recently&#44; an analysis of the Stockholm Healthcare database&#44; including 21 028 AF patients claiming a first DOAC prescription from 2011 to 2018&#44; showed a persistence rate of 70&#37; after a median follow-up of two years&#44; although 85&#37; of the patients were under treatment at the end of the study due to re-initiation of treatment&#46; Adherence in those that continued on medication remained stable at 90&#37; throughout the study period&#46; Non-persistence and poor adherence were both associated with increased stroke risk&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Non-adherence is a complex problem and results from the interplay between patients&#44; physicians and health care systems&#44; and the treatment itself&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">According to the World Health Organization&#44; there are five aspects influencing adherence&#58; factors related to the health care system and providers &#40;namely doctor-patient relation and costs&#41;&#59; factors related to treatment &#40;complexity of dosing regimen&#44; side effects and lack of immediate results&#41;&#59; disease-related factors &#40;disease severity&#44; treatment impact and comorbidities&#41;&#59; and patient-related factors &#40;health literacy&#44; socioeconomical status&#44; fear of side effects&#44; unintentional non-adherence&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In Portugal&#44; a study performed in 2008 by the Portuguese Association of Pharma Industry&#44; including a cohort of 1400 participants&#44; representative of the mainland Portuguese population&#44; identified the following as frequent reasons for non-compliance&#58; forgetting to take the medication &#40;46&#46;7&#37;&#41;&#59; abandoning therapy due to clinical improvement &#40;26&#46;6&#37;&#41;&#59; and side effects &#40;22&#46;2&#37;&#41;&#46; More concerning was that of those surveyed&#44; 31&#46;7&#37; were afraid of questioning their doctor&#44; 28&#46;1&#37; did not pay attention when the therapeutic regimen was being explained&#44; 20&#46;5&#37; did not understand the advantages of the treatment&#44; and 12&#46;5&#37; did not trust their doctor&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Understanding individual reason&#40;s&#41; for non-compliance is vital to establish effective interventions&#44; which need to be tailored and frequently multifactorial&#46; But first&#44; we should acknowledge that non-adherence is not just a patient&#39;s choice&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">There are several key interventions that can have a huge impact on results&#46; Health care system strategies such as reducing out of pocket costs&#44; allowing for long-term prescription refills &#40;finally approved in Portugal&#41; and incentives in primary care for adequate treatment of preventable diseases&#44; like thromboembolic events in AF&#44; are relevant for ensuring therapy continuance&#46; Education for patients and caregivers&#44; especially on how to manage complications or on the consequences of therapy discontinuation or inadequate dosing must be improved&#44; involving nurses and pharmacists in the process&#46; Finally&#44; making time to establish a stronger doctor-patient relationship&#44; in a safe and open environment that allows for discussion and shared decisions&#44; is of the utmost importance if we want our patients to make wise choices&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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Patient adherence to direct oral anticoagulants: To take or not to take, is it a patient's choice?
Adesão do doente aos anticoagulantes orais diretos: tomar ou não tomar, uma escolha do doente?
Cristina Gavina
Serviço de Cardiologia, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleDisplayedQuote" id="dsq0005"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#8221;Drugs don&#8217;t work in patients who don&#8217;t take them&#46;&#8221;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">C&#46; Everett Koop&#44; MD&#44; US Surgeon General&#44; 1985</p></span></p><p id="par0010" class="elsevierStylePara elsevierViewall">Not many drugs in this century can claim to be &#8220;game changers&#8221; in disease management as is the case with direct oral anticoagulants &#40;DOACs&#41;&#46; Their introduction led to a true revolution in anticoagulation&#44; reaching a greater number of patients&#44; with a wide range of indications&#44; safer profile&#44; and more convenient use and dosage than that of vitamin K antagonists &#40;VKAs&#41;&#46; Recently&#44; epidemiological data have suggested that atrial fibrillation &#40;AF&#41; related strokes are decreasing as the uptake of DOACs is increasing&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> Yet&#44; for drugs to work they must be properly prescribed by physicians and patients must be compliant&#44; particularly in chronic diseases such as AF&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Adherence is defined as the extent to which patients can follow the recommendations for prescribed treatments&#46; It is particularly important in a therapy that relies on full compliance and adequate dosing for efficacy and safety in preventing thromboembolic events&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the article by Br&#237;zido et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a>&#44; using data from AF patients followed in a specialized cardiology outpatient clinic from 2016 to 2018&#44; a concerning scenario was depicted&#46; Half of the patients were considered non-adherent&#44; only one in three patients were fully adherent and nearly one in five changed DOACs during the study&#46; Likewise&#44; treatment for secondary prevention of thromboembolic events &#40;16&#37; of all patients&#41; had no impact on adherence&#46; As expected&#44; higher out of pocket costs&#44; bid posology and longer treatment duration were predictors of non-compliance&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">This was a cross-sectional&#44; retrospective analysis of a cohort of 264 patients with low bleeding risk &#40;median HASBLED score of 1&#41;&#44; followed by cardiologists at a high-volume tertiary center&#46; This is certainly a selected population&#44; 30&#37; of whom had vascular disease and 34&#37; were on antiplatelet therapy&#46; One can speculate that the setting may be more dismal outside cardiology outpatient clinics&#44; where patients are older&#44; have more comorbidities&#44; with a higher bleeding risk and more irregular follow-up&#46; Non-adherence was defined as medical refill adherence &#60;90&#37;&#44; a threshold considered appropriate given the nature of the intervention&#46; There are several ways to assess adherence&#44; but medical refill is probably one of the simplest and can be determined by any doctor at any time&#44; given precious information that can help to address barriers to compliance&#46; Therefore&#44; this study is an import call to action to doctors following AF patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Non-adherence comes at a cost&#46; A meta-analysis of over 500 studies on medication compliance revealed an average non-adherence rate of 25&#37;&#44; with variations according to disease&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> Good adherence has been associated with increased survival&#44; probably also due to the &#8220;healthy adherent effect&#8221; since patients compliant with placebo also have better survival&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> Adherence is&#44; in fact&#44; the reflection of several health-related factors&#44; comprising behavior changes toward a healthier lifestyle&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Recently&#44; an analysis of the Stockholm Healthcare database&#44; including 21 028 AF patients claiming a first DOAC prescription from 2011 to 2018&#44; showed a persistence rate of 70&#37; after a median follow-up of two years&#44; although 85&#37; of the patients were under treatment at the end of the study due to re-initiation of treatment&#46; Adherence in those that continued on medication remained stable at 90&#37; throughout the study period&#46; Non-persistence and poor adherence were both associated with increased stroke risk&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Non-adherence is a complex problem and results from the interplay between patients&#44; physicians and health care systems&#44; and the treatment itself&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">According to the World Health Organization&#44; there are five aspects influencing adherence&#58; factors related to the health care system and providers &#40;namely doctor-patient relation and costs&#41;&#59; factors related to treatment &#40;complexity of dosing regimen&#44; side effects and lack of immediate results&#41;&#59; disease-related factors &#40;disease severity&#44; treatment impact and comorbidities&#41;&#59; and patient-related factors &#40;health literacy&#44; socioeconomical status&#44; fear of side effects&#44; unintentional non-adherence&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In Portugal&#44; a study performed in 2008 by the Portuguese Association of Pharma Industry&#44; including a cohort of 1400 participants&#44; representative of the mainland Portuguese population&#44; identified the following as frequent reasons for non-compliance&#58; forgetting to take the medication &#40;46&#46;7&#37;&#41;&#59; abandoning therapy due to clinical improvement &#40;26&#46;6&#37;&#41;&#59; and side effects &#40;22&#46;2&#37;&#41;&#46; More concerning was that of those surveyed&#44; 31&#46;7&#37; were afraid of questioning their doctor&#44; 28&#46;1&#37; did not pay attention when the therapeutic regimen was being explained&#44; 20&#46;5&#37; did not understand the advantages of the treatment&#44; and 12&#46;5&#37; did not trust their doctor&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Understanding individual reason&#40;s&#41; for non-compliance is vital to establish effective interventions&#44; which need to be tailored and frequently multifactorial&#46; But first&#44; we should acknowledge that non-adherence is not just a patient&#39;s choice&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">There are several key interventions that can have a huge impact on results&#46; Health care system strategies such as reducing out of pocket costs&#44; allowing for long-term prescription refills &#40;finally approved in Portugal&#41; and incentives in primary care for adequate treatment of preventable diseases&#44; like thromboembolic events in AF&#44; are relevant for ensuring therapy continuance&#46; Education for patients and caregivers&#44; especially on how to manage complications or on the consequences of therapy discontinuation or inadequate dosing must be improved&#44; involving nurses and pharmacists in the process&#46; Finally&#44; making time to establish a stronger doctor-patient relationship&#44; in a safe and open environment that allows for discussion and shared decisions&#44; is of the utmost importance if we want our patients to make wise choices&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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