Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors

International Journal of Clinical Pharmacy, Jul 2015

Background Angiotensin converting enzyme inhibitors (ACEIs) are among the most frequently prescribed groups of medications. ACEI-induced adverse drug reactions (ADRs) are the main reason to discontinue or switch ACEI treatment. ADRs information is not available in prescription databases. Objective To identify a proxy for ACEI-induced ADRs in prescription databases. Setting The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the Netherlands and has included 14,926 subjects aged 45 years or older. Methods All ACEI starters from 2000 to 2011 were identified using prescription data within the Rotterdam Study. Participants were classified into 4 mutually exclusive groups: continuing, discontinuing, switching to angiotensin receptor blockers (ARBs), and switching to other antihypertensives. For categorization, the maximum time-interval between two prescription periods was set at 3 and 6 months. Subsequently, primary care physician files were searched and clinical events were classified as definite ADRs, probable ADRs, possible ADRs and definite non-ADRs. Finally the accuracy of different prescription patterns as indicators of ADRs was evaluated. Main outcome measure Positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of the prescription patterns of the 4 groups were calculated. Results Totally, 1132 ACEI starters were included. The PPV for a definite ADR was 56.1 % for switchers to ARB, while the PPVs for switchers to other antihypertensives, and discontinuation were 39.5 and 19.5 %, respectively. After including probable ADRs and possible ADRs, PPVs for switchers to ARB increased to 68.3 and 90.5 %. A 6-month interval gave slightly higher PPVs compared to a 3-month interval (maximum 6.1 % higher). The differences in NPVs between 3 and 6-months interval groups were approximately 1.0 %. Conclusions Switching ACEIs to ARBs is the best marker for ACEI-induced ADRs in prescription databases.

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Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors

Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors Seyed Hamidreza Mahmoudpour 0 1 2 3 4 5 Folkert W. Asselbergs 0 1 2 3 4 5 Catherine E. de Keyser 0 1 2 3 4 5 Patrick C. Souverein 0 1 2 3 4 5 Albert Hofman 0 1 2 3 4 5 Bruno H. Stricker 0 1 2 3 4 5 Anthonius de Boer 0 1 2 3 4 5 Anke-Hilse Maitland-van der Zee 0 1 2 3 4 5 0 Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute , Utrecht , The Netherlands 1 Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht , 3508 GA Utrecht , The Netherlands 2 Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University , Universiteitsweg 99, David de Wied Building, 3508 TB Utrecht , The Netherlands 3 Department of Internal Medicine, Erasmus Medical Center , Gravendijkwal 230, Rotterdam 3015 CE , The Netherlands 4 Department of Epidemiology, Erasmus Medical Center , Rotterdam , The Netherlands 5 Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London , London , UK Background Angiotensin converting enzyme inhibitors (ACEIs) are among the most frequently prescribed groups of medications. ACEI-induced adverse drug reactions (ADRs) are the main reason to discontinue or switch ACEI treatment. ADRs information is not available in prescription databases. Objective To identify a proxy for ACEI-induced ADRs in prescription databases. Setting The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the Netherlands and has included 14,926 subjects aged 45 years or older. Methods All ACEI starters from 2000 to 2011 were identified using prescription data within the Rotterdam Study. Participants were classified into 4 mutually exclusive groups: continuing, discontinuing, switching to angiotensin receptor blockers (ARBs), and switching to other antihypertensives. For categorization, the maximum time-interval between two prescription periods was set at 3 and 6 months. Subsequently, primary care physician files were searched and clinical events were classified as definite ADRs, probable ADRs, possible ADRs and definite non-ADRs. Finally the accuracy of different prescription patterns as indicators of ADRs was evaluated. Main outcome measure Positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of the prescription patterns of the 4 groups were calculated. Results Totally, 1132 ACEI starters were included. The PPV for a definite ADR was 56.1 % for switchers to ARB, while the PPVs for switchers to other antihypertensives, and discontinuation were 39.5 and 19.5 %, respectively. After including probable ADRs and possible ADRs, PPVs for switchers to ARB increased to 68.3 and 90.5 %. A 6-month interval gave slightly higher PPVs compared to a 3-month interval (maximum 6.1 % higher). The differences in NPVs between 3 and 6-months interval groups were approximately 1.0 %. Conclusions Switching ACEIs to ARBs is the best marker for ACEI-induced ADRs in prescription databases. ACEI; ADR; Adverse drug reaction; Angiotensin converting enzyme inhibitors; Electronic healthcare database; Positive predictive value; Pharmacoepidemiology; Pharmacovigilance; PPV; Impacts on Practice - On behalf of the PREDICTION-ADR consortium. & Anke-Hilse Maitland-van der Zee Because adverse drug reactions (ADRs) are poorly registered in health care databases, it is difficult to conduct reliable studies of drug-induced ADRs within those databases without suitable proxies. • In prescription databases, switching from Angiotensin Converting Enzyme Inhibitors to Angiotensin Receptor Blockers is the best indicator for the ACEI-induced adverse drug reactions. • Applying the validated definition as a marker to investigate genetic and environmental risk factors associated with the occurrence of ACEI-induced ADRs can increase the efficiency of epidemiological and pharmacovigilance studies of ADRs. Angiotensin converting enzyme inhibitors (ACEIs) are commonly prescribed for a wide range of indications in both cardiovascular and renal disease, including hypertension, heart failure, myocardial infarction, renal failure and diabetic nephropathy [1]. They are first choice in cardiovascular protection in the group of renin angiotensin aldosterone system (RAAS) inhibitors [2]. It has been shown that ACEIs reduce the risk of all-cause mortality and cardiovascular mortality in both patients with hypertension or diabetes mellitus [3, 4]. ACEIs are one of the most frequently prescribed groups of medications worldwide, in the US they were prescribed more than 150 million times per year since 2006 [5]. In the Netherlands there were around 9 million ACEI prescriptions in 2013 [6]. Furthermore, ramipril was the first antihypertensive medication in 2013 with more than 24 million prescriptions dispensed in community pharmacies in (...truncated)


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Seyed Hamidreza Mahmoudpour, Folkert W. Asselbergs, Catherine E. de Keyser, Patrick C. Souverein, Albert Hofman, Bruno H. Stricker, Anthonius de Boer, Anke-Hilse Maitland-van der Zee. Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors, International Journal of Clinical Pharmacy, 2015, pp. 1095-1103, Volume 37, Issue 6, DOI: 10.1007/s11096-015-0159-3