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Losartan vs Candesartan for Heart Failure—Reply

Losartan vs Candesartan for Heart Failure—Reply In Reply: Dr Lund and Ms Benson are concerned that those with candesartan use had more severe heart failure, leading to confounding by indication. First, Lund and Benson question the general validity of ICD codes for the identification of heart failure, and reference a systematic review1 showing significant variation across different data sources. However, the specific data source used in our study for the identification of heart failure patients has been validated with positive predictive values ranging from 81% to 100%.2,3 This should be well within what is considered an adequate predictive value. Additionally, the study patient characteristics (Table 1 in article), such as the high baseline prevalence of cardiovascular disorders and risk factors (eg, 49% with ischemic heart disease and 18% with diabetes), together with the 37% mortality (during a median 1.9 years of follow-up), reflect a study population with severe morbidity, typical for patients with heart failure. Lund and Benson also suggest that patients with heart failure are more likely to be prescribed candesartan given clinical recommendations, whereas losartan would more likely be prescribed for a hypertension indication. However, guidelines4 do not recommend any specific ARB for use in patients with heart failure. Both candesartan and losartan are indicated for heart failure in Denmark. Additionally, given the fact that both groups were identified on the basis of a first-time hospitalization with a heart failure diagnosis and that those prescribed losartan had a similar or higher prevalence of cardiovascular comorbidity than candesartan users (eg, myocardial infarction in 23% vs 20%), it is unlikely that those prescribed losartan used it for hypertension rather than the heart failure diagnosis that was assigned during the actual hospitalization. Lund and Benson also state that concomitant ACE inhibitor use was prevalent in our study. However, the 80% prevalence of ACE inhibitor use does not reflect concomitant use but rather use during a 3-year baseline period prior to ARB treatment initiation. The high prevalence of prior ACE inhibitor use is thus attributable to the fact that the bulk of study patients switched treatment from ACE inhibitors to ARBs. In their fifth point, Lund and Benson suggest that the prevalence of common heart failure etiologies was too low in our study. However, the 22% prevalence of myocardial infarction together with an 8% prevalence of unstable angina agrees with an estimated population attributable risk for development of heart failure of 13% for women and 34% for men.5 To conclude, there is little support for the concerns raised by Lund and Benson. The different results from our study and the study by Eklind-Cervenka et al6 are more likely explained by different dosage distributions of candesartan and losartan in the study populations. In that study,6 those with candesartan use were significantly more likely to achieve target dose vs those with losartan use, which likely favored the benefit of candesartan. When comparing more therapeutically equal doses of candesartan and losartan, we found no significant benefit of candesartan compared with losartan. Because no study has shown superiority of candesartan over losartan in comparable doses, statements regarding treatment recommendations supporting candesartan before losartan should be avoided. Back to top Article Information Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Pasternak reported receiving grants from the Danish Medical Research Council. Mr Svanström and Dr Hviid reported no disclosures. References 1. Quach S, Blais C, Quan H. Administrative data have high variation in validity for recording heart failure. Can J Cardiol. 2010;26(8):306-31220931099PubMedGoogle ScholarCrossref 2. Mard S, Nielsen FE. Positive predictive value and impact of misdiagnosis of a heart failure diagnosis in administrative registers among patients admitted to a university hospital cardiac care unit. Clin Epidemiol. 2010;2:235-23921042557PubMedGoogle Scholar 3. Thygesen SK, Christiansen CF, Christensen S, Lash TL, Sørensen HT. The predictive value of ICD-10 diagnostic coding used to assess Charlson comorbidity index conditions in the population-based Danish National Registry of Patients. BMC Med Res Methodol. 2011;11:8321619668PubMedGoogle ScholarCrossref 4. Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):1977-201619324967PubMedGoogle ScholarCrossref 5. Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure. JAMA. 1996;275(20):1557-15628622246PubMedGoogle ScholarCrossref 6. Eklind-Cervenka M, Benson L, Dahlström U, Edner M, Rosenqvist M, Lund LH. Association of candesartan vs losartan with all-cause mortality in patients with heart failure. JAMA. 2011;305(2):175-18221224459PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Losartan vs Candesartan for Heart Failure—Reply

JAMA , Volume 308 (4) – Jul 25, 2012

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Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2012.7644
Publisher site
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Abstract

In Reply: Dr Lund and Ms Benson are concerned that those with candesartan use had more severe heart failure, leading to confounding by indication. First, Lund and Benson question the general validity of ICD codes for the identification of heart failure, and reference a systematic review1 showing significant variation across different data sources. However, the specific data source used in our study for the identification of heart failure patients has been validated with positive predictive values ranging from 81% to 100%.2,3 This should be well within what is considered an adequate predictive value. Additionally, the study patient characteristics (Table 1 in article), such as the high baseline prevalence of cardiovascular disorders and risk factors (eg, 49% with ischemic heart disease and 18% with diabetes), together with the 37% mortality (during a median 1.9 years of follow-up), reflect a study population with severe morbidity, typical for patients with heart failure. Lund and Benson also suggest that patients with heart failure are more likely to be prescribed candesartan given clinical recommendations, whereas losartan would more likely be prescribed for a hypertension indication. However, guidelines4 do not recommend any specific ARB for use in patients with heart failure. Both candesartan and losartan are indicated for heart failure in Denmark. Additionally, given the fact that both groups were identified on the basis of a first-time hospitalization with a heart failure diagnosis and that those prescribed losartan had a similar or higher prevalence of cardiovascular comorbidity than candesartan users (eg, myocardial infarction in 23% vs 20%), it is unlikely that those prescribed losartan used it for hypertension rather than the heart failure diagnosis that was assigned during the actual hospitalization. Lund and Benson also state that concomitant ACE inhibitor use was prevalent in our study. However, the 80% prevalence of ACE inhibitor use does not reflect concomitant use but rather use during a 3-year baseline period prior to ARB treatment initiation. The high prevalence of prior ACE inhibitor use is thus attributable to the fact that the bulk of study patients switched treatment from ACE inhibitors to ARBs. In their fifth point, Lund and Benson suggest that the prevalence of common heart failure etiologies was too low in our study. However, the 22% prevalence of myocardial infarction together with an 8% prevalence of unstable angina agrees with an estimated population attributable risk for development of heart failure of 13% for women and 34% for men.5 To conclude, there is little support for the concerns raised by Lund and Benson. The different results from our study and the study by Eklind-Cervenka et al6 are more likely explained by different dosage distributions of candesartan and losartan in the study populations. In that study,6 those with candesartan use were significantly more likely to achieve target dose vs those with losartan use, which likely favored the benefit of candesartan. When comparing more therapeutically equal doses of candesartan and losartan, we found no significant benefit of candesartan compared with losartan. Because no study has shown superiority of candesartan over losartan in comparable doses, statements regarding treatment recommendations supporting candesartan before losartan should be avoided. Back to top Article Information Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Pasternak reported receiving grants from the Danish Medical Research Council. Mr Svanström and Dr Hviid reported no disclosures. References 1. Quach S, Blais C, Quan H. Administrative data have high variation in validity for recording heart failure. Can J Cardiol. 2010;26(8):306-31220931099PubMedGoogle ScholarCrossref 2. Mard S, Nielsen FE. Positive predictive value and impact of misdiagnosis of a heart failure diagnosis in administrative registers among patients admitted to a university hospital cardiac care unit. Clin Epidemiol. 2010;2:235-23921042557PubMedGoogle Scholar 3. Thygesen SK, Christiansen CF, Christensen S, Lash TL, Sørensen HT. The predictive value of ICD-10 diagnostic coding used to assess Charlson comorbidity index conditions in the population-based Danish National Registry of Patients. BMC Med Res Methodol. 2011;11:8321619668PubMedGoogle ScholarCrossref 4. Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):1977-201619324967PubMedGoogle ScholarCrossref 5. Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure. JAMA. 1996;275(20):1557-15628622246PubMedGoogle ScholarCrossref 6. Eklind-Cervenka M, Benson L, Dahlström U, Edner M, Rosenqvist M, Lund LH. Association of candesartan vs losartan with all-cause mortality in patients with heart failure. JAMA. 2011;305(2):175-18221224459PubMedGoogle ScholarCrossref

Journal

JAMAAmerican Medical Association

Published: Jul 25, 2012

References