Letters
Author Affiliation: Robarts Research Institute, Western University, London, Ontario, Canada. Corresponding Author: J. David Spence, MD, FRCPC, Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, ON N6G 2V2, Canada ([email protected]). Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease pooled cohort risk equations. JAMA. 2014;311(14):1406-1415. 2. Krumholz HM. The new cholesterol and blood pressure guidelines: perspective on the path forward. JAMA. 2014;311(14):1403-1405. 3. Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke. 1999;30(12):2513-2516. 4. Schneider AT, Kissela B, Woo D, et al. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites. Stroke. 2004;35(7):1552-1556. 5. Sillesen H, Amarenco P, Hennerici MG, et al; Stroke Prevention by Aggressive Reduction in Cholesterol Levels Investigators. Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke. 2008;39(12):3297-3302.
In Reply Based on published studies,1-3 we think there are clear benefits for statins for the primary and secondary prevention of stroke. The Cholesterol Treatment Trialists’ Collaboration4 meta-analysis from 2010 showed a hazard ratio of 0.85 (95% CI, 0.80-0.90) for stroke per 1-mmol/L reduction of lowdensity lipoprotein cholesterol with statin use vs placebo; 0.80 (99% CI, 0.73-0.88) for ischemic stroke, 1.10 (99% CI, 0.861.42) for hemorrhagic stroke, and 0.88 (99% CI, 0.76-1.02) for unknown stroke type. Although heterogeneity between primary and secondary prevention trials was not reported, similar patterns appeared to be present for primary and secondary prevention trials. Trials of statin therapy have not reported results specific to ischemic stroke subtypes. Therefore, we cannot infer that the benefits of statins are present only for certain types of ischemic strokes (eg, large vessel vs small vessel vs cardioembolic). The hypothesis that statins have differential benefits on subtypes of ischemic stroke is an interesting and important question. However, investigation of subtypes of stroke was beyond the scope of the study we conducted. We think that it may be useful for future randomized trials to investigate whether statins reduce the risk of only certain subtypes of ischemic stroke. The goal of the REGARDS study analysis was to evaluate the validity of the American College of Cardiology (ACC)/ American Heart Association (AHA) Pooled Cohort risk equations in a population for whom the decision to initiate statins may be based on predicted atherosclerotic cardiovascular disease risk. For this reason, we chose to follow the definition of cardiovascular disease set forth in the ACC/AHA guideline on risk assessment5 and include all ischemic stroke outcomes. The performance of the ACC/AHA Pooled Cohort risk equations for coronary events per se is not known and determining the performance was beyond the scope of our study. Nonetheless, the excellent calibration of the Pooled Cohort risk equations when using a similar definition to that used in the ACC/AHA derivation is noteworthy and should 750
provide clinicians confidence when using these risk equations as part of the decision-making process surrounding the initiation of statins. Paul Muntner, PhD George Howard, DrPh Monika M. Safford, MD Author Affiliations: Department of Epidemiology, University of Alabama, Birmingham (Muntner); Department of Biostatistics, University of Alabama, Birmingham (Howard); Department of Medicine, University of Alabama, Birmingham (Safford). Corresponding Author: Paul Muntner, PhD, Department of Epidemiology, University of Alabama, 1665 University Blvd, Ste 230J, Birmingham, AL 35294 ([email protected]). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Muntner reported receiving grants and personal fees from Amgen outside the submitted work. Dr Safford reported receiving grants from Amgen and diaDexus outside the submitted work. No other disclosures were reported. 1. Ridker PM, Danielson E, Fonseca FA, et al; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. 2. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7-22. 3. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344(8934):1383-1389. 4. Baigent C, Blackwell L, Emberson J, et al; Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. 5. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;129(25)(suppl 2):S49-S73.
Treatment for Opioid Use Disorder To the Editor The Viewpoint by Drs Olsen and Scharfstein1 addressed an important and timely topic, the stigma of opioid use disorder and its treatment. Olsen and Scharfstein appropriately emphasized the importance of medication-assisted treatment as a mainstay of intervention for and treatment of opioid addiction. However, while the therapeutic armamentarium for this disorder is limited, it is not as limited as Olsen and Scharfstein suggested. The authors emphasized 2 treatments in particular, methadone and buprenorphine. However, there is a third medication approved by the US Food and Drug Administration that also deserves mention, naltrexone. Naltrexone is a non– narcotic opioid antagonist available as both short-acting daily oral and extended-release once monthly injectable products. Extended-release naltrexone is specifically indicated for the prevention of relapse to opioid dependence following opioid detoxification as part of a comprehensive management program that includes psychosocial support.2 Given the heterogeneity of the needs of different patients, and the inherent complexities of opioid use disorder, awareness of the full array of therapeutic options is important. Jeffrey J. Stoddard, MD
JAMA August 20, 2014 Volume 312, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Purdue University User on 05/21/2015
jama.com
Letters
Author Affiliation: Alkermes Inc, Waltham, Massachusetts. Corresponding Author: Jeffrey J. Stoddard, MD, Alkermes Inc, 852 Winter St, Waltham, MA 02451 ([email protected]). Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported being the vice president for medical professional services at Alermes Inc, a manufacturer of an extended-release naltrexone product. 1. Olsen Y, Sharfstein JM. Confronting the stigma of opioid use disorder—and its treatment. JAMA. 2014;311(14):1393-1394. 2. US Food and Drug Administration. Naltrexone for extended-release injectable suspension (marketed as Vivitrol) Information. http://www.fda.gov /drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders /ucm103334.htm. Accessed May 27, 2014.
In Reply Dr Stoddard notes that our Viewpoint on the stigma associated with the treatment of opioid use disorder did not discuss naltrexone. In 2010, the US Food and Drug Administration approved the extended-release formulation of naltrexone for relapse prevention of opioid use disorder based on evidence of efficacy against placebo. The omission in our Viewpoint was intentional. Our goal was to confront the common, inaccurate, and dangerous assertion that long-term therapy with methadone or buprenorphine (both agonist medications) is merely substituting one addiction for another. This misconception inhibits physicians from providing and patients from seeking needed, effective, and compassionate care. As an antagonist medication usually used for less than 6 months, naltrexone does not face the same degree of misunderstanding. Compared with the decades of scientific evidence supporting the safety and effectiveness of methadone and buprenorphine, there is substantially less experience and data associated with extended-release naltrexone. A few studies1-3 suggest that the efficacy of naltrexone is no better and in some cases inferior to either agonist treatment. More definitive research is under way. There are many reasons physicians and patients might choose one approved therapy over another. Stigma should not be one of them. Yngvild Olsen, MD, MPH Joshua Sharfstein, MD Author Affiliations: Institutes for Behavior Resources Inc, Baltimore, Maryland (Olsen); Maryland Department of Health and Mental Hygiene, Baltimore (Sharfstein). Corresponding Author: Yngvild Olsen, MD, MPH, Institutes for Behavior Resources Inc, 2104 Maryland Ave, Baltimore, MD 21218 (yngvild.olsen@gmail .com).
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Olsen reported seeing patients at the Institutes for Behavior Resources, a private, non-profit organization that provides opioid use disorder treatment; and receiving compensation for speaking on opioid use disorder and its treatment at educational events sponsored by the Office of Problem Solving Courts, a Maryland state agency, and by a hospital system in Maryland. No other disclosures were reported. 1. Larney S, Gowing L, Mattick RP, Farrell M, Hall W, Degenhardt L. A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence. Drug Alcohol Rev. 2014;33(2):115-128. 2. Ahmadi J, Ahmadi K, Ohaeri J. Controlled, randomized trial in maintenance treatment of intravenous buprenorphine dependence with naltrexone, methadone or buprenorphine: a novel study. Eur J Clin Invest. 2003;33(9):824829. 3. Reece AS. Favorable mortality profile of naltrexone implants for opiate addiction. J Addict Dis. 2010;29(1):30-50.
CORRECTION Incorrect Date: In the Review article entitled “A Systematic Assessment of Benefits and Risks to Guide Breast Cancer Screening Decisions” published in the April 2, 2014, issue of JAMA (2014;311[13]:1327-1335. doi:10.1001/jama.2014.1398), a date was incorrectly reported. In the third paragraph of the Results section, fifth sentence, “January 2014” should have read “February 2014.” This article was corrected online.
Guidelines for Letters Letters discussing a recent JAMA article should be submitted within 4 weeks of the article's publication in print. Letters received after 4 weeks will rarely be considered. Letters should not exceed 400 words of text and 5 references and may have no more than 3 authors. Letters reporting original research should not exceed 600 words of text and 6 references and may have no more than 7 authors. They may include up to 2 tables or figures but online supplementary material is not allowed. All letters should include a word count. Letters must not duplicate other material published or submitted for publication. Letters not meeting these specifications are generally not considered. Letters being considered for publication ordinarily will be sent to the authors of the JAMA article, who will be given the opportunity to reply. Letters will be published at the discretion of the editors and are subject to abridgement and editing. Further instructions can be found at http://jama.com/public /InstructionsForAuthors.aspx. A signed statement for authorship criteria and responsibility, financial disclosure, copyright transfer, and acknowledgment and the ICMJE Form for Disclosure of Potential Conflicts of Interest are required before publication. Letters should be submitted via the JAMA online submission and review system at http: //manuscripts.jama.com. For technical assistance, please contact [email protected]. Section Editor: Jody W. Zylke, MD, Deputy Editor.
jama.com
JAMA August 20, 2014 Volume 312, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Purdue University User on 05/21/2015
751
Author Affiliation: Robarts Research Institute, Western University, London, Ontario, Canada. Corresponding Author: J. David Spence, MD, FRCPC, Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, ON N6G 2V2, Canada ([email protected]). Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease pooled cohort risk equations. JAMA. 2014;311(14):1406-1415. 2. Krumholz HM. The new cholesterol and blood pressure guidelines: perspective on the path forward. JAMA. 2014;311(14):1403-1405. 3. Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke. 1999;30(12):2513-2516. 4. Schneider AT, Kissela B, Woo D, et al. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites. Stroke. 2004;35(7):1552-1556. 5. Sillesen H, Amarenco P, Hennerici MG, et al; Stroke Prevention by Aggressive Reduction in Cholesterol Levels Investigators. Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke. 2008;39(12):3297-3302.
In Reply Based on published studies,1-3 we think there are clear benefits for statins for the primary and secondary prevention of stroke. The Cholesterol Treatment Trialists’ Collaboration4 meta-analysis from 2010 showed a hazard ratio of 0.85 (95% CI, 0.80-0.90) for stroke per 1-mmol/L reduction of lowdensity lipoprotein cholesterol with statin use vs placebo; 0.80 (99% CI, 0.73-0.88) for ischemic stroke, 1.10 (99% CI, 0.861.42) for hemorrhagic stroke, and 0.88 (99% CI, 0.76-1.02) for unknown stroke type. Although heterogeneity between primary and secondary prevention trials was not reported, similar patterns appeared to be present for primary and secondary prevention trials. Trials of statin therapy have not reported results specific to ischemic stroke subtypes. Therefore, we cannot infer that the benefits of statins are present only for certain types of ischemic strokes (eg, large vessel vs small vessel vs cardioembolic). The hypothesis that statins have differential benefits on subtypes of ischemic stroke is an interesting and important question. However, investigation of subtypes of stroke was beyond the scope of the study we conducted. We think that it may be useful for future randomized trials to investigate whether statins reduce the risk of only certain subtypes of ischemic stroke. The goal of the REGARDS study analysis was to evaluate the validity of the American College of Cardiology (ACC)/ American Heart Association (AHA) Pooled Cohort risk equations in a population for whom the decision to initiate statins may be based on predicted atherosclerotic cardiovascular disease risk. For this reason, we chose to follow the definition of cardiovascular disease set forth in the ACC/AHA guideline on risk assessment5 and include all ischemic stroke outcomes. The performance of the ACC/AHA Pooled Cohort risk equations for coronary events per se is not known and determining the performance was beyond the scope of our study. Nonetheless, the excellent calibration of the Pooled Cohort risk equations when using a similar definition to that used in the ACC/AHA derivation is noteworthy and should 750
provide clinicians confidence when using these risk equations as part of the decision-making process surrounding the initiation of statins. Paul Muntner, PhD George Howard, DrPh Monika M. Safford, MD Author Affiliations: Department of Epidemiology, University of Alabama, Birmingham (Muntner); Department of Biostatistics, University of Alabama, Birmingham (Howard); Department of Medicine, University of Alabama, Birmingham (Safford). Corresponding Author: Paul Muntner, PhD, Department of Epidemiology, University of Alabama, 1665 University Blvd, Ste 230J, Birmingham, AL 35294 ([email protected]). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Muntner reported receiving grants and personal fees from Amgen outside the submitted work. Dr Safford reported receiving grants from Amgen and diaDexus outside the submitted work. No other disclosures were reported. 1. Ridker PM, Danielson E, Fonseca FA, et al; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. 2. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7-22. 3. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344(8934):1383-1389. 4. Baigent C, Blackwell L, Emberson J, et al; Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. 5. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;129(25)(suppl 2):S49-S73.
Treatment for Opioid Use Disorder To the Editor The Viewpoint by Drs Olsen and Scharfstein1 addressed an important and timely topic, the stigma of opioid use disorder and its treatment. Olsen and Scharfstein appropriately emphasized the importance of medication-assisted treatment as a mainstay of intervention for and treatment of opioid addiction. However, while the therapeutic armamentarium for this disorder is limited, it is not as limited as Olsen and Scharfstein suggested. The authors emphasized 2 treatments in particular, methadone and buprenorphine. However, there is a third medication approved by the US Food and Drug Administration that also deserves mention, naltrexone. Naltrexone is a non– narcotic opioid antagonist available as both short-acting daily oral and extended-release once monthly injectable products. Extended-release naltrexone is specifically indicated for the prevention of relapse to opioid dependence following opioid detoxification as part of a comprehensive management program that includes psychosocial support.2 Given the heterogeneity of the needs of different patients, and the inherent complexities of opioid use disorder, awareness of the full array of therapeutic options is important. Jeffrey J. Stoddard, MD
JAMA August 20, 2014 Volume 312, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Purdue University User on 05/21/2015
jama.com
Letters
Author Affiliation: Alkermes Inc, Waltham, Massachusetts. Corresponding Author: Jeffrey J. Stoddard, MD, Alkermes Inc, 852 Winter St, Waltham, MA 02451 ([email protected]). Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported being the vice president for medical professional services at Alermes Inc, a manufacturer of an extended-release naltrexone product. 1. Olsen Y, Sharfstein JM. Confronting the stigma of opioid use disorder—and its treatment. JAMA. 2014;311(14):1393-1394. 2. US Food and Drug Administration. Naltrexone for extended-release injectable suspension (marketed as Vivitrol) Information. http://www.fda.gov /drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders /ucm103334.htm. Accessed May 27, 2014.
In Reply Dr Stoddard notes that our Viewpoint on the stigma associated with the treatment of opioid use disorder did not discuss naltrexone. In 2010, the US Food and Drug Administration approved the extended-release formulation of naltrexone for relapse prevention of opioid use disorder based on evidence of efficacy against placebo. The omission in our Viewpoint was intentional. Our goal was to confront the common, inaccurate, and dangerous assertion that long-term therapy with methadone or buprenorphine (both agonist medications) is merely substituting one addiction for another. This misconception inhibits physicians from providing and patients from seeking needed, effective, and compassionate care. As an antagonist medication usually used for less than 6 months, naltrexone does not face the same degree of misunderstanding. Compared with the decades of scientific evidence supporting the safety and effectiveness of methadone and buprenorphine, there is substantially less experience and data associated with extended-release naltrexone. A few studies1-3 suggest that the efficacy of naltrexone is no better and in some cases inferior to either agonist treatment. More definitive research is under way. There are many reasons physicians and patients might choose one approved therapy over another. Stigma should not be one of them. Yngvild Olsen, MD, MPH Joshua Sharfstein, MD Author Affiliations: Institutes for Behavior Resources Inc, Baltimore, Maryland (Olsen); Maryland Department of Health and Mental Hygiene, Baltimore (Sharfstein). Corresponding Author: Yngvild Olsen, MD, MPH, Institutes for Behavior Resources Inc, 2104 Maryland Ave, Baltimore, MD 21218 (yngvild.olsen@gmail .com).
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Olsen reported seeing patients at the Institutes for Behavior Resources, a private, non-profit organization that provides opioid use disorder treatment; and receiving compensation for speaking on opioid use disorder and its treatment at educational events sponsored by the Office of Problem Solving Courts, a Maryland state agency, and by a hospital system in Maryland. No other disclosures were reported. 1. Larney S, Gowing L, Mattick RP, Farrell M, Hall W, Degenhardt L. A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence. Drug Alcohol Rev. 2014;33(2):115-128. 2. Ahmadi J, Ahmadi K, Ohaeri J. Controlled, randomized trial in maintenance treatment of intravenous buprenorphine dependence with naltrexone, methadone or buprenorphine: a novel study. Eur J Clin Invest. 2003;33(9):824829. 3. Reece AS. Favorable mortality profile of naltrexone implants for opiate addiction. J Addict Dis. 2010;29(1):30-50.
CORRECTION Incorrect Date: In the Review article entitled “A Systematic Assessment of Benefits and Risks to Guide Breast Cancer Screening Decisions” published in the April 2, 2014, issue of JAMA (2014;311[13]:1327-1335. doi:10.1001/jama.2014.1398), a date was incorrectly reported. In the third paragraph of the Results section, fifth sentence, “January 2014” should have read “February 2014.” This article was corrected online.
Guidelines for Letters Letters discussing a recent JAMA article should be submitted within 4 weeks of the article's publication in print. Letters received after 4 weeks will rarely be considered. Letters should not exceed 400 words of text and 5 references and may have no more than 3 authors. Letters reporting original research should not exceed 600 words of text and 6 references and may have no more than 7 authors. They may include up to 2 tables or figures but online supplementary material is not allowed. All letters should include a word count. Letters must not duplicate other material published or submitted for publication. Letters not meeting these specifications are generally not considered. Letters being considered for publication ordinarily will be sent to the authors of the JAMA article, who will be given the opportunity to reply. Letters will be published at the discretion of the editors and are subject to abridgement and editing. Further instructions can be found at http://jama.com/public /InstructionsForAuthors.aspx. A signed statement for authorship criteria and responsibility, financial disclosure, copyright transfer, and acknowledgment and the ICMJE Form for Disclosure of Potential Conflicts of Interest are required before publication. Letters should be submitted via the JAMA online submission and review system at http: //manuscripts.jama.com. For technical assistance, please contact [email protected]. Section Editor: Jody W. Zylke, MD, Deputy Editor.
jama.com
JAMA August 20, 2014 Volume 312, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Purdue University User on 05/21/2015
751
