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Rapid Responses to:
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Electronic letters published:
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif){kind=icon}
In Response:
The ACE inhibitor/ARB Controversy: Solution to a Vexing Measurement Problem
Dosing of ACE inhibitors and ARBs in chronic heart failure and acute myocardial infarction
ARBs: Dose and side effect considerations
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Victor C Lee, MD Zynx Health Incorporated, David C. Rhew, MD, Glenn D. Braunstein, MD
Send rapid response to journal:
vlee{at}zynx.com Victor C Lee, et al.
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To the Editor: We are pleased to hear that the Centers for Medicare and Medicaid Services (CMS), Joint Commission on Accreditation of Healthcare Organizations (JCAHO), and several other collaborating organizations concur that angiotensin-receptor blockers (ARBs) will no longer be excluded from the CMS and JCAHO quality indicators for heart failure and acute myocardial infarction (MI). The implementation of the revised heart failure and acute MI measures in two phases makes practical sense as described in the letter by McClellan and colleagues as well as on the JCAHO Web site(1). We respectfully disagree with Dr. Peeters’ statement that the current quality indicators should remain unchanged. A prior meta-analysis by Jong and colleagues (2) showed no statistically significant difference in mortality or heart failure hospitalization rates between ARBs and placebo in patients with heart failure and left ventricular dysfunction. Thus, it was logical that ARB therapy was not part of the JCAHO and CMS quality measures for CHF and AMI at that time. However, current data (3) show that ARB therapy results in statistically significant reductions in mortality and heart failure hospitalizations for patients with heart failure and left ventricular dysfunction. Irrespective of whether ARBs are considered to be first- or second-line agents to ACE inhibitors, ARBs should be included as part of the heart failure and acute MI quality indicators because these agents improve clinical outcomes. We agree with Dr. Peeters and Mr. Regier that the efficacy of ACE inhibitors and ARBs may be dependent upon their relative dosing. We did not perform separate analyses based on dosing, however, because the target doses for the ARBs in our study varied widely and we are not aware of standardized criteria for the interconversion of ARB doses. Finally, we agree with Mr. Regier that in our table of study characteristics, the doses of valsartan and captopril in the VALIANT study were reported as the target doses from the initial hospitalization, but should have been the target doses upon 3-month follow-up, which were twice as high. Victor C. Lee, MD Zynx Health Incorporated Los Angeles, CA 90024 David C. Rhew, MD Zynx Health Incorporated Los Angeles, CA 90024 Glenn D. Braunstein, MD Cedars-Sinai Health System Los Angeles, CA 90048 References (1) Joint Commission on Accreditation of Healthcare Organizations. Change in ACEI for LVSD measures (HF-3, AMI-3): Incorporation of ARBs. Accessed at http://www.jcaho.org/pms/core+measures/changeinaceiforlvsdmeasuresincorparbs.pdf on 23 December 2004. (2) Jong P, Demers C, KcKelvie RS, Liu PP. Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2002;39:463-70. (3) Lee VC, Rhew DC, Dylan M, Badamgarav E, Braunstein GD, Weingarten SR. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med. 2004 Nov 2;141(9):693-704. (4) Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldmanmd AM, Francis GS, et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America. Circulation. 2001;104:2996-3007. Conflict of Interest:None declared |
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Jerod M Loeb, PhD Joint Commission on Accreditation of Healthcare Organizations, Mark B. McClellan, Carolyn M.Clancy, Gary S. Francis, Alice K. Jacobs, Kenneth W. Kizer, Margaret E. O'Kane, Michael J. Wolk
Send rapid response to journal:
jloeb{at}jcaho.org Jerod M Loeb, et al.
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As noted in the article, “Meta-Analysis: Angiotensin-Receptor Blockers in Chronic Heart Failure and High-Risk Acute Myocardial Infarction,“ the evidence for use of angiotensin-receptor blockers (ARBs) for chronic heart failure (HF) and acute myocardial infarction (AMI) with left ventricular systolic dysfunction has evolved, and relevant performance measures now need to be revised. The Centers for Medicare & Medicaid Services (CMS) and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) have been working toward this goal with the American Heart Association (AHA), the American College of Cardiology (ACC) and the Heart Failure Society of America (HFSA) since the publication of the VALsartan In Acute myocardial iNfarcTion (VALIANT) (1) and Candesartan in Heart Failure Assessment of Reduction in Morbidity and mortality (CHARM) (2) trials. In response to this growing body of evidence, CMS and JCAHO have concluded that ARBs should no longer be excluded from measures of quality care in the treatment of these conditions and have agreed to change the ACE inhibitor performance measures for AMI and HF, effective January 1, 2005. Several clinical practice guidelines still recommend angiotensin converting enzyme (ACE) inhibitors as the first choice of therapy because of the greater amount of evidence, with ARBs recommended in ACE intolerant patients (3,4,5). However, the new ST-elevation myocardial infarction (STEMI) guidelines give ARBs a Class IIa recommendation, indicating that the weight of evidence favors their use as an alternative to ACE inhibitors. With the support of the evidence and the guidelines, JCAHO and CMS -- at a summit of stakeholders sponsored by the Agency for Healthcare Research and Quality (AHRQ) and the National Quality Forum (NQF) on November 3rd, 2004 -- proposed revised AMI and HF measures that would allow the prescription of either ACE inhibitors or ARBs to satisfy the measure. The revised measures were supported by the American Heart Association, the American College of Cardiology, the Heart Failure Society of America, the National Committee for Quality Assurance, the Agency for Healthcare Research and Quality and were endorsed by the National Quality Forum. As the science of measuring performance in healthcare is relatively new, there are currently no explicit rules for changing an accepted measure in response to advances in research. Assuring that measures reflect current scientific knowledge is imperative. One of the most remarkable aspects of the aforementioned measure revision process has been the process itself, which has required a closely integrated effort on the part of the many organizations that have been involved in the definition and endorsement of these measures. The relatively timely implementation of these updated measures became possible only through the collaborative effort of many organizations committed to high quality care. The measure change will be accomplished in two phases for practical reasons relating to the feasibility of making rapid changes in measure software being employed around the country. Beginning with January 1, 2005 discharges, the CMS and JCAHO data dictionary will be changed to capture any discharge prescription for an ACE inhibitor or an ARB as meeting the intent of the measure. A notation of ‘contraindication to both ACEI and ARB’ will exclude patients from the measure. Full implementation of the change is anticipated to be effective next fall and will capture ACE inhibitors and ARBs separately, along with separate exclusion criteria for ‘contraindication to ACEI’ and ‘contraindication to ARB.’ Mark B. McClellan, MD, PhD Administrator of the Centers for Medicare & Medicaid Services (CMS) Jerod M. Loeb, PhD Executive Vice President, Division of Research Joint Commission on Accreditation of Healthcare Organizations (JCAHO) Carolyn M. Clancy, MD Director, Agency for Healthcare Research and Quality (AHRQ) Gary S. Francis, MD President, Heart Failure Society of America (HFSA) Alice K. Jacobs, MD, FACC, FAHA President, American Heart Association (AHA) Kenneth W. Kizer, MD, MPH President and Chief Executive Officer of the National Quality Forum (NQF) Margaret E. O’Kane President, National Committee for Quality Assurance (NCQA) Michael J. Wolk, MD, FACC President, American College of Cardiology (ACC) References: 1) Pfeffer MA, McMurray JJ, Velazquez EF, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349:1893-1906. 2) Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003;362:772-776. 3) Antman EM, Anbe DT, Armstrong PW, et al. American College of Cardiology; American Heart Association; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction – executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004 Aug 4;44(3):671-719. 4) Hunt SA, Baker DW, Chin MH et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America. Circulation. 2001 Dec 11;104(24): 2996-3007. . 5) Mosca L, Appel LJ, Benjamin EJ, Berra K et al. Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women. Circulation. 2004;109:672-692 6) Executive Council of the Heart Failure Society of America. Implications of recent clinical trials for heart failure performance measures. HFSA Position Statement. J Card Fail. 2004;10:4-5 7) Masoudi FA, Rathore SS, Wang Y, et al. National patterns of use and effectiveness of angiotensin-converting enzyme inhibitors in older patients with heart failure and left ventricular systolic dysfunction. Circulation. 2004;110:724-731. Conflict of Interest:None declared |
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Michael J. Peeters, PharmD Texas Tech University HSC- School of Pharmacy, James P. Tsikouris, PharmD
Send rapid response to journal:
michael.peeters{at}ttuhsc.edu Michael J. Peeters, et al.
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It would be remissed not to draw attention to the dosing of the angiotensin- converting-enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) in the recent article by Lee et al.(1) In the recent ARB trials newly incorporated into this meta-analysis, much larger doses of ARBs were utilized than in prior trials. Earlier comparison trials showing trends towards ACEi superiority over ARBs, used routine ACEi doses but lower ARB doses.(2,3) When ACEi and ARBs are used in the higher doses examined more recently, ARBs appear to be a suitable alternative to ACEi.(4,5) (ie. in OPTIMAAL, losartan 50 mg/day was used versus VALIANT’s valsartan 320 mg/day, while both compared to captopril 150 mg/day.) The volume of evidence favoring ACEi in both chronic heart failure (CHF) and acute myocardial infarction (AMI) are vastly greater than with ARBs, and current JACHO quality indicators should remain unchanged. ACEi intolerance necessitating ARB use represents a relatively small population, and would not likely lead to a significant increase in indicator measure numbers. Current AHA/ACC recommendations suggest multiple ACEi attempts if ACEi-induced cough is suspected. Quality indicators are meant as a measure and comparison of an institution’s implementation of evidence-based best practices. Moreover, current ARB product labeling and monograph information, except for valsartan, does not state the higher dosing required in CHF or AMI, but rather contains the lower hypertension dosing suggestions. In addition, simple economic comparison when ARBs are used in these higher doses (and assuming comparable efficacy to ACEi), the difference in medication cost vastly favors ACEi by a ten-fold margin. Subtherapeutic ARB dosing is a potential problem, especially among practitioners not familiar with this specific study literature. While ACEi use is improving nationally and providers are becoming more familiar with target ACEi doses, routine use of ARB therapy seems fraught with errors at present. 1. Lee VC, Rhew DC, Dylan M, Badamgarav E, Braunstein GD, Weingarten SR. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med 2004; 141:693-704. 2. Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomized trial- the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355:1582-87. 3. Dickstein K, Kjekshus J, and the OPTIMAAL Steering Committee. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomized trial. Lancet 2002; 360:752-60. 4. JJV McMurray, Ostergren J, Swedburg K, Granger CB, Held P, Michelson EL, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003; 362:767-71. 5. Pfeffer MA, McMurray JJV, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893-906. Conflict of Interest:None declared |
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Loren D. Regier, BSP, BA www.RxFiles.ca - Saskatoon City Hospital, Saskatoon, SK, Canada S7K 0M7, Brent Jensen BSP
Send rapid response to journal:
regierl{at}rxfiles.ca Loren D. Regier, et al.
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The Meta-Analysis on ARBs appears to have missed out on two points that could be important for optimizing patient outcomes. First, in the Post-MI setting, the target dose for Valsartan in VALIANT was 160mg twice daily, much higher than the 80mg twice daily reported in the meta-analysis (see Table: Study Characteristics). The dose of the captopril was 50mg three times daily. (Mean doses at one year were 247mg/day for valsartan and 117mg/day in the captopril group, both clearly above the "target" dose reported in the meta-analysis). Dosing considerations are important because in the earlier OPTIMAL trial, losartan 50mg daily had worse cardiovascular death outcomes than captopril 50mg three times daily. One proposed explanation for this was that the losartan dose may have been too low. Based on the few outcome trials to date, it appears that higher doses of ARBs may be needed in the Post-MI setting if we are to consider them equivelent alternatives to ACE inhibitors. A second item of note is the lack of additional outcome benefit but increase in adverse events for the combination arm (valsartan plus captopril) of VALIANT. 1. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan in Acute Myocardial Infarction Trial Investigators (VALIANT). Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003 Nov 13;349(20):1893- 906. Epub 2003 Nov 10. 2. Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan.; OPTIMAAL Steering Committee of the OPTIMAAL Study Group. Lancet 2002 Sep 7;360(9335):752-60. Conflict of Interest:None declared |
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