ACEI or ARB for LVSD (HF-3, AMI-3): ACE-inhibitor and ARB Contraindication/Intolerance May 2, 2005 Blockade of the renin angiotensin system with angiotensin converting enzyme (ACE) inhibitors has been established as the cornerstone of medical therapy in patients with heart failure and left ventricular systolic dysfunction (LVSD). Numerous randomized clinical trials over the last two decades established the efficacy of ACE inhibitors in reducing adverse outcomes (mortality, hospitalization, and physical limitation) in this patient population. 1-5 As the result of these trials results in populations with heart failure from a broad range of etiologies, ACE inhibitors are indicated in all patients with LVSD regardless of etiology in the absence of intolerance or a contraindication to treatment. 6 Unfortunately, not all patients tolerate ACE-inhibitors and are not able to take any medication in the class chronically because of intolerance. There are several reasons why patients are not able to take ACE-inhibitors, but the more common reasons include chronic cough (a phenomenon caused in some patients by ACE inhibitors possibly related to increased bradykinin levels); angioedema (a rare but potentially serious side effect); hypotension; hyperkalemia; and worsening renal function. Although most patients will tolerate an ACE inhibitor, side effects may preclude the use of these drugs in an important minority, depriving these patients of a potentially life prolonging benefit. The angiotensin receptor blockers (or ARBs) are another class of drugs that act to inhibit the renin angiotensin system, thus representing possible alternatives to ACE inhibitors in patients with heart failure. Because the efficacy of ACE inhibitors had been established before the ARBs became available, ARB efficacy had to be compared with that of an active control of ACE inhibitors. Although the early trials comparing ARB with ACE inhibitors in patients with heart failure and LVSD consistently demonstrated that ARB were generally better tolerated than ACE inhibitors, these trials were unable to establish the non-inferiority of ARB compared to ACE inhibitors. 7, 8 However, a more recent large trial in a post MI population with heart failure and LVSD (VALIANT) demonstrated that ARB were both better tolerated and were no less efficacious than ACE inhibitors. 9 As a result of this study, the performance measures for the treatment of heart failure were changed to consider either ACE inhibitors or ARB as acceptable first-line therapy for patients with heart failure and left ventricular systolic dysfunction. 10 This raises the question of whether a documented contraindication or intolerance to ACE inhibitors constitutes adequate implicit documentation of a contraindication to ARB. In some patients, such as those with severe aortic stenosis or bilateral renal artery stenosis, neither drug class is recommended. However, published data provide several reasons supporting the position that in general, the reasons for avoiding use of ACE inhibitors are adequately different from those for ARB to require separate documentation of the rationale for avoiding both drug classes. First, some of the side effects of ACE inhibitors, specifically cough and angioedema, are virtually not seen with ARB treatment. It is important to note that while angioedema is admittedly rare, cough is one of the more common reasons for discontinuing ACE inhibitor treatment. Second head-tohead trials have consistently shown that ARB are better tolerated, implying that a proportion of ACE-intolerant patients could be successfully treated with ARB. 7-9, 11, 12 Finally, a randomized clinical trial demonstrated the safety and efficacy of ARB in a population with heart failure, LVSD, Page 1 of 7
and a documented intolerance to ACE inhibitors (CHARM-Alternative). 13 Importantly, this trial recruited patients with a wide range of causes of ACE inhibitor intolerance, including those clearly specific to ACE inhibitors (e.g. cough or angioedema) as well as those that possibly could result from treatment either with an ACE inhibitor or an ARB (e.g. symptomatic hypotension or renal dysfunction). 14 In sum, both ACE inhibitors and ARB are considered appropriate first-line therapy for the treatment of patients with heart failure and LVSD barring a contraindication to therapy. Although there is some overlap in the contraindications to their use, existing data indicates significant differences in side effect profiles and tolerability between the two classes. The redesigned heart failure quality measure acknowledges both the data suggesting similar efficacy (by considering either class of drug as acceptable first-line treatment), as well as data demonstrating differences in tolerability and contraindications (by requiring documentation of reasons for non-use separately for both classes). REFERENCES (1) The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325(5):293-302. (2) The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992;327(10):685-91. (3) The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316(23):1429-35. (4) Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ, Jr., Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992;327(10):669-77. (5) Torp-Pedersen C, Kober L. Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation. Lancet 1999;354(9172):9-12. (6) Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, Ganiats TG, Goldstein S, Gregoratos G, Jessup ML, Noble RJ, Packer M, Silver MA, Stevenson LW, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Jacobs AK, Hiratzka LF, Russell RO, Smith SC, Jr. 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). J Am Coll Cardiol 2001;38(7):2101-13. (7) Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, Konstam MA, Riegger G, Klinger GH, Neaton J, Sharma D, Thiyagarajan B. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355(9215):1582-7. (8) 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. Lancet 2002;360(9335):752-60. (9) Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP, Solomon SD, Swedberg K, Van de WF, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349(20):1893-906. Page 2 of 7
(10) McClellan MB, Loeb JM, Clancy CM, Francis GS, Jacobs AK, Kizer KW, O'Kane ME, Wolk MJ. Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in chronic heart failure. Ann Intern Med 2005;142(5):386-7. (11) Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I, Deedwania PC, Ney DE, Snavely DB, Chang PI. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997;349(9054):747-52. (12) Greenberg BH. Role of angiotensin receptor blockers in heart failure: not yet RESOLVD. Circulation 1999;100(10):1032-4. (13) Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, Ostergren J, Pfeffer MA, Swedberg K. 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(9386):772-6. (14) McMurray J, Ostergren J, Pfeffer M, Swedberg K, Granger C, Yusuf S, Held P, Michelson E, Olofsson B. Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure-assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur J Heart Fail 2003;5(3):261-70. FAQs Answer: Is it true that with the new ACEI/ARB measure, we now must have documentation of contraindications to both drugs if they are not on either? We have to write "No ACEIs or ARBs because..."? It is true that effective 1/1/05+ discharges, there must be documented contraindications to BOTH ACEIs and ARBs in order for the case to be excluded from the ACEI/ARB measure (barring other exclusions Pt. expired, left AMA, etc.). This double contraindication can take varying forms: 1) ACEI allergy AND ARB allergy. Examples: a. "ACEI allergy" in H&P, and "Allergies: ARBs" in nursing admission assessment b. ACEI/ARB allergy" per progress note 2) Moderate or severe aortic stenosis (counts as contraindication to both ACEI and ARB). 3) Physician, nurse practitioner, or physician assistant documentation of BOTH a reason for not prescribing ACEI at discharge AND a reason for not prescribing an ARB at discharge. Examples: a. Chronic renal failure. No ACEIs/ARBs per discharge summary b. Hypotensive - no ACEIs per progress note, and Will not add ARB due to hypotension per consultation report c. "Problems with ACEIs in past" in H&P, and "Hold Cozaar" in physician orders d. Progress note states Pt. refusing all medications Page 3 of 7
4) Reason documented by physician, nurse practitioner, or physician assistant for not prescribing an ARB at discharge AND an ACEI allergy 5) Reason documented by physician, nurse practitioner, or physician assistant for not prescribing an ACEI at discharge AND an ARB allergy As you can see, ACEIs and ARBs don't always have to be mentioned together, and there will be occasions when one reason will automatically count as a contraindication to both ACEIs and ARBs (e.g., Pt. refusing all medications ). Please see the Contraindication to Both ACEI and ARB at Discharge definition for more information and examples (copied and pasted below for your convenience). Answer: Are there any contraindications that apply to both medications? At this time, moderate/severe aortic stenosis is the only clinical condition that automatically counts as a contraindication to both ACEIs and ARBs. Answer: How will the measure algorithms handle cases that don t have both a contraindication to ACEI and a contraindication to ARB documented? If cases where contraindications to BOTH ACEI and ARB are not documented, and either an ACEI OR an ARB is prescribed, the case will pass the ACEI/ARB measure otherwise, if an ACEI or ARB is not prescribed, such cases will fail. We have an instance where the a CHF patient had renal failure, and the physician cited this as the reason for not prescribing ACEIs, but there is no documentation regarding ARBs. Shouldn t the same contraindication apply to ARBs? Can we count this as sufficient documentation for contraindication to both ACEIs & ARBs? Answer: No, this does not count as a contraindication to both ACEIs and ARBs - Documentation needs to be more specific. Abstractors should NOT make inferences that an ARB was not prescribed because of the same reason an ACEI was not prescribed (and visa versa). We agree there are conditions (e.g., hypotension, renal disorders, hyperkalemia) that many physicians would consider as contraindications to both ACEIs and ARBs. Unfortunately, a complete list of such contraindications, which is widely accepted and agreed upon by physicians, cardiology organizations, etc., does not appear to exist at present. We have consulted ACC/AHA regarding this issue, and we plan to continue discussing this with all of our partnering organizations, in the course of measure evolution. We strongly urge providers to focus on more explicit documentation of contraindications/reasons for not prescribing ACEIs AND contraindications/reasons for not prescribing ARBs. Page 4 of 7
Data Element Name: Collected For: Definition: Contraindication to Both ACEI and ARB at Discharge AMI-3, HF-3 Contraindications/reasons for not prescribing either angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) include: (1) ACEI allergy AND ARB allergy, (2) moderate or severe aortic stenosis, (3) physician, nurse practitioner, or physician assistant documentation of BOTH a reason for not prescribing ACEI at discharge AND a reason for not prescribing an ARB at discharge, (4) reason documented by physician, nurse practitioner, or physician assistant for not prescribing an ARB at discharge AND an ACEI allergy, or (5) reason documented by physician, nurse practitioner, or physician assistant for not prescribing an ACEI at discharge AND an ARB allergy. ACEIs and ARBs widen or dilate blood vessels, lowering blood pressure and making it easier for the heart to pump blood. They also block the bad effects of an important hormone on the heart. These things help prevent deterioration in heart function over time. NOTE: Refer to Appendix C, Table 1.2 for a comprehensive list of ACEIs and Table 1.7 for a comprehensive list of ARBs. Suggested Data Collection Is BOTH a potential contraindication/reason for not prescribing an angiotensin converting enzyme inhibitor (ACEI) at discharge AND a potential contraindication/reason for not prescribing an angiotensin receptor blocker (ARB) at discharge documented? Format: Length: Type: Occurs: 1 Alphanumeric 1 Allowable Values: Y (Yes) Documentation that the patient has BOTH a potential contraindication/reason for not prescribing an ACEI at discharge AND a potential contraindication/reason for not prescribing an ARB at discharge, as evidenced by one or more of the following: ACEI allergy AND ARB allergy Moderate or severe aortic stenosis (This is a contraindication to both ACEIs and ARBs) Physician, nurse practitioner, or physician assistant documentation of BOTH a reason for not prescribing ACEI at discharge AND a reason for not prescribing an ARB at discharge Reason documented by physician, nurse practitioner, or physician assistant for not prescribing an ARB at discharge AND an ACEI allergy Reason documented by physician, nurse practitioner, or physician assistant for not prescribing an ACEI at discharge AND an ARB alergy Page 5 of 7
N (No) There is no documentation of BOTH a potential contraindication/reason for not prescribing an ACEI at discharge AND a potential contraindication/reason for not prescribing an ARB at discharge, or unable to determine from medical record documentation. Notes for Abstraction: This data element should be answered independently and irrespective of whether the patient was prescribed ACEI and/or ARB at discharge. When there is documentation of an allergy or sensitivity, regard this as documentation of an allergy regardless of what type of reaction might be noted. Do not attempt to distinguish between true allergies/sensitivities and intolerances, side effects, etc. (e.g., Allergies: ACEIs Cough consider as ACEI allergy). Documentation of an allergy/sensitivity to one particular ACEI or one particular ARB is acceptable to take as an ACEI allergy or ARB allergy (e.g., Allergic to Valsartan - consider as ARB allergy). Allergy documentation does NOT need to refer to the entire class of ACEIs or ARBs. Moderate or severe aortic stenosis includes both a current finding of moderate or severe aortic stenosis AND a history of moderate or severe aortic stenosis without mention of repair or replacement, valvuloplasty, or commissurotomy When determining whether there is a reason documented by a physician, nurse practitioner, or physician assistant for not prescribing an ACEI or an ARB at discharge: o Some reasons apply only to ACEIs or only to ARBs (e.g., Hx severe cough with ACEs, Hypotensive - no ARBs, No ACEIs. Patient already on ARBs ). In order to count as a contraindication in these cases, there must also be documentation of an allergy to the other medication OR a reason documented by a physician, nurse practioner, or physician assistant for not prescribing the other medication at discharge. In other cases, one documented reason applies to both ACEIs and ARBs ( e.g., Chronic renal failure. No ACEs/ARBs, Comfort care only - no medications ). o Reasons for no ACEIs and reasons for no ARBs must be explicitly documented (e.g., K+5.5 No ACEI ) or clearly implied (e.g., Severe hypotension with ACEIs in past, Hx ACEI-induced cough, ARBs contraindicated, Intolerant of ACE inhibitors, Problems with ARBs in past, c/o severe cough, will dc Vasotec, Pt. refusing all medications, Terminal care, no further treatment ). If reasons are not mentioned in the context of ACEIs/ARBs, do not make inferences (e.g., Do not assume that an ACEI or an ARB is not prescribed because of the patient's chronic renal disease). o Reasons do NOT need to be documented at the time of discharge or otherwise associated specifically with discharge prescription. Documentation of contraindications anytime during the hospital stay are acceptable (e.g., ACEI held midhospitalization due to acute renal failure -consider as reason for Page 6 of 7
no ACEI at discharge, even if documentation indicates that the acute renal failure had resolved by the time of discharge). o Disregard documentation of a temporary hold, discontinuation, or initiation of an ACEI or ARB, which is made conditional (e.g., Hold Captopril if cough persists, Stop Cozaar if BP < 90 systolic, Consider ACE therapy after BP stabilizes ). Suggested Data Sources: Consultation notes Diagnostic test reports Discharge instruction sheet Discharge summary Emergency department record History and physical Medication administration record Nursing notes Physician orders Progress notes Guidelines for Abstraction: Inclusion Moderate/severe aortic stenosis (AS) aortic stenosis described as 3+, 4+, or critical aortic stenosis, degree of severity not specified aortic valve area of < 1.0 square cms Refer to Appendix C, Table 1.2 for a comprehensive list of ACEIs and Table 1.7 for a comprehensive list of ARBs Exclusion ACEI allergy ACEI allergy described using one of the following qualifiers: cannot exclude, cannot rule out, may have, may have had, may indicate, possible, suggestive of, suspect, or suspicious ARB allergy ARB allergy described using one of the following qualifiers: cannot exclude, cannot rule out, may have, may have had, may indicate, possible, suggestive of, suspect, or suspicious Moderate/severe aortic stenosis (AS) aortic insufficiency only aortic regurgitation only aortic stenosis described as 1+ or 2+ moderate/severe aortic stenosis, or any of the other moderate/severe aortic stenosis inclusion terms, described using one of the following qualifiers: cannot exclude, cannot rule out, may have, may have had, may indicate, possible, suggestive of, suspect, or suspicious subaortic stenosis Page 7 of 7