Congestive heart failure drugs to avoid: Difference between revisions
Jump to navigation
Jump to search
| Line 44: | Line 44: | ||
*The [[PDE-3 inhibitors]] such as<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2011-04-08}}</ref> [[Cilostazol]] and the PDE-4 inibitor <ref name="pmid11159509">{{cite journal |author=Storen EC, Tefferi A |title=Long-term use of anagrelide in young patients with essential thrombocythemia |journal=[[Blood]] |volume=97 |issue=4 |pages=863–6 |year=2001 |month=February |pmid=11159509 |doi= |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=11159509 |accessdate=2011-04-08}}</ref> [[Anagrelide]] should be avoided in patients with CHF, because of an increase risk of [[high-output heart failure]] and fluid retention that is associated with those drugs.<ref name="pmid1731512">{{cite journal |author= |title=Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Anagrelide Study Group |journal=[[The American Journal of Medicine]] |volume=92 |issue=1 |pages=69–76 |year=1992 |month=January |pmid=1731512 |doi= |url= |accessdate=2011-04-08}}</ref> | *The [[PDE-3 inhibitors]] such as<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2011-04-08}}</ref> [[Cilostazol]] and the PDE-4 inibitor <ref name="pmid11159509">{{cite journal |author=Storen EC, Tefferi A |title=Long-term use of anagrelide in young patients with essential thrombocythemia |journal=[[Blood]] |volume=97 |issue=4 |pages=863–6 |year=2001 |month=February |pmid=11159509 |doi= |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=11159509 |accessdate=2011-04-08}}</ref> [[Anagrelide]] should be avoided in patients with CHF, because of an increase risk of [[high-output heart failure]] and fluid retention that is associated with those drugs.<ref name="pmid1731512">{{cite journal |author= |title=Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Anagrelide Study Group |journal=[[The American Journal of Medicine]] |volume=92 |issue=1 |pages=69–76 |year=1992 |month=January |pmid=1731512 |doi= |url= |accessdate=2011-04-08}}</ref> | ||
*[[PDE-5 inhibitors]] such as [[sildenafil]], [[vardenafil]], and [[tadalafil]], are widely used in the management of [[erectile dysfunction]] in men. The use of those agents with any form of [[nitrate]] therapy is contraindicated because of severe [[hypotensive]] effect that can be life threatening.<ref name="pmid17785618">{{cite journal |author=Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ |title=Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension |journal=[[Circulation]] |volume=116 |issue=14 |pages=1555–62 |year=2007 |month=October |pmid=17785618 |doi=10.1161/CIRCULATIONAHA.107.716373 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=17785618 |accessdate=2011-04-08}}</ref> In a trial where sildenafil and placebo were randomly assigned to 34 HF patients, no significant difference of symptomatic [[hypotension]] was observed, but HF patients with borderline low blood pressure and/or low volume status are | *[[PDE-5 inhibitors]] such as [[sildenafil]], [[vardenafil]], and [[tadalafil]], are widely used in the management of [[erectile dysfunction]] in men. The use of those agents with any form of [[nitrate]] therapy is contraindicated because of severe [[hypotensive]] effect that can be life threatening.<ref name="pmid17785618">{{cite journal |author=Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ |title=Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension |journal=[[Circulation]] |volume=116 |issue=14 |pages=1555–62 |year=2007 |month=October |pmid=17785618 |doi=10.1161/CIRCULATIONAHA.107.716373 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=17785618 |accessdate=2011-04-08}}</ref> In a trial where sildenafil and placebo were randomly assigned to 34 HF patients, no significant difference of symptomatic [[hypotension]] was observed, but HF patients with borderline [[low blood pressure]] and/or low volume status are at risk of severe [[hypotension]] and should avoid any [[PDE-5 inhibitors]] use. There is some data to suggest that [[sildenafil]] may be of benefit in patients who have [[heart failure]] associated with severe [[pulmonary hypertension]]. | ||
===Chemotherapy=== | ===Chemotherapy=== | ||
Revision as of 00:28, 25 April 2013
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Drugs like nonsteroidal anti-inflammatory drugs, antiarrhythmic agents, and calcium channel blockers should be avoided in patients with congestive heart failure as they are known to have negative or deleterious effects on cardiac contractility, the neurohormonal system, or may cause sodium retention.
Drugs to Be Avoided in Congestive Heart Failure
Calcium Channel Blockers
There is no direct role of calcium channel blockers in the management of CHF. Given that some agents have a negative inotropic effect, it has been hypothesized that calcium channel blockers might increase adverse outcomes among patients with CHF due to systolic dysfunction[1]. Vasoelective calcium channel blockers such as amlodipine and felodipine have not been linked to adverse outcomes among patients with congestive heart failure, but there is likewise no evidence of efficacy for these drugs in the management of CHF.[2] If a congestive heart failure patient has either angina or hypertension as a concomitant disease, amlodipine and felodipine appear to be safe for the treatment of these patients.
Antiarrhythmic Agents
Negative inotropic effect exerted by most antiarrhythmic drugs can precipitate HF in patients with reduced LV function. The reduction in LV function can also reduce the elimination of these drugs leading to further drug toxicity. Other antiarrhythmic drugs can induce some proarrhythmic effect, especially class 1 agents and class 3 agents Ibutilide and sotalol (which has a negative inotropic effect);[3] the same class 3 agents in addition to dofetilide can induce torsades to pointes. Amiodarone is considered the safest of the antiarrhythmic drugs because of its minimal proarrhythmic effect and is generally the preferred drug for treating arrhythmias in HF patients.Dronedarone should be avoided in patients who were hospitalized with CHF (this is a boxed warning). Disopyramide is contraindicated in patients with heart failure
Nonsteroidal Anti-Inflammatory Drugs (NSAID)
The administration of non-selective NSAIDs in CHF patients has been linked to:
- An increased risk of CHF exacerbation
- A decline in renal function
- Abnormal responses to both ACEIs and diuretics
- Poorer survival in observational studies, particularly in the post MI period
COX-2 selective inhibitors
Observational data suggest that these agents may be linked with an increase in congestive heart failure exacerbations as well as an increased mortality.[4]
Aspirin
Aspirin is often prescribed as primary prevention in patients with risk factors for cardiovascular disease or as secondary prevention in patients with established cardiovascular disease. However, among patients with congestive heart failure, the risks and benefits of aspirin are not as well established. Concern has arisen regarding the potential interaction between aspirin with ACEIs and beta blockers. At this time the American College of Chest Physicians guidelines indicate that it is reasonable to withhold aspirin among patients who have non-ischemic heart failure, while it may be reasonable to continue aspirin among those patients who have ischemic heart failure.
- Although there is some data to suggest that aspirin may attenuate some of the hemodynamic benefits of ACE inhibitors, there is no data indicating that the beneficial clinical outcomes associated with ACE inhibitors is reduced.
- There is likewise some data to suggest that aspirin may attenuate the benefit of beta blockers on the left ventricular ejection fraction among patients with congestive heart failure.
Oral Hypoglycemic Agents
- Metformin is associated with lactic acidosis, which can be fatal in patients with HF.[5]
- Administration of thiazolidinediones is associated with fluid retention which may in turn cause volume overload and worsening of patients with HF.[6]
Antidepressants
Depression among patients with congestive heart failure is associated with poorer clinical outcomes including higher mortality [7] Questions have been raised as to whether it is the depression itself that directly harms congestive heart failure patients or whether the harm is mediated by treatment with drugs such as tricyclic antidepressants. It appears that it is the depression itself and not the drugs used to treat depression that is independently associated with worse clinical outcomes. There is no difference in the risk of adverse outcomes among heart failure patients treated with either tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs).
Phosphodiesterase inhibitors PDE
- The PDE-3 inhibitors such as[8] Cilostazol and the PDE-4 inibitor [9] Anagrelide should be avoided in patients with CHF, because of an increase risk of high-output heart failure and fluid retention that is associated with those drugs.[10]
- PDE-5 inhibitors such as sildenafil, vardenafil, and tadalafil, are widely used in the management of erectile dysfunction in men. The use of those agents with any form of nitrate therapy is contraindicated because of severe hypotensive effect that can be life threatening.[11] In a trial where sildenafil and placebo were randomly assigned to 34 HF patients, no significant difference of symptomatic hypotension was observed, but HF patients with borderline low blood pressure and/or low volume status are at risk of severe hypotension and should avoid any PDE-5 inhibitors use. There is some data to suggest that sildenafil may be of benefit in patients who have heart failure associated with severe pulmonary hypertension.
Chemotherapy
Cardiotoxic chemotherapeutic agents as Cyclophosphamide, Trastuzumab, Bevacizumab and Anthracyclines, should be avoided in CHF patients [12]
Tumor Necrosis Factor alpha inhibitors TNF-alpha
New onset or worsening of pre-existing heart failure have been linked to TNF-alpha inhibitors.[13] Infliximab has been specifically contraindicated in doses over 5mg/kg in patients with heart failure.
Antihistamines
Some second generation antihistamines as terfenadine and astemizole have been reported to cause long QT syndrome and should not be used in HF patients.[14]
- Serum potassium should be closely monitored in HF patients, in order of preventing either hypokalemia or hyperkalemia, which could greatly affect cardiac excitability and conduction, leading to sudden cardiac death.[15]
Serum potassium should be maintained between 4.0 to 5.0 mEq per liter range, because low potassium level may affect digitalis and antiarrhythmic drugs treatment, while high potassium level can prevent the use of treatments known to prolong life.[15]
Supervision of HF patients with close monitoring of treatment and diet is a very important aspect of the follow-up process in those individuals. Body weight and medications should be closely monitored, because any minor change in those parameters can have a significant effect over symptoms and hospitalization of patients with HF.[16] Patient education is a crucial aspect of the management of HF, patient and family surveillance over any new change of symptoms or body weight is important in allowing early detection of those changes and implementing new treatment strategies to reduce further complications.[17]
2009 ACC/AHA Focused Update and 2005 Guidelines for the Diagnosis and Management of Chronic Heart Failure in the Adult (DO NOT EDIT) [18][19]
Antiarrhythmics in Patients Presenting With Heart Failure (DO NOT EDIT) [18][19]
| Class I |
| "1. Drugs known to adversely affect the clinical status of patients with current or prior symptoms of heart failure and reduced left ventricular ejection fraction (LVEF) should be avoided or withdrawn whenever possible (e.g., nonsteroidal anti-inflammatory drugs, most antiarrhythmic drugs, and most calcium channel blocking drugs.[4][20][21][22][23][24][25](Level of Evidence: B) " |
References
- ↑ Packer M, Kessler PD, Lee WH (1987). "Calcium-channel blockade in the management of severe chronic congestive heart failure: a bridge too far". Circulation. 75 (6 Pt 2): V56–64. PMID 3552317. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Reed SD, Friedman JY, Velazquez EJ, Gnanasakthy A, Califf RM, Schulman KA (2004). "Multinational economic evaluation of valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT)". American Heart Journal. 148 (1): 122–8. doi:10.1016/j.ahj.2003.12.040. PMID 15215801. Retrieved 2011-04-07. Unknown parameter
|month=ignored (help) - ↑ Torp-Pedersen C, Møller M, Bloch-Thomsen PE, Køber L, Sandøe E, Egstrup K, Agner E, Carlsen J, Videbaek J, Marchant B, Camm AJ (1999). "Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group". The New England Journal of Medicine. 341 (12): 857–65. doi:10.1056/NEJM199909163411201. PMID 10486417. Retrieved 2011-04-07. Unknown parameter
|month=ignored (help) - ↑ 4.0 4.1 Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A (1998). "NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics". Archives of Internal Medicine. 158 (10): 1108–12. PMID 9605782. Retrieved 2011-04-08. Unknown parameter
|month=ignored (help) - ↑ Gan SC, Barr J, Arieff AI, Pearl RG (1992). "Biguanide-associated lactic acidosis. Case report and review of the literature". Archives of Internal Medicine. 152 (11): 2333–6. PMID 1444694. Retrieved 2011-04-08. Unknown parameter
|month=ignored (help) - ↑ Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM (2005). "Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study". Circulation. 111 (5): 583–90. doi:10.1161/01.CIR.0000154542.13412.B1. PMID 15699279. Retrieved 2011-04-08. Unknown parameter
|month=ignored (help) - ↑ Swenson JR, Doucette S, Fergusson D (2006). "Adverse cardiovascular events in antidepressant trials involving high-risk patients: a systematic review of randomized trials". Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 51 (14): 923–9. PMID 17249635. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B (2006). "ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation". Circulation. 113 (11): e463–654. doi:10.1161/CIRCULATIONAHA.106.174526. PMID 16549646. Retrieved 2011-04-08. Unknown parameter
|month=ignored (help) - ↑ Storen EC, Tefferi A (2001). "Long-term use of anagrelide in young patients with essential thrombocythemia". Blood. 97 (4): 863–6. PMID 11159509. Retrieved 2011-04-08. Unknown parameter
|month=ignored (help) - ↑ "Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Anagrelide Study Group". The American Journal of Medicine. 92 (1): 69–76. 1992. PMID 1731512. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ (2007). "Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension". Circulation. 116 (14): 1555–62. doi:10.1161/CIRCULATIONAHA.107.716373. PMID 17785618. Retrieved 2011-04-08. Unknown parameter
|month=ignored (help) - ↑ Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001). "Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2". The New England Journal of Medicine. 344 (11): 783–92. doi:10.1056/NEJM200103153441101. PMID 11248153. Retrieved 2011-04-08. Unknown parameter
|month=ignored (help) - ↑ Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT (2003). "Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial". Circulation. 107 (25): 3133–40. doi:10.1161/01.CIR.0000077913.60364.D2. PMID 12796126. Retrieved 2011-04-08. Unknown parameter
|month=ignored (help) - ↑ Yap YG, Camm AJ (2003). "Drug induced QT prolongation and torsades de pointes". Heart (British Cardiac Society). 89 (11): 1363–72. PMC 1767957. PMID 14594906. Retrieved 2011-04-08. Unknown parameter
|month=ignored (help) - ↑ 15.0 15.1 Packer M, Gottlieb SS, Kessler PD (1986). "Hormone-electrolyte interactions in the pathogenesis of lethal cardiac arrhythmias in patients with congestive heart failure. Basis of a new physiologic approach to control of arrhythmia". The American Journal of Medicine. 80 (4A): 23–9. PMID 2871753. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Rich MW, Beckham V, Wittenberg C, Leven CL, Freedland KE, Carney RM (1995). "A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure". The New England Journal of Medicine. 333 (18): 1190–5. doi:10.1056/NEJM199511023331806. PMID 7565975. Retrieved 2011-04-10. Unknown parameter
|month=ignored (help) - ↑ Philbin EF (1999). "Comprehensive multidisciplinary programs for the management of patients with congestive heart failure". Journal of General Internal Medicine. 14 (2): 130–5. PMID 10051785. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ 18.0 18.1 Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and Lung Transplantation; Heart Rhythm Society. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005 Sep 20; 112(12): e154-235. Epub 2005 Sep 13. PMID 16160202
- ↑ 19.0 19.1 Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG et al. (2009) 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 119 (14):1977-2016. DOI:10.1161/CIRCULATIONAHA.109.192064 PMID: 19324967
- ↑ Herchuelz A, Derenne F, Deger F, Juvent M, Van Ganse E, Staroukine M, Verniory A, Boeynaems JM, Douchamps J (1989). "Interaction between nonsteroidal anti-inflammatory drugs and loop diuretics: modulation by sodium balance". The Journal of Pharmacology and Experimental Therapeutics. 248 (3): 1175–81. PMID 2703968. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ Gottlieb SS, Robinson S, Krichten CM, Fisher ML (1992). "Renal response to indomethacin in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy". The American Journal of Cardiology. 70 (9): 890–3. PMID 1529943. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ Bank AJ, Kubo SH, Rector TS, Heifetz SM, Williams RE (1991). "Local forearm vasodilation with intra-arterial administration of enalaprilat in humans". Clinical Pharmacology and Therapeutics. 50 (3): 314–21. PMID 1655327. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ "Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators". The New England Journal of Medicine. 321 (6): 406–12. 1989. doi:10.1056/NEJM198908103210629. PMID 2473403. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ "Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. The Cardiac Arrhythmia Suppression Trial II Investigators". The New England Journal of Medicine. 327 (4): 227–33. 1992. doi:10.1056/NEJM199207233270403. PMID 1377359. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ Pratt CM, Eaton T, Francis M, Woolbert S, Mahmarian J, Roberts R, Young JB (1989). "The inverse relationship between baseline left ventricular ejection fraction and outcome of antiarrhythmic therapy: a dangerous imbalance in the risk-benefit ratio". American Heart Journal. 118 (3): 433–40. PMID 2476016. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help)