Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B): Difference between revisions

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(/* Patients With Cardiac Structural Abnormalities or Remodeling who have not Developed Heart Failure Symptoms (Stage B) (DO NOT EDIT) Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates J...)
(/* Patients With Cardiac Structural Abnormalities or Remodeling who have not Developed Heart Failure Symptoms (Stage B) (DO NOT EDIT) Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates J...)
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| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' All [[Congestive heart failure treatment of patients at high risk for developing heart failure (Stage A)|Class I recommendations for Stage A]] should apply to patients with cardiac structural abnormalities who have not developed [[HF]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A, B and C as appropriate]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' All [[Congestive heart failure treatment of patients at high risk for developing heart failure (Stage A)|Class I recommendations for Stage A]] should apply to patients with cardiac structural abnormalities who have not developed [[HF]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A, B and C as appropriate]])'' <nowiki>"</nowiki>
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| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Evidence-based [[beta-blockers]] and [[ACEIs]] should be used in all patients with a recent or remote history of [[MI]] regardless of [[EF]] or presence of [[HF]].<ref name="pmid11356434">{{cite journal| author=Dargie HJ| title=Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. | journal=Lancet | year= 2001 | volume= 357 | issue= 9266 | pages= 1385-90 | pmid=11356434 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11356434  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11829548 Review in: ACP J Club. 2002 Jan-Feb;136(1):7] </ref><ref name="pmid10091816">{{cite journal| author=Exner DV, Dries DL, Waclawiw MA, Shelton B, Domanski MJ| title=Beta-adrenergic blocking agent use and mortality in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a post hoc analysis of the Studies of Left Ventricular Dysfunction. | journal=J Am Coll Cardiol | year= 1999 | volume= 33 | issue= 4 | pages= 916-23 | pmid=10091816 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10091816  }} </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Evidence-based [[beta-blockers]] and [[ACEIs]] should be used in all patients with a recent or remote history of [[MI] and a reduced [[EF]].<ref name="pmid11356434">{{cite journal| author=Dargie HJ| title=Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. | journal=Lancet | year= 2001 | volume= 357 | issue= 9266 | pages= 1385-90 | pmid=11356434 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11356434  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11829548 Review in: ACP J Club. 2002 Jan-Feb;136(1):7] </ref><ref name="pmid10091816">{{cite journal| author=Exner DV, Dries DL, Waclawiw MA, Shelton B, Domanski MJ| title=Beta-adrenergic blocking agent use and mortality in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a post hoc analysis of the Studies of Left Ventricular Dysfunction. | journal=J Am Coll Cardiol | year= 1999 | volume= 33 | issue= 4 | pages= 916-23 | pmid=10091816 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10091816  }} </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
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| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' [[Beta-blockers]] are indicated in all patients without a history of [[MI]] who have a reduced [[LVEF]] with no [[HF]] symptoms. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' [[Beta-blockers]] are indicated in all patients without a history of [[MI]] who have a reduced [[LVEF]] with no [[HF]] symptoms. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' [[Angiotensin converting enzyme inhibitors]] should be used in patients with a reduced [[EF]] and no symptoms of [[HF]], even if they have not experienced [[MI]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' [[Angiotensin converting enzyme inhibitors]] should be used in patients with a reduced [[EF]] and no symptoms of [[HF]], even if they have not experienced [[MI]].<ref name="pmid12788569">{{cite journal| author=Jong P, Yusuf S, Rousseau MF, Ahn SA, Bangdiwala SI| title=Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study. | journal=Lancet | year= 2003 | volume= 361 | issue= 9372 | pages= 1843-8 | pmid=12788569 | doi=10.1016/S0140-6736(03)13501-5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12788569  }} </ref><ref name="pmid1463530">{{cite journal| author=| title=Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigattors. | journal=N Engl J Med | year= 1992 | volume= 327 | issue= 10 | pages= 685-91 | pmid=1463530 | doi=10.1056/NEJM199209033271003 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1463530  }} </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' An [[ARB]] should be administered to post-[[MI]] patients without [[HF]] who are intolerant of [[ACEIs]] and have a low [[LVEF]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' An [[ARB]] should be administered to post-[[MI]] patients without [[HF]] who are intolerant of [[ACEIs]] and have a low [[LVEF]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>

Revision as of 22:36, 10 August 2013



Resident
Survival
Guide
Congestive Heart Failure Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Systolic Dysfunction
Diastolic Dysfunction
HFpEF
HFrEF

Causes

Differentiating Congestive heart failure from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Clinical Assessment

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

Cardiac MRI

Echocardiography

Exercise Stress Test

Myocardial Viability Studies

Cardiac Catheterization

Other Imaging Studies

Other Diagnostic Studies

Treatment

Invasive Hemodynamic Monitoring

Medical Therapy:

Summary
Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
Diuretics
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
Nitrates
Hydralazine
Positive Inotropics
Anticoagulants
Angiotensin Receptor-Neprilysin Inhibitor
Antiarrhythmic Drugs
Nutritional Supplements
Hormonal Therapies
Drugs to Avoid
Drug Interactions
Treatment of underlying causes
Associated conditions

Exercise Training

Surgical Therapy:

Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
Implantation of Intracardiac Defibrillator
Ultrafiltration
Cardiac Surgery
Left Ventricular Assist Devices (LVADs)
Cardiac Transplantation

ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
Patients with current or prior symptoms of heart failure (Stage C)
Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
Quality Metrics/Performance Measures

Implementation of Practice Guidelines

Congestive heart failure end-of-life considerations

Specific Groups:

Special Populations
Patients who have concomitant disorders
Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B) On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

CDC on Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B) in the news

Blogs on Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

Directions to Hospitals Treating Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

Risk calculators and risk factors for Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

Congestive Heart Failure Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Systolic Dysfunction
Diastolic Dysfunction
HFpEF
HFrEF

Causes

Differentiating Congestive heart failure from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Clinical Assessment

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

Cardiac MRI

Echocardiography

Exercise Stress Test

Myocardial Viability Studies

Cardiac Catheterization

Other Imaging Studies

Other Diagnostic Studies

Treatment

Invasive Hemodynamic Monitoring

Medical Therapy:

Summary
Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
Diuretics
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
Nitrates
Hydralazine
Positive Inotropics
Anticoagulants
Angiotensin Receptor-Neprilysin Inhibitor
Antiarrhythmic Drugs
Nutritional Supplements
Hormonal Therapies
Drugs to Avoid
Drug Interactions
Treatment of underlying causes
Associated conditions

Exercise Training

Surgical Therapy:

Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
Implantation of Intracardiac Defibrillator
Ultrafiltration
Cardiac Surgery
Left Ventricular Assist Devices (LVADs)
Cardiac Transplantation

ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
Patients with current or prior symptoms of heart failure (Stage C)
Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
Quality Metrics/Performance Measures

Implementation of Practice Guidelines

Congestive heart failure end-of-life considerations

Specific Groups:

Special Populations
Patients who have concomitant disorders
Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B) On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

CDC on Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B) in the news

Blogs on Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

Directions to Hospitals Treating Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

Risk calculators and risk factors for Congestive heart failure treatment of patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Saleh El Dassouki, M.D. [2]; Lakshmi Gopalakrishnan, M.B.B.S. [3]

Overview

Patients who have had an myocardial infarction or evidence of left ventricular remodeling are at considerable risk of developing heart failure even if they do not present with any symptoms of heart failure.[1] Reducing the risk of additional injury and retarding the evolution and progression of LV remodeling is thus very important in considerably decreasing the incidence of heart failure. Initial appropriate measures include those listed as Class 1 recommendations for patients in Stage A.

The use of nutritional supplements in patients with a recent or remote MI with or without LV remodeling has not been proved to reduce the risk of heart failure.[2] The aldosterone antagonist eplerenone on the other hand has been shown to reduce morbidity and mortality in patients with low ejection fraction and heart failure after an MI that has already been treated with ACEIs and beta blockers.

Patients with an Acute MI

Various procedures such as the infusion of a fibrinolytic agent or the use of percutaneous coronary intervention can reduce the risk of death and development of heart failure in patients who are experiencing an acute MI[3].[4] [5] Administration of beta blockers combined with ACEIs or ARB in patients with acute MI can decrease the risk of reinfarction or death when initiated within days after the ischemic event, especially in patients whose course is complicated by HF; Those drugs can be administered separately,[6] but the neurohormonal blockade achieved by the combination previously mentioned (beta blockers and ACEIs or ARB) has been demonstrated to produce additive benefits.

Patients With History of MI but Normal Left Ventricular Ejection Fraction

A history of MI, even in patients with normal left ventricular ejection fraction should prompt a vigorous treatment of both hypertension and hyperlipidemia, because of their immense benefit in decreasing the risk of further left ventricular dysfunction especially in patients with a prior ischemic event[7].[8] Patient with a recent MI should also be treated with ACEIs and beta blockers,[9] which have been proven to reduce the risk of death when started days or weeks after an ischemic cardiac event. Evidence from 2 other large-scale studies has shown that long term therapy with an ACEI can also decrease the risk of a major cardiovascular event, even when treatment is initiated months or years after MI[6].[10][11].

Patients with Chronic Reduction of Left Ventricular Ejection Fraction but No Symptoms

As previously discussed, long term treatment with an ACEI have been shown to reduce the risk of HF in patients with ischemic cardiac events without left ventricular dysfunction[12]. This is also true in case of asymptomatic patients with reduced left ventricular function, whether due to a remote ischemic injury or to a nonischemic cardiomyopathy. The usage of ARBs in asymptomatic patients with reduced LVEF have not been fully studied yet and has not been implemented in the treatment of those patients. On the other hand, asymptomatic patients with a low EF have benefited from treatment with ARBs according new studies, particularly in patients who cannot tolerate ACEI. Another important agent recommended in the management of patients with a low EF and no symptoms (especially patients with history of CAD) is beta blockers,[13] although adequate controlled clinical trials are lacking to fully support this recommendation.

No data have been obtained to date to recommend Digoxin in asymptomatic patients with reduced LVEF, except in those with Atrial Fibrillation; the reason behind this, is that Digoxin has only a minimal effect on disease progression in symptomatic patients, [14]so it is unlikely that the drug would be beneficial in those with no symptoms. Calcium Channel Blockers are not recommended as well in patients with asymptomatic reduction of LVEF, but they have not been shown to have adverse effects and may be helpful for the management of concomitant conditions such as hypertension. However, the usage of calcium channel blockers with negative inotropic effects in patients with EF below 40% after MI is not recommended. [15]

Patients whose cardiomyopathy is associated with a rapid arrhythmia of supraventricular origin (e.g. atrial flutter or atrial fibrillation) should be closely monitored because such arrhyhmias may contribute to a further impairment of ventricular function and may either induce or exacerbate the development of cardiomyopathy.[16]

Asymptomatic Patients With Valvular Heart Disease

Patients with severe aortic or mitral valve stenosis or insufficiency should be considered for valvular replacement or surgical repair.[17][18] Poor surgical candidates should be considered for TAVI. Long term therapy with vasodilators as hydralazine and nifedipine has not yet been proven to reduce risk of HF or death in long term studies,[19] however patients with severe aortic insufficiency and preserved LV function may benefit from such treatment to minimize structural changes in the ventricle but these drugs are usually poorly tolerated in this setting.[20]There are no trial or long term studies which prove that these vasodilators are beneficial in severe mitral insufficiency.

2009 ACC/AHA Focused Update and 2005 Guidelines for the Diagnosis and Management of Chronic Heart Failure in the Adult (DO NOT EDIT) [21]

Patients With Cardiac Structural Abnormalities or Remodeling who have not Developed Heart Failure Symptoms (Stage B) (DO NOT EDIT) [21]

Class I
"1. All Class I recommendations for Stage A should apply to patients with cardiac structural abnormalities who have not developed HF. (Level of Evidence: A, B and C as appropriate) "
"2. Evidence-based beta-blockers and ACEIs should be used in all patients with a recent or remote history of [[MI] and a reduced EF.[22][23] (Level of Evidence: B) "
"3. Beta-blockers are indicated in all patients without a history of MI who have a reduced LVEF with no HF symptoms. (Level of Evidence: C) "
"4. Angiotensin converting enzyme inhibitors should be used in patients with a reduced EF and no symptoms of HF, even if they have not experienced MI.[24][12] (Level of Evidence: A) "
"5. An ARB should be administered to post-MI patients without HF who are intolerant of ACEIs and have a low LVEF. (Level of Evidence: B) "
"6. Patients who have not developed HF symptoms should be treated according to contemporary guidelines after an acute MI. (Level of Evidence: C)"
"7. Coronary revascularization should be recommended in appropriate patients without symptoms of HF in accordance with contemporary guidelines (see ACC/AHA Guidelines for the Management of Patients With Chronic Stable Angina). (Level of Evidence: A)"
"8. Valve replacement or repair should be recommended for patients with hemodynamically significant valvular stenosis or regurgitation and no symptoms of HF in accordance with contemporary guidelines. (Level of Evidence: B) "
Class III (No Benefit)
"1. Digoxin should not be used in patients with low EF, sinus rhythm, and no history of HF symptoms, because in this population, the risk of harm is not balanced by any known benefit. (Level of Evidence: C) "
"2. Use of nutritional supplements to treat structural heart disease or to prevent the development of symptoms of HF is not recommended. (Level of Evidence: C) "
"3. Calcium channel blockers with negative inotropic effects may be harmful in asymptomatic patients with low LVEF and no symptoms of HF after MI (Patients in Stage C). (Level of Evidence: C) "
Class IIa
"1. Angiotensin converting enzyme inhibitors or ARBs can be beneficial in patients with hypertension and LVH and no symptoms of HF. (Level of Evidence: B) "
"2. Angiotensin II receptor blockers can be beneficial in patients with low EF and no symptoms of HF who are intolerant of ACEIs. (Level of Evidence: C) "
"3. Placement of an ICD is reasonable in patients with ischemic cardiomyopathy who are at least 40 days post-MI, have an LVEF of 30% or less, are NYHA functional class I on chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. (Level of Evidence: B) "
Class IIb
"1. Placement of an ICD might be considered in patients without HF who have nonischemic cardiomyopathy and an LVEF less than or equal to 30% who are in NYHA functional class I with chronic optimal medical therapy and have a reasonable expectation of survival with good functional status for more than 1 year. (Level of Evidence: C) "

Vote on and Suggest Revisions to the Current Guidelines

External Links

References

  1. Flather MD, Yusuf S, Køber L, Pfeffer M, Hall A, Murray G, Torp-Pedersen C, Ball S, Pogue J, Moyé L, Braunwald E (2000). "Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group". Lancet. 355 (9215): 1575–81. PMID 10821360. Retrieved 2011-04-04. Unknown parameter |month= ignored (help)
  2. Pitt B, Williams G, Remme W, Martinez F, Lopez-Sendon J, Zannad F, Neaton J, Roniker B, Hurley S, Burns D, Bittman R, Kleiman J (2001). "The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure Efficacy and Survival Study" (PDF). Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 15 (1): 79–87. PMID 11504167. Retrieved 2011-04-04. Unknown parameter |month= ignored (help)
  3. Guerci AD, Gerstenblith G, Brinker JA, Chandra NC, Gottlieb SO, Bahr RD, Weiss JL, Shapiro EP, Flaherty JT, Bush DE (1987). "A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty". The New England Journal of Medicine. 317 (26): 1613–8. doi:10.1056/NEJM198712243172601. PMID 2960897. Retrieved 2011-04-04. Unknown parameter |month= ignored (help)
  4. "GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico". Lancet. 343 (8906): 1115–22. 1994. PMID 7910229. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  5. "Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators". Lancet. 342 (8875): 821–8. 1993. PMID 8104270. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  6. 6.0 6.1 Vantrimpont P, Rouleau JL, Wun CC, Ciampi A, Klein M, Sussex B, Arnold JM, Moyé L, Pfeffer M (1997). "Additive beneficial effects of beta-blockers to angiotensin-converting enzyme inhibitors in the Survival and Ventricular Enlargement (SAVE) Study. SAVE Investigators". Journal of the American College of Cardiology. 29 (2): 229–36. PMID 9014971. Retrieved 2011-04-04. Unknown parameter |month= ignored (help)
  7. Kostis JB, Davis BR, Cutler J, Grimm RH, Berge KG, Cohen JD, Lacy CR, Perry HM, Blaufox MD, Wassertheil-Smoller S, Black HR, Schron E, Berkson DM, Curb JD, Smith WM, McDonald R, Applegate WB (1997). "Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP Cooperative Research Group". JAMA : the Journal of the American Medical Association. 278 (3): 212–6. PMID 9218667. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  8. "Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg". JAMA : the Journal of the American Medical Association. 213 (7): 1143–52. 1970. PMID 4914579. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  9. "A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results". JAMA : the Journal of the American Medical Association. 247 (12): 1707–14. 1982. PMID 7038157. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  10. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000). "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators". The New England Journal of Medicine. 342 (3): 145–53. doi:10.1056/NEJM200001203420301. PMID 10639539. Retrieved 2011-04-05. Unknown parameter |month= ignored (help)
  11. Fox KM (2003). "Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study)". Lancet. 362 (9386): 782–8. Retrieved 2011-04-05. Unknown parameter |month= ignored (help)
  12. 12.0 12.1 "Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigattors". The New England Journal of Medicine. 327 (10): 685–91. 1992. doi:10.1056/NEJM199209033271003. PMID 1463530. Retrieved 2011-04-05. Unknown parameter |month= ignored (help)
  13. Chadda K, Goldstein S, Byington R, Curb JD (1986). "Effect of propranolol after acute myocardial infarction in patients with congestive heart failure". Circulation. 73 (3): 503–10. PMID 3948357. Retrieved 2011-04-05. Unknown parameter |month= ignored (help)
  14. "The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group". The New England Journal of Medicine. 336 (8): 525–33. 1997. doi:10.1056/NEJM199702203360801. PMID 9036306. Retrieved 2011-04-05. Unknown parameter |month= ignored (help)
  15. "The effect of diltiazem on mortality and reinfarction after myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group". The New England Journal of Medicine. 319 (7): 385–92. 1988. doi:10.1056/NEJM198808183190701. PMID 2899840. Retrieved 2011-04-05. Unknown parameter |month= ignored (help)
  16. Grogan M, Smith HC, Gersh BJ, Wood DL (1992). "Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy". The American Journal of Cardiology. 69 (19): 1570–3. PMID 1598871. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  17. Connolly HM, Oh JK, Orszulak TA, Osborn SL, Roger VL, Hodge DO, Bailey KR, Seward JB, Tajik AJ (1997). "Aortic valve replacement for aortic stenosis with severe left ventricular dysfunction. Prognostic indicators". Circulation. 95 (10): 2395–400. PMID 9170402. Retrieved 2011-04-06. Unknown parameter |month= ignored (help)
  18. Bolling SF, Pagani FD, Deeb GM, Bach DS (1998). "Intermediate-term outcome of mitral reconstruction in cardiomyopathy". The Journal of Thoracic and Cardiovascular Surgery. 115 (2): 381–6, discussion 387–8. PMID 9475533. Retrieved 2011-04-06. Unknown parameter |month= ignored (help)
  19. Scognamiglio R, Rahimtoola SH, Fasoli G, Nistri S, Dalla Volta S (1994). "Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function". The New England Journal of Medicine. 331 (11): 689–94. doi:10.1056/NEJM199409153311101. PMID 8058074. Retrieved 2011-04-06. Unknown parameter |month= ignored (help)
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