Effect of Captopril on Mortality and Morbidity in Patients with Left Ventricular Dysfunction after Myocardial Infarction

Pfeffer, Marc A.; Braunwald, Eugene; Moyé, Lemuel A.; Basta, Lofty L.; Brown, Edward J.; Cuddy, T. Edward; Davis, Barry R.; Geltman, Edward M.; Goldman, Steven; Flaker, Greg C.; Klein, M.; Lamas, Gervasio A.; Packer, Milton; Rouleau, Jacques R.; Rouleau, Jean L.; Rutherford, John D.; Wertheimer, J; Hawkins, C. Morton

doi:10.1056/nejm199209033271001

Cited by 5,389 publications

(2,128 citation statements)

References 33 publications

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“…In mid‐1990s, the American Heart Association and the American College of Cardiology published the first clinical guidelines for heart failure (HF) 2, 3. Based in large part on the results of the SOLVD (Studies of Left Ventricular Dysfunction),4 SAVE (Survival and Ventricular Enlargement),5 CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study),6 COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival Study),7 MERIT‐HR (Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure),8 and CIBIS‐II (Cardiac Insufficiency Bisoprolol Study II)9 trials, HF guidelines have consistently focused on the benefits of neurohormonal therapy to delay progression and improve survival for patients with HF with reduced ejection fraction (HFrEF). More recent guidelines have also included emphasis on the importance of achieving and maintaining decongestion regardless of ejection fraction 10, 11, 12…”

Section: Introductionmentioning

confidence: 99%

Reasons for Guideline Nonadherence at Heart Failure Discharge

Gilstrap

Stevenson

Small

et al. 2018

JAHA

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BackgroundCardiology has advanced guideline development and quality measurement. Recognizing the substantial benefits of guideline‐directed medical therapy, this study aims to measure and explain apparent deviations in heart failure (HF) guideline adherence by clinicians at hospital discharge and describe any impact on readmission rates.Methods and ResultsThe extent of decongestion and prescription of neurohormonal therapy were recorded prospectively for 226 HF discharges, including 132 (58%) from an academic hospital and 94 (42%) from a community hospital. Among all discharges, 25% were discharged with residual congestion (30% academic versus 18% community, P=0.070). Among discharges of patients with HF with reduced ejection fraction, 37% (45% academic versus 18% community, P<0.001) were discharged without β‐blocker therapy or with lower doses than at admission. Moreover, 46% of patients with HF with reduced ejection fraction (48% academic versus 39% community, P=0.390) were discharged without an angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker or with lower doses than at admission. Renal dysfunction was the most common reason for discharge with congestion, and hypotension the most common reason for discharge with no or decreased neurohormonal therapy. There was a trend toward higher 90‐day readmission rates after discharge with residual congestion.ConclusionsClinicians frequently deviate from guidelines in both academic and community hospitals; however, this deviation may not always indicate poor quality. Application of guidelines recommended for stable populations is increasingly limited for hospitalized patients by hypotension, renal dysfunction, and inotrope use. Patients with renal dysfunction, hypotension, and recent inotrope use merit further study to determine best practices and possibly to adjust quality metrics for HF severity.

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Section: Introductionmentioning

confidence: 99%

Reasons for Guideline Nonadherence at Heart Failure Discharge

Gilstrap

Stevenson

Small

et al. 2018

JAHA

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“…Angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) have been shown in multiple large clinical trials to improve symptoms, reduce hospitalizations, and improve survival in patients with HF with reduced ejection fraction (HFrEF) 3, 4, 5, 6, 7. The American College of Cardiology (ACC)/American Heart Association (AHA) clinical guidelines make it a Class I, Level A recommendation to use ACEi/ARB therapy in patients with HFrEF both to “prevent symptomatic heart failure” and to “reduce morbidity and mortality.”8 In addition, the ACC/AHA HF Performance Measures recommend ACEi/ARB for outpatients with HFrEF and ACEi/ARB therapy at the time of hospital discharge for inpatients with HFrEF 9.…”

Section: Introductionmentioning

confidence: 99%

Initiation, Continuation, or Withdrawal of Angiotensin‐Converting Enzyme Inhibitors/Angiotensin Receptor Blockers and Outcomes in Patients Hospitalized With Heart Failure With Reduced Ejection Fraction

Gilstrap

Fonarow

Desai

et al. 2017

JAHA

118

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BackgroundGuidelines recommend continuation or initiation of guideline‐directed medical therapy, including angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB), in hospitalized patients with heart failure with reduced ejection fraction.Methods and ResultsUsing the Get With The Guidelines‐Heart Failure Registry, we linked clinical data from 16 052 heart failure with reduced ejection fraction (ejection fraction ≤40%) patients with Medicare claims data. We divided ACEi/ARB‐eligible patients into 4 categories based on admission and discharge ACEi/ARB use: continued (reference group), started, discontinued, or not started on therapy. A multivariable Cox proportional hazard model was used to determine the association between ACEi/ARB category and outcomes. Most, 90.5%, were discharged on ACEi/ARB (59.6% continued and 30.9% newly started). Of those discharged without ACEi/ARB, 1.9% were discontinued, and 7.5% were eligible but not started. Thirty‐day mortality was 3.5% for patients continued and 4.1% for patients started on ACEi/ARB. In contrast, 30‐day mortality was 8.8% for patients discontinued (adjusted hazard ratio [HR adj] 1.92; 95% CI 1.32‐2.81; P<0.001) and 7.5% for patients not started (HR adj 1.50; 95% CI 1.12‐2.00; P=0.006). The 30‐day readmission rate was lowest among patients continued or started on therapy. One‐year mortality was 28.2% for patients continued and 29.7% for patients started on ACEi/ARB compared to 41.6% for patients discontinued (HR adj 1.35; 95% CI 1.13‐1.61; P<0.001) and 41.7% (HR adj 1.28; 95% CI 1.14‐1.43; P<0.001) for patients not started on therapy.ConclusionsCompared with continuation, withdrawal of ACEi/ARB during heart failure hospitalization is associated with higher rates of postdischarge mortality and readmission, even after adjustment for severity of illness.

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“…Similar mortality benefits were later demonstrated for captopril and ramipril in the Survival And Ventricular Enlargement Trial and The Acute Infarction Ramipril Efficacy Study trials in 1992 and 1993, respectively (Pfeffer et al ., 1992; The AIRE Study Group, 1993). In 1992, the Studies of Left Ventricular Dysfunction Prevention trial further demonstrated reduced HF incidence and cardiovascular mortality with enalapril, in patients with asymptomatic HFrEF (Cleland et al ., 2006).…”

Section: Evidence‐based Pharmacological Agentsmentioning

confidence: 99%

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Loudon

Noordali

Gollop

et al. 2016

British J Pharmacology

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Many conditions culminate in heart failure (HF), a multi‐organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence‐base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite.

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Effect of Captopril on Mortality and Morbidity in Patients with Left Ventricular Dysfunction after Myocardial Infarction

Cited by 5,389 publications

References 33 publications

Reasons for Guideline Nonadherence at Heart Failure Discharge

Reasons for Guideline Nonadherence at Heart Failure Discharge

Initiation, Continuation, or Withdrawal of Angiotensin‐Converting Enzyme Inhibitors/Angiotensin Receptor Blockers and Outcomes in Patients Hospitalized With Heart Failure With Reduced Ejection Fraction

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

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