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"angiotensin converting enzyme"

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Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), or Direct Renin Inhibitors (DRI) for Adults with Hypertension

Presentation: Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), or Direct Renin Inhibitors (DRI) for Adults With Hypertension

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Background: Pharmacological Blockade of the Renin-Angiotensin System

Presentation: Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), or Direct Renin Inhibitors (DRI) for Adults With Hypertension

Keywords: renin-angiotensin system | pharmacological blockade | angiotensinogen | angiotensin converting enzyme | angiotensin II

This slide presents a table consisting of three columns, with one header row and one data row. Column one is labeled Comparison, Column two is labeled Strength of Evidence and Column three is labeled Conclusions With Description of Applicability. In the single data row the contents of each cell is as follows. Column One: Myocardial debulking versus watchful waiting. Column Two: Low. Column Three: When compared with watchful waiting, the use of myocardial debulking reduced hospitalizations without affecting survival. These results are predominantly limited to patients 65 years of age and older with NYHA class II and III disease. This is similar to the population with heart failure in the United States. In a subgroup analysis, benefits were accentuated in patients not receiving standard medical therapy with ACE inhibitors and ß-blockers, thus limiting applicability. No harms were being evaluated. These trials were conducted in select, large, tertiary medical centers and may not be applicable to other settings.

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Summary Table for Body of Evidence Applicability

Presentation: Assessing Applicability

Keywords: applicability | body of evidence | strength of evidence | subgroup analysis

This slide set is based on a comparative effectiveness review (CER) titled, Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin II-Receptor Blockers (ARBs) Added to Standard Medical Therapy for Treating Stable Ischemic Heart Disease (IHD), that was developed by the University of Connecticut/Hartford Hospital Evidence-based Practice Center for the Agency for Healthcare Research and Quality (AHRQ) and is available online at effectivehealthcare.ahrq.gov (Contract No. 290-2007-10067-I). CERs represent comprehensive systematic reviews of the literature usually comparing two or more types of treatment, such as different drugs, for the same disease. Primary clinical trials were identified from searches of MEDLINE (1966 to February 2009), Embase (1974 to February 2009), and the Cochrane Central Register of Controlled Trials (1966 to February 2009). The methods used to develop this CER followed version 1.0 of the Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews published by AHRQ (draft available at: http://effectivehealthcare.ahrq.gov/repFiles/2007_10DraftMethodsGuide.pdf).

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Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II-Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Keywords: comparative effectiveness | effective health care | angiotensin-converting enzyme inhibitor | angiotensin II-receptor blocker | ischemic heart disease | left ventricular systolic function

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Outline of Material

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Keywords: effective health care | informed decisionmaking | key questions | comparative effectiveness

Despite standard medical therapy, patients with stable ischemic heart disease and preserved left ventricular systolic function continue to experience considerable morbidity and mortality. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II-receptor blockers (ARBs) have established benefit in patients with heart failure and left ventricular dysfunction. The available evidence for prophylactic use of ACEIs and ARBs in patients without heart failure and with preserved left ventricular systolic function is less clear.

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Rationale for Additional Therapies for Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Keywords: angiotensin II-receptor blocker | angiotensin-converting enzyme inhibitor | treatment rationale | stable ischemic heart disease

$A closer look at the current American College of Cardiology and American Heart Association guidelines reveals that angiotensin-converting enzyme inhibitors (ACEIs) are indicated for patients who have chronic heart failure or myocardial infarction and left ventricular dysfunction, which is defined as a left ventricular ejection fraction ?40%. Angiotensin II receptor blockers (ARBs) are reserved for patients who cannot tolerate ACEIs. In patients with heart failure, combining an ACEI with an ARB has been shown to provide additional benefits over an ACEI alone. However, it is unclear if ACEIs or ARBs impact the risk of future cardiovascular events in patients without left ventricular systolic dysfunction (LVSD).$

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Guidelines for the Use of ACEIs, ARBs, or Both to Treat Patients With Cardiac Disease (1)

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Keywords: American Heart Association | angiotensin II-receptor blocker | angiotensin-converting enzyme inhibitor | cardiac disease | guidelines | heart failure | American College of Cardiology

Clinical trials have been conducted to evaluate the use of ACEIs, ARBs, or both in patients with stable ischemic heart disease but without heart failure or left ventricular systolic dysfunction (patients with an LVEF >40%). Previous systematic reviews have not included recent ACEI trials conducted in this population. Additionally, no systematic review has evaluated ARB therapy or ACEI and ARB combination therapy in this population. From this body of evidence, the benefits and harms associated with the use of these therapies in this population of patients may be discerned.

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Guidelines for the Use of ACEIs, ARBs, or Both to Treat Patients With Cardiac Disease (2)

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Keywords: angiotensin II-receptor blocker | angiotensin-converting enzyme inhibitor | left ventricular systolic function | stable ischemic heart disease

Despite standard therapy, patients with stable ischemic heart disease and preserved left ventricular systolic function continue to be at risk for future cardiovascular events. The Renin-Angiotensin-Aldosterone System (RAAS) is critical for regulating blood pressure, electrolyte balance, and fluid volume homeostasis and plays a pivotal role in the pathogenesis of hypertension, congestive heart failure, and diabetic nephropathy. Pharmacological agonists of this system include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). These drugs block adverse effects of the RAAS by blocking the activity of angiotensin II. Through the stimulation of angiotensin II type-1 receptors, angiotensin II may have several potentially harmful activities including induction of aldosterone production, which can cause sodium retention and increased fluid retention that, in turn, leads to an increase in blood pressure, increased aldosterone production, which can possibly lead to promotion of pathogenic remodeling (i.e., atherosclerosis and fibrosis), constriction of blood vessels, which can lead to increased blood pressure, and potential reduction in the availability of nitric oxide through the production of free radicals and the induction of endothelial dysfunction that may impact endothelial wall integrity. ACEIs act on the RAAS by blocking the conversion of angiotensin I into angiotensin II and inhibiting the breakdown of bradykinin, which is a potent vasodilator. ARBs block the angiotensin II type-1 receptor and reduce the pharmacologic effects of angiotensin II, regardless of whether angiotensin II is created by the angiotensin-converting enzyme or by pathways that do not include this enzyme. ACEIs and ARBs may potentially provide several pharmacological effects over and above that of blood pressure reduction alone, which may impact cardiovascular events.

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Pharmacologic Effects of Antagonists on the Renin-Angiotensin-Aldosterone System

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Keywords: angiotensin II-receptor blocker | angiotensin-converting enzyme inhibitor | renin-angiotensin-aldosterone system | pharmacology

The comparative effectiveness review topic, Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II-Receptor Blockers Added to Standard Medical Therapy for Treating Stable Ischemic Heart Disease, was nominated in a public process. Sufficient research into the current literature determined that there was a need for the available evidence on the addition of ACEIs and ARBs to standard medical therapy for patients with stable ischemic heart disease and preserved left ventricular systolic function (LVSF) and that there was an adequate number of clinical trials to be included in a comparative effectiveness review (CER). Based on this research, the Agency for Healthcare Research and Quality (AHRQ) commissioned the University of Connecticut/Hartford Hospital Evidence-Based Practice Center to prepare the CER with input from a Technical Expert Panel. This advisory panel was comprised of experts in different specialties, including cardiologists, a cardiovascular pharmacist/pharmacologist, and a health policy pharmacist. The panel identified important issues, reviewed proposed methods, defined parameters for the review of evidence, and helped to refine the key clinical questions that the research would subsequently address. Once formulated, the key clinical questions were published online and were made available for public commentary in order to refine the scope and focus of the research questions. A comprehensive systematic review of the literature was then conducted using several well-known databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. All methods used in the review followed version 1.0 of AHRQ’s Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews (available at: http://effectivehealthcare.ahrq.gov/repFiles/2007_10DraftMethodsGuide.pdf) and the trial end points were determined a priori. Based on the findings of the review, a draft CER was prepared and published online for public comment, and the draft underwent rigorous peer review to improve the final product. After the CER was finalized, the complete report was published on the Internet (available at: http://effectivehealthcare.ahrq.gov/ehc/products/57/335/bodyfinal.pdf) and a condensed version was published in the Annals of Internal Medicine (available at: http://www.annals.org/content/early/2009/10/19/0003-4819-151-12-200912150-00162.full).

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The CER Development Process

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Keywords: effective health care | peer-review process | systematic review | comparative effectiveness

A comparative effectiveness review (CER) titled, Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin II-Receptor Blockers (ARBs) Added to Standard Medical Therapy for Treating Stable Ischemic Heart Disease (IHD), was developed by the University of Connecticut/Hartford Hospital Evidence-based Practice Center for the Agency for Healthcare Research and Quality (AHRQ) and published online (available at: http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=334). This CER was based on a comprehensive systematic review of the literature. The methods for developing this CER followed the Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews, Version 1.0, published by AHRQ (available at http://effectivehealthcare.ahrq.gov/repFiles/2007_10DraftMethodsGuide.pdf). The clinical outcomes and harms of interest are outlined in this slide and were determined a priori. The benefit endpoints include total mortality, cardiovascular (CV) death, nonfatal myocardial infarction (MI), stroke, composite endpoint (CV death, nonfatal MI, stroke), revascularization, and quality-of-life measures. The harms endpoints include hyperkalemia, cough, angioedema, hypotension, rash, blood dyscrasias, syncope, and withdrawal from a trial.

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Comparative Effectiveness Review: Outcomes of Interest

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Keywords: benefits | harms | outcomes of interest | comparative effectiveness

$This CER focused on a population of patients with stable ischemic heart disease (IHD) and preserved left ventricular systolic function (LVSF). The clinical trials evaluated in this CER included ischemic heart disease patients without left ventricular systolic dysfunction, which was defined as having a left ventricular ejection fractions greater than 40%. The key questions centered around the comparative effectiveness of 1) adding an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to standard medical therapy versus standard medical therapy alone, 2) combining an ACEI with an ARB and adding them to standard medical therapy versus adding an ACEI alone to standard medical therapy, or 3) adding an ACEI or an ARB to standard medical therapy versus standard medical therapy alone in patients with stable IHD and preserved LVSF who are in close proximity to a revascularization procedure. The comparative effectiveness of ACEIs versus ARBs was not a focus of the CER. This CER focused on a population of patients with stable IHD who also have preserved LVSF. The key questions centered around the comparative effectiveness of ACEIs or ARBs added to standard medical therapy versus standard medical therapy alone; or centered around the combined use of ACEIs and ARBs added to standard medical therapy versus an ACEI added to standard medical therapy. Among the clinical trials included in this general category, some were conducted where recent coronary revascularization procedures were a prerequisite for enrollment. These clinical trials were evaluated separately from those in which this was not a prerequisite.$

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Clinical Questions Addressed by the CER for Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Keywords: benefits | clinical questions | harms | treatment modalities | comparative effectiveness

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