ACE Inhibitors In Heart Failure Research Articles

Personalized Medicine: An Idea Whose Time is Approaching

The field of Cardiology has seen major advancements in the past 50 years, including the advent of cardiac catheterization, bypass surgery, angioplasty, defibrillators and ablation. Basic research and clinical trials have defined the efficacy and safety of a range of treatments such as statin therapy for coronary artery disease and ACE inhibitors for heart failure. As a result, this has lead to the development and widespread use of clinical guidelines that have helped reduce cardiac mortality by more than 50% over the past 30 years. The 21st century is poised to implement an even higher standard of evidence-based medicine - namely, therapy personalized to an individual's genetic variants. The gene is the most fundamental biological unit of the human body, responsible for generating and regulating proteins that perform the body's functions. Genes and their regulators determine which, when and how many proteins are synthesized in response to a host of signals, which makes genetics a major factor in many diseases. In fact, it is well recognized that more than 50% of one's predisposition to coronary artery disease is genetic. While coronary artery disease (CAD) is still the number-one killer in the Western world, the availability of the DNA sequence of human genes could mean its demise in the 21st century.

Personalized Medicine: An Idea Whose Time Is Approaching

INTRODUCTION The field of Cardiology has seen major advancements in the past 50 years, including the advent of cardiac catheterization, bypass surgery, angioplasty, defibrillators and ablation. Basic research and clinical trials have defined the efficacy and safety of a range of treatments such as statin therapy for coronary artery disease and ACE inhibitors for heart failure. As a result, this “evidence-based medicine” has lead to the development and widespread use of clinical guidelines that have helped reduce cardiac mortality by more than 50% over the past 30 years. The 21st century is poised to implement an even higher standard of evidence-based medicine — namely, therapy personalized to an individual's genetic variants. The gene is the most fundamental biological unit of the human body, responsible for generating and regulating proteins that perform the body's functions. Genes and their regulators determine which, when and how many proteins are synthesized in response to a host of signals, which mak...

Is Addition of Angiotensin Receptor Blockade Superior to Increasing Dose of ACE-Inhibitor in Patients Receiving Low-Dose ACE-Inhibitors for Heart Failure?

Is Addition of Angiotensin Receptor Blockade Superior to Increasing Dose of ACE-Inhibitor in Patients Receiving Low-Dose ACE-Inhibitors for Heart Failure?

Contemporary Use of Digoxin in the Management of Cardiovascular Disorders

Digitalis is the oldest compound in cardiovascular medicine that continues to be used in contemporary clinical practice.1 Evidence supporting the beneficial effects of digoxin on hemodynamic, neurohormonal, and electrophysiological parameters has been accumulated from >200 years of clinical experience and research (Table 1).2 View this table: TABLE 1. Effects of Digoxin Digoxin was approved for heart failure in 1998 under current regulations by the Food and Drug Administration on the basis of the Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED), Randomized Assessment of Digoxin on Inhibitors of the Angiotensin Converting Enzyme (RADIANCE), and Digitalis Investigators Group (DIG) clinical trials.3–5 It was also approved for the control of ventricular response rate for patients with atrial fibrillation. The most recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend digoxin for symptomatic chronic heart failure for patients with reduced systolic function (Class IIa recommendation: weight of evidence/opinion is in favor of usefulness/efficacy), preserved systolic function (Class IIb: usefulness/efficacy is less well established by evidence/opinion), and/or rate control for atrial fibrillation with a rapid ventricular response (Class IIa).6 The new Heart Failure Society of America guidelines for heart failure provide similar recommendations.7 Despite its relatively recent approval by the Food and Drug Administration and the guideline recommendations, digoxin use is decreasing in patients with heart failure.8 In the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) registry, only 30% of patients with left ventricular systolic dysfunction were being treated with digoxin before admission. Digoxin was added in only 8% of patients before discharge despite the fact that they had signs and symptoms of heart failure while receiving diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs) and β-blockers.9,10 This decrease in digoxin use is likely the result of several factors. …

Change in the use of Renin-Angiotensin System Blockers in Older Patients Fulfilling the HOPE Criteria

have become increasingly useful in the management of cardiovascular diseases. The Heart Outcomes Prevention Evaluation (HOPE) study showed a significant reduction in cardiovascular endpoints when high-risk patients were given ACE inhibitors (ACE-I). Though controversy exists, angiotensin II receptor blockers (ARBs) may be almost as beneficial as ACE-Is in heart failure, renal microalbuminuria and in endothelial protection. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomised Assessment Study in ACE-iNtolerant subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) will confirm whether ACE-Is and ARBs are equivalent in cardiovascular protection. Change in the use of Renin-Angiotensin System Blockers in Older Patients Fulfilling the HOPE Criteria

Review finds combining angiotensin receptor blockers with ACE inhibitors in heart failure may only benefit people with contraindications to β blockersAbstracted from: Dimopoulos K, Salukhe TV, Coats AJ, et al. Meta-analyses of mortality and morbidity effects of an angiotensin receptor blocker in patients with chronic heart failure already receiving an ACE inhibitor (alone or with a beta-blocker). Int J Cardiol

Review finds combining angiotensin receptor blockers with ACE inhibitors in heart failure may only benefit people with contraindications to β blockersAbstracted from: Dimopoulos K, Salukhe TV, Coats AJ, et al. Meta-analyses of mortality and morbidity effects of an angiotensin receptor blocker in patients with chronic heart failure already receiving an ACE inhibitor (alone or with a beta-blocker). Int J Cardiol

Suboptimal use of ACE inhibitors in heart failure

Suboptimal use of ACE inhibitors in heart failure

Novel effects of ACE inhibitors in heart failure?

Novel effects of ACE inhibitors in heart failure?

European survey of primary care physician perceptions on heart failure diagnosis and management (Euro-HF).

To survey a random sample of primary care physicians across six European countries regarding their perceptions of diagnostic and prescribing issues in heart failure, and to consider factors that might be associated with physician under-performance. Qualitative, postal questionnaire-based, validated survey in the native tongue of a random sample of 200 primary care physicians in each of five European countries (France, Germany, Italy, The Netherlands and Spain) and of 250 U.K. primary care physicians. Respondents provided: details of practice characteristics; the usual way a diagnosis of heart failure was established; access to investigations; names of drugs prescribed in heart failure, with estimates of the proportion of patients supplied with particular classes; and physician attitudes regarding the evidence base (in terms of benefits and risks) for treatments used. Outcomes were physician perceptions and attitudes about heart failure diagnosis and treatment. Adjusted response rates varied from 17% (France) to 56% (Britain). Primary care physicians underestimate the prevalence of heart failure. Most patients are diagnosed on symptoms and signs alone, with only 32% having further investigations or referral. Although most primary care physicians stated they prescribe ACE inhibitors in heart failure, this was for only 47-62% of patients, and at doses below those identified as effective in trials. Most prescribing doctors (91%) believe there is strong evidence of reduced mortality in heart failure patients using ACE inhibitors, but 51% also consider ACE inhibitors have substantial risks with their use. Limitations of the data include the general problem of questionnaires, whether responses accord with actual clinical practice, and, specific to these data, the low response rate in some countries (although the study does provide information from nearly 300 randomly selected primary care physicians across Europe). New preliminary insights include exposition of the 'low tech' approach to heart failure diagnosis across Europe: doctors report the use of symptoms and signs alone; the lack of direct (open) access to objective investigations, such as echocardiography, which almost guarantees that misdiagnoses will occur; and the under-utilization and under-dosing with ACE inhibitors. The main factor influencing under-use would appear to be the exaggerated perceptions of treatment risk amongst primary care physicians that dominate the widespread and accurate knowledge of treatment benefits.

Prevention of cardiovascular disease in hypertensive patients with normal renal function

Hypertension is an important risk factor for cardiovascular disease (CVD) in patients with normal renal function. After reviewing over two decades of clinical trial data and an even longer history of epidemiologic data, multiple consensus panels worldwide have made recommendations for the aggressive treatment of hypertension using both lifestyle modification and drug therapy. These data and recommendations provide the basis of the recommendations for preventing CVD in patients with renal disease. Most patients should have elevated blood pressure (BP) lowered to less than 140 mm Hg systolic and less than 90 mm Hg diastolic. Earlier and more aggressive intervention is recommended in high-risk hypertensive patients with risk factors (especially diabetes mellitus) or evidence of target organ damage or clinical CVD. Lifestyle changes are indicated as either initial therapy or concomitant therapy in all hypertensive patients to lower BP and to normalize other CVD risk factors. There is general agreement that clinical outcome data from controlled clinical trials should guide the selection of antihypertensive agents. Currently, these data are only available for thiazide diuretics and beta-blockers for most hypertensive patients with normal renal function and for the dihydropyridine calcium channel blockers in older hypertensive patients with isolated systolic hypertension. However, data may support the use of other agents in hypertensives with selected comorbidity (eg, ACE inhibitors in heart failure, beta-blockers after myocardial infarction, and so forth). However, with only 25% of hypertensive patients controlled to less than 140/90 mm Hg, achieving blood pressure control remains the most important goal in managing hypertension in this population. (Am J Kidney Dis 1998 Nov;32(5 Suppl 3):S66-79)

Novel mechanism for efficacy of ACE inhibitors in heart failure: Matrix metalloproteinase inhibitors

Novel mechanism for efficacy of ACE inhibitors in heart failure: Matrix metalloproteinase inhibitors

Guidelines for use of ACE inhibitors in heart failure

Guidelines for use of ACE inhibitors in heart failure

Guidelines for use of ACE inhibitors in heart failure

Guidelines for use of ACE inhibitors in heart failure

Prorenin, renin, angiotensinogen, and angiotensin-converting enzyme in normal and failing human hearts. Evidence for renin binding.

A local renin-angiotensin system in the heart is often invoked to explain the beneficial effects of ACE inhibitors in heart failure. The heart, however, produces little or no renin under normal conditions. We compared the cardiac tissue levels of renin-angiotensin system components in 10 potential heart donors who died of noncardiac disorders and 10 subjects with dilated cardiomyopathy (DCM) who underwent cardiac transplantation. Cardiac levels of renin and prorenin in DCM patients were higher than in the donors. The cardiac and plasma levels of renin in DCM were positively correlated, and extrapolation of the regression line to normal plasma levels yielded a tissue level close to that measured in the donor hearts. The cardiac tissue-to-plasma concentration (T/P) ratios for renin and prorenin were threefold the ratio for albumin, which indicates that the tissue levels were too high to be accounted for by admixture with blood and diffusion into the interstitial fluid. Cell membranes from porcine cardiac tissue bound porcine renin with high affinity. The T/P ratio for ACE, which is membrane bound, was fivefold the ratio for albumin. Cardiac angiotensinogen was lower in DCM patients than in the donors, and its T/P ratio was half that for albumin, which is compatible with substrate consumption by cardiac renin. These data in patients with heart failure support the concept of local angiotensin production in the heart by renin that is taken up from the circulation. Membrane binding may be part of the uptake process.

ACE inhibitors in heart failure: prospects and limitations.

ACE inhibitors have been shown to be effective in reducing the morbidity and mortality of patients with left ventricular systolic dysfunction, but their application to clinical practice in this situation is still limited. In part, the failure to prescribe an ACE inhibitor to a patient with left ventricular systolic dysfunction is due to perceptions regarding their side effects, such as cough and renal dysfunction. Relatively few patients with left ventricular systolic dysfunction and a serum creatinine > or = 2 mg/dl receive an ACE inhibitor in clinical practice. In this situation one should consider an agent such as fosinopril, which is metabolized by the liver as well as secreted by the kidney. In patients with moderate renal dysfunction, fosinopril has been well tolerated without an increase in serum creatinine. In patients who develop cough due to an ACE inhibitor, consideration should be given to an angiotensin II type 1 receptor blocking agent, such as losartan. The relative safety and efficacy of an ACE inhibitor compared with an angiotensin II type 1 receptor blocking agent is being explored in a prospective randomized trial (Evaluation of Losartan In The Elderly [ELITE]), as well as the safety and pharmacological effectiveness of adding an angiotensin II receptor antagonist to an ACE inhibitor (Randomized Angiotensin receptor antagonists-ACE-inhibitor Study [RAAS]). There may also be a role for the combination of an aldosterone receptor antagonists and an ACE inhibitor in patients with left ventricular systolic dysfunction. Once an ACE inhibitor is administered to a patient with left ventricular systolic dysfunction it should be continued indefinitely. ACE inhibitors may be of value not only in preventing the progression of heart failure but also in reversing endothelial dysfunction and preventing the development of atherosclerosis and its consequences, such as myocardial infarction.

UK GPs underuse ACE inhibitors for heart failure

UK GPs underuse ACE inhibitors for heart failure

ACE inhibitors for heart failure: a question of dose

ACE inhibitors for heart failure: a question of dose

When to use ACE inhibitors in heart failure.

When to use ACE inhibitors in heart failure.

Strengthening the Case for ACE Inhibitors in Heart Failure

Strengthening the Case for ACE Inhibitors in Heart Failure