Heart failure ACE inhibitors

Because of the high renin status of patients with heart failure, ACE inhibitors should be initiated at low doses to avoid orthostatic hypotension. 

Diabetes mellitus (type 1) proteinuria ACE inhibitors Heart failure ACE inhibitors Diuretics... 

In addition to their benefits in patients with established heart failure, ACE inhibitors also are effective for prevention of heart failure. The SOLVD prevention trial showed that enalapril decreased the risk of hospitalization for worsening heart failure and reduced the composite end point of death and heart failure hospitalization in patients with asymptomatic left ventricular dysfunction. The development of diabetes mellitus, an important risk factor for cardiovascular disease that also increases morbidity and mortality in heart failure patients, is reduced by enalapril in patients with chronic heart failure. In a post-hoc analysis of the Heart Outcomes Prevention Evaluation (HOPE) trial, ramipril reduced the development of new-onset heart failure by nearly 25% in patients with normal EFs and no symptoms of heart failure. ... 

Angiotensin-converting enzyme inhibitors are effective in the treatment of hypertension and congestive heart failure. ACE inhibitors also prevent bra-dykinin metabolism and, as a result, may produce the side effect of cough and angioedema. Many of the known ACE inhibitors were developed without the aid of computational chemistry techniques. However, a number of studies have used computational methods to design mimics of other nonpeptidic ACE inhibitors. 

Enalapril (notably marketed as Renitec and Vasotec by Merck, Whitehouse Station, NJ) is an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension and some types of chronic heart failure. ACE inhibitors like enalapril prevent the raising of blood pressure by constricting blood vessels using ACE. Enalapril has been shown to decrease the death rate in systolic heart failure. ... 

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

Angiotensin converting enzyme (ACE) plays a central role in cardiovascular hemostasis. Its major function is the generation of angiotensin (ANG) II from ANGI and the degradation of bradykinin. Both peptides have profound impact on the cardiovascular system and beyond. ACE inhibitors are used to decrease blood pressure in hypertensive patients, to improve cardiac function, and to reduce work load of the heart in patients with cardiac failure. 

In some patients with hypertension and in all patients with cardiac failure, the renin-angiotensin system is activated to an undesired degree, burdening the heart. The consequences of diminished ANG II generation by ACE inhibitors are multiple. In patients with hypertension, blood pressure is reduced as a result... 

ACE inhibitors are approved for the treatment of hypertension and cardiac failure [5]. For cardiac failure, many studies have demonstrated increased survival rates independently of the initial degree of failure. They effectively decrease work load of the heart as well as cardiac hypertrophy and relieve the patients symptoms. In contrast to previous assumptions, ACE inhibitors do not inhibit aldosterone production on a long-term scale sufficiently. Correspondingly, additional inhibition of aldosterone effects significantly reduces cardiac failure and increases survival even further in patients already receiving diuretics and ACE inhibitors. This can be achieved by coadministration of spironolactone, which inhibits binding of aldosterone to its receptor. 

In clinical trials, ATI antagonists have proven to be as effective as ACE inhibitors in hypertension, congestive heart failure, and renal failure [3]. The favorable side effect profile of ATI antagonists argues for a greater use of these diugs. At present, due to still higher costs, they are indicated in patients who do not tolerate ACE inhibitor treatment. 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

P-Blockers and ACE inhibitors are also indicated for post-myocardial infarction for the reduction of cardiovascular morbidity and mortality, as are aldosterone antagonists, in post-myocardial infarction patients with reduced left ventricular systolic function and diabetes or signs and symptoms of heart failure.2,48... 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

STE ACS, class I recommendation in patients with clinical signs of heart failure or EF less than 40% and intolerant of an ACE inhibitor, class lla in patients with clinical signs of heart failure or EF less than 40% and no documentation of ACE inhibitor intolerance. 

Many patients cannot tolerate chronic ACE inhibitor therapy secondary to adverse effects outlined below. Alternatively, the angiotensin receptor blockers (ARBs), can-desartan and valsartan, have been documented in trials to improve clinical outcomes in patients with heart failure.68,69 Therefore, either an ACE inhibitor or candesartan or valsartan are acceptable choices for chronic therapy for patients who have a low ejection fraction (EF) and heart failure following MI. Since more than five different ACE inhibitors have proven benefits in MI while only two ARBs have been studied, the benefits of ACE inhibitors are generally considered a... 

Besides hypotension, the most frequent adverse reaction to an ACE inhibitor is cough, which may occur in up to 30% of patients. Patients with an ACE inhibitor cough and either clinical signs of heart failure or LVEF less than 40% may be prescribed an ARB.3 Other, less common but more serious adverse effects to ACE inhibitors and ARBs include acute renal failure, hyperkalemia, and angioedema. 

To reduce mortality, administration of an aldosterone antagonist, either eplerenone or spironolactone, should be considered within the first 2 weeks following MI in all patients who are already receiving an ACE inhibitor (or ARB) and have an EF of equal to or less than 40% and either heart failure symptoms or diagnosis of diabetes mellitus.3 Aldosterone plays an important role in heart failure and in MI because it promotes vascular and myocardial fibrosis, endothelial dysfunction, hypertension, left ventricular hypertrophy, sodium retention, potassium and magnesium loss, and arrhythmias. Aldosterone antagonists have been shown in experimental and human studies to attenuate these adverse effects.70 Spironolactone decreases all-cause mortality in patients with stable, severe heart failure.71... 

---