Heart failure (HF) is associated with very high morbidity and mortality. Until recently, patients with HF were managed with a combination of digoxin and diuretics. These drugs alleviated symptoms but were not shown to affect mortality. In the last 10 years, many studies have shown evidence of decreased mortality among patients with HF using new (angiotensin II-converting enzyme [ACE] inhibitors, angiotensin I- or Il-receptor blockers) and old (spironolactone, hydralazine, and nitrates) classes of drugs, as well as drugs previously thought to be contraindicated (P-blockers). canadian pharmacy online

A MEDLINE search using “heart failure” and the subheading “drug therapy” looked for large (> 1000 patients, where possible) double-blind, controlled studies. Those found were supplemented from the reference lists of previously published articles. This article discusses drugs considered to be standard of care in management of systolic heart failure. Where applicable, the New York Heart Association (NYHA) classification for indications for specific drug classes is noted. buy tamsulosin online

This article will deal solely with systolic dysfunction (left ventricular ejection fraction [LVEF] <40%); HF will refer only to systolic heart failure. We know that patients with HF develop compensatory mechanisms in response to low cardiac output. The sympathetic nervous system is activated, as is the renin-angiotensin-aldosterone system. Such activation eventually worsens the load on the heart and worsens the HF. Most current therapies are aimed at these compensatory systems.

Angiotensin II-converting enzyme inhibitors
Many trials have produced level 1 evidence that ACE inhibitors significantly reduce mortality in HF. All patients with preserved renal function should be started on ACE inhibitors. It is important to try to reach target doses (Table 1) for maximum benefit. These patients can often tolerate a systolic blood pressure (BP) of 80 to 90 mm Hg. Serum creatinine and potassium levels should be checked before and 1 week after starting the drug because only small non-progressive elevations in levels are acceptable; creatinine should be kept lower than 220 umol/L. Buy Metaxalone 400 mg

A recent review of the Studies of Left Ventricular Dysfunction database revealed that use of enalapril was associated with a 33% increase in risk of poorer renal function (increase in creatinine of <45 umol/L). Diabetes, older age, and use of diuretics increased risk in all patients (treated and placebo). Enalapril, however, appeared to be renoprotective in diabetic patients. P-Blockade and increased ejection fraction were renoprotective in all patients. Buy Celebrex online

P-Adrenergic blockers
Patients with NYHA Class II or III HF who have been stable for at least 4 weeks should consider, based on level 1 evidence from two trials, cautious introduction of a P-blocker to counteract the effects of an activated sympathetic nervous system. Initially, patients will have a small drop in LVEF and consequently might deteriorate in the first 1 or 2 months. Carvedilol, a third-generation P-blocker and the drug first studied, has mostly P-adrenergic effects but also some a-adrenergic effects and is an antioxidant as well. All-cause mortality was decreased by 65% (from 7.8% to 3.2%)in that trial. Subsequently, metoprolol, a second-generation P-blocker with mostly P-adrenergic effects and no antioxidant effect, has also been shown to benefit patients with NYHA Class II to IV HF. All-cause mortality was decreased by 34% (Table 1).

Table 1. Target doses
DRUG NAME – DOSAGE

————————————————————-
ANGIOTENSIN II-CONVERTING ENZYME INHIBITORS
Captopril (Capoten) – 50 mg thrice daily
Enalapril (Vasotec) – 10 mg twice daily
Fosinopril (Monopril) – 30 mg once daily
Lisinopril (Zestril)- 10-40 mg once daily
Perindopril (Coversyl) – 8 mg once daily
Quinapril (Accupril) – 40 mg once daily
Ramipril (Altace) – 10 mg once daily
———————————–
P-ADRENERGIC BLOCKERS
Carvedilol (Coreg) – 3.125 mg twice dailytitrated (doubled) every 4 weeks to a target dose of 25 mg twice daily
Metoprolol (Lopresor) – 25 mg titrated to 200 mg once daily
———————————–
ALDOSTERONE RECEPTOR BLOCKER
Spironolactone (Aldactone) – 25 mg once daily. Dose was titrated to 50 mg at 8 weeks if diuresis was required
———————————-
HYDRALAZINE OR NITRATES
Hydralazine (Apresoline) – 75 mg four times daily
Isosorbide dinitrate (Isordil) – 40 mg four times daily
———————————-
ANGIOTENSIN I- OR II-RECEPTOR BLOCKERS
Candesartan (Atacand) – 16 mg once daily
Irbesartan (Avapro) – 160 mg once daily
Losartan (Cozaar) 25mg once daily
Valsartan (Diovan) 160 mg once daily
——————————————————————————-

Aldosterone receptor blocker (spironolactone)
Recently, the Randomized Aldactone Evaluation Study (RALES) 8 has produced level 1 evidence that adding merely 25 mg of spironolactone to a regimen involving ACE inhibitors, with or without digoxin or furosemide, improves the survival rate of patients with NYHA Class III and IV HF with a significant reduction in deaths (30%) from HF and sudden death. We now believe that ACE inhibition does not entirely suppress production of aldosterone, which affects atrial natriuretic peptide levels, causes myocardial fibrosis, and damages the vascular system. Spironolactone’s benefits are likely due to blocking these processes. Buy Ezetimibe 10 mg

Patients with moderate to severe HF should be taking spironolactone even if diuresis is not required. Creatinine levels higher than 220 umol/L or potassium levels higher than 5.0 umol/L are contraindications. Gynecomastia is the most common side effect. Serum potassium levels should be monitored, although this was not found to be a problem at study doses. Loop diuretics can be titrated accordingly. Buy Hyzaar online

The small subset of patients taking P-blockers upon entry into this trial did not show benefit (level 2 evidence), although the trial might not have gone on long enough to demonstrate it. The trial was discontinued early because of the decrease in mortality of the whole spironolactone group (Table 1).

Hydralazine and nitrates
If patients have renal dysfunction and, therefore, cannot take ACE inhibitors, then a combination of hydralazine and isosorbide dinitrate decreases mortality rates (as shown by level 1 evidence from the Vasodilator in Heart Failure Trials), although not to the same degree as ACE inhibitors do. The four times daily dosing regimen could affect some patients’ compliance (Table 1 ).

Angiotensin I- or II-receptor blockers
If renal function is preserved and patients are intolerant of ACE inhibitors (usually because of cough or angioedema), angiotensin I- or II-receptor blockers (ARB) are a good alternative. Each of these drugs blocks one of the seven known angiotensin receptors (either receptor 1 or 2). They have no effect on the bradykinin system so do not cause cough. Buy Fenofibrate 160 mg

Small studies such as the Evaluation of Losartan in the Elderly (ELITE) trial involving 722 patients provide level 2 evidence that losartan and captopril have equivalent effects (losartan has marginally better outcomes). There are, however, many large trials with overwhelming evidence supporting use of ACE inhibitors. Therefore, until further studies back up ARB trials, patients with a nuisance cough should be encouraged to continue taking their ACE inhibitors. If they cannot tolerate the cough, switching to an ARB is appropriate. Very small studies11 suggest a benefit in adding an ARB to maximal ACE inhibition to more completely suppress the renin-angiotensin-aldosterone system (Table 1).

Loop diuretics and digoxin
These medications have not been shown to reduce mortality, but can be used effectively for relief of acute or chronic symptoms. Proper dosing with loop diuretics is important to resolve edema and improve symptoms. Underdosing reduces the efficacy of ACE inhibitors and increases risk of в-blocker side effects. Overdosing can lead to arrhythmias if digoxin is used. Digoxin is especially useful for patients with atrial fibrillation. As ACE inhibitors and spironolactone are used and titrated to target doses, loop diuretics can be decreased; serum potassium should be monitored closely. Order Lipitor online

Acetysalicylic acid and warfarin
All patients with HF should receive 325 mg of ASA once daily for cardioprotection. Rapid atrial fibrillation should be treated quickly because these patients need their atrial kick and do not tolerate rapid heart rates. Atrial fibrillation is common; patients who have it should receive anticoagulation therapy with warfarin to attain an international normalized ratio (INR) of 2.0 to 3.0. Buy Ramipril drug

Patients with HF have comorbid diseases, and risk reduction with management of diabetes, lipids, and ischemia has positive effects on the heart. Patients should be made aware of the signs of worsening HF (increased fatigue, dyspnea, ankle swelling, weight gain); of the importance of diet, daily weight monitoring, medication compliance, and limitation of alcohol; and of the benefits of staying physically active. Understanding that the numerous, often expensive medications should both make them feel better and improve survival might help to increase their compliance. Buy Losartan 25mg online

Category: Diseases / Tags: Drugs, heart failure

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