Heart failure blockers

Key words Heart failure, (1-Blocker, ACE inhibitor, Pharmacogenetic, Pharmacogenomic, Polymorphism,... 

The cardiac effects of the calcium antagonists, ie, slowed rate (negative chronotropy) and decreased contractile force (negative inotropy), are prominent in isolated cardiac preparations. However, in the intact circulation, these effects may be masked by reflex compensatory adjustments to the hypotension that these agents produce. The negative inotropic activity of the calcium antagonists may be a problem in patients having heart failure, where contractility is already depressed, or in patients on concomitant -adrenoceptor blockers where reflex compensatory mechanisms are reduced. 

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. 

These drags are contraindicated in patients with an allergy to the (3 blockers, in patients with sinus bradycardia, second- or third-degree heart block, heart failure, and those with asthma, emphysema, or hypotension. The drug are used cautiously in patients with diabetes, thyrotoxicosis, and peptic ulcer. 

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... 

The ACC/AHA recommends that P-blockers be initiated in all patients with NYHA FC I to IV or ACC/AHA stages B through D heart failure if clinically stable.1 To date, only three p-blockers have been shown to reduce mortality in systolic HF, including the selective prantagonists bisoprolol and metoprolol succinate, and the non-selective pr, p2-, and arantagonist carvedilol.29 33 The positive findings should not be extrapolated to be indicative of a class effect, as bucindolol did not exhibit a beneficial effect on mortality when studied for HF, and there is limited information with propranolol and atenolol. 

FIGURE 3-1. Treatment algorithm for chronic heart failure. ACE, angiotensin-converting enzyme ARB, angiotensin receptor blocker EF, ejection fraction HF, heart failure LV, left ventricular Ml, myocardial infarction SOB shortness of breath. Table 3-5 describes staging of heart failure. 

STE and NSTE ACS, class I recommendation in all patients without contraindications for oral P-blockers, class I (NSTE ACS) and I la (STE ACS) for IV P-blockers, class lib recommendation for patients with moderate left ventricular failure with signs of heart failure provided they can be closely monitored. 

The most serious side effects of P-blocker administration early in ACS are hypotension, bradycardia, and heart block. While initial, acute administration of P-blockers is not appropriate for patients who present with decompensated heart failure, initiation of P-blockers maybe attempted before hospital discharge in the majority of patients following treatment of acute heart failure. P-Blockers are continued indefinitely. 

Adverse effects and contraindications of calcium channel blockers are described in Table 5-2. Verapamil, diltiazem, and first-generation dihydropyridines should also be avoided in patients with acute decompensated heart failure or left... 

As described in the previous section, calcium channel blockers should not be administered to most patients with ACS. Their role is a second-line treatment for patients with certain contraindications to P-blockers and those with continued ischemia despite P-blocker and nitrate therapy. Administration of either amlodipine, diltiazem, or verapamil is preferred.2 Agent selection is based on heart rate and left ventricular dysfunction (diltiazem and verapamil are contraindicated in patients with bradycardia, heart block, or systolic heart failure). Dosing and contraindications are described in Table 5-2. 

Although P-blockers should be avoided in patients with decompensated heart failure from left ventricular systolic dysfunction complicating an MI, clinical trial data suggest that it is safe to initiate P-blockers prior to hospital discharge in these patients once heart failure symptoms have resolved.64 These patients may actually benefit more than those without left ventricular dysfunction.65 In patients who cannot tolerate or have a contraindication to a P-blocker, a calcium channel blocker can be used to prevent anginal symptoms, but should not be used routinely in the absence of such symptoms.2,3,62... 

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... 

Intravenous diltiazem can be used cautiously for up to 24 hours in patients with non-decompensated heart failure, bpm, beats per minute CCB, calcium channel blocker (diltiazem or verapamil) HF, heart failure LV, left ventricular LVEF, left ventricular ejection fraction. 

FIGURE 6-6. Decision algorithm for long-term ventricular rate control with oral drug therapy for patients with paroxysmal or permanent atrial fibrillation, bpm, beats per minute CCB, calcium channel blocker (diltiazem or verapamil) HF, heart failure LV, left ventricular function LVEF, left ventricular ejection fraction. (Algorithm adapted with permission from Tisdale JE, Moser LR. Tachyarrhythmias. In Mueller BA, Bertch KE, Dunsworth TS, et al. (eds.) Pharmacotherapy Self-Assessment Program, 4th ed. Kansas City American College of Clinical Pharmacy 2001 ... 

Medications can increase the risk of hyperkalemia in patients with CKD, including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, used for the treatment of proteinuria and hypertension. Potassium-sparing diuretics, used for the treatment of edema and chronic heart failure, can also exacerbate the development of hyperkalemia, and should be used with caution in patients with stage 3 CKD or higher. 

An angiotensin receptor blocker may be prescribed for patients with ACE inhibitor cough and a low LVEF and heart failure after MI. Example doses include the following ... 

Blocker therapy is appropriate to further modify disease in LV dysfunction and is a component of this first-line regimen (standard therapy) for these patients. Because of the risk of exacerbating heart failure, they must be started in very low doses and titrated slowly to high doses based on tolerability. Bisoprolol, carvedilol, and metoprolol succinate are the only /j-blockers proven to be beneficial in LV dysfunction. 

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