Drug Topics - June 16, 2008 - (Page 48)

48 DRUG TOPICS JUNE 16, 2008 www.drugtopics.com CONTINUING EDUCATION Use in renal impairment also poses concerns as they lose effectiveness with creatinine clearances of less than 40 mL/min. Preference is often given to thiazide diuretics for patients with concomitant hypertension and only mild fluid retention as it offers more consistent blood pressure control than loop diuretics. goals. Patients with low SDC (0.5-0.8 ng/mL) had lower risk of mortality versus placebo and those with higher SDC (> 1.2 ng/mL) were at increased risk of mortality. For these reasons, digoxin is currently considered for patients with persistent symptoms already being treated with an ACE inhibitor, Bblocker, and diuretic. If digoxin is added to therapy, the recommended target SDC is 0.5-1.0 ng/mL. Doses typically seen for this population are 0.125 mg/day or 0.25 mg/day. Every other day dosing may be needed for patients with impaired renal function, age greater than 70, and those with lean body mass. Once patients are started on therapy, proper monitoring includes periodic renal function assessment and SDC levels. Drugs with potential to interact with digoxin should be evaluated before added to therapy. Toxic signs and symptoms of digoxin include: vomiting, bradycardia, mental status changes, hyperkalemia, and cardiac problems such as AV block or atrial and ventricular dysrhythmias. Severity of toxicity depends on patient-specific factors such as preexisting state of health and age. Patient counseling is essential for self-monitoring of toxic symptoms and the need for urgent care. Aldosterone antagonists (Spironolactone) Secretion of aldosterone plays a critical role in deleterious effects of HF. Actions such as retention of sodium and water, activation of the sympathetic nervous system, promotion of magnesium and potassium loss, and inhibition of the parasympathetic system are involved in the pathogenesis of HF. Although ACE inhibitors act on the renin-angiotensin-aldosterone system and acutely lower aldosterone levels, the decrease is not sustained. Discovery of this occurrence supported the use of an agent to more directly block the effects of aldosterone such as an aldosterone receptor antagonist (ARA). The two most commonly used agents in this class are spironolactone and eplenerone. The Randomized Aldactone Evaluation Study (RALES) in 1999 showed reduced mortality (including sudden cardiac death) in patients with NYHA classes III-IV HF receiving 25 mg/day. The latter agent, a more selective aldosterone antagonist, received support for use from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) in 2003. This study revealed a 15% decrease in total mortality when added to standard HF therapy in patients post-MI with a LVEF of 40% or less and clinical HF signs. A primary concern with ARAs is the ability to increase potassium levels, especially when a patient is likely to be on an ACE inhibitor concurrently. Patients on these agents need to be monitored closely for both serum potassium levels and renal function. Patients should also be counseled to avoid salt substitutes and potassium supplements (commonly added with loop diuretics). Additionally, doses should not exceed those established in clinical trials. Angiotensin receptor blockers Angiotensin receptor blockers (ARBs) theoretically provide benefits over ACE inhibitors. By blocking angiotensin II directly at its site of action, bradykinin accumulation is prevented, bypassing the accepted mechanism of ACE inhibitor induced cough. In contrast, it is now known that the buildup of bradykinin produces some of the HF benefits rather than blockade of angiotensin II formation, which cause some of the ACE inhibitor side effects. Fewer trials exist for ARBs than ACE inhibitors, although several placebo-controlled trials looking at long-term use of ARBs have shown beneficial hemodynamic, neurohormonal, and clinical effects typically seen with interference of the RAAS. The Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM)-Alternative trial demonstrated improved outcomes in patients with preserved LVEF previously intolerant to ACE inhibitors. Recommendations for use of ARBs are as reasonable alternatives to ACE inhibitors with support for HF patients with intolerance to ACE inhibitors exhibiting current or prior symptoms of HF or those with reduced LVEF. Angioedema and cough are most common intolerances, although caution should be used with patients previously experiencing angioedema with an ACE inhibitor as this concerning adverse effects has also been reported with ARB initiation, but to a lesser extent. Data from studies using both an ACE inhibitor and ARB are still ongoing and the support of this combination is not yet recommended. As with ACE inhibitors, ARBs should be started at low doses and titrated slowly to reach target doses. Appropriate monitoring includes blood pressure, renal function, and potassium levels and should be evaluated within one to two weeks after starting therapy and following dose adjustments. Patients receiving an ACE inhibitor or aldosterone receptor antagonist should be Digoxin Once thought to be a cornerstone of chronic HF therapy, digoxin is not currently recommended for asymptomatic patients. To date, no trials have shown a mortality benefit and its principal effect is on symptom relief and decreased hospitalization. For this reason, patients with moderate and severe HF or those with supraventricular tachyarrhythmias such as atrial fibrillation may derive the most benefit. Due to its narrow therapeutic index and potential adverse effects and drug interactions, careful consideration needs to be given before this agent is added to the patient’s management. In addition to its overall role in HF management, the appropriate serum digoxin concentration (SDC) has also been debated. Two studies have retrospectively shown that patients with low SDC (< 0.9 ng/mL) were less likely to experience worsening of HF symptoms when compared with placebo. Additional evaluation of the Digitalis Investigation Group (DIG) trial also supported the benefit of lower SDC http://www.drugtopics.com

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Drug Topics - June 16, 2008 Contents Latebreakers Letters Latebreakers in Depth Pharmacists Lose in Final ESRD Rule New Drug Helps Palliative Patients on Opioids Take Care of Business Oral Treatment Reduces Multiple Sclerosis Flare-ups Beware of Inflammatory Masses From Implantable Infusion Systems Safer Therapeutic Options Emerging for Atrial Fibrillation Congressional Committee Chair Calls for Action Against Hospital Infections This Software System Helps Hospitals Manage Anticoagulation Therapy Rx Care Community Practice JP at Large Self-Care Cover Story Long-Term Care Chains and Business Technology Technology Update Continuing Education New Products Advertisers Index Classified Viewpoint

Drug Topics - June 16, 2008

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