Clinical Twisters: Hypertension: Upping the ante

September 17, 2007

Patient appears asymptomatic for heart failure; has hypertension and diabetes, what is the maximum dose of Losartan?

A new medical resident calls your hospital pharmacy to ask the maximum dose of losartan (Cozaar, Merck). His patient, a 51-year-old African-American man (BMI=23), has an average blood pressure of 150/90 despite total daily doses of 10 mg amlodipine; 25 mg atenolol; 80 mg furosemide; 40 mg lisinopril; and 100 mg losartan. When you access the patient's profile, you discover he also takes potassium 10 mEq/day, ranitidine 150 mg twice daily, simvastatin 40 mg/day, and insulin 70/30. His diabetes appears well controlled, but he has had nocturnal dyspnea previously that was attributed to heart failure (HF). He has no current HF symptoms. What do you suggest?

Prior to providing recommendations, review the patient's medical record for cardiac evaluation (ejection fraction, NYHA classification), kidney function (CrCl, SCr), potassium levels, and so on. Review his medication reconciliation record for nonprescription drugs, herbal/dietary supplements, and medications from multiple physicians.

Currently, the patient appears asymptomatic for HF and his diabetes is controlled; however, he remains hypertensive (>130/80).

HF pharmacotherapy targets neurohormonal blockade with ACE inhibitors (ACEIs), beta-blockers, aldosterone blockers, and digoxin. These medications (except digoxin) have demonstrated a reduction in mortality and hospitalization; digoxin reduces HF symptoms. Medications from these classes (excluding digoxin) also contribute to the management of HTN.

Unless hyperkalemia and/or impaired kidney function are present, medications should be administered at recommended target doses. Because this patient's treatment includes an ACEI/ARB combination as well as a potassium supplement, serum potassium should be assessed.

Continue lisinopril (ACEI) as currently titrated to recommended maximum dose and consider substituting isosorbide dinitrate/hydralazine (BiDil, NitroMed) for losartan (A-HeFT Trial) that, via its vasodilatory nitric-oxide-dependent endothelial mechanism, is effective in the African-American population.

Consider metoprolol succinate, carvedilol (Coreg, GlaxoSmithKline), or bisoprolol titrated to the respective daily target doses of 200 mg, 25-50 mg, and 10 mg, in lieu of atenolol for beta-blockade.

Since aldosterone blockers are recommended in HF, treatment with spironolactone 25 mg or eplerenone (Inspra, Pfizer) 25 mg daily should be considered. Consider kidney function and serum potassium levels prior to dosing.

If HF symptoms return, consider digoxin 0.125 mg daily and adjust for kidney function if necessary.

Although amlodipine is safe in HF, it gives no mortality benefits and is administered for HTN in this patient.

L. Traywick Till Jr., Pharm.D. Trident Regional Medical CenterCharleston, S.C.

Since this patient is taking four antihypertensives and a diuretic, resistant HTN should be considered. First we suggest optimizing his current regimen. Changing atenolol to carvedilol would offer potential benefits for HF plus dual mechanisms for blood-pressure lowering. Another consideration is adding a thiazide diuretic that may offer increased efficacy for HTN in the African-American population. A secondary cause to consider is hyper-aldosteronism-based on blood pressure elevation despite multiple antihypertensives and requirement of potassium supplementation with ACEI and ARB. Once regimen is optimized, consider screening for hyperaldosteronism.

Hyperaldosteronism diagnostic findings include a plasma aldosterone: plasma renin activity ratio >25 and low serum potassium (<3.5 mEq/L) with urinary potassium >30 mEq/24 hours. An aldosterone antagonist, i.e., spironolactone, would be the agent of choice for this diagnosis (25-400 mg/day). If this secondary cause is addressed with an aldosterone antagonist, one or more other agents may no longer be needed. Consider discontinuing losartan first since the patient is already on an ACEI, an indicated antihypertensive for diabetes and HF. Also, treatment of hyperaldosteronism may eliminate need for potassium supplementation because potassium excretion will decrease as aldosterone is corrected. Serum potassium should be monitored closely.

The patient's blood pressure should be monitored regularly to assess the need for further medication changes to obtain blood pressure goal <130/80 mmHg.

Joni Foard, Pharm.D., CDE Assistant Professor of PharmacyUniversity of Tennessee College of PharmacyClinical Pharmacist, Ambulatory CareHolston Medical Group

Russell Cabanaw, Pharm.D. Pharmacy Practice Resident, Ambulatory CareUniversity of Tennessee College of PharmacyHolston Medical Group