Spironolactone Over Clonidine in Treating Resistant HTN: Do You Agree?

Tejas P. Desai, MD


August 02, 2018

As the global prevalence of hypertension increases, healthcare providers are caring for patients for whom standard antihypertensive therapy is failing. This dilemma often occurs in patients who are on at least three antihypertensive medications. Providers might be at a loss for how to treat such patients who are refractory to initial therapy.

A study published in Hypertension is an interesting randomized controlled trial that evaluates two potential medications used as a fourth-line agent to treat resistant hypertension: spironolactone or clonidine tablet.

Nearly 30 healthcare centers in Brazil participated in this randomized trial. Enrolled patients had uncontrolled hypertension despite taking three different classes of antihypertensive medications (chlorthalidone 25 mg daily; enalapril 20 mg twice daily; losartan 50 mg twice daily, and/or amlodipine 5 mg twice daily). These patients were given either (1) spironolactone 12.5 mg daily and titrated up to 50 mg daily or (2) clonidine 0.1 mg twice daily and titrated up to 0.3 mg twice daily.

Blood pressure readings were taken in the office and at home; controlled in-office blood pressure was defined as < 140/90 mm Hg, and controlled ambulatory blood pressure was defined at < 130/80 mm Hg. The study followed the patients for 12 weeks.

In this trial that assessed two generic antihypertensive medications, approximately 1600 patients were randomized but only 113 patients were ultimately studied. After 12 weeks, both groups showed a non-statistically different decrease in in-office systolic and diastolic blood pressures. However, those receiving spironolactone showed a statistically significant decrease in ambulatory systolic and diastolic pressures. The spironolactone group showed a decrease of 11.8 mm Hg (systolic) and 6.3 mm Hg (diastolic) compared with clonidine (7.3 and 3.9 mm Hg, respectively).

The overall side effects in either group were similar. Whereas no gynecomastia was detected during the 12-week study period, patients receiving spironolactone had greater instances of asymptomatic hyperkalemia and azotemia.

What Are Your Thoughts on Spironolactone?

This is an interesting study that analyzes two lower-order antihypertensive medications. Both medications are generic and usually considered to be suboptimal antihypertensive agents, primarily because of their adverse effects. Although the in-office blood pressure readings showed no difference, individuals taking spironolactone had a trend toward improved blood pressure and a statistical improvement in the ambulatory setting. The study suggests that spironolactone should be considered the fourth-line agent in treating patients with resistant hypertension.

Would you reach for spironolactone? Have you found another medication to be more helpful? Tell us in the comments below.

Follow Tejas P. Desai, MD, on Twitter: @nephondemand


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