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Diuretic therapy and ventricular arrhythmias in persons 65 years of age and older
1Division of Cardiology, Sunnybrook Medical Center, Toronto, Canada.
Insights
Lower doses of hydrochlorothiazide (HCTZ) did not increase ventricular arrhythmias in elderly patients. Combining HCTZ with amiloride showed no significant benefit in reducing arrhythmias, despite maintaining normal serum potassium levels.
Area of Science:
- Cardiology
- Pharmacology
- Geriatrics
Background:
- Thiazide diuretics, particularly at high doses, have been linked to ventricular arrhythmias.
- Lower recommended dosages of hydrochlorothiazide are now common, necessitating re-evaluation of their safety profile.
Purpose of the Study:
- To assess the effect of hydrochlorothiazide 50 mg daily, alone and with amiloride 5 mg, on ventricular arrhythmias in elderly patients.
- To determine if amiloride co-administration mitigates potential arrhythmias associated with hydrochlorothiazide.
Main Methods:
- A randomized, double-blind, crossover study involving 37 elderly patients (mean age 81).
- Three treatment phases: hydrochlorothiazide, hydrochlorothiazide + amiloride, and placebo.
- 24-hour Holter monitoring and serum potassium levels were measured after each phase.
Main Results:
- Hydrochlorothiazide significantly reduced serum potassium (3.5 mEq/L) compared to placebo (4.1 mEq/L) and hydrochlorothiazide + amiloride (4.1 mEq/L).
- Serious ventricular arrhythmias occurred in 13/37 on HCTZ, 15/37 on placebo, and 9/37 on HCTZ + amiloride.
- No statistically significant increase in ventricular premature complexes was observed with hydrochlorothiazide compared to placebo, though a significant difference in hourly frequency was noted versus HCTZ + amiloride.
Conclusions:
- Hydrochlorothiazide 50 mg daily did not increase the frequency or severity of ventricular ectopic activity in this elderly population.
- Concurrent amiloride did not offer a significant protective effect against arrhythmias, despite maintaining normal serum potassium levels.
Abstract:
Comparatively high doses of thiazide diuretics have been implicated as a possible cause of ventricular arrhythmias. With the advent of lower recommended dosages, the effect of hydrochlorothiazide 50 mg daily alone and in combination with the potassium-sparing drug, amiloride 5 mg, on the frequency and severity of ventricular arrhythmias was examined in 37 elderly patients. The mean age was 81 +/- 2 years. The study used a randomized, double-blind, crossover design with 3 treatment phases: hydrochlorothiazide, hydrochlorothiazide + amiloride and placebo. A 24-hour Holter monitor recording and serum potassium measurement were obtained at the end of each treatment. Mean serum potassium was significantly (p less than 0.001) reduced with hydrochlorothiazide (3.5 +/- 1 mEq/liter) compared with placebo (4.1 +/- 0.1) and hydrochlorothiazide + amiloride (4.1 +/- 0.1). Serious ventricular arrhythmias occurred in 13 of 37 patients receiving hydrochlorothiazide compared with 15 of 37 receiving placebo and 9 of 37 receiving hydrochlorothiazide + amiloride. Patients who exhibited ventricular ectopy during the placebo phase tended to have an increase in the number of ventricular premature complexes receiving hydrochlorothiazide, although the difference was not statistically significant. There was a significant (p = 0.045) difference in the hourly ventricular premature complex frequency for hydrochlorothiazide compared with hydrochlorothiazide + amiloride. Patients with hypokalemia did not exhibit greater ventricular ectopic activity than those with a normal serum potassium, and concurrent digoxin therapy did not affect arrhythmia occurrence. Hydrochlorothiazide, 50 mg daily, did not affect the frequency or severity of ventricular ectopic activity in this elderly population.