EPITHELIAL SODIUM CHANNEL (ENaC) INHIBITORS














Amiloride + HCTZ vs HCTZ for Potassium and BP Effects in Hypertension, Can Med Assoc J, (1985) [PubMed abstract]
  • A small study published in the Canadian Medical Assoc Journal enrolled 266 patients with hypertension
Main inclusion criteria
  • Diagnosis of essential hypertension and DBP 95 - 109 mmHg after 2 weeks off meds
  • Potassium ≥ 3.5 mmol/L
Main exclusion criteria
  • History of hyperkalemia
  • BUN > 30 mg/dl
  • Serum creatinine > 20% above ULN
  • Myocardial infarction within 6 months
  • History of arrhythmia requiring therapy
Baseline characteristics
  • Average age 53 years
  • Average weight - 170 lbs
Randomized treatment groups
  • Group 1 (133 patients) - HCTZ 50 mg + Amiloride 5 mg once daily for 8 weeks
  • Group 2 (133 patients) - HCTZ 50 mg once daily for 8 weeks
  • There was a 2 - 4 week washout period where all blood pressure medications were stopped
  • If DBP did not decrease to < 90 after 2 weeks, dose of study drug could be doubled
Primary outcomes
  • 1. Change in blood pressure
  • 2. Change in potassium
Results

Duration: 8 weeks
Outcome Amiloride/HCTZ HCTZ Comparisons
Average baseline blood pressure 156/99 157/99 N/A
Average baseline potassium level 4.23 mmol/L 4.16 mmol/L N/A
Primary outcome (change in potassium) 3.91 3.69 p<0.05
Primary outcome (change in blood pressure) 138/88 138/87 p>0.05
Percent of patients with potassium < 3.5 mmol/L 14% 29% p=0.0026
  • The study originally enrolled 338 patients, but a number of patients were excluded or dropped out and were not counted in the final analysis so the study was not intention-to-treat

Findings: In light of growing concerns about the cardiovascular complications of hypokalemia, hydrochlorothiazide-amiloride appears preferable to hydrochlorothiazide alone for the treatment of some patients with hypertension
Triamterene vs Potassium Supplements for Potassium Restoration in Patients Receiving HCTZ, Arch Intern Med, (1989) [PubMed abstract]
  • A study published in the Archives of Internal Medicine enrolled 252 patients with hypertension who were hypokalemic while being treated with HCTZ 50 mg/day for up to 4 weeks
Main inclusion criteria
  • DBP < 100 mmHg
  • Serum potassium < 3.5 mmol/L
Main exclusion criteria
  • Taking BP med other than thiazide diuretic
  • Renal insufficiency
  • History of myocardial infarction
  • Heart failure
  • Fasting blood glucose > 140 mg/dl
  • Using insulin
Baseline characteristics
  • Average age 51 years
  • Average magnesium level - 1.63 mmol/L
Randomized treatment groups
  • Group 1 (86 patients) - HCTZ 50 mg + KCL 20 mmol for 4 weeks
  • Group 2 (82 patients) - HCTZ 50 mg + KCL 40 mmol for 4 weeks
  • Group 3 (79 patients) - HCTZ 50 mg + Triamterene 75 mg for 4 weeks
  • Study treatment was open-label
Primary outcome: Change in potassium
Results

Duration: 4 weeks
Outcome HCTZ + KCL 20 HCTZ + KCL 40 HCTZ + Triamterene Comparisons
Average baseline potassium level (mmol/L) 3.31 3.27 3.25 N/A
Primary outcome (increase in potassium, mmol/L) 0.31 0.48 0.48 2 or 3 vs 1 p<0.05
Change in magnesium levels (mmol/L) -0.01 -0.01 +0.09 p<0.0001 for 3
  • There was no significant difference between the groups in blood pressure response
  • The incidence of adverse events was similar between the groups

Findings: In conclusion, the combination of hydrochlorothiazide with triamterene is effective in correcting the hypokalemia seen in some patients treated with hydrochlorothiazide alone and has the additional advantage of obviating the magnesium wasting that may result from diuretic therapy.