Low serum K tied to increased mortality risk in heart failure

June 08, 2007

Sophia-Antipolis, France - Hypokalemia is associated with an increased mortality risk independently of NYHA functional class, drugs used in therapy, and use of potassium supplements, according to a post hoc analysis[1] of data from a randomized trial conducted in the 1990s[2].

"Low serum potassium in HF may be caused by diuretic therapy or may be a marker of increased neurohormonal activity and disease progression," according to the authors, who say their study has implications for contemporary HF management. Its findings argue against the use of diuretics in euvolemic patients with milder HF and for an emphasis on potassium-sparing diuretics in those with more symptomatic disease and volume overload, write Dr Ali Ahmed (University of Alabama, Birmingham) and associates.

Their analysis, which defined hypokalemia as a serum potassium <4 mEq/L, is based on patients followed for 32 months in the US-Canadian Digitalis Investigation Group (DIG) trial who had levels <5.5 mEq/L. The DIG trial, which predated the recommended use of beta blockers in heart failure, had entered patients with chronic systolic or diastolic HF of any etiology. The current report appears in the June 2007 issue of the European Heart Journal.

The cohort's 1187 patients with serum potassium <4 mEq/L were matched with the same number who had higher levels based on propensity scores encompassing a broad range of demographic, clinical, and treatment-related factors. Nearly all of those features became covariates in an analysis that showed low potassium to be independently associated with increased all-cause and cardiovascular mortality and death due to progressive HF. Similar but nonsignificant trends were seen for all-cause, cardiovascular, and MI- and stroke-related hospitalization.

Mortality risks associated with serum potassium <4 mEq/L in heart failure

End point HR (95% CI)* p
All-cause mortality 1.25 (1.07-1.46) 0.006
CV mortality 1.27 (1.06-1.51) 0.009
Death from progressive HF 1.36 (1.05-1.75) 0.020
*Adjusted for demographics, HF etiology, cardiovascular diseases, diabetes, medications (including digoxin, ACE inhibitors, diuretics), use of potassium-sparing diuretics, potassium supplementation, HF signs and symptoms, NYHA functional class, chest X-ray findings, and serum creatinine

Hypokalemia hasn't been well defined in heart failure, although in the hypertension literature the definition has been variously said to be serum potassium of <3.5 mEg/L or <4.0 mEq/L, according to Ahmed. The current analysis supports a minimum of 4 mEq/L up to at least 5.5 mEq/L as the optimal safe range for HF patients, consistent with other proposals in the literature[3], he told heartpwire .

Based on their findings and the established evidence base, Ahmed and his colleagues recommend the following treatment approaches:

  • Avoid diuretics in patients in NYHA class 1-2 who are receiving contemporary recommended drug therapy and have adequate fluid balance.

  • Patients in NYHA 3-4 heart failure with volume overload should receive diuretics, which could include spironolactone (or potentially eplerenone for post-MI patients) to help prevent hypokalemia.

  • Potassium supplements may be an alternative to aldosterone antagonists.

"But we think it might be safer to give spironolactone [instead of potassium supplements] because of its proven benefit in terms of reducing mortality," Ahmed said. "No one knows what potassium supplements will do [in heart failure]."

How relevant are findings based on the vintage DIG trial to today's generation of heart-failure patients who, unlike those in DIG, are taking beta blockers or are generally supposed to be taking them? Those drugs are grossly underused in heart failure today, Ahmed noted, observing that about one half of HF is chronic and only about one half of HF patients who should receive beta blockers actually get them. That, he said, would mean the drugs are today used in only about one fourth of HF patients and, therefore, the DIG analysis likely applies to about three fourths of heart failure today. "That's the way I look at it."

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