Researchers Find Lower Sweet Spot for Potassium Levels in MI Reply

Current guidelines for the treatment of acute MI recommend that serum potassium be maintained between 4.0 and 5.0 mEq/L, and some believe that the upper limit could be raised to 5.5, but evidence is based on small, outdated studies. Now a new study published in JAMA suggests that the ideal potassium range should be adjusted downward.

Abhinav Goyal and colleagues performed a retrospective cohort study of 38,689 MI patients. They found a U-shaped relationship between the postadmission potassium level and in-hospital mortality, with the lowest rate of death found in patients with potassium levels between 3.5 and 4.5.

Postadmission Potassium Level and Mortality Rate (Adjusted Odds Ratio):

  • <3.0: 46.2% (8.11)
  • 3.0- <3.5: 11.4% (1.45)
  • 3.5- <4.0: 4.8% (1)
  • 4.0- <4.5: 5.0% (1.25)
  • 4.5- <5.0: 10% (1.96)
  • 5.0- <5.5: 24.8% (3.27)
  • >5.5: 61.4% (6.44)

The authors pointed out that the clinical status of the patient may have been a cause rather than an effect of the potassium level. Since large randomized
trials of this topic are unlikely, the authors recommend that “overly aggressive repletion of potassium levels (which is often automated through the implementation of hospital order sets) may not be advisable in patients with AMI (particularly in those with levels between 3.5 and 3.9 mEq/L), as potassium levels of at least 4.5 mEq/L are associated with harm.”

In an accompanying editorial, Benjamin Scirica and David Morrow acknowledge the limitations of the available data but support the recommendations of the study authors and state that for patients with potassium levels below 3.5, potassium repletion “remains reasonable,” but repletion for levels between 3.5 and 4.0 and target levels greater than 4.5 “do not appear justified.”

Here is the press release from JAMA:

Study Evaluates Relationship Between Blood Potassium Levels After Heart Attack and In-Hospital Mortality

CHICAGO – Patients hospitalized after a heart attack who had blood potassium levels of between 3.5 and less than 4.5 mEq/L (milliEquivalents per liter) had a lower risk of death than patients with potassium levels that were higher or lower than this range, according to a study in the January 11 issue of JAMA. Clinical practice guidelines recommend maintaining serum potassium levels between 4.0 and 5.0 mEq/L in patients after a heart attack.

“Potassium homeostasis [equilibrium] is critical to prevent adverse events in patients with cardiovascular disease. Several studies have demonstrated a relationship between low serum potassium levels, usually less than 3.5 mEq/L, and the risk of ventricular arrhythmias in patients with acute myocardial infarction [AMI; heart attack]. On the basis of these studies, experts and professional societies have recommended maintaining potassium levels between 4.0 and 5.0 mEq/L, or even 4.5 to 5.5 mEq/L, in AMI patients. However, most prior studies were conducted before the routine use of beta-blockers, reperfusion therapy, and early invasive management in eligible patients with AMI,” according to background information in the article. In addition, these studies were small. “Therefore, there is a lack of current, adequately powered studies that define the optimal range of serum potassium levels with respect to mortality and other important clinical outcomes in patients with AMI.”

Abhinav Goyal, M.D., M.H.S., of the Emory Rollins School of Public Health, Atlanta, and colleagues conducted a study to determine the relationship between serum potassium levels and in-hospital mortality in AMI patients in the era of beta-blocker and reperfusion therapy. The study included 38,689 patients with biomarker-confirmed AMI, admitted to 67 U.S. hospitals between January 2000 and December 2008. All patients had in-hospital serum potassium measurements and were categorized by average postadmission serum potassium level.

Of the study patients, 2,679 (6.9 percent) died during hospitalization. The researchers found that compared with the reference group (3.5-<4.0 mEq/L; mortality rate, 4.8 percent), mortality was comparable for patients with postadmission potassium levels of 4.0 to less than 4.5 mEq/L (5.0 percent). Mortality was twice as great for potassium levels of 4.5 to less than 5.0 mEq/L (10.0 percent), and was even greater at higher potassium levels. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L.

Of the 38 689 patients with AMI, 1,707 (4.4 percent) had an episode of ventricular fibrillation, ventricular flutter, or cardiac arrest during hospitalization. Rates of ventricular arrhythmias or cardiac arrest were higher (compared with the reference group, 3.5 <4.0 mEq/L) only for the lowest and highest average postadmission potassium levels (<3.0 mEq/L and 5.0 mEq/L or greater).

“In conclusion, our large study of patients with AMI challenges current clinical practice guidelines that endorse maintaining serum potassium levels between 4.0 and 5.0 mEq/L. These guidelines are based on small, older studies that focused only on ventricular arrhythmias (and not mortality) and were conducted before the routine use of beta-blockers, reperfusion therapy, and early invasive management in AMI patients. Our data suggest that the optimal range of serum potassium levels in AMI patients may be between 3.5 and 4.5 mEq/L and that potassium levels of greater than 4.5 mEq/L are associated with increased mortality and should probably be avoided,” the authors write.

(JAMA. 2012;307[2]:157-164)

Editorial: Potassium Concentration and Repletion in Patients With Acute Myocardial Infarction

In an accompanying editorial, Benjamin M. Scirica, M.D., M.P.H., and David A. Morrow, M.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, Boston, comment on the findings of this study.

“ … it remains clinically reasonable to avoid significant hypokalemia [abnormally low potassium level; <3.5 mEq/L] in patients post-AMI, particularly with significant, sustained, ventricular ectopy or other high-risk features. The data from the report by Goyal et al cannot establish that treatment of hypokalemia alters outcome. However, as noted by the authors, an adequately sized randomized trial of potassium repletion in AMI is unlikely to ever be performed and thus, decisions about care must be formulated on the basis of best available information. Given that it is an inexpensive and relatively low-risk intervention, repletion of potassium for levels of less than 3.5 mEq/L remains reasonable. However, based on the report by Goyal et al, viewed together with previous smaller studies, potassium repletion for concentrations of 3.5 mEq/L to 4.0 mEq/L and routinely targeting levels greater than 4.5 mEq/L, do not appear justified.”

(JAMA. 2012;307[1]:195-196)

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