Oral potassium supplement use and outcomes in chronic heart failure: A propensity-matched study

doi:10.1016/j.ijcard.2008.11.195

International Journal of Cardiology

Volume 141, Issue 2, 28 May 2010, Pages 167-174

https://doi.org/10.1016/j.ijcard.2008.11.195 Get rights and content

Abstract

Background

Hypokalemia is common in heart failure (HF) and is associated with increased mortality. Potassium supplements are commonly used to treat hypokalemia and maintain normokalemia. However, their long-term effects on outcomes in chronic HF are unknown. We used a public-use copy of the Digitalis Investigation Group (DIG) trial dataset to determine the associations of potassium supplement use with outcomes using a propensity-matched design.

Methods

Of the 7788 DIG participants with chronic HF, 2199 were using oral potassium supplements at baseline. We estimated propensity scores for potassium supplement use for each patient and used them to match 2131 pairs of patients receiving and not receiving potassium supplements. Matched Cox regression models were used to estimate associations of potassium supplement use with mortality and hospitalization during 40 months of median follow-up.

Results

All-cause mortality occurred in 818 (rate, 1327/10,000 person-years) and 802 (rate, 1313/10,000 person-years) patients respectively receiving and not receiving potassium supplements (hazard ratio {HR} when potassium supplement use was compared with nonuse, 1.05; 95% confidence interval {CI}, 0.94–1.18; P = 0.390). All-cause hospitalizations occurred in 1516 (rate, 4777/10,000 person-years) and 1445 (rate, 4120/10,000 person-years) patients respectively receiving and not receiving potassium supplements (HR, 1.15; 95% CI, 1.05–1.26; P = 0.004). HRs (95% CI) for hospitalizations due to cardiovascular causes and worsening HF were respectively 1.19 (95% CI, 1.08–1.32; P = 0.001) and 1.27 (1.12–1.43; P < 0.0001).

Conclusion

The use of potassium supplements in chronic HF was not associated with mortality. However, their use was associated with increased hospitalization due to cardiovascular causes and progressive HF.

Introduction

Hypokalemia is common in heart failure (HF) and is associated with poor outcomes [1]. Oral potassium supplements are often used to treat hypokalemia and maintain normokalemia in HF patients with low serum potassium levels. However, the long-term effects of potassium supplement use on outcomes in chronic HF are unknown. The objective of this study was to examine the associations of potassium supplement use with mortality and hospitalization in a propensity-matched cohort of ambulatory chronic HF patients.

Section snippets

Study patients

The Digitalis Investigation Group (DIG) trial was a multi-center randomized clinical trial, the design and results of which have been reported previously [2], [3]. Briefly, 7788 ambulatory chronic HF patients (6800 had left ventricular ejection fraction ≤ 45%) in normal sinus rhythm receiving angiotensin-converting enzyme inhibitors and diuretics were randomized to receive digitalis or placebo. Overall, 2199 (28%) patients were receiving oral potassium supplements at baseline and 5589 (72%)

Patient characteristics

Patients (n = 4262) had a mean (± SD) age of 64 (± 11) years, 28% were women and 16% were nonwhites. There were significant pre-match imbalances in key baseline covariates including gender, race, comorbidity, disease severity and baseline serum potassium, all of which were balanced after matching (Table 1). Absolute standardized differences for all measured covariates were below 5% indicating negligible post-match bias (Fig. 1).

Potassium supplement use and mortality

During a median follow-up of 40 months, 1620 (38%) patients died from

Discussion

Findings from the current analysis demonstrate that oral potassium supplement use was not associated with all-cause mortality in chronic HF, but was associated with increased all-cause hospitalization, which was mostly driven by cardiovascular and HF hospitalizations. Considering that the use of potassium supplements is a marker of hypokalemia, the lack of an independent association between potassium supplement use and all-cause mortality suggests that potassium supplements may have eliminated

Acknowledgement

“The Digitalis Investigation Group (DIG) study was conducted and supported by the NHLBI in collaboration with the DIG Investigators. This manuscript was prepared using a limited access dataset obtained by the NHLBI and does not necessarily reflect the opinions or views of the DIG Study or the NHLBI.”

The authors of this manuscript certify that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [31].

Funding/Support

Dr. Ahmed is supported by the

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This study investigated associations between incident hyperkalemia during acute heart failure (HF) hospitalizations and changes in renin-angiotensin-aldosterone system (RAAS) inhibitors.
Hyperkalemia is a potential complication of RAAS inhibitors. For patients with HF, fear of hyperkalemia may lead to failure to deliver guideline-recommended doses of RAAS inhibitors.
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Overall, serum potassium concentrations increased from 4.3 ± 0.6 mEq/l at baseline to 4.5 ± 0.6 mEq/l at discharge or day 7 (p < 0.001). Patients developing incident hyperkalemia (n = 564; 35%) were more often taking mineralocorticoid antagonists (MRAs) therapy prior to hospitalization and were more likely to have them down-titrated during hospitalization, independent of confounders. Incident hyperkalemia was not associated with adverse outcomes. Yet, down-titration of MRAs during hospitalization was independently associated with 180-day mortality (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.15 to 2.60), regardless of incident hyperkalemia (p_interaction >0.10). Patients with incident hyperkalemia who were discharged with the same or increased dose of MRAs (HR: 0.52; 95% CI: 0.32 to 0.85) or angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) (HR: 0.47; 95% CI: 0.29 to 0.77) had a lower 180-day mortality.
Incident hyperkalemia is common in patients hospitalized for acute HF and is not associated with adverse outcomes. Incident hyperkalemia is associated with down-titration of MRAs, but patients who maintained or increased their dose of MRAs and/or ACE inhibitors/ARB during acute HF hospitalization had better 180-day survival.
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The propensity score was estimated using a nonparsimonious multivariable logistic regression model, with CRPA as the dependent variable and all the baseline characteristics that are presented in Table 1 as covariates. Standardized differences were used to assess prematch imbalances and postmatch balance for all of the baseline covariates, and the findings are presented as a Love plot.19 A standardized difference of less than 10% suggests negligible bias.20
This study aimed to estimate the impact of carbapenem-resistant Pseudomonas aeruginosa (CRPA) on clinical and economic outcomes in a Chinese tertiary care hospital.
Patients were assigned to a carbapenem-susceptible P aeruginosa group or to a CRPA group and matched using propensity score matching. In-hospital mortality, length of stay (LOS), LOS after culture, total hospital costs, daily hospital cost, and 30-day readmission were comparatively analyzed. Subgroup analysis was performed to determine the associations between the subgrouping factors and in-hospital mortality in patients with CRPA isolates.
Within the propensity-matched cohort, in-hospital mortality (12.6% vs 7.8%; P   =   .044), LOS (median 29.0 vs 25.5 days; P   =   .026), LOS after culture (median 18.5 vs 14.0 days; P   =   .029), total hospital costs (median $6,082.0 vs $4,954.2; P  =  .015), and daily hospital cost (median $236.1 vs $223.6; P  =  .045) were significantly higher in CRPA patients than in carbapenem-susceptible P aeruginosa patients. Subgroup analysis revealed a significant interaction between CRPA and age (P  =  .009).
Prevention and control of CRPA among hospitalized patients, especially among those over the age of 65 years, is a good measurement for the reduction of mortality and medical costs derived from CRPA infection or colonization.
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Effects of potassium supplementation on vascular function remain conflicting. This meta-analysis aimed to summarized current literature to fill the gaps in knowledge.
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Seven randomized controlled trials examining 409 participants were included, with dosage of potassium ranging from 40 to 150 mmol/day, and duration of intervention from 6 days to 12 months. Pooling results revealed a significant improvement in PP (SMD − 0.280, 95% CI − 0.493 to − 0.067, p = 0.010), but no improvement in PWV (SMD − 0.342, 95% CI − 1.123 to 0·440, p = 0.391), AI (SMD − 0.114, 95% CI − 0.282 to 0.054, p = 0.184), FMD (SMD 0·278, 95% CI − 0.321 to 0.877, p = 0.363), GTN (SMD − 0.009, 95% CI − 0.949 to 0.930, p = 0.984), and ICAM-1 (SMD − 0.238, 95% CI − 0.720 to 0.244, p = 0.333).
Potassium supplementation was associated with significant improvement of PP, rather than other measurements of vascular function. However, the small number of researches and wide variation of evidences make it difficult to make a definitive conclusion.
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Unfortunately, no information was available on potassium supplementation in both the PROTECT and COACH cohorts. However in a different study, no effect of potassium supplementation on all-cause mortality was found, suggesting that its effects as a confounder are limited.29 In addition, no information was available on usage of thiazide diuretics.
Serum potassium is routinely measured at admission for acute heart failure (AHF), but information on association with clinical variables and prognosis is limited. Potassium measurements at admission were available in 1,867 patients with AHF in the original cohort of 2,033 patients included in the Patients Hospitalized with acute heart failure and Volume Overload to Assess Treatment Effect on Congestion and Renal FuncTion trial. Patients were grouped according to low potassium (<3.5 mEq/l), normal potassium (3.5 to 5.0 mEq/l), and high potassium (>5.0 mEq/l) levels. Results were verified in a validation cohort of 1,023 patients. Mean age of patients was 71 ± 11 years, and 66% were men. Low potassium was present in 115 patients (6%), normal potassium in 1,576 (84%), and high potassium in 176 (9%). Potassium levels increased during hospitalization (0.18 ± 0.69 mEq/l). Patients with high potassium more often used angiotensin-converting enzyme inhibitors and mineralocorticoid receptor antagonists before admission, had impaired baseline renal function and a better diuretic response (p = 0.005), independent of mineralocorticoid receptor antagonist usage. During 180-day follow-up, a total of 330 patients (18%) died. Potassium levels at admission showed a univariate linear association with mortality (hazard ratio [log] 2.36, 95% confidence interval 1.07 to 5.23; p = 0.034) but not after multivariate adjustment. Changes of potassium levels during hospitalization or potassium levels at discharge were not associated with outcome after multivariate analysis. Results in the validation cohort were similar to the index cohort. In conclusion, high potassium levels at admission are associated with an impaired renal function but a better diuretic response. Changes in potassium levels are common, and overall levels increase during hospitalization. In conclusion, potassium levels at admission or its change during hospitalization are not associated with mortality after multivariate adjustment.
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Therapy with evidence-based heart failure (HF) medications has been shown to be associated with lower risk of 30-day all-cause readmission in patients with HF and reduced ejection fraction (HFrEF).
We examined the association of aldosterone antagonist use with 30-day all-cause readmission in this population. Of the 2443 Medicare beneficiaries with HF and left ventricular EF ≤ 35% discharged home from 106 Alabama hospitals during 1998–2001, 2060 were eligible for spironolactone therapy (serum creatinine ≤ 2.5 for men and ≤ 2 mg/dl for women, and serum potassium < 5 mEq/L). After excluding 186 patients already receiving spironolactone on admission, the inception cohort consisted of 1874 patients eligible for a new discharge prescription for spironolactone, of which 329 received one. Using propensity scores for initiation of spironolactone therapy, we assembled a matched cohort of 324 pairs of patients receiving and not receiving spironolactone balanced on 34 baseline characteristics (mean age 72 years, 42% women, 33% African American).
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Published by Elsevier B.V.

Oral potassium supplement use and outcomes in chronic heart failure: A propensity-matched study

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Study patients

Patient characteristics

Potassium supplement use and mortality

Discussion

Acknowledgement

Am Heart J

J Clin Epidemiol

Control Clin Trials

Physiol Behav

Br Vet J

J Am Coll Cardiol

Int J Cardiol

A propensity-matched study of the association of low serum potassium levels and mortality in chronic heart failure

Eur Heart J

Rationale, design, implementation, and baseline characteristics of patients in the DIG trial: a large, simple, long-term trial to evaluate the effect of digitalis on mortality in heart failure

Control Clin Trials

The effect of digoxin on mortality and morbidity in patients with heart failure

N Engl J Med

The central role of propensity score in observational studies for causal effects

Biometrika

Reducing bias in observational studies using subclassification on the propensity score

J Am Stat Assoc

Using propensity score to help design observational studies: application to the tobacco litigation

Health Serv Outcomes Res Methodol

On principles for modeling propensity scores in medical research

Pharmacoepidemiol Drug Saf

Heart failure, chronic diuretic use, and increase in mortality and hospitalization: an observational study using propensity score methods

Eur Heart J