-
1.
Effect of Perioperative Glucose-Insulin-Potassium Therapy in Patients Undergoing On-Pump Cardiac Surgery: A Meta-Analysis.
Li, Q, Yang, J, Zhang, J, Yang, C, Fan, Z, Yang, Y, Zheng, T, Yang, J
The heart surgery forum. 2020;(1):E063-E069
Abstract
OBJECTIVE The role of glucose-insulin-potassium (GIK) infusion during cardiac surgery has held interest for so many years without a clear answer. The aim of this meta-analysis was to evaluate the effect of GIK therapy on outcomes in patients undergoing on-pump cardiac surgery. METHODS A comprehensive online review was performed in The Web of Science, Embase, Medline, PubMed, and The Cochrane Library databases from 2000 to 2019. Eligible studies included randomized controlled trials (RCTs) that compared GIK treatment with placebo or standard care during on-pump cardiac surgery. Risk ratios (RR) were used for binary outcomes and mean difference (MD) was used for continuous variables; both with their 95% confidence intervals (CI). RESULTS A total of 18 RCTs involving 2,131 patients met the inclusion criteria. Compared with the control group, the GIK treatment significantly reduced in-hospital mortality (RR = 0.56, 95% CI: 0.32-0.97; P = .04), postoperative myocardial infarctions (MI) (RR = 0.71, 95% CI: 0.56-0.91; P = .006), the use of inotropic support (RR = 0.53, 95% CI: 0.45-0.63; P < .00001), and length of stay in the intensive care unit (ICU) (MD = -0.33, 95% CI: -0.52--0.14; P = .0007). Moreover, GIK treatment seemed to be associated with fewer postoperative atrial fibrillation (AF) (RR = 0.81, 95% CI: 0.64-1.03; P = .09). CONCLUSIONS In patients undergoing on-pump cardiac surgery, GIK infusion has a beneficial role in mortality during hospital stay and demonstrates superior efficacy versus standard care for reduction in postoperative MI, AF, ICU length of stay as well as inotropic agent requirements.
-
2.
Twenty-Four-Hour Urinary Sodium and Potassium Excretion in China: A Systematic Review and Meta-Analysis.
Tan, M, He, FJ, Wang, C, MacGregor, GA
Journal of the American Heart Association. 2019;(14):e012923
Abstract
Background In China, high sodium and low potassium intakes result in elevated blood pressure, a major cause of cardiovascular disease, yet the intake estimates lack accuracy and nutritional strategies remain limited. Methods and Results We aimed to determine sodium and potassium intake by systematically searching for and quantitatively summarizing all published 24-hour urinary sodium and potassium data (ie, the most accurate method). MEDLINE , EMBASE , Scopus, China National Knowledge Infrastructure, and Wanfang were searched up to February 2019. All studies reporting 24-hour urinary sodium or potassium in China were included; hospitalized patients were excluded. Data were pooled using random-effects meta-analysis and heterogeneity was explored with meta-regression. Sodium data were reported in 70 studies (n=26 767), 59 of which also reported potassium (n=24 738). Mean sodium and potassium excretions were 86.99 mmol/24 h (95% CI , 69.88-104.10) and 14.65 mmol/24 h (95% CI , 11.10-18.20) in children aged 3 to 6 years, 151.09 mmol/24 h (95% CI , 131.55-170.63) and 25.23 mmol/24 h (95% CI , 22.37-28.10) in children aged 6 to 16 years, and 189.07 mmol/24 h (95% CI , 182.14-195.99) and 36.35 mmol/24 h (95% CI , 35.11-37.59) in adults aged >16 years. Compared with southern China, sodium intake was higher in northern China ( P<0.0001) but is declining ( P=0.0066). Conclusions Average sodium intake in all age groups across China is approximately double the recommended maximum limits, and potassium intake is less than half that recommended. Despite a decline, sodium intake in northern China is still among the highest in the world, and the North-South divide persists. Urgent action is needed to simultaneously reduce sodium and increase potassium intake across China.
-
3.
Pivotal clinical trials, meta-analyses and current guidelines in the treatment of hyperkalemia.
Bianchi, S, Regolisti, G
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(Suppl 3):iii51-iii61
Abstract
Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with advanced stages of chronic kidney disease (CKD), is a potentially life-threatening clinical condition due to an increased risk of fatal arrhythmias, and strongly impacts the quality of life and prognosis of CKD patients. Moreover, while renin-angiotensin-aldosterone system inhibitors (RAASIs) represent the most cardio-nephro-protective drugs used in clinical practice, the treatment with these drugs per se increases serum potassium (sK) values, particularly when heart failure and diabetes mellitus coexist. In fact, the onset or recurrence of HK is frequently associated with not starting, down-titrating or withdrawing RAASIs, and is an indication to begin renal replacement treatment in end-stage renal disease. Current strategies aimed at preventing and treating chronic HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials. Indeed, dietary potassium restriction, the use of sodium bicarbonate or diuretics, the withdrawal or down-titration of RAASIs, or the administration of old potassium binders, namely sodium polystyrene sulphonate and calcium polystyrene sulphonate, have limited efficacy and are poorly tolerated; therefore, these strategies are not suitable for long-term control of sK. As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for HK. The development of new potassium binders may change the treatment landscape in the near future. This review summarizes the current evidence on the treatment of chronic HK in cardio-renal patients.
-
4.
Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry.
Irvin, MR, Sitlani, CM, Noordam, R, Avery, CL, Bis, JC, Floyd, JS, Li, J, Limdi, NA, Srinivasasainagendra, V, Stewart, J, et al
The pharmacogenomics journal. 2019;(1):97-108
-
-
Free full text
-
Abstract
We evaluated interactions of SNP-by-ACE-I/ARB and SNP-by-TD on serum potassium (K+) among users of antihypertensive treatments (anti-HTN). Our study included seven European-ancestry (EA) (N = 4835) and four African-ancestry (AA) cohorts (N = 2016). We performed race-stratified, fixed-effect, inverse-variance-weighted meta-analyses of 2.5 million SNP-by-drug interaction estimates; race-combined meta-analysis; and trans-ethnic fine-mapping. Among EAs, we identified 11 significant SNPs (P < 5 × 10-8) for SNP-ACE-I/ARB interactions on serum K+ that were located between NR2F1-AS1 and ARRDC3-AS1 on chromosome 5 (top SNP rs6878413 P = 1.7 × 10-8; ratio of serum K+ in ACE-I/ARB exposed compared to unexposed is 1.0476, 1.0280, 1.0088 for the TT, AT, and AA genotypes, respectively). Trans-ethnic fine mapping identified the same group of SNPs on chromosome 5 as genome-wide significant for the ACE-I/ARB analysis. In conclusion, SNP-by-ACE-I /ARB interaction analyses uncovered loci that, if replicated, could have future implications for the prevention of arrhythmias due to anti-HTN treatment-related hyperkalemia. Before these loci can be identified as clinically relevant, future validation studies of equal or greater size in comparison to our discovery effort are needed.
-
5.
Association of Low Serum Potassium Levels and Risk for All-Cause Mortality in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.
Zhang, Y, Chen, P, Chen, J, Wang, L, Wei, Y, Xu, D
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2019;(1):22-31
Abstract
Dyskalemia is a risk factor for mortality in patients without CKD, but the effect of hypokalemia in patients with CKD remains uncertain. PubMed, Embase, Cochrane, and Ovid databases were searched from inception to December 31, 2017 for studies that reported all-cause and cardiovascular mortality or events in patients with CKD (any stage). Pooled hazard ratios (HR) and corresponding 95% CI were calculated. A total of 11 clinical studies enrolling 57 234 subjects with CKD were included in the meta-analysis. Compared with control serum potassium (SK) levels, low SK (SK <4.0 mEq/L) was associated with higher risk of all-cause mortality in a random-effects model (HR = 1.57; 95% CI: 1.25-1.97). Moderate low SK (<3.5 mEq/L) increased risk of all-cause mortality by 105%. Mild low SK (3.5~4.0 mEq/L) also increased all-cause mortality risk (HR = 1.18, 95% CI: 1.11-1.26). Low SK was also associated with increased cardiovascular mortality (HR = 1.40, 95% CI: 1.22-1.62) and ESRD risk (HR = 1.35, 95% CI: 1.18-1.54). SK <4.0 mEq/L was associated with higher mortality risk in CKD patients, especially in those with SK <3.5 mEq/L. Additional prospective studies will be necessary to explore this relationship, as well as whether correcting hypokalemia decreases mortality in patients with CKD.
-
6.
Serum potassium levels and mortality of patients with acute myocardial infarction: A systematic review and meta-analysis of cohort studies.
Xi, H, Yu, RH, Wang, N, Chen, XZ, Zhang, WC, Hong, T
European journal of preventive cardiology. 2019;(2):145-156
Abstract
BACKGROUND The evidence of current epidemiological studies investigating the association between serum potassium levels and mortality of acute myocardial infarction (AMI) patients is controversial and inadequate. DESIGN Systematic review and meta-analysis. METHODS Two researchers independently searched the PubMed, EMBASE and Web of Science databases to identify observational studies published prior to 31 October 2017. Similarly, two researchers separately extracted data and any differences were resolved by discussion. Pooled relative risks and 95% confidence intervals (CIs) were computed with an inverse variance-weighted random-effects model. Heterogeneity among studies was assessed with the I2 statistic. RESULTS Seven cohort studies were included for analysis. Compared with the reference group (3.5 to <4.0 mEq/L), the pooled relative risks of mortality were 1.15 (95% CI = 1.00-1.32), 1.09 (95% CI = 0.97-1.24), 1.42 (95% CI = 1.19-1.70) and 1.85 (95% CI = 1.39-2.47) for AMI patients with a potassium level of<3.5, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mEq/L, respectively. For admission and post-admission potassium, although J-shaped associations were also indicated, non-significant results were observed for AMI patients with potassium levels of <3.5 mEq/L when compared with the reference group. Notably, in subgroup analyses of study characteristics, stratified by study quality, geographic location, type of outcome, number of cases, type of AMI, and adjustment for potential confounders, the findings were broadly consistent across strata. CONCLUSIONS These findings indicate that both lower (<3.5 mEq/L) and higher (≥4.5 mEq/L) serum potassium levels are associated with an increased risk of mortality of patients with AMI.
-
7.
Association of serum potassium concentration with mortality and ventricular arrhythmias in patients with acute myocardial infarction: A systematic review and meta-analysis.
Colombo, MG, Kirchberger, I, Amann, U, Dinser, L, Meisinger, C
European journal of preventive cardiology. 2018;(6):576-595
Abstract
Background Challenging clinical practice guidelines that recommend serum potassium concentration between 4.0-5.0 mEq/L or ≥4.5 mEq/L in patients with acute myocardial infarction, recent studies found increased mortality risks in patients with a serum potassium concentration of ≥4.5 mEq/L. Studies investigating consequences of hypokalemia after acute myocardial infarction revealed conflicting results. Therefore, the aim of this systematic review and meta-analysis was to combine evidence from previous studies on the association of serum potassium concentration with both short and long-term mortality as well as the occurrence of ventricular arrhythmias. Design Systematic review and meta-analysis. Methods A structured search of MEDLINE and EMBASE databases yielded 23 articles published between 1990 and January 2017 that met the inclusion criteria. Study selection, data extraction and quality assessment were carried out by three reviewers. Random effects models were used to pool estimates across the included studies and sensitivity analyses were performed when possible. Results Twelve studies were included in the meta-analysis. Both pooled results from six studies investigating short-term mortality and from five studies examining long-term mortality revealed significantly increased risks in patients with serum potassium concentrations of <3.5 mEq/L, 4.5-<5.0 mEq/L and ≥5.0 mEq/L after acute myocardial infarction. In addition, a serum potassium concentration of <3.5 mEq/L was significantly associated with the occurrence of ventricular arrhythmias. Conclusions Mortality, both short and long term, and the occurrence of ventricular arrhythmias in patients with acute myocardial infarction seem to be negatively associated with hypokalemic serum potassium concentration. There is evidence for adverse consequences of serum potassium concentrations of ≥4.5 mEq/L. Due to the heterogeneity among existing studies, further research is necessary to confirm the need to change clinical practice guidelines.
-
8.
The tolerability and safety profile of patiromer: a novel polymer-based potassium binder for the treatment of hyperkalemia.
Pitt, B, Garza, D
Expert opinion on drug safety. 2018;(5):525-535
Abstract
Hyperkalemia (HK) occurs often among patients with chronic kidney disease (CKD) and heart failure (HF) and those treated with renin-angiotensin-aldosterone system inhibitors (RAASI). Even small deviations from normal potassium levels carry increased risk of mortality. Patiromer is approved for treatment of HK and has been shown in clinical trials to reduce serum potassium among patients with HK and comorbid conditions. Areas covered: We review pooled data from two clinical trials of patiromer in patients with CKD and HK, safety of patiromer in special populations, drug-drug interaction (DDI) studies, and other studies in healthy volunteers. Expert opinion: Potassium must be maintained within a narrow range to avoid increased risk of mortality. Patients with CKD and HF and those receiving RAASI require careful monitoring of potassium levels. Patiromer effectively reduces serum potassium, and gastrointestinal adverse events (AEs) are the most common patiromer-associated AEs. Effective management of HK with patiromer may allow use of RAASI at optimal doses as recommended by treatment guidelines. Future research should examine the potential for potassium binders, including patiromer, to extend use of RAASI in appropriate patient populations.
-
9.
Association of Abnormal Serum Potassium Levels with Arrhythmias and Cardiovascular Mortality: a Systematic Review and Meta-Analysis of Observational Studies.
Hoppe, LK, Muhlack, DC, Koenig, W, Carr, PR, Brenner, H, Schöttker, B
Cardiovascular drugs and therapy. 2018;(2):197-212
Abstract
PURPOSE To provide the first systematic review and meta-analysis of observational studies on the association of abnormal serum potassium and cardiovascular outcomes. METHODS Medline and ISI Web of Knowledge were systematically searched from inception until November 24, 2017. Data synthesis of relevant studies was performed using random effects model meta-analyses. RESULTS Meta-analyses included 310,825 participants from 24 studies. In the older general population, low serum potassium was associated with a 1.6-fold increased risk of supraventricular arrhythmias (risk ratio [95% confidence interval] 1.62 [1.02-2.55]). Contrarily, high serum potassium was associated with increased cardiovascular mortality (CVM) (1.38 [1.14-1.66]). In patients with acute myocardial infarction, the risk of ventricular arrhythmias was increased for high serum potassium (2.33 [1.60-3.38]). A U-shaped association was observed with a composite cardiovascular outcome in hypertensive patients (2.6-fold increased risk with hypokalemia and 1.7-fold increased risk with hyperkalemia), with CVM in dialysis patients (1.1-fold increased risk with hypokalemia and 1.4-fold increased risk with hyperkalemia) and with CVM in heart failure patients (albeit not statistically significant). Further, only hyperkalemia was associated with an increased risk of a composite cardiovascular outcome in both dialysis (1.12 [1.03-1.23]) and chronic kidney disease (1.34 [1.06-1.71]) patients. CONCLUSIONS Controlled clinical trials are needed to determine which populations may profit from more frequent potassium-monitoring and subsequent interventions, e.g., change or withdrawal of potassium-influencing drugs, in order to restore normal values and prevent cardiovascular outcomes. REGISTRATION DETAILS Registration in PROSPERO (Centre for Reviews and Dissemination University of York, York, UK): CRD42016048897 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=48897 ).
-
10.
The effect of potassium supplementation on blood pressure in hypertensive subjects: A systematic review and meta-analysis.
Filippini, T, Violi, F, D'Amico, R, Vinceti, M
International journal of cardiology. 2017;:127-135
Abstract
BACKGROUND Several intervention studies have investigated the relation between potassium intake and blood-pressure, particularly in hypertensive subjects. However, uncertainties still exist about the existence and the amount of such an effect, and about the role of some potential effect-modifiers, including the baseline potassium intake and geographical area. METHODS We carried out a systematic review of the evidence concerning such relation in hypertensive subjects, performing a meta-analysis and a meta-regression of RCT with selective and validated long-term (≥4weeks) potassium supplementation. We also implemented 'unconventional' search strategies in order to identify all potentially interesting studies. RESULTS Overall, potassium supplementation decreased systolic blood pressure of 4.48mmHg (95% CI 3.07-5.90) and diastolic blood pressure of 2.96mmHg (1.10-4.82). There was little evidence of dose-response relation between blood-pressure decrease and potassium supplementation, as assessed through total achieved potassium intake in the intervention groups, difference in achieved potassium intake, and study duration. However, lower (<90mmol/day) potassium intake at baseline was associated with a higher blood-pressure lowering effect, as were higher sodium intake (particularly ≥4g/day), higher sodium-to-potassium ratio and the absence of any anti-hypertensive drug treatment. Trials conducted in Southern Europe showed the highest blood-pressure lowering effect compared with the remaining regions. CONCLUSIONS Potassium supplementation in hypertensives was generally associated with decreased blood pressure, particularly in high sodium consumers, subjects not on hypertensive drug treatment, and those in the lowest category of potassium intake. An adequate dietary intake of potassium, in the order of 90mmol/day, should be achieved for blood pressure control.