Home arrow News arrow ACEIs More Likely Than Other Antihypertensive Drugs to Cause Hyperkalemia
ACEIs More Likely Than Other Antihypertensive Drugs to Cause Hyperkalemia Print E-mail
User Rating: / 0
PoorBest 
Post by Administrator   
พุธ, 14 ตุลาคม 2009
        October 8, 2009 — Angiotensin-converting enzyme inhibitors (ACEIs) are more likely than other antihypertensive drugs to cause hyperkalemia, according to the results of a study reported in the September 28 issue of the Archives of Internal Medicine. However, the risk for hyperkalemia is small in nondiabetic patients with hypertensive chronic kidney disease (CKD) treated with ACEIs, particularly if baseline and follow-up glomerular filtration rate (GFR) exceed 40 mL/minute/1.73 m2 and if patients receive a diuretic. "Hyperkalemia from ACEI use has been frequently described, and ACEIs are often underprescribed in patients with CKD because of concerns of hyperkalemia," write Joy M. Weinberg, MD, from Lenox Hill Hospital in New York, NY, and colleagues from the African American Study of Hypertension and Kidney Disease Collaborative Research Group. "The incidence and factors associated with hyperkalemia in patients with...CKD treated with...ACEIs and other antihypertensive drugs was investigated using the African American Study of Kidney Disease and Hypertension (AASK) database."
In the AASK trial, 1094 nondiabetic adults with hypertensive CKD (GFR, 20 - 65 mL/minute/1.73 m2) were observed for 3.0 to 6.4 years and randomly assigned to treatment with an ACEI, beta-blocker, or dihydropyridine calcium channel blocker. For this analysis, the main endpoints were a serum potassium level greater than 5.5 mEq/L (to convert to millimoles per liter, multiply by 1.0), or a clinical center–initiated hyperkalemia stop point.
Among 6497 potassium measurements, 80 hyperkalemic events were identified in 51 participants, including 76 events identified by a central laboratory result and 4 events identified by a clinical center–initiated hyperkalemia stop point.
The hazard ratio (HR) for hyperkalemia in patients with a GFR between 31 and 40 mL/minute/1.73m2 vs a GFR higher than 50 mL/minute/ 1.73 m2 after multivariable adjustment was 3.61 (95% confidence interval [CI], 1.42 - 9.18; P = .007). For a GFR lower than 30 mL/minute/1.73 m2, HR was 6.81 (95% CI, 2.67 - 17.35; P < .001). Risk for hyperkalemia was not increased if GFR was 41 to 50 mL/minute/1.73 m2.
There were more episodes of hyperkalemia with ACEI use vs calcium channel blocker use (HR, 7.00; 95% CI, 2.29 - 21.39; P < .001) or with beta-blocker use (HR, 2.85; 95% CI, 1.50 - 5.42; P = .001). Risk for hyperkalemia was decreased by 59% when diuretics were used.
"In nondiabetic patients with hypertensive CKD treated with ACEIs, the risk of hyperkalemia is small, particularly if baseline and follow-up GFR is higher than 40 mL/min/1.73 m2," the study authors write. "Including a diuretic in the regimen may markedly reduce risk of hyperkalemia."
Limitations of this study include probably insufficient power to detect a difference in the rate of hyperkalemia between dose levels of ACEIs and limited generalizability to other drugs in the classes studied, to ethnic groups other than African Americans, and to a general routine care setting. In addition, the number of hyperkalemic events in the group with a GFR of less than 20 mL/minute/1.73m2 was probably underestimated.
"In the setting of nondiabetic, hypertensive CKD, the risk of hyperkalemia is inversely related to GFR and BMI [body mass index], regardless of antihypertensive treatment," the study authors conclude. "After initiation of antihypertensive therapy, the risk of hyperkalemia is greatest with ACEI use, intermediate with BB [beta-blocker] use, and lowest with CCB [calcium channel blocker] use."
The AASK trial was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and received additional financial support from the Office of Research in Minority Health and drug donations from Pfizer Inc, AstraZeneca Pharmaceuticals, and King Pharmaceuticals. The study authors have disclosed no relevant financial relationships.
Arch Intern Med. 2009;169:1587-1594. Abstract
Clinical Context
In nondiabetic patients with CKD, ACEIs may slow the progression of renal disease. However, ACEIs may cause hyperkalemia via interfering with production and/or secretion of aldosterone, thereby impairing renal potassium excretion.
Beta-blocker use may also cause hyperkalemia by redistributing potassium from intracellular to extracellular compartments. AASK was a randomized clinical trial in nondiabetic African Americans with hypertensive CKD, designed to evaluate the effects of 3 different classes of antihypertensive agents on progression of renal disease.
Study Highlights
• When the trial phase of AASK was complete, the National Institute of Diabetes and Digestive and Kidney Diseases-appointed Data Safety Monitoring Board asked the investigators to use the AASK database to determine factors associated with development of hyperkalemia.
• This report describes the incidence of hyperkalemia associated with use of different classes of antihypertensive drugs in the AASK, as well as independent associations of hyperkalemia with other clinically measured factors.
• In the AASK trial, 1094 nondiabetic adults with hypertensive CKD, defined as a GFR of 20 to 65 mL/minute/1.73 m2, were observed for 3.0 to 6.4 years.
• Participants were randomly assigned to receive an ACEI, beta-blocker, or dihydropyridine calcium channel blocker.
• For this analysis, the main endpoints were serum potassium level of more than 5.5 mEq/L or a hyperkalemia stop point initiated by each clinical center.
• Among 6497 potassium measurements obtained, 80 events were identified in 51 subjects.
• Of these 80 events, 76 events were driven by a central laboratory result and 4 by a clinical center-initiated hyperkalemia stop point.
• After multivariable adjustment, the HR for hyperkalemia in patients with a GFR between 31 and 40 mL/minute/1.73 m2 (vs a GFR > 50 mL/minute/1.73 m2) was 3.61 (95% CI, 1.42 - 9.18; P = .007).
• HR for hyperkalemia in patients with a GFR of less than 30 mL/minute/1.73 m2 was 6.81 (95% CI, 2.67 - 17.35; P < .001).
• Risk for hyperkalemia was not increased in patients with a GFR of 41 to 50 mL/minute/1.73 m2.
• Use of ACEIs was associated with more episodes of hyperkalemia (HR vs calcium channel blocker use, 7.00; 95% CI, 2.29 - 21.39; P < .001; HR vs beta-blocker use, 2.85; 95% CI, 1.50 - 5.42; P = .001).
• Risk for hyperkalemia was decreased by 59% in association with diuretic use.
• Other independent risk factors for the development of hyperkalemia, regardless of antihypertensive drug class, were older age, baseline protein excretion, and both baseline and follow-up GFR and potassium levels.
• BMI of 25 kg/m2 or less was associated with significantly increased risk for hyperkalemia vs a BMI of more than 25 kg/m2.
• Baseline urinary protein-to-creatinine ratio, a marker of renal dysfunction, was independently associated with hyperkalemic events.
• The investigators concluded that the risk for hyperkalemia was small in nondiabetic patients with hypertensive CKD treated with ACEIs, particularly if baseline and follow-up GFR were more than 40 mL/minute/1.73 m2.
• They also suggested that including a diuretic in the regimen may markedly reduce the risk for hyperkalemia.
• Limitations of this study include probable underestimation of the number of hyperkalemic events in the group with a GFR of less than 20 mL/minute/1.73 m2 and limited power to detect a difference in the rate of hyperkalemia between dose levels of ACEIs.
• In addition, generalizability may be limited to other drugs in the classes studied, to ethnic groups other than African Americans, and to a general routine care setting.
Clinical Implications
• According to an analysis of data from AASK, the risk for hyperkalemia is small in nondiabetic patients with hypertensive CKD treated with ACEIs, particularly if baseline and follow-up GFR are more than 40 mL/minute/1.73 m2. Use of ACEIs was associated with more episodes of hyperkalemia vs calcium channel blocker use or beta-blocker use.
• Diuretic use was associated with a reduced risk for hyperkalemia. Independent risk factors for the development of hyperkalemia, regardless of antihypertensive drug class, were older age, baseline protein excretion, and both baseline and follow-up GFR and potassium levels.
< Previous   Next >