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作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　October 8, 2009 — 根據一項於9月28日內科醫學誌發表的研究結果，相較於其他降血壓藥物，血管張力素轉化酵素抑制劑（ACEIs）更可能造成高血鉀。然而，非糖尿病與高血壓慢性腎臟疾病（CKD）接受ACEIs類藥物治療患者，風險較低，特別是如果起始與追蹤腎絲球廓清率（GFR）超過40 mlmin/1.73 m2的患者或者是接受利尿劑治療病患。
　　
　　來自紐約州紐約市Lenox Hill醫院的Joy M. Weinberg醫師，與其來自非裔美人高血壓及腎臟疾病聯合研究團隊的同事們寫到，使用ACEIs類藥物相關的高血鉀經常被報導，且ACEIs類藥物經常因為擔心高血鉀而減少處方。他們使用非裔美人腎臟與高血壓（AASK）資料庫研究接受ACEIs類藥物以及其他降血壓藥物治療之CKD病患發生高血鉀的盛行率與危險因子。
　　
　　在AASK研究中，1,094位非糖尿病的成人高血壓CKD病患（GFR介於20-65 ml/min/1.73 m2）被觀察3.0~6.4年，且被隨機分派接受ACEIs類藥物、乙型阻斷劑或是非羥基吡啶鈣離子阻斷劑治療。這項分析的終點為血清鉀離子濃度超過5.5 mEq/L（為了換算成mmol/L，乘以1.0），或是臨床中心發起的高血鉀終點。
　　
　　在6497次的鉀離子量測中，51位受試者共發生了80件高血鉀事件，包括76件由中央實驗室檢驗結果確認，以及4件由臨床中心發起的高血鉀終點。
　　
　　GFR介於31~40 ml/min/1.73 m2，相較於GFR大於50 ml/min/1.73 m2的病患，高血鉀的危險比值（HR）為3.61（95% CI為1.42-9.18；P=0.007）。對於GFR低於30 ml/min/1.73 m2的病患，HR為6.81（95% CI為2.67-17.35；P<0.001）。如果GFR介於41~50 ml/min/1.73 m2的病患，高血鉀風險並未增加。
　　
　　使用ACEIs類藥物，相較於鈣離子阻斷劑（HR為7.00；95% CI為2.29-21.39；P<0.001）、或是乙型阻斷劑（HR為2.85；95% CI為1.50-5.42；P=0.001），發生更多的高血鉀事件。當使用利尿劑時，可以降低高血鉀風險達59%。
　　
　　研究作者們寫到，非糖尿病的高血壓病患，接受ACEIs類藥物，發生高血鉀的風險是很低的，特別是如果起始或後續追蹤GFR高於40ml/min/1.73 m2。納入利尿劑於療程中將可以顯著降低高血鉀風險。
　　
　　這項研究的限制包括沒有足夠統計力量偵測不同劑量ACEIs類藥物發生高血鉀機率的差異，且同一類的其他藥物、非裔美人以外人種、以及一般常規照護下的應用性有限。除此之外，GFR低於20 ml/min/1.73 m2組發生高血鉀事件的數目可能是被低估的。
　　
　　作者的結論是，在非糖尿病、高血壓CKD族群，高血鉀風險與GFR、身體質量指數（BMI）成反比，不論你接受的降血壓藥物是什麼。在開始降血壓治療後，使用ACEIs類藥物的風險最高，乙型阻斷劑其次，鈣離子阻斷劑最低。
　　
　　AASK研究由國家糖尿病、消化與腎臟疾病機構贊助，且接受少數族群健康研究辦公室的額外資金贊助，還有輝瑞藥廠、阿斯特捷利康藥廠與King藥廠的藥物捐贈。研究作者們表示已無相關資金上的往來。

ACEIs More Likely Than Other Antihypertensive Drugs to Cause Hyperkalemia

By Laurie Barclay, MD
Medscape Medical News

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.