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Long-term safety of high-dose angiotensin receptor blocker therapy in hypertensive patients with chronic kidney disease.
J Hypertens Suppl. 2006 Mar; 24(1):S95-9.JH

Abstract

BACKGROUND

Reducing urinary protein excretion in patients with renal disease is an important therapeutic target to prevent the progression of renal and cardiovascular disease. Drugs such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARBs), which block the actions of the renin-angiotensin-aldosterone system, are recommended because they reduce blood pressure and proteinuria. Recently, the use of higher doses of ARBs, up to three times the maximal approved dose, resulted in further reductions in protein excretion. Despite the effectiveness of this therapeutic approach, no long-term safety analysis has been conducted in patients receiving high-dose ARB treatment.

OBJECTIVE

To study the long-term safety of high-dose ARB treatment.

METHODS

We observed 48 patients [44 men and 4 women; ages 64 +/- 15 years (mean +/- SD), weight 88 +/- 28 kg, estimated glomerular filtration rate 53 +/- 23 ml/min] receiving treatment with high doses (1.5-5 times greater than the maximum approved dose) of ARBs, for 40 +/- 24 months (range 6-98 months).

RESULTS

The average ARB dose tended to increase over time and was 3.2 +/- 1.2 times greater at the end of the study than that at the start. Systolic blood pressure was similar at the beginning and end of the study period (132 +/- 20 and 125 +/- 20 mmHg, respectively), but diastolic blood pressure showed a decrease throughout the study and was significantly reduced (P < 0.05) in association with 1.5x and 2x the maximum ARB dose (73 +/- 11 and 72 +/- 10 mmHg, respectively) when compared with baseline (78 +/- 11 mm Hg). There was a trend (P > 0.05) for increases in concentrations of serum potassium (0.2 +/- 0.9 mmol/l) and creatinine (0.3 +/- 0.7 mg/dl) with increases in dose from baseline to the end of the study. Serum creatinine concentration was greater (P < 0.05) at the periods of 3x and 4x the maximum dose, but this represented increases of only 12 and 20% from baseline, respectively.

CONCLUSIONS

High-dose ARB treatment in patients with chronic renal disease is not associated with any clinically significant long-term negative effects on serum creatinine or potassium and is thus a important therapeutic modality with which to achieve further reductions in urinary protein excretion.

Authors+Show Affiliations

College of Arts and Sciences, Boston University, Boston, Massachusetts, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16601581

Citation

Weinberg, Adam J., et al. "Long-term Safety of High-dose Angiotensin Receptor Blocker Therapy in Hypertensive Patients With Chronic Kidney Disease." Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension, vol. 24, no. 1, 2006, pp. S95-9.
Weinberg AJ, Zappe DH, Ramadugu R, et al. Long-term safety of high-dose angiotensin receptor blocker therapy in hypertensive patients with chronic kidney disease. J Hypertens Suppl. 2006;24(1):S95-9.
Weinberg, A. J., Zappe, D. H., Ramadugu, R., & Weinberg, M. S. (2006). Long-term safety of high-dose angiotensin receptor blocker therapy in hypertensive patients with chronic kidney disease. Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension, 24(1), S95-9.
Weinberg AJ, et al. Long-term Safety of High-dose Angiotensin Receptor Blocker Therapy in Hypertensive Patients With Chronic Kidney Disease. J Hypertens Suppl. 2006;24(1):S95-9. PubMed PMID: 16601581.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term safety of high-dose angiotensin receptor blocker therapy in hypertensive patients with chronic kidney disease. AU - Weinberg,Adam J, AU - Zappe,Dion H, AU - Ramadugu,Rajeev, AU - Weinberg,Marc S, PY - 2006/4/8/pubmed PY - 2006/7/6/medline PY - 2006/4/8/entrez SP - S95 EP - 9 JF - Journal of hypertension. Supplement : official journal of the International Society of Hypertension JO - J Hypertens Suppl VL - 24 IS - 1 N2 - BACKGROUND: Reducing urinary protein excretion in patients with renal disease is an important therapeutic target to prevent the progression of renal and cardiovascular disease. Drugs such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARBs), which block the actions of the renin-angiotensin-aldosterone system, are recommended because they reduce blood pressure and proteinuria. Recently, the use of higher doses of ARBs, up to three times the maximal approved dose, resulted in further reductions in protein excretion. Despite the effectiveness of this therapeutic approach, no long-term safety analysis has been conducted in patients receiving high-dose ARB treatment. OBJECTIVE: To study the long-term safety of high-dose ARB treatment. METHODS: We observed 48 patients [44 men and 4 women; ages 64 +/- 15 years (mean +/- SD), weight 88 +/- 28 kg, estimated glomerular filtration rate 53 +/- 23 ml/min] receiving treatment with high doses (1.5-5 times greater than the maximum approved dose) of ARBs, for 40 +/- 24 months (range 6-98 months). RESULTS: The average ARB dose tended to increase over time and was 3.2 +/- 1.2 times greater at the end of the study than that at the start. Systolic blood pressure was similar at the beginning and end of the study period (132 +/- 20 and 125 +/- 20 mmHg, respectively), but diastolic blood pressure showed a decrease throughout the study and was significantly reduced (P < 0.05) in association with 1.5x and 2x the maximum ARB dose (73 +/- 11 and 72 +/- 10 mmHg, respectively) when compared with baseline (78 +/- 11 mm Hg). There was a trend (P > 0.05) for increases in concentrations of serum potassium (0.2 +/- 0.9 mmol/l) and creatinine (0.3 +/- 0.7 mg/dl) with increases in dose from baseline to the end of the study. Serum creatinine concentration was greater (P < 0.05) at the periods of 3x and 4x the maximum dose, but this represented increases of only 12 and 20% from baseline, respectively. CONCLUSIONS: High-dose ARB treatment in patients with chronic renal disease is not associated with any clinically significant long-term negative effects on serum creatinine or potassium and is thus a important therapeutic modality with which to achieve further reductions in urinary protein excretion. SN - 0952-1178 UR - https://www.unboundmedicine.com/medline/citation/16601581/Long_term_safety_of_high_dose_angiotensin_receptor_blocker_therapy_in_hypertensive_patients_with_chronic_kidney_disease_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=16601581.ui DB - PRIME DP - Unbound Medicine ER -