Colleague's E-mail is Invalid. Your message has been successfully sent to your colleague. Save my selection. The aim of the study was to evaluate the uricosuric effect of the angiotensin II receptor antagonist, losartan, in hypertensive patients with renal transplants who are treated with cyclosporin A CsA.
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Therapy with losartan compared to irbesartan was performed in a Chinese sample of hypertensive patients with elevated serum uric acid SUA levels. There were patients randomized to losartan and to irbesartan , and of these, patients completed the study in the losartan group and in the irbesartan group. No severe AEs were found for either treatment group.
Therapy with losartan decreased SUA levels significantly more than irbesartan in Chinese patients with hypertension and elevated SUA levels, demonstrating the unique uricosuric effect of this ARB in this ethnic group. Elevated serum uric acid SUA is closely associated with several painful conditions, such as gout, kidney stones, vascular disease, renal disease, and cardiovascular events.
Other studies found that SUA is not an independent risk factor for cardiovascular disease or is even considered to be benign, except when associated with gout and kidney stones. Losartan, an angiotensin II receptor antagonist, is an effective antihypertensive drug that also has a uricosuric effect due to its molecular disposition or physical property. The institutional Review Board of the Fu Wai Hospital approved this study and all subjects gave written informed consent.
This was a multicentre 20 clinical institutions , randomized, double-blind, and parallel clinical trial to compare the effects on SUA levels and the antihypertensive efficacy of losartan and irbesartan in a Chinese patient sample with mild to moderate essential hypertension and elevated SUA. The duration of the study was 11 weeks, which included 1 week of screening Figure 1.
During the day preceding, as well as, on the day of blood sample collection, patients recorded their food and beverage intake in a diary card. Fasting blood samples from all patients at screening were analysed for serum urate, serum glucose, total cholesterol, triglycerides, and high-density lipoprotein, serum potassium and creatinine.
Laboratory tests were performed at screening, end of run-in, and at the end of active treatment of 8 weeks. The analysis of the primary and continuous secondary parameters was performed by paired or unpaired Student's t -tests SPSS. Data found to be non-normally distributed were checked for statistical significance by the Wilcoxon's test SPSS.
The primary end point was a comparison between the two treatment groups of the change in SUA from baseline to 8 weeks. There were patients screened, of whom patients were randomized to losartan and to irbesartan Figure 2.
Of these, eligible patients completed the study with losartan and with irbesartan. There were nine patients who did not complete the trial after randomization because of poor compliance. The other patients were dropped from the study because they did not follow the protocol strictly.
As shown in Table 1 , both treatment groups were well matched for baseline clinical characteristics and demographics. The response of SUA to treatment was similar for men and women. Box plots of serum urate in the losartan and irbesartan treatment groups. The demarcations on each plot, progressing from the top down, represent 95th, 75th, 50th median , 25th and 5th percentiles. P -values indicate the significance of the median differences between the losartan and irbesartan treatment groups by the Wilcoxon's test.
The dotted reference line represents the median baseline values. Figure 4 demonstrates the blood pressure response to treatment. Both losartan and irbesartan treatments caused a significant decrease in blood pressure and there was no difference in either systolic or diastolic blood pressure between the two treatment regimens. The blood pressure reductions from baseline to the end of 8 week were statistically significant SiDBP: Graph depicting the change in blood pressure for both the losartan and irbesartan treatment.
Lipid and glucose levels were mainly unaffected by treatment Table 2. At baseline total cholesterol measurements were 5. The increase of serum potassium and decrease of serum creatinine had statistically significant, but the values were in the normal ranges and had no clinical meaning.
No severe adverse events were found in this trial for either treatment group. This was the first time to evaluate the effects of two AT 1 receptor antagonists on SUA in hypertensive patients with hyperuricaemia in Chinese population, which is the largest sample study in this field so far. The primary objective of this study was to compare the effects of losartan and irbesartan on uric acid levels in a Chinese patient sample with mild to moderate essential hypertension and elevated levels of SUA.
Also, we evaluated the antihypertensive efficacy of losartan and irbesartan and determined the treatment effects on lipid and glucose levels in these patients. In the LIFE study, losartan was shown to decrease the elevated levels of uric acid that hypertensives experience. Losartan attenuated the increase in SUA by comparison to the atenolol-treated group over the entire duration of the study of 4.
These results suggest that the unique uricosuric quality of losartan may be an added benefit of this particular angiotensin receptor blocker. Previously, it was shown that losartan induced a significant decrease in SUA levels in patients with hypertension, elevated levels of SUA, and gout, and that effect was not shared by irbesartan. In a small sample of Japanese men, losartan induced a slight time-dependent decrease in the SUA concentration from 5.
Owing to the lack of controlled intervention studies, SUA has been established as an independent risk factor for cardiovascular disease only via statistical adjustment; an association is well accepted, but causality is not. Puig et al. The small sample size of patients evaluated in those studies may partly be responsible for the inconsistent results. In the present study, confounding variables that may influence uric acid levels, such as race, diet, drugs, exercise, renal insufficiency, were considered as exclusion criteria at baseline.
In this study, losartan treatment induced a significant decrease in SUA levels in Chinese patients with hypertension and high levels of uric acid, which is in agreement with the results reported by several others, 2 , 9 , 11 , 12 irbesartan had no significant effect on SUA. Since serum urate is elevated in renal dysfunction or inappropriate diet and may be a marker for cardiovascular disease and a thiazide is often co-prescribed with an angiotensin receptor blocker, the uricosuric effect of losartan may be useful to counteract any rise in urate or increase in risk of gout.
Losartan has no indication for the treatment of elevated levels of SUA, but is indicated for the treatment of hypertension. Several studies have indicated that increased SUA might be an independent risk factor for hypertension-associated morbidity and mortality, so losartan may be a good option in hypertensive patients with elevated levels of SUA. It may be worth pointing out that the uricosuric effect of losartan might be particularly useful in patients with renal dysfunction and those on diuretics for hypertension and heart failure.
However, the primary aims of this study were to compare the effects of losartan and irbesartan on the SUA levels and the antihypertensive efficacy in Chinese patients with mild to moderate essential hypertension and high levels of SUA.
The patients complicating with other diseases such as heart failure, acute myocardial infarction, etc. So these patients that were known to benefit from angiotensin receptor blockers were excluded in this study.
The subjects enrolled in this study just had mild to moderate hypertension, in whom monotherapy should be effective. This is the limitation of this study. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension ; 41 6 : — Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout.
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J Hypertens ; 17 7 : — Fang Qi. People's Medical Officer Press: Beijing, , pp. Google Scholar. Pilot study of the uricosuric effect of DuP, a new angiotensin II receptor antagonist, in healthy subjects. Eur J Clin Pharmacol ; 42 3 : — Pharmacodynamic activity of intravenous E, an angiotensin II antagonist, in patients with essential hypertension. Am J Hypertens ; 7 12 : — Ann Rheum Dis ; 62 6 : — Effect of the angiotensin II receptor antagonist losartan on uric acid and oxypurine metabolism in healthy subjects.
Intern Med ; 41 10 : — Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension. Controlled trial of losartan given concomitantly with different doses of hydrochlorothiazide in hypertensive patients. Blood Press ; 5 1 : 32— Download references. Correspondence to G Liu. Reprints and Permissions. Dang, A. Effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia in Chinese population. J Hum Hypertens 20, 45—50 Download citation.
Received : 09 March Revised : 16 August Accepted : 22 August Published : 10 November
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Department of Pharmacy, Kanazawa National Hospital. Angiotensin II receptor antagonist losartan potassium is demonstrated to have uricosuric effect. We investigated the usefulness of the uricosuric action in the combination therapy using losartan potassium, and furosemide increase serum uric acid concentration. As for 4 groups the serum uric acid concentration and change rate were compared of around the losartan and furosemide intake. As a result change rate of F group and FL group was increased Change rate of F group was increased than FL group; however, there was no significant difference between the two groups. These results suggested that uricosuric effects of losartan might a meliorated the uric acid retention effect of furosemide therapy.
The effect of angiotensin II receptor blockers on hyperuricemia
Studies were excluded that did not explore fractional excretion or serum uric acid as an endpoint, if patients did not have a diagnosis of gout or hyperuricemia at baseline, or if they were non-English language. A total of eight studies met the inclusion criteria. Losartan demonstrated statistically significant reductions in serum uric acid levels or increases in fractional excretion of uric acid in all studies, whereas no other ARB reached statistical benefit. The effect of ARBs on the occurrence of gout attacks or other clinical outcomes were not represented. Four studies evaluated safety effects of these agents indicating abnormalities such as minor changes in lab values.