Sowmya P, Balaji c, Elizabeth A. A, Punnagai P. Comparative Study on the Efficacy of Losartan and Amlodipine in Reducing Microalbuminuria in Patients with Primary Hypertension, a Randomized open Label Parallel Group Study. Biomed Pharmacol J 2019;12(3).

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Manuscript received on :24-May-2019
Manuscript accepted on :12 Sep 2019
Published online on: 28-09-2019

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Plagiarism Check: Yes
Reviewed by: Vijay Rekulapally
Second Review by: Anusha Dhakshinamoorthi
Final Approval by: Dr. Ian James Martin

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Sowmya P¹, Balaji c²*, Arul Amutha Elizabeth³ and Punnagai⁴

¹Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai,

²Department of Rheumatology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai

³Department of Pharmacology, Sree Balaji Medical College and hospitals, chrompet , Chennai Tamilnadu.

⁴Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai Tamilnadu.

Corresponding Author E-mail: dr.mailbalu@gmail.com

DOI : https://dx.doi.org/10.13005/bpj/1767

Abstract

Majority of the cardiovascular and renal diseases has been associated with Hypertension Primary hypertension also called as essential or idiopathic hypertension tends to be familial and the prevalence increases with age. Microalbuminuria has been correlated with microvascular damage in hypertension patients.To Compare the Efficacy of Losartan and Amlodipine in reducing microalbuminuria in patients with primary hypertension.An open labeled parellel group cross sectioned study was conducted in Sree Balaji medical college and hospital, Department of General Medicine Chrompet during the period of March 2015 to December 2015. In our research study suggested that there are major differences between Angiotensin receptor blockers and calcium chaneel blockers in reducing microalbuminuria in essential hypertension. After 6-month of losartan treatment, the reduction in urine albumin level  is statistically highly significant (p<0.01) 71.17±66.04**. compared with baseline101.95±94.70. After 6 months of Amlodipine treatment group resulted in statistically not significant (p>0.05) in urine albumin excretion level 99.85±96.35 compared with baseline 101.11±95.28 in essential hypertensive patients .Hence  this study shows that losartan after administration for 6 months ,conferred significant advantages over amlodipine in terms of reduction of urinary albumin levels levels in hypertension patients

Keywords

Arbs and Ccbs; Microalbuminuria; Primary Hypertension

Introduction

Hypertension affects almost one billion individual worldwide (1). Hypertension accounts for 13.5 % of mortality annually. 90-95% of the patients are considered as primary hypertension in which etiology is due to life style changes and genetic factors (2).

Albuminuria is one of the best indicators of poor renal outcomes of essential hypertension and type 2 diabetes(3). It is also approved as a recent indicator of cardiovascular outcomes (4). Renal and Cardiovascular adverse effects are reduced by reducing albumin levels in the urine

Losartan is the first orally available drug, selective, competitive Angiotensin II receptor type 1 antagonist, its active metabolite is 5 –carboxylic acid which is a very long acting and 30 -40 times more potent. It has a prominent effect in urinary albumin excretion (5).Amlodipine is the dihydropyridine type calcium channel blocker .It is peripheral arterial vasodilator which causes reduction in peripheral arterial resistance and blood pressure.

The anti-hypertensive drugs used now are mostly designed to effect pathophysiological, cellular and biochemical mechanism involved in hypertension and not to address the disorders involved in urine albumin excretion. Several animal and human studies suggested that AT II receptor blocker and CCB have remarkable reduction in microalbuminuria (6). Hence this study was conducted in primary hypertension patients to reduce microalbuminuria by comparing the efficacy of Losartan (AT II Receptor Antagonist) with Amlodipine (CCB ) .

Objective

To Compare the Efficacy of Losartan and Amlodipine in reducing microalbuminuria in patients with primary hypertension

Materials and Methods

An open labeled parellel cross sectioned study was conducted in the General Medicine, Department at Sree Balaji medical college and hospital, Chrompet during March 2015 to December 2015”. The study was approved by institutional ethics committee and written consent obtained from the patient. The study subjects were assigned randomly using a computer generated randomization chart to either of the two groups group A and group B ,each group consists of 50 patients of primary hypertension . The “inclusion criteria are Adult patients of age >18 years. Newly diagnosed Hypertensive patients with ≥140/90 mm Hg of blood pressure  , or <1 year   period of  hypertension patients without taking any antihypertensive medications. and hypertensive patients with a blood pressure ≥140/90 mm Hg, for more than 1 year period and taking 2 or more anti-hypertensive medications but still BP is not controlled). The exclusion criteria are patient with sensitivity to ARB or CCB , breast-feeding, pregnant . Patient with  clinical cardiovascular disease , renal and hepatic disease (creatinine >2.2mg/dl).  Patient with >180/ 110 mm Hg of blood pressure systolic. Type II Diabetes Mellitus and patients with secondary hypertension.

Procedure

Urine microalbumin will be analyzed using immunoturbidimetry method by collecting spot urine samples done during initiation of study, after 3 months, and after 6 months of treatment.

Statistical Analysis

The analysis of the Data was assessed by SPSS software for Windows (version 10). The results were convey as mean±SD. ANOVA test of One-way analysis  was used to measure the baseline data . The end result values was calculated at the end of 24-Week treatment minus the value obtained at baseline. The significance differences between and within groups was analysed by ANOVA. Student’s t-test are assessed to compare Before and after treatment values. At   the   end   of   the   duration of the study   losartan and amlodipine effect   on microalbumin levels were compared    in   terms   of therapeutic efficacy and adverse effects. p -values (p<0.05) were treated as statistically significant in two tailed test.

Results

Table 1 : Matching of the two groups according to their baseline characteristics and metabolic parameters

Table 2: Gender Distribution

Statistical analysis was done by using χ ² . p value was not significant.

There was a male preponderance in both the groups.

Table 3 : Effect of Losartan on Urine Albumin Excretion

Table 4 : Effect Of Amlodipine  On Urine Albumin Excretion

Table 5:   Incidence of Adverse Effects

Figure 1: Effect of losartan on SBP and DBP Click here to View figure

Figure 2: Effect of Amlodipine on Systolic BP and Diastolic BP Click here to View figure

Figure 3 : Effect of Losartan and Amlodipine  on Urine Albumin Excretion Click here to View figure

Figure 4 : Compare the effect of Losartan and Amlodipine  on Uric Acid Click here to View figure

Figure 5 : Evaluate the Effect of Losartan and Amlodipine  on Serum creatinine Click here to View figure

Figure 6 : The Effect of Losartan and Amlodipine  on serum urea Click here to View figure

Discussion

The current study shows that after 6 months of treatment, both losartan and amlodipine significantly (p<0.01) reduced SBP and DBP compared with baseline (figure 1 and 2). The blood pressure in hypertensive patients is controlled due to the blockade of RAS with ARBs i.e.  Losartan has antihypertensive and conferring cerebral, cardiac and renal target-organ protection by exhibiting their pleiotropic effects (7). Ca²⁺channel blocker (Amlodipine) is a very effective antihypertensive agent that lowers blood pressure primarily through arteriolar vasodilatation and decreasing peripheral vascular resistance.  Ca²⁺channel blocker may reduce the cardiovascular risk to a greater extent than BP lowering effect (8).

After  6-month of losartan treatment, the reduction in urine albumin level is significant (p<0.01) from a baseline value of 101.95±94.70 to 71.17±66.04 (Table 3). Amlodipine treatment group urine albumin excretion level resulted in statistically not significant (p>0.05) compared with baseline101.11±95.28 to 99.85±96.35 (Table 4). The  reductions in urine albumin levels achieved with losartan were significantly greater ( p<0.05) than those by Amlodipine (Figure 3).But the reduction in uric acid, serum creatinine and serum urea   levels achieved with losartan group were not significant (p>0.05) than amlodipine groups (Figure 4,5,6).

The beneficial effects of an ARB have been demonstrated in mild to moderate hypertensive patients with prevention of early kidney damage being independent of the antihypertensive activity(9). Losartan has been shown to reduce microalbuminuria by restoring the effect on renal hemodynamics, proximal tubular function, but calcium channel blockers like Amlodipine has no change in proximal tubular function (10). The effect of losartan on insulin resistance is found to be positive or neutral, thus producing a better effective control on diabetes (11).

Amlodipine therapy has limited albumin sparing effect because the levels of urinary albumin excretion is not reduced in this study implies statistically not significant even they are effective in reducing the blood pressure in essential hypertension. The amlodipine effect on albumin excretion might be prevented due to inhibition of reabsorption of albumin at the proximal tubules

Limitations

Small  sample size and Short duration of study.

Acknowledgement

I am very grateful to the Department of Pharmacology and general medicine for giving the support

References

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2. Poulter NR, Prabhakaran D, Caulfield M. Hypertension. Lancet. 2015; 386: 801–812.
3. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med. 1984; 310(6): 356–360.
4. Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Halle JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA . 2001; 286(4): 421–426.
5. Bakris GL, Mensah GA. Pathogenesis and clinical physiology of hypertension. Cardiol Clin.2002; 20(2):195-206.
6. AySA1, Cakar M, Karaman M, Balta S, Demirkol S, Unlu M, Kurt O, Altun B, Akhan M, Arslan E, Koc B, BulucuF . Amlodipine seems to be superior to valsartan in decreasing microalbuminuria in newly diagnosed hypertensive patients: a novel effect to be explained with hyperfiltration ? . Clic Exp Hypertens .2013; 35(3): 357-360.
7. Steven G. Chrysant, MD, PhD and George S. Chrysant, MD. The Pleiotropic Effects of Angiotensin Receptor Blockers. The Journal of Clinical Hypertension .2006; 8:  261-268.
8. Staessen JA, Fagard R, Thijs L, et al. randomized double –blind comparision of placebo and active treatment for older patients with isolated systolic hypertension. Lancet. 1997; 350: 757–776.
9. Murayama S, Hirano T, Sakaue T, Okada K, Ikejiri R, Adachi M . Low-dose candesartan cilexetil prevents early kidney damage in type 2 diabetic patients with mildly elevated blood pressure. Hypertens Res. 2003 ; 26: 453-458
10. Hallvard Holdaaas, Anders Hartmann, Knutjoachim Berg, Kirsten Lund and per Fauchald .Renal Effects of Losartan and Amlodipine in Hypertensive Patients with Non-Diabetic Nephropathy. Nephrol Dial Transplant. 1998 ; 13:  3096-3102.
11. Jose V. Lozano, Jose L. Llisterri 1, J Aznar 2 and Josep Redon. losartan reduces microalbuminuria in hypertensive microalbuminuric type 2 diabetics.  Nephrology dialysis transplantation. 2001 ; 16(1) : 85-89.