{"id":28548,"date":"2019-09-25T10:48:40","date_gmt":"2019-09-25T10:48:40","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=28548"},"modified":"2021-08-27T06:48:50","modified_gmt":"2021-08-27T06:48:50","slug":"comparative-study-on-the-efficacy-of-losartan-and-amlodipine-in-reducing-microalbuminuria-in-patients-with-primary-hypertension-a-randomized-open-label-parallel-group-study","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol12no3\/comparative-study-on-the-efficacy-of-losartan-and-amlodipine-in-reducing-microalbuminuria-in-patients-with-primary-hypertension-a-randomized-open-label-parallel-group-study\/","title":{"rendered":"Comparative Study on the Efficacy of Losartan and Amlodipine in Reducing Microalbuminuria in Patients with Primary Hypertension, a Randomized open Label Parallel Group Study"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

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).<\/p>\n

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<\/p>\n

Losartan is the first orally available drug, selective, competitive Angiotensin II receptor type 1 antagonist, its active metabolite is 5 \u2013carboxylic 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.<\/p>\n

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 ) .<\/p>\n

Objective<\/strong><\/p>\n

To Compare the Efficacy of Losartan and Amlodipine in reducing microalbuminuria in patients with primary hypertension<\/p>\n

Materials and Methods<\/strong><\/p>\n

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\u201d<\/strong>. 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 \u201c<\/strong>inclusion criteria are Adult patients of age >18 years. Newly diagnosed Hypertensive patients with \u2265140\/90 mm Hg of blood pressure \u00a0, or <1 year\u00a0 \u00a0period of \u00a0hypertension patients without taking any antihypertensive medications. and hypertensive patients with a blood pressure \u2265140\/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\u00a0 clinical cardiovascular disease , renal and hepatic disease (creatinine >2.2mg\/dl).\u00a0 Patient with >180\/ 110 mm Hg of blood pressure systolic. Type II Diabetes Mellitus and patients with secondary hypertension.<\/p>\n

Procedure<\/strong><\/p>\n

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.<\/p>\n

Statistical Analysis<\/strong><\/p>\n

The analysis of the Data was assessed by SPSS software for Windows (version 10). The results were convey as mean\u00b1SD. ANOVA test of One-way analysis \u00a0was 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\u2019s t<\/em>-test are assessed to compare Before and after treatment values. At\u00a0\u00a0 the\u00a0\u00a0 end\u00a0\u00a0 of\u00a0\u00a0 the\u00a0\u00a0 duration of the study \u00a0\u00a0losartan and amlodipine effect \u00a0\u00a0on microalbumin levels were compared\u00a0\u00a0\u00a0 in\u00a0\u00a0 terms\u00a0\u00a0 of therapeutic efficacy and adverse effects. p -values (p<0.05) were treated as statistically significant in two tailed test.<\/p>\n

Results<\/strong><\/p>\n

Table 1 : Matching of the two groups according to their baseline characteristics <\/strong>and metabolic parameters<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
 <\/p>\n

Variable<\/strong><\/td>\n

Group A<\/strong><\/p>\n

Losartan (50)<\/strong><\/p>\n

Mean \u00b1 S.D<\/td>\n

Group B<\/strong><\/p>\n

Amlodipine\u00a0 (50)<\/strong><\/p>\n

Mean \u00b1 S.D<\/td>\n<\/tr>\n

Age (years)<\/strong><\/td>\n\u00a0\u00a0 49.46 \u00b1 9.58<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 50.28 \u00b1 10.5<\/p>\n

 <\/td>\n<\/tr>\n

No.of yrs in Hypertension\u00a0\u00a0 <\/strong><\/td>\n\u00a0\u00a0 5.96\u00b13.78<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 5.48\u00b13.61<\/p>\n

 <\/td>\n<\/tr>\n

SBP(mmHg)<\/strong><\/td>\n\u00a0\u00a0 152.18\u00b18.04<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 151.54\u00b17.83<\/p>\n

 <\/td>\n<\/tr>\n

DBP(mmHg)<\/strong><\/td>\n\u00a0\u00a0 95.56\u00b14.78<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 95.38\u00b14.12<\/p>\n

 <\/td>\n<\/tr>\n

UAE(mg\/dl)<\/strong><\/td>\n\u00a0\u00a0 101.95\u00b194.71<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 101.11\u00b195.28<\/p>\n

 <\/td>\n<\/tr>\n

Uric acid (mg\/dl)<\/strong><\/td>\n\u00a0\u00a0 5.66\u00b10.88<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 5.67\u00b10.84<\/p>\n

 <\/td>\n<\/tr>\n

Serum Creatinine (mg\/dl)<\/strong><\/td>\n\u00a0\u00a0 1.43\u00b10.52<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 1.44\u00b10.49<\/p>\n

 <\/td>\n<\/tr>\n

Serum Urea(mg\/dl)<\/strong><\/td>\n\u00a0\u00a0 25.89\u00b12.19<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 25.18\u00b12.29<\/p>\n

 <\/td>\n<\/tr>\n

AST (U\/L)\u00a0 \u00a0\u00a0 \u00a0\u00a0\u00a0\u00a0\u00a0 <\/strong><\/td>\n\u00a0\u00a0 27.06 \u00b1 7.5<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 26.8 \u00b1 7.7<\/p>\n

 <\/td>\n<\/tr>\n

ALT (U\/L) <\/strong><\/td>\n\u00a0\u00a0 28.56 \u00b1 6.5<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 28.6\u00b1 7.0<\/td>\n<\/tr>\n
Haemoglobin (gm\/dl)<\/strong><\/td>\n\u00a0\u00a0 12.82 \u00b1 3.2<\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0 12.78 \u00b1 2.8<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 2: Gender Distribution<\/strong><\/p>\n\n\n\n\n\n\n\n
Gender<\/strong><\/p>\n

 <\/p>\n

 <\/td>\n

Group-A<\/strong><\/p>\n

(Losartan)<\/strong><\/td>\n

Group-B<\/strong><\/p>\n

(Amlodipine)<\/strong><\/td>\n

Pearson<\/strong><\/p>\n

chi-square\u00a0\u00a0 test<\/strong><\/td>\n<\/tr>\n

Number<\/strong><\/td>\n%<\/strong><\/td>\nNumber<\/strong><\/td>\n%<\/strong><\/td>\n<\/tr>\n
Male<\/strong><\/td>\n\u00a0 26<\/td>\n\u00a052%<\/td>\n\u00a0 27<\/td>\n\u00a054%<\/td>\n <\/p>\n

\u03c72<\/sup>=0.00<\/p>\n

 <\/td>\n<\/tr>\n

Female<\/strong><\/td>\n\u00a0 24<\/td>\n\u00a048%<\/td>\n\u00a0 23<\/td>\n\u00a046%<\/td>\n<\/tr>\n
Total<\/strong><\/td>\n\u00a0 50<\/td>\n100%<\/td>\n\u00a0 50<\/td>\n100%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Statistical analysis was done by using \u03c7 2 <\/sup>. <\/strong>p value was not significant.<\/p>\n

There was a male preponderance in both the groups.<\/p>\n

Table 3 : Effect of Losartan on Urine Albumin Excretion<\/strong><\/p>\n\n\n\n\n
Urine albumin<\/strong><\/p>\n

excretion<\/strong><\/td>\n

Baseline<\/strong><\/td>\n3 months<\/strong><\/td>\n6 months<\/strong><\/td>\n<\/tr>\n
Mean \u00b1S.D<\/strong><\/td>\n101.95\u00b194.70<\/td>\n84.65\u00b179.12**<\/td>\n71.17\u00b166.04**<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 4 : Effect Of Amlodipine\u00a0 On Urine Albumin Excretion<\/strong><\/p>\n\n\n\n\n
Urine albumin<\/strong><\/p>\n

excretion<\/strong><\/td>\n

Baseline<\/strong><\/td>\n3 months<\/strong><\/td>\n6 months<\/strong><\/td>\n<\/tr>\n
Mean \u00b1S.D<\/strong><\/td>\n101.11\u00b195.28<\/td>\n100.51\u00b196.99NS<\/sub><\/td>\n99.85\u00b196.35NS<\/sub><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 5:\u00a0\u00a0 Incidence of Adverse Effects<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
S.No<\/strong><\/p>\n

\u00a0<\/strong><\/td>\n

Adverse effect<\/strong><\/p>\n

no (%)<\/strong><\/td>\n

Losartan group\u00a0\u00a0\u00a0\u00a0 (50)<\/strong><\/td>\nAmlodipine group<\/strong><\/p>\n

(50)<\/strong><\/td>\n<\/tr>\n

1<\/td>\nNausea<\/td>\n–<\/td>\n2(4%)<\/td>\n<\/tr>\n
2<\/td>\nFatigue<\/td>\n1(2%)<\/td>\n–<\/td>\n<\/tr>\n
3<\/td>\nDizziness<\/td>\n2(4%)<\/td>\n1(2%)<\/td>\n<\/tr>\n
4<\/td>\nHead ache<\/td>\n3(6%)<\/td>\n4(8%)<\/td>\n<\/tr>\n
5<\/td>\nAbdominal pain<\/td>\n–<\/td>\n1(2%)<\/td>\n<\/tr>\n
<\/td>\nTotal<\/td>\n6<\/td>\n8<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 1:<\/strong> Effect of losartan on SBP and DBP<\/strong><\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 2: Effect of Amlodipine on Systolic BP and Diastolic BP<\/strong><\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 3 : Effect of Losartan and Amlodipine\u00a0 on Urine Albumin Excretion<\/strong><\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 4 : Compare the effect of Losartan and Amlodipine\u00a0 on Uric Acid<\/strong><\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 5 : Evaluate the Effect of Losartan and Amlodipine\u00a0 on Serum creatinine<\/strong><\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 6 : The Effect of Losartan and Amlodipine\u00a0 on serum urea<\/strong><\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Discussion<\/strong><\/p>\n

The current study shows that after 6 months of treatment, both losartan and amlodipine significantly (p<\/em><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.\u00a0 Losartan has antihypertensive and conferring cerebral, cardiac and renal target-organ protection by exhibiting their pleiotropic effects (7). Ca2+<\/sup>channel blocker (Amlodipine) is a very effective antihypertensive agent that lowers blood pressure primarily through arteriolar vasodilatation and decreasing peripheral vascular resistance. \u00a0Ca2+<\/sup>channel blocker may reduce the cardiovascular risk to a greater extent than BP lowering effect (8).<\/p>\n

After \u00a06-month of losartan treatment, the reduction in urine albumin level is significant (p<0.01) from a baseline value of 101.95\u00b194.70 to 71.17\u00b166.04 (Table 3). Amlodipine treatment group urine albumin excretion level resulted in statistically not significant (p>0.05) compared with baseline101.11\u00b195.28 to 99.85\u00b196.35 (Table 4). The\u00a0 reductions in urine albumin levels achieved with losartan were significantly greater ( p<\/em><0.05) than those by Amlodipine (Figure 3).But the reduction in uric acid, serum creatinine and serum urea\u00a0\u00a0 levels achieved with losartan group were not significant (p>0.05) than amlodipine groups (Figure 4,5,6).<\/p>\n

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).<\/p>\n

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<\/p>\n

Limitations<\/strong><\/p>\n

Small \u00a0sample size and Short duration of study.<\/p>\n

Acknowledgement <\/strong><\/p>\n

I am very grateful to the Department of Pharmacology and general medicine for giving the support<\/p>\n

References<\/strong><\/p>\n

    \n
  1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al.<\/strong> Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure . <\/em> 2003; 42(6): 1206-1252.<\/li>\n
  2. Poulter NR, Prabhakaran D, Caulfield M. Hypertension. <\/em>Lancet. 2015; 386: 801\u2013812.<\/li>\n
  3. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes.<\/em> N Engl J Med. 1984; 310(6): 356\u2013360.<\/li>\n
  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.<\/em> JAMA . 2001; 286(4): 421\u2013426.<\/li>\n
  5. Bakris GL, Mensah GA. Pathogenesis and clinical physiology of hypertension<\/em>. Cardiol Clin.2002; 20(2):195-206.<\/li>\n
  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 ? . <\/em>Clic Exp Hypertens .<\/em>2013; 35(3): 357-360.<\/li>\n
  7. Steven G. Chrysant, MD, PhD and George S. Chrysant, MD. The Pleiotropic Effects of Angiotensin Receptor Blockers. <\/em>The Journal of Clinical Hypertension .2006; 8:\u00a0 261-268.<\/li>\n
  8. Staessen JA, Fagard R, Thijs L, et al. randomized double \u2013blind comparision of placebo and active treatment for older patients with isolated systolic hypertension.<\/em> Lancet. 1997; 350: 757\u2013776.<\/li>\n
  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. <\/em>Hypertens Res. 2003 ; 26: 453-458<\/li>\n
  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. <\/em>Nephrol Dial Transplant. 1998 ; 13:\u00a0 3096-3102.<\/li>\n
  11. Jose V. Lozano, Jose L. Llisterri 1, J Aznar 2 and Josep Redon. losartan reduces microalbuminuria in hypertensive microalbuminuric type 2 diabetics. <\/em>\u00a0Nephrology dialysis transplantation. 2001 ; 16(1) : 85-89.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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