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2232

ANALYZING ACEI-FUROSEMIDE AND ARB-FUROSEMIDE DRUGS

COMBINATION ON HYPERTENSION AND CHRONIC KIDNEY

DISEASE PATIENTS

Hesti Effendi

, Helmi Arifin, Nasrul Zubir

Faculty of Pharmacy, Andalas University, Padang, West Sumatra, Indonesia

hestieffendi@gmail.com

ARTICLE INFO

ABSTRACT

Published: January 20

, 2023

The purpose of this study was to compare the efficacy of ACE-inhibitor +

Furosemide and ARB + Furosemide in lowering creatinine, urea, and blood

pressure in individuals with hypertension and chronic renal disease. This is

a retrospective study in which data were extracted from the medical records

of patients with hypertension and chronic kidney disease in the Internal

Medicine Ward of the General Hospital dr. M. Jamil Padang in West

Sumatera. A 2-by-3 ANOVA hypothesis test design was utilized. The

hypothesis was evaluated using an alpha value of 0.05. The results

demonstrated that the ARB + Furosemide combination was superior to the

ACE-Inhibitor + Furosemide combination by 86.2%. In addition, this study

demonstrated that the medication combinations ACE inhibitor plus

furosemide and ARB plus furosemide were equally efficient in lowering

creatinine, urea, and blood pressure in individuals with hypertension and

chronic renal disease. The researchers found that antihypertensive

medicines, including the ACE-Inhibitor + Furosemide combination and the

ARB + Furosemide combination, can be administered at levels determined

by the patient's clinical situation. Also, while selecting a pharmacological

combination between an ACE inhibitor and furosemide or an ARB and

furosemide, it is important to consider the adverse effects of the drugs. For

instance, it is preferable to combine ARB with Furosemide.

Keywords: ACEI-Furosemide,

ARB-Furosemide, drugs combination,

chronic kidney disease

This work is licensed under CC

BY-SA 4.0

INTRODUCTION

Hypertension is one of the diseases that are widely found in society and even though it has

been treated, there are still many whose blood pressure is not controlled (Fischer & O’Hare, 2010;

Tessy, 2006). In Indonesia, the prevalence of hypertension is around 26% (Indonesia’s Ministry

of Health, 2013) and is high. In addition, hypertension is also found in more than 80% of patients

with chronic kidney disease and contributes to aggravating kidney disease (Toto, 2005).

From data in several nephrology centers in Indonesia, it is estimated that the incidence of

chronic kidney disease ranges from 100-150 per 1 million population and the prevalence reaches

200-250 cases per 1 million population (Bakri, 2005). The results of Riskesdas 2013 also showed

that the prevalence increased with age, with a sharp increase in the age group of 35-44 years

compared to the age group of 25-34 years. The prevalence in men (0.3%) is higher than in women

(0.2%).

Uncontrolled hypertension is caused by inappropriate drug combinations and many

medications that have side effects and contraindications (Fischer & O’Hare, 2010; Tessy, 2006).

For example, potassium-sparing diuretics can cause the risk of hyperkalemia, especially in chronic

kidney disease patientsand patients with ACE inhibitor treatment (Dipiro et al., 2014).

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

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2023

Hypertension in chronic kidney disease will increase the risk of harm including decreased

kidney function and kidney failure, accelerated development of cardiovascular disease, and death

(Levey et al., 2002). Blood pressure in chronic kidney disease patients with hypertension should

always be monitored, with recommended blood pressure targets can reach < 130 mmHg for

systolic pressure and < 80 mmHg for diastolic pressure (Becker & Wheeler, 2010; Toto, 2005).

Therefore, antihypertensive drugs are needed that can be well tolerated and have minimal side

effects so that compliance with their use is also better (Tessy, 2006).

The purpose of the use of antihypertensive drugs in patients with chronic kidney disease is

not only to lower blood pressure, but also to restrain the progression of decreased renal function

(Hou, 2008). In addition, it is also necessary to be aware of the occurrence of proteinuria and also

need to use antihypertensive drugs that can reduce the excretion of urine protein (Hou, 2008).

Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) are

the first choice antihypertensives because they are known to be most consistent in lowering

proteinuria and maintaining kidney function in patients with chronic kidney disease (Chobanian et

al., 2003; Hou, 2008).

To achieve blood pressure targets and the occurrence of water and salt retention due to

impaired kidney function, many patients with chronic kidney disease require a combination of two

or more antihypertensives (Brookes, 2004; Hou, 2008). Diuretics are the first option that can be

combined with ACE inhibitors or ARBs (Chobanian et al., 2003; Hou, 2008). Diuretics can lower

the volume of extracellular fluid, have a potentiating effect with ACE inhibitors or ARBs in

lowering blood pressure and reducing the risk of cardiovascular disease (Levey et al., 2002). Loop

diuretics are recommended for chronic kidney disease patients because they can work quickly even

among patients with impaired renal function (Brookes, 2004; Mycek et al., 2001).

This study aimed to see the effect of the combination of ACE-inhibitor + Furosemid drugs

with the combination of ARB + Furosemid. In addition, this study also examined the effect of drug

doses (Less dose, exact dose, and over dose) on lowering blood pressure, changes in blood

creatinine levels and blood ureum levels in chronic kidney disease patients with hypertension in

the internal medicine inpatient ward of Dr. M. Djamil Padang Hospital. Since there are two free

variables (Drug combination and drug dose) the study also examined the effect of drug

combination alongside drug dose on changes in lowering blood pressure, changes in blood

creatinine levels and blood ureum levels in chronic kidney disease patients with hypertension. The

influence of the combination of these two variables is usually called the interaction effect. It is also

based on the fact that this topic is rarely discussed and the closest one to this is by Diniah et al

(2022) which brings out how combinations of Furosemide, Amlodipine, and Candesartan are given

to chronic kidney disease patients.

METHOD

This type of research is ex-post facto research. Ex-post facto research is research whose data

has already happened before. Researchers only collect data by measuring independent and

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

2234 | I n d o n e s i a n J o u r n a l o f M u l t i d i s c i p l i n a r y S c i e n c e , 2 ( 4 ) , Jan,

2023

dependent variables that have already occurred, then analyzing the relationships of these variables

according to the design of their research.

This study studied the average difference in changes in blood creatinine levels, the average

blood ureum level and the average difference in blood pressure caused by the use of a combination

of ACE-Inhibitors with Furosemid and the use of ARB with Furosemid. In addition, it was also

studied the effect of the dose given. Data obtained from the recording of medical records of patients

with hypertension and chronic kidney disease.

The population in this study was hypertensive patients and chronic kidney disease in the

Inpatient ward of RSUP Dr. M. Djamil Padang. As for the sample, it is hypertension and chronic

kidney disease patients who were treated in the Inpatient ward of RSUP Dr. M. Djamil Padang

from July 2016 to June 2017, with the following inclusion and exclusion criteria:

1) Inclusion: Hypertensive and chronic kidney disease patients who received ACE-

Inhibitor+Furosemid and ARB+Furosemid drug therapy, patients aged at least 18 years,

and Patients with data on blood ureum levels and blood creatinine levels.

2) Exclusion: Hypertensive and chronic kidney disease patients with complications that can

affect the examination of blood ureum and blood creatinine levels, as well as patients who

receive drug therapy that affects blood ureum levels and blood creatinine.

Researchers analyzed the data obtained by applying descriptive analysis (Mean, standard

deviation, percentage and graph of the average change in blood creatinine levels, average blood

ureum cadara and average blood pressure for each group based on drug combination, drug dose

and drug combination interaction with drug dose) and predictive analysis (Test difference two rata

and test difference more than two average). Hypotheses that test differences of two mean are tested

with a t-test, while hypotheses that test differences of more than two averages are tested with a test

F. Hypotheses are tested at alpha 0.05.

RESULT AND DISCUSSION

Test the Two-Mean Difference Hypothesis

First hypothesis: There was a Difference in the Average Blood Creatinine Levels After Therapy,

between the Group of Patients Taking the Combination of the Drug ACE-Inhibitor + Furosemid

with the Combination of ARB + Furosemid

Statistical hypothesis:

Ho : μ Creatinine-ACE-I+F = μ creatinine-ARB+F

Ha : μ Creatinine-ACE-I+F ≠ μ Creatinine-ARB+F

Table 1. Conclusion of the First Hypothesis Test

Combination

Creatinine Average

Sig

ACEI+F

6,08

1,338*

0,695

ARB+F

394

3,74

*Insignificant

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

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2023

With a value of t = 1.338 , p > 0.05 means that H0 is accepted. Statistically there was no

difference in the average change in creatinine levels between the group of patients taking the

combination of the drug ACE-inhibitor + Furosemid with the combination of the drug ARB +

Furosemid.

Second Hypothesis: There was a Difference in the Average Blood Ureum Levels After Therapy,

Between the Group of Patients Taking the Combination of the Drug ACE-Inhibitor +

Furosemid with the Combination of ARB + Furosemid

Statistical hypothesis:

Ho : μ Ureum-ACE-I+F = μ Ureum-ARB+F

Ha : μ Ureum-ACE-I+F ≠ μ Ureum-ARB+F

Table 2. Second Hypothesis Test Conclusion

Combination

Ureum Average

Sig.

ACEI+F

113,50

2,50*

0,126

ARB+F

53,81

*Insignificant

With a value of t = 2.50, p > 0.05 means that H0 is accepted. Statistically there was no

difference in the average change in ureum levels between the group of patients taking the

combination of the drug ACE-inhibitor + Furosemid with the combination of ARB + Furosemid.

Third Hypothesis: There was a Difference in the Average Blood Pressure of Systole After

Therapy, Between the Group of Patients Taking the Combination of the Drug ACE-Inhibitor +

Furosemid with the Combination of ARB + Furosemid

Statistical hypothesis:

Ho : µ TD. Systole-ACE-I+F = µ TD. Systole-ARB+F

Ha : µ TD. Systole-ACE-I+F ≠ µ TD. Systole-ARB+F

Table 3. Third Hypothesis Test Conclusion

Combination

Systole Blood Pressure Average

Sig.

ACEI+F

2,61

0,661

ARB+F

*Insignificant

With a value of t = 2.61, p > 0.05 means that H0 is accepted, statistically there is no difference

in the average change in the TD of Sistol between the group of patients taking the combination of

the drug ACE-inhibitor + Furosemid with the combination of ARB + Furosemid.

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

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2023

Fourth Hypothesis: There is a Difference in the Average Diastole Blood Pressure, Between the

Combination of ACE-Inhibitor + Furosemid and the Combination of ARB + Furosemid Drugs

Statistical hypothesis:

Ho : µ TD. Diastole-ACE-I+F = µ TD. Diastole-ARB+F

Ha : µ TD. Diastole-ACE-I+F ≠ µ TD. Diastole-ARB+F

Table 4. Conclusion of the Fourth Hypothesis Test

Combination

Diastole Blood Pressure Average

Sig.

ACEI+F

0,115*

0,977

ARB+F

*Insignificant

With a value of t = 0.115, p > 0.05 means that H0 is accepted, statistically there is no

difference in changes in diastole blood pressure between the group of patients taking the

combination of the drug ACE-inhibitor + Furosemid with the combination of ARB + Furosemid.

Test the Three Hypotheses Difference Averages

Fifth Hypothesis: There is a Difference in Change Average in Blood Creatinine Levels among

Patients Using Exact, Over, and Less Doses

Statistical hypothesis:

Ho : μExact Dose = μOver Dose = μLess Dose

Ha : μExact Dose ≠ μOver Dose ≠ μLess Dose

Table 5. Conclusion of the Fifth Hypothesis Test

Drug

Dosage

Change Average in Creatinine

Sig.

Less

2,77

0,654*

0,523

Exact

4,87

Over

3,87

*Insignificant

With a value of F = 0.654, p > 0.05 means that H0 is accepted, statistically there is no

difference in the average change in blood creatinine among the group of underdosed, appropriate

and excess dosed.

Sixth Hypothesis: There is a Difference in Average Changes in Blood Ureum Levels among

Patients Who Use Appropriate, Excess, and Less Doses

Statistical hypothesis:

Ho : μExact Dose = μOver Dose = μLess Dose

Ha : μExact Dose ≠ μOver Dose ≠ μLess Dose

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

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2023

Table 6. Conclusion of the Sixth Hypothesis Test

Drug

Dosage

Change Average in Ureum

Sig.

Less

51,54

0,939*

0,395

Exact

77,08

Over

51,46

*Insignificant

With a value of F = 0.939, p > 0.05 means that H0 is accepted, statistically there is no

difference in the average change in blood ureum among the group of underdosed, appropriate and

excess dosed.

Seventh Hypothesis: There is a Difference in Average Change in Systole Blood Pressure among

Patients Using Exact, Over, and Less Doses

Statistical hypothesis:

Ho : μExact Dose = μOver Dose = μLess Dose

Ha : μExact Dose ≠ μOver Dose ≠ μLess Dose

Table 7. Conclusion of the Seventh Hypothesis Test

Drug

Dosage

Average Change in Systole Blood Pressure

Sig.

Less

2,215*

0,114

Exact

Over

*Insignificant

With a value of F = 2.215, p > 0.05 means that H0 is accepted, statistically there is no

difference in the average change in systole blood pressure among the pasein groups that were

underdosed, appropriate and excessive.

Eighth Hypothesis: There is a Difference in the Change Average in Diastole Blood Pressure

among Patients Using Exact, Over, and Less Doses

Statistical hypothesis:

Ho : μExact Dose = μOver Dose = μLess Dose

Ha : μExact Dose ≠ μOver Dose ≠ μLess Dose

Table 8. Conclusion of the Eighth Hypothesis Test

Drug

Dosage

Change Average in Diastole Blood Pressure

Sig.

Less

3,707*

0,028

Exact

Over

**Significant

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

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2023

With a value of F = 3.707, p < 0.05 means that H0 is rejected, statistically there is a difference

in the average change in diastole blood pressure among the group of patients who were underdosed,

appropriate and excessive.

Test the Hypothesis of Group Difference Averages Based on Drug Combination Categories

and Drug Doses

Ninth Hypothesis: There was a Difference in the Average Change in Blood Creatinine Levels

among Patients Treated with a Combination of ACE-Inhibitor + Furosemid and ARB-

Furosemide Drugs Using Exact, Over, and Less Doses

Statistical hypothesis:

Ho : μCreatinineACE-I+F-Less = μCreatinineACE-I+F-Exact = μCreatinineACE- I+FOver

= μCreatinineARB+FLess = μCreatinineARB+FExact = μCreatinineARB+FOver

Ha : μCreatinineACE-I+F-Less ≠ μCreatinineACE-I+F-Exact ≠ μCreatinineACE-I+FOver

≠ μCreatinineARB+FLess ≠ μ CreatinineINARB+FExactARB-Over ≠ μCreatinineARB-Over

Table 9. Conclusion of the Ninth Hypothesis Test

Combination and Drug Dose Interactions

Blood Creatinine Levels

Sig.

ACEI-F Less Dose

0,701*

0,625

ACEI-F Exact Dose

6,07

ACEI-F Over Dose

10,3

ARB-F Less Dose

2,6

ARB-F Exact Dose

4,47

ARB-F Over Dose

3,62

*Insignificant

Table 9 information shows that with an F value of 0.701 there was no difference in the

average blood creatinine levels of patients grouped according to the drug combination category

and the drug dose category.

Tenth Hypothesis: There was a Difference in the Change Average in Blood Ureum Levels

among Patients Treated with a Combination of the Drugs ACE-Inhibitor + Furosemid and

ARB-Furosemid by Using Exact, Over, and Less Doses

Statistical hypothesis:

Ho : μUreumACE-I+F-Less = μUreumACE-I+F-Exact = μUreumACE- I+FOver =

μUreumARB+FLess = μUreumARB+FExact = μUreumARB+FOver

Ha : μUreumACE-I+F-Less ≠ μUreumACE-I+F-Exact ≠ μUreumACE-I+FOver ≠

μUreumARB+FLess ≠ μUreumINARB+FExactARB-Over ≠ μUreumARB-Over

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

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2023

Table 10. Tenth Hypothesis Test Conclusion

Combination and Drug Dose Interactions

Blood Ureum Levels

Sig.

ACEI-F Less Dose

1,892*

0,106

ACEI-F Exact Dose

129

ACEI-F Over Dose

ARB-F Less Dose

47,5

ARB-F Exact Dosage

58,5

ARB-F Over Dose

52,2

*Insignificant

Table 10 information shows that with an F value of 1.892 there was no difference in the

average blood ureum levels of patients grouped according to the combination category of oabat

and the category of drug doses.

Eleventh Hypothesis: There was a Difference in the Change Average in Systole Blood Pressure

among Patients Treated with a Combination of the Drugs ACE-Inhibitor + Furosemid and

ARB-Furosemid Using Exact, Over, and Less Doses

Statistical hypothesis:

Ho : μSystoleBloodPressureACE-I+F-Less = μSystoleBloodPressureACE-I+F-Exact =

μSystoleBloodPressureACE-I+FOver = μSystoleBloodPressureARB+FLess =

μSystoleBloodPressureARB+FExact = μSystoleBloodPressureARB+FOver

Ha : μSystoleBloodPressureACE-I+F-Less ≠ μSystoleBloodPressureACE-I+F-Exact ≠

μSystoleBloodPressureACE-I+FOver ≠ μSystoleBloodPressureARB+FLess ≠

μSystoleBloodPressureINARB+FExactARB-Over ≠ μSystoleBloodPressureARB-Over

Table 11. Conclusion of the Eleventh Hypothesis Test

Combination and Drug Dosage Interactions

Systole Blood Pressure

Sig.

ACEI-F Dose Less

2,501**

0,035

ACEI-F Exact Dose

ACEI-F Excess Dose

ARB-F Less Dose

ARB-F Exact Dosage

ARB-F Excess Dose

**Significant

Table 11 information shows that with an F value of 2.501 there is a difference in the average

blood pressure of systole patients grouped according to the drug combination category and the

drug dose category.

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

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2023

Twelfth Hypothesis: There was a Difference in the Change Average in Diastole Blood Pressure

among Patients Treated with a Combination of the Drug ACE-Inhibitor + Furosemid and ARB-

Furosemid Using Exact, Over, and Less Doses

Statistical hypothesis:

Ho : μDiastoleBloodPressureACE-I+F-Less = μDiastoleBloodPressureACE-I+F-Exact =

μDiastoleBloodPressureACE-I+FOver = μDiastoleBloodPressureARB+FLess =

μDiastoleBloodPressureARB+FExact = μDiastoleBloodPressureARB+FOver

Ha : μDiastoleBloodPressureACE-I+F-Less ≠ μDiastoleBloodPressureACE-I+F-Exact ≠

μDiastoleBloodPressureACE-I+FOver ≠ μDiastoleBloodPressureARB+FLess ≠

μDiastoleBloodPressureINARB+FExactARB-Over ≠ μDiastoleBloodPressureARB-Over

Table 12. Twelfth Hypothesis Test Conclusion

Combination and Drug Dose Interactions

Diastole Blood Pressure

Sig.

ACEI-F Less Dose

3,482**

0,006

ACEI-F Exact Dose

ACEI-F Over Dose

ARB-F Less Dose

ARB-F Exact Dose

ARB-F Over Dose

**Significant

Table 12 information shows that with an F value of 3.482 there is a difference in the average

diastole blood pressure of patients grouped according to the drug combination category and the

drug dose category.

Patient Demographic Data

From the research conducted, it was found that the most hypertensive and chronic kidney

disease patients were aged 45-59 years, namely 57 people (52.3%). It is almost in line with a report

from the Indonesian Renal Registry (IRR) in 2013 the most age group was in the 45-54 year group,

which was 30.26%.

The high prevalence of CKD with age is undoubtedly one that reflects the presence of a

variety of different CKD risk factors such as hypertension. However, high levels of CKD with age

gain can also occur due to a decrease in kidney function associated with age. Results from the

Baltimore Longitudinal Study of Aging (BLSA) show that average kidney function tends to

decline with aging even among those without comorbidities (Prakash & O’Hare, 2009). Structural

and functional changes in the kidneys have been linked to the aging process. With age renal

atrophy and cortical thickness decrease by about 10% per decade after the age of 30. It is associated

with histological changes in renal scarring (Hsieh & Power, 2009).

Based on the sex category of hypertensive patients and chronic kidney disease, the most in

this study was the male sex, which was 68 people (62.4%). It is in line with the results of Riskesdas

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

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2023

2013 which showed that the prevalence in men (0.3%) was higher than that of women (0.2%). This

result is also in line with the results of a study conducted by Ferry S. Poluan, Cerelia Sugeng, and

Eko Surachmanto at RSUP Prof. Dr. R. D. Kandou Manado which showed that of the 71 patients

who met the inclusion criteria based on sex, there were 44 (61%) male patients and 27 (39%)

female patients. It is because men have a greater risk because they tend to have a less healthy

lifestyle that triggers oxidative stress more than women (Aitken et al., 2014). One of the behaviors

that has a serious risk to health is smoking. Benedict et al. stated that smoking causes a person to

be at risk of suffering from chronic renal failure 2 times higher than individuals who do not smoke

(Benedict et al., 2011).

Of the categories of length of time patients were treated, the most patients in this study were

for 1-7 days, namely 56 people (51.4%). The low length of treatment indicates that the patient has

been able to return home in a short period of time in an improved state. This is in line with the

results of research conducted by Muchtar et al at RSUP Prof. Dr. R. D. Kandou Manado which

showed that the highest number of patients treated for 6 days was 14 people (26.42%).

For the main classification category of disease diagnoses, the most patients in this study were

patients with renal hypertension diagnoses, namely 57 people (52.3%). This is in line with a report

from the Indonesian Renal Registry (IRR) in 2014, where the number of patients with hypertensive

kidney disease was 4699 patients (36.8%). This is also in line with research conducted by

Adhiatma et al at Tugurejo Hospital Semarang which shows that there is a meaningful relationship

between hypertension and the incidence of chronic renal failure.

This can be explained where there is a chronic increase in pressure and strain on small

arterioles and glomeruli will cause these vessels to scleros. Sclerotic lesions of small arteries,

arterioles and glomeruli cause the occurrence of nephrosclerosis. This lesion begins with the

leakage of plasma through the intimal membrane of these vessels, this results in the formation of

fibrinoid deposits in the lining of the vascular media, which is accompanied by a progressive

thickening of the vessel wall which will later make the blood vessel vasoconstriction and will clog

the blood vessel (Guyton & Hall, 2007). Blockage of arteries and arterioles will cause glomerular

damage and tubule atrophy, so that the entire nephron is damaged, which causes chronic renal

failure (Budiyanto, 2009).

Use of Drug Combination Therapy

From the category of types of drug combination therapy groups, it was found that the use of

ARB + Furosemid drug combinations was more than the combination of ACE-inhibitors +

Furosemid, which was 94 people (86.2%). This is in line with research conducted by Yuswantina,

et al at RSI Sultan Agung Semarang where the most antihypertensive group is the ARB group,

which is 70.83% compared to ACE-Inhibitors as much as 6.3%. This is because ARB has a

mechanism of action by directly inhibiting the angiotensin II receptor type 1 (AT1) which mediates

the known effects of angiotensin II in humans including, vasocontriction, aldosterone release,

sympathetic activation, antidiuretic hormone release and efferen arteriole constriction from the

glomerulus. ARB does not block type II angiotensin receptors (AT2) so that the beneficial effects

Analyzing ACEI-Furosemide and ARB-Furosemide Drugs Combination on Hypertension and Chronic

Kidney Disease Patients

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2023

of AT2 stimulation such as vasodilation, tissue repair, and inhibition of cell growth remain intact

with the use of ARB (Muchid, 2008). This is also thought to be caused by side effects of ACE

inhibitors that often occur and bother patients, namely dry cough with a percentage of events of

10-20%. This side effect occurs as a result of the effects of ACE-inhibitors in lowering bradykinin

inactivity (Mycek et al., 2001).

Description of the Change Average in Indicators of Hypertension and Chronic Kidney

Disease

Change Averages in Blood Creatinine Levels, Blood Ureum Levels, Blood Pressure of Systole

and Diastole According to Drug Combinations

Changes in the average blood creatinine levels, blood ureum levels, systole blood pressure

and diastole blood pressure indicate a higher percentage of changes in the combination of ace-

inhibitor + furosemid drugs. Where for the change in the average blood creatinine level with the

combination of drugs ACE-Inhibitor + Furosemid was 49.8% and with the combination of drugs

ARB + Furosemid 33.2%. For the change in the average blood ureum level with the combination

of drugs ACE-inhibitor + Furosemid was 57.4% and with the combination of drugs ARB +

Furosemid 26.1%. For the average change in blood pressure systole with the combination of drugs

ACE-inhibitor + Furosemid was 20.5% and with the combination of drugs ARB + Furosemid

13.4%. As for the average change in diastole blood pressure with the combination of drugs ACE-

inhibitor + Furosemid is 12.5% and with the combination of drugs ARB + Furosemid 10.9%.

Change Average in Blood Creatinine Levels, Blood Ureum Levels, Blood Pressure of Systole

and Diastole According to Drug Doses

Changes in mean blood creatinine levels, blood ureum levels, and systole blood pressure

indicate a higher percentage change is at the right dose. Where for the change in the average blood

creatinine level at the right dose was 51.94%, while for doses less 27.17% and excess doses

32.54%. For changes in the average blood ureum level at the right dose was 38.62%, while for

doses less 23.30% and excess doses 25.25%. For the average change in blood pressure systole at

the right dose was 16.7%, while for doses less 10% and excess doses 13.4%. As for the change in

the average blood pressure diastole shows a higher percentage change is in the excess dose which

is 13.7%, while for the dose less 10.75% and for the exact dose 9%.

Change Average in Blood Creatinine Levels, Blood Ureum Levels, Blood Pressure of Systole

and Diastole According to Drug Combinations and Drug Doses

Changes in the average blood creatinine levels, for the combination of ACE-Inhibitor +

Furosemid drugs with less dose is 2 mg/dl, the exact dose is 6,07 mg/dl and the excess dose is 10,3

mg/dl. As for the combination of ARB + Furosemid with less dose the change in the average blood

creatinine level was 2.6 mg/dl, the exact dose was 4.47 mg/dl, and the excess dose was 3.62 mg/dl.

This suggests that the average change in higher blood creatinine is in a combination of ACE-

Inhibitor + Furosemid with excess doses.

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Changes in the average blood ureum levels, for a combination of ACE-Inhibitors +

Furosemid at less doses were 8 mg/dl, the exact dose was 129 mg/dl, and the excess dose was 32

mg/dl. As for the combination of ARB + Furosemid at a dose of less 47.5 mg/dl, the exact dose is

58.5 mg/dl and the excess dose is 52.2 mg/dl. This suggests that the average change in the blood

ureum is higher in the combination of ACE-Inhibitor + Furosemid at the right dose.

The average change in systole blood pressure, for a combination of ACE-Inhibitor +

Furosemid at less doses is 50 mmHg, the exact dose is 30 mmHg, and the excess dose is 20 mmHg.

As for the combination of ARB + Furosemid at a dose of less 14 mmHg, the exact dose is 22

mmHg and the excess dose is 20 mmHg. This suggests that the average change in higher systole

blood pressure was in a combination of ACE-Inhibitor + Furosemid at less dose.

The average change in diastole blood pressure, for a combination of ACE-Inhibitors +

Furosemid at less dose is 30 mmHg, the exact dose is 8 mmHg, and the excess dose is 20 mmHg.

As for the combination of ARB + Furosemid at a dose of less 9 mmHg, the exact dose is 9 mmHg

and the excess dose is 13 mmHg. This suggests that the average change in higher diastole blood

pressure is in the combination of ACE-inhibitor + Furosemid at less doses.

In general, it can be seen that changes in the average blood creatinine levels, blood ureum

levels, systole blood pressure and diastole blood pressure for the combination of ARB + Furosemid

drugs at less doses, the exact dose and the excess dose show values that do not differ too large, this

is supported by the theory where ARB has a flat dose-response curve, which means that doses

above low or moderate doses will not reduce blood pressure drastically and also blood creatinine

values and blood ureum. As for the combination of ACE-inhibitor + Furosemid, it is necessary to

observe the dosage used carefully, and should be started with a low dose because acute hypotension

may occur. It is necessary to multiply by 1/2 the normal dose and the dose is increased slowly

(Muchid, 2006).

CONCLUSION

In general, it can be concluded that this study shows that the combination of the drugs ACE-

Inhibtor + Furosemid and ARB + Furosemid is equally effective in lowering creatinine levels,

ureum levels and blood pressure in people with hypertension and chronic kidney pain. Although

in reality the use of the ARB + Furosemid combination is more (86.2%) than the ACE-Inhibitor +

Furosemid combination (13.8%). From the point of view of doses categorized into less doses,

appropriate doses, and excess doses, although clinically there were differences in changes in

creatinine levels, ureum levels and blood pressure in people with hypertension and chronic kidney

pain, there was no statistically change between the three dose categories.

In more detail, the results of this study concluded that there is no difference in the

effectiveness of blood creatinine reduction between the combination of ACE-Inhibitor +

Furosemid drugs with ARB + Furosemid, there is no difference in the effectiveness of blood ureum

reduction between the combination of ACE-Inhibtor + Furosemid drugs with ARB + Furosemid,

there is no difference in the effectiveness of blood pressure reduction between the combination of

ACE-Inhibitor + Furosemid drugs with ARB + Furosemid, and there is no difference in the

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effectiveness of decreasing blood creatinine in between exact, excessive, and less doses of the

drug. In addition, there was no difference in the effectiveness of the decrease in blood ureum

among the appropriate, excessive, and less doses of the drug; there is no difference in the

effectiveness of blood pressure reduction among appropriate, excessive, and less drug doses; no

interaction between the combination of the drug and the dose of the drug in determining the

effectiveness of the decrease in blood creatinine; no interaction between the combination of the

drug and the dosage of the drug in determining the effectiveness of the decrease in blood ureum;

and there is an interaction between the combination of the drug and the dose of the drug in

determining the effectiveness of the decrease in blood pressure.

The administration of antihypertensive drugs both a combination of ACE-Inhibtor +

Furosemid and ARB + Furosemid to lower creatinine, ureum and blood pressure can be used at a

dose appropriate to the clinical state of the patient. The selection of drug combinations among the

combination of ACE-Inhibitor + Furosemid or the combination of ARB + Furosemid is worth

noting the side effects of the drug. For example, in the morning, patients who suffer from coughing

after taking ACE-Inhibitor drugs should be used in a combination of ARB + Furosemid.

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