INTRODUCTION:

Heart failure is a clinical syndrome marked with the heart inability to pump in sufficient quantities of blood are needed for body’s metabolism. Heart failure as disorders that result in a reduction of ventricular filling (diastolic dysfunction) or myocardial contractility (systolic dysfunction). Heart failure due to diastolic dysfunction usually do not respond optimally to positive inotropic drugs (1). Handling and treatment should be appropriate to improve the quality of life and slow down of the disease progression. Mild heart failure therapy normally started with ACEI (Angiotensin Converting Enzyme Inhibitors).

However, the higher risk of hyperkalemia in heart failure patients treated with aldosterone antagonists (eg, spironolactone) in high-dose administration with ACEI⁽²⁾.Diuretics, especially furosemide is the preference drug for heart failure treatment. However, the patients who received high-dose of furosemide (> 80 mg) more likely to have hypokalemia during follow-up (5.8 ± 3.7 years) compared with patients who received low-dose of furosemide (<80 mg) (43,1% vs. 6.5%, p<0.001)⁽³⁾.

Based on Anutapura Hospital annual report, in 2017 congestive heart failure ranked sixth with a percentage of 8.1% for the top ten leading causes of inpatients mortality. In 2016 there are 276 patients patients with heart failure and in 2017 has increased to 285 patients.

According Aldahl et. al that hypokalemia and hyperkalemia strongly associated with increased of mortality. Levels of potassium in the interval of 2.8 to 3.4mmol/L (14.4%, P = <0.001) and 5.0 to 7.4mmol/L (21.1% P = <0.001) was associated with an increase in short-term mortality in patients with chronic heart failure⁽⁴⁾. Referring to the research Hubby et al, in heart failure patients who received the combination of ACEI and diuretic therapy, a total of 37 patients, 5 (13.5%) of them experienced hypokalemia and 2 (5.4%) hyperkalemia⁽⁵⁾.

The prevalence of heart failure in the Anutapura Hospital Palu is high categories and potassium balance disorders can increase mortality and morbidity. This fact push the researcher to conduct a study on the evaluation of combination ACEI and diuretics administration on potassium levels of congestive heart failure patients in the Anutapura Hospital City of Palu period 2016-2018.

METHODS:

This is a quantitative research with retrospective approach as assessed profile potassium levels before and after combination therapy of ACEI and diuretics were gained from medical records of patients with congestive heart failure who underwent inpatient at Anutapura Hospital, city of Palu period 2016 -2018. The samples in this study are patients with congestive heart failure based on inclusion and exclusion criteria. The inclusion criteria are patients diagnosed with congestive heart failure with or without comorbidities, patients undergoing inpatient period 2016-2018, get a combination drug therapy of ACEI and diuretics, potassium examination before and after therapy ACEI. While exclusion criteria of patients with incomplete or missing medical records, the patient died, the withdraw patients as own request, patients who have disorders of potassium balance before receiving combination therapy of ACEI and diuretics. The data analyzed with statistical methods using paired T-test to observe potassium levels before and after therapy.

RESULT:

The distribution the demographic data of inpatients with congestive heart failure at Anutapura Hospitla city of Palu period 2016-2018 by sex, age and clinical manifestations can be seen in the table 1.

Table 1. Demographic and Clinical Manifestations of Patients with Congestive Heart Failure

Characteristics	Number (n=38)	Percentage (%)
Sex
Male	27	71,05
Female	11	28,94
Years
19-34	1	2,63
35-50	11	28,94
51-65	15	39,47
66-80	11	28,94
Clinical Manifestations	Number (n=38)	Percentage (%)
Dyspnea	37	97,36
Chest Pain	10	26,31
Udem perifer	7	18,42
Nausea	5	13,15
abdominal bloating Heartburn	3 3	7,89 7,89
Cough	2	5,26
Gag	2	5,26
Ascites	2	5,26
Pulmonary Congestion	1	2,63
Abdominal Pains	1	2,63
Limp	1	2,63

The severity of congestive heart failure of patients hospitalized at Anutapura Hospital city of Palu period 2016-2018 can be seen in Table 2.

Table 2 The Severity of Congestive Heart Failure Patients

Severity	Number (n=38)	Percentage (%)
NYHA I	0	0
NYHA II	3	7,89
NYHA III	24	63,15
NYHA IV	11	28,94

Note: NYHA : New York Heart Association

Profile of primary treatment given to congestive heart failure patients are hospitalize at Anutapura Hospital city of Palu period 2016-2018 can be seen in Table 3.

Examination of potassium serum in congestive heart failure patients who received ACEI and diuretic therapy that hospitalized in Anutapura Hospital city of Palu period 2016-2018 can be seen in table 4.

Table 3. Profile of primary treatment given to congestive heart failure patients

Therapy Group	Group	Medicine	Number(n=38)	Percentage (%)
Cardiovascular	ACEI	Captopril	25	65,78
		Lisinopril	16	42,10
		Ramipril	2	5,26
	Loop Diuretics	Furosemide	38	100
	Potassium-sparing diuretics	Spironolactone	24	63,15
	CCB (Calcium Channel Blocker)	Amlodipine	6	15,78
	Beta Blocker	Bisoprolol	5	13,15
	Cardiac Glycosides	Digoxin	11	28,94
	Nitrat	ISDN	19	50

Table 4 Examination of potassium serum of congestive heart failure patients who received ACEI and diuretic therapy

Therapy	Interpretation of Potassium Serum (n=25)
	Baseline	Evaluation
	Normal (%)	Hypokalemia (%)	Normal (%)	Hyperkalemia (%)
Combination of ACEI, Furosemide and Spironolactone	25 Patient (100)	6 Patient (24)	19 Patient (76)	0 Patient (0)
Therapy	Interpretation of Potassium Serum (n=13)
	Baseline	Evaluation
	Normal (%)	Hypokalemia (%)	Normal (%)	Hyperkalemia (%)
Combination of ACEI and Furosemide	13 Patient (100)	0 Patient (0)	13 Patient (100)	0 Patient (0)

Table 5. Profile potassium serum of congestive heart failure patients

Regimen	Number	Mean		Deviation	p value
Regimen	Number	Baseline	Evaluation	Deviation	p value
Combination of ACEI, Furosemide and Spironolactone	25	3,95 mmol/L	3,85 mmol/L	0,1 mmol/L	0,061
Combination of ACEI and Furosemide	13	4,20 mmol/L	4,14 mmol/L	0,06 mmol/L	0,070

Profile potassium serum of congestive heart failure patients hospitalized at Anutapura Hospital City of Palu period 2016-2018 can be seen in table 5.

DISCUSSION:

Based on medical records the research conducted at the Anutapura Hospital City of Palu period 2016-2018, acquired as many as 38 samples of congestive heart failure patients. The secondary data obtained from the medical records of patients. In table 1 of the patient demographic data, can be seen that congestive heart failure patients more a male than female. This is according to Hubby et al stated that the male patient more than female ie 31 patients out of a total 37 patients. Heart failure is most experienced at the male than female, this allegedly associated with physical activity undertaken male more than women, lifestyle factors such as smoking and alcohol consumption⁽⁶⁾.

Based on Table 1, the age group of congestive heart failure patients are highest in 51-65 years, followed by age of 66-80 and 35-50 years, and the lowest at the age of 19-34 years. In accordance with the research of Hubby et al, state the most age range is 51-65 years with number of 18 patients (48.37%) of 37 patients (5). The people will be more at risk of heart disease comparable with the age. Increases of CHF at age 40 or more. This is related to the aging process which leads to increased atherosclerosis in blood vessels (7). Atherosclerosis causes disruption of blood flow to the heart, causing an imbalance between myocardial oxygen requirements to supply oxygen (8). In old age, the changes in the heart anatomy and cardiac function. Additionally, the increased risk factors of heart disease such as hypertension and diabetes (9).

In table 1, the clinical manifestations of congestive heart failure patients, that often found are shortness breath (dyspnea). In accordance with the literatures Dipiro et al stated the main manifestation of congestive heart failure are dyspnea and fatigue. The presence various of symptoms may widely and differences among patients, some patients experience shortness breath without fluid retention, while others patients may have excess volume which is marked of shortness breath. In heart failure patients an increase in blood volume resulting in venous pressure and pulmonary capillary rises, causing interstitial and bronchial edema, increased airway resistance, and dyspnea⁽⁷⁾.

In Table 2, on the severity of congestive heart failure patients is mostly use in NYHA III. This is consistent with the finding of Kurniasi, that state the severity congestive heart failure patients most of NYHA III categories. On severity of NYHA III, there is significant activity limitation and there are no complaints at the rest, but mild physical activity induce the fatigue, palpitations or shortness breath (10). This is consistent with the findings of the study, based on data collected from patients plumpness had dyspnea.

Table 3 showed the profile of the treatment, it can be concluded that the combination of ACEI and diuretic (furosemide, spironolactone) is used as the primary therapy of congestive heart failure patients. ACEI is the basis of pharmacotherapy for patients with heart failure. These drugs block the conversion of angiotensin I to angiotensin II than makes the decreased aldosterone, but not eliminated. Decreased angiotensin II and aldosterone, may reduced the side effects of the neurohormone, including ventricular remodeling, myocardial fibrosis, myocyte apoptosis, cardiac hypertrophy, release of norepinephrine, vasoconstriction, retention of sodium and water, ACEI therapy plays important role in preventing deterioration of myocardial function progressively mediated with RAAS (Renin Angiotensin Aldosterone System).

Diuretic therapy, besides as a sodium restriction also recommended to all patients with clinical evidence of fluid retention. If the excess liquid had overcome, the patient will require chronic diuretic therapy to maintain euvolemia. Loop diuretics (furosemide) are usually required to restore and maintain euvolemia in heart failure. Spironolactone is an aldosterone antagonist that works by blocking the mineralocorticoid receptor, the target site for aldosterone. In the kidney, aldosterone antagonist inhibits the reabsorption of sodium and potassium excretion. Aldosterone antagonists in heart, inhibit the cardiac extracellular matrix and collagen deposition (7).

In Table 4, the examination of potassium serum showed that the profile of congestive heart failure patients before receiving treatment, all patients were in the normal range. After receiving the combination of ACEI, furosemide and spironolactone therapy of 6 patients (25%) had hypokalemia, of 19 patients (76%) have normal potassium levels, and nothing patients with hypokalemia. Meanwhile, in the combination of ACEI and furosemide administration, before and after receiving treatment all patients within the normal range, it is describes that all patients have a normal potassium levels.

In Table 5 the profile of potassium serum patients with congestive heart failure, showed that patients who received the ACEI, furosemide and spironolactone combination had a normal potassium level but is almost in hypokalemia. Based on the study, potassium levels before and after ACEI and diuretic therapy was tested using Shapiro Wilk normality and the results obtained showed the data distributed normally.

Differences in means levels of potassium before and after receiving combination of ACEI therapy, furosemide and spironolactone and ACEI - furosemide respectively are 0.1mmol/L (p= 0.061) and 0.06mmol/L (p = 0.070). The test results using a paired samples t-test showed p values > 0.05 indicates no significant differences the levels of potassium before and after administrated ACEI and diuretic therapy.

In this study, potassium levels of patients decreased but most of them had potassium levels still within normal range. This is similar to the results of Hubby et al, found that there was no significant differences between the potassium level before and after receiving the combined therapy of captopril and furosemide p = 0.432 (p > 0.05)⁽⁵⁾.

There are several things of potassium homeostasis. Furosemide can cause hypokalemia, this drugs works through inhibiting the reabsorption of salt in the pars descendens, in addition improve the distribution of Na+ to the ductus kolingentes. This condition leads to increased secretion of K+ and H+ that can cause hypokalemia (11). ACEI can cause hyperkalemia through a mechanism of action that inhibits the formation of angiotensin II and disrupt circulation of aldosterone in the adrenal gland. Aldosterone directly affect renal potassium handling. Aldosterone secretion disruption it will cause a failure in potassium excretion in the kidney (12). In addition potassium homeostasis can also be disrupted due to fluid loss of GI which is overload by potassium as a result of diarrhea or vomiting. Typical potassium loss in feces is about 10 mEq (10mmol) each day⁽⁷⁾.

CONCLUSION:

The administrated combination of ACEI, furosemide and spironolactone the mean potassium levels before and after therapy respectively are 3.95mmol/L and 3.85 mmol/L (p = 0.061), while the combination of ACEI and furosemide the mean potassium levels before and after therapy respectively are 4,20mmol/L and 4.14mmol/L (p = 0.070). In the combination of ACEI, furosemide and spironolactone from a total of 25 patients, hypokalemia 6 patients (24%), normal 19 patients (76%) and hyperkalemia 0 patients (0%), while the combination of ACEI and furosemide, from a total of 13 patients, all patients have normal potassium levels.

CONFLICT OF INTEREST:

The authors declare no potential conflict of interest in this research, authorship and article publication.

ACKNOWLEDGMENT:

The authors sincerely thank to all people who have contributions and supports this research, especially the director of Anutapura Hospital city of Palu that has provided assistance in the planning, execution and completion of this study.

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Received on 14.07.2019 Modified on 18.08.2019

Research J. Pharm. and Tech 2020; 13(2):747-750.

DOI: 10.5958/0974-360X.2020.00141.9