Research Article - Interventional Cardiology (2020) Volume 12, Issue 4
6-months Outcome of the Effects of Sacubitril/Valsartan Combination in the Treatment of Chronic Heart Failure
Ulviyya Eyubova Aladdin*Department of III Internal Diseases, Azerbaijan Medical University, Baku, Azerbaijan
- *Corresponding Author:
- Ulviyya Eyubova Aladdin
Department of III Internal Diseases
Azerbaijan Medical University, Baku, Azerbaijan
E-mail: eyubovaulviyya@mail.ru
Received date: June 01, 2020; Accepted date: July 23, 2020; Published date: 28, 2020
Abstract
Background: In recent years, the European Cardiology Association reports that 26 million people worldwide suffer from heart failure. This figure is increasing every year for a number of reasons (obesity, diabetes, smoking, hypertension, and alcohol).
Purpose: The aim of our study is to investigate clinical changes (complaints, functional class, etc.) and echocardiographic effects in patients with chronic heart failure after six months of treatment with traditional complex treatment of chronic heart failure with the addition of sacubitril/valsartan.
Methods: The study included 30 patients over the age of 61 who suffered from chronic heart failure among the population of Baku, Azerbaijan. (21 males, 9 females, 69.3 ± 1.3 - middle age). The study evaluated the clinical indications and transthoracic echocardiography results of the patients prior to admission of the sacubitril/valsartan complex and 6 months after taking it.
Results: In the evaluation of the results of the echocardiographic examination and clinical indications (complains, functional class and etc.) 6 months after the use of the sacubitril/ valsartan combination in patients, positive changes were found in the majority of patients compared with the indications of previous 6 months.
Conclusion: In the individual statistical analysis of the results revealed, the addition of the sacubitril/valsartan complex to the treatment of patients was improving overall condition of the patients.
Keywords
Heart failure; Heart failure with reduced ejection fraction; Sacubitril/valsartan
Abbreviations
SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; LVES: Left Ventricle End-Systolic Diameter; LVED: Left Ventricle End-Diastolic Diameter; LVEF: Left Ventricular Ejection Fraction; PASP: Pulmonary Artery Systolic Pressure; FC: Functional Classification; *indexed “a”: Results of after 6 months (aafter)
Introduction
In recent years, the European Cardiology Association reports that 26 million people worldwide suffer from heart failure [1]. This figure is increasing every year for a number of reasons (obesity, diabetes, smoking, hypertension, alcohol) [2-7]. Most patients with heart failure die within the first 5 years [8,9].
The current principles of treatment for patients with heart failure are based on the pathogenetic concept of chronic cardiac failure resulting from the long-term activation of the neurohumoral system. Theoretically, the combined use of different groups of neurohumoral modulators may provide additional benefits as a result of the complete blockade of neurohormones in the treatment of patients with chronic heart failure. The essence of such a concept is quite simple: the more the different levels of neurohumoral regulation are blocked, the better the outcome [10].
Currently, in the world practice the use of an inhibitor of neprilysin is widely used in the treatment of chronic heart failure. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers can be substituted with sacubitril complex, an angiotensin receptor blocker and neprilysin inhibitor in the treatment of chronic heart failure patients with adequate blood pressure II-III functional grade (NYHA). In this case, the angiotensin receptor neprilysin inhibitor should not be given within 36 hours after the last dose of the angiotensin converting enzyme inhibitor [11]. A detailed study of the PARADIGM-HF study revealed that the sacubitril/valsartan combination had a positive effect in the treatment of patients with low heart rate chronic heart failure. In the PARADIGM-HF study, it was found that conservative treatment with sacubitril/valsartan was more effective than that used with enalapril. Thus, increased levels of endogenous natriuretic peptides have been found to reduce the incidence of recurrent morbidity and mortality in patients with low pulmonary heart failure [12].
Sacubitril/valsartan is an orally administered supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, which was recently approved in the US and the EU for the treatment of chronic heart failure (NYHA class II – IV) with reduced ejection fraction. In the large, randomized, double-blind, PARADIGM-HF trial, sacubitril/valsartan reduced the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure (composite primary endpoint) significantly more than the angiotensin converting enzyme (ACE) inhibitor enalapril. Sacubitril/valsartan was also superior to enalapril in reducing death from any cause and in limiting the progression of heart failure. Sacubitril/valsartan was generally well tolerated, with no increase in life-threatening adverse events. Symptomatic hypotension was significantly more common with sacubitril/valsartan than with enalapril; the incidence of angioedema was low. Therefore, sacubitril/ valsartan is a more effective replacement for an ACE inhibitor or an ARB in the treatment of HFrEF, and is likely to influence the basic approach to treatment [13,14].
Methods
The study included 30 patients over the age of 25 who were diagnosed with chronic heart failure among the population of Baku, Azerbaijan. The diagnosis of chronic heart failure has been confirmed by anamnesis, objective and instrumental examination methods.
Inclusion criteria: chronic heart failure in anamnesis; circulatory insufficiency (functional grade II-IV, NHYA); Left ventricular discharge fraction <40%.
Exclusion criteria: acute myocardial infarction; hypertrophic cardiomyopathy; congenital heart defects; patients under 25; heart failure caused by oncology patients.
According to the inclusion criteria, the study included a total of 30 patients, including 21 men (70%) and 9 women (30%). The mean age of the patients was 69.3 ± 1.3. Each patient was given a combination of sacubitril/valsartan twice daily (100 mg in the morning and 100 mg in the evening) in addition to the conservative treatment of chronic heart failure for 6 months. The clinical demographic characteristics of the patients included in the study are presented in Table 1.
| Characteristics | N=30 | |
|---|---|---|
| Absolute | % | |
| Male | 21 | 70 |
| Female | 9 | 30 |
| Age (mean) | 69.3 ± 1.3 | |
| Classes of Heart failure; the New York Heart Association (NYHA) Functional Classification | ||
| II FC | 11 | 36.70% |
| III FC | 18 | 60% |
| IV FC | 1 | 3.30% |
| hypertension | 16 | 53.30% |
| Type 2 Diabetes | 23 | 76.70% |
| Obesity | 14 | 46.70% |
| Smoking | 20 | 66.60% |
Table 1: Clinical and demographic characteristics of patients.
Statistical analysis
The study compared the results of clinical indicators (heart failure complaints, functional grade assessment, systolic and diastolic blood pressure) and echocardiography indicators before and after treatment. Statistical analysis of variance (ANOVA test) and Wilcoxon Signed Ranks test were performed. Tables 2 and 3 show the statistical results. The functional classification was tested by the Wilcoxon Signed Ranks test and the Chi-square test, the Pearson criterion (Table 4).
| Characteristics | N | Mean | Std. Deviation | Std. Error | 95% Confidence Interval for Mean | Minimum | Maximum | F | Sig. | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Lower Bound | Upper Bound | ||||||||||
| SBP | Before treatment | 30 | 113.8 | 4.5 | 0.8 | 112.2 | 115.5 | 110 | 120 | 1.803 | 0.185 |
| After treatment | 30 | 112.4 | 3.5 | 0.6 | 111.1 | 113.8 | 110 | 120 | |||
| DBP | Before treatment | 30 | 69.2 | 6.8 | 1.2 | 66.6 | 71.7 | 60 | 80 | 3.389 | 0.071 |
| After treatment | 30 | 69.2 | 6.5 | 1.2 | 63.6 | 68.4 | 60 | 80 | |||
| LVES | Before treatment | 30 | 43.1 | 11.6 | 2.1 | 38.8 | 47.5 | 30 | 77 | 0.082 | 0.776 |
| After treatment | 30 | 42.3 | 11 | 2 | 38.2 | 46.4 | 30 | 77 | |||
| LVED | Before treatment | 30 | 57.7 | 10.5 | 1.9 | 53.8 | 61.7 | 44 | 85 | 0.093 | 0.761 |
| After treatment | 30 | 56.9 | 9.8 | 1.8 | 53.3 | 60.6 | 44 | 85 | |||
| LVEF | Before treatment | 30 | 35.9 | 4.8 | 0.9 | 34.1 | 37.7 | 20 | 42 | 2.567 | 0.115 |
| After treatment | 30 | 38 | 5.1 | 0.9 | 36 | 39.9 | 23 | 45 | |||
| PASP | Before treatment | 30 | 27.8 | 6.2 | 1.1 | 25.5 | 30.1 | 20 | 41 | 0.926 | 0.34 |
| After treatment | 30 | 26.3 | 5.6 | 1 | 24.2 | 28.4 | 18 | 39 | |||
Table 2: Test ANOVA.
| Characteristics | N | Mean Rank | Sum of Ranks | |
|---|---|---|---|---|
| SBPa - SBP | Negative Ranks | 8 | 5.06 | 40.5 |
| Positive Ranks | 1 | 4.5 | 4.5 | |
| Ties | 21 | |||
| DBPa-DBP | Negative Ranks | 16 | 9.13 | 146 |
| Positive Ranks | 1 | 7 | 7 | |
| Ties | 13 | |||
| LVEDa - LVED | Negative Ranks | 8 | 4.5 | 36 |
| Positive Ranks | 0 | 0 | 0 | |
| Ties | 22 | |||
| LVESa - LVES | Negative Ranks | 9 | 5 | 45 |
| Positive Ranks | 0 | 0 | 0 | |
| Ties | 21 | |||
| LVEFa - LVEF | Negative Ranks | 0 | 0 | 0 |
| Positive Ranks | 24 | 12.5 | 300 | |
| Ties | 6 | |||
| PASPa - PASP | Negative Ranks | 19 | 10 | 190 |
| Positive Ranks | 1 | 20 | 20 | |
| Ties | 10 | |||
| FCs - FC | Negative Ranks | 20 | 10.5 | 210 |
| Positive Ranks | 0 | 0 | 0 | |
| Ties | 10 | |||
Table 3: Test Wilcoxon signed ranks.
| Characteristics | Qr1 | ||||
|---|---|---|---|---|---|
| Before treatment | After treatment | ||||
| Count | Column N % | Count | Column N % | ||
| FC | I FC | 0 | 0.00% | 4 | 13.30% |
| II FC | 11 | 36.70% | 22 | 73.30% | |
| III FC | 18 | 60.00% | 4 | 13.30% | |
| IV FC | 1 | 3.30% | 0 | 0.00% | |
| Pearson Chi-Square Tests | |||||
| Qr1 | |||||
| FC | Chi-square | 17.576 | |||
| Df | 3 | ||||
| Sig. | 0.001 | ||||
Table 4: Test statistics ranks.
Discussion
Although no statistically significant difference was found in the ANOVA test, the statistical accuracy of the individual assessments by the Wilcoxon Signed Ranks test was obtained. The results of individual statistical analysis of the pre- and post-treatment clinical and echocardiographic examinations were as follows: P<0.028 during the analysis of the SBP results at pre- and post-treatment measurements; P<0.001 during the analysis of DBP results at pre- and post-treatment measurements; P<0.007 when analyzing the results of LVES at pre- and post-treatment measurements; P<0.011 during the analysis of the results of LVED at preand post-treatment measurements; when analyzing the results of the LVEF at pre- and post-treatment measurements, p<0.000; When analyzing PASP results at pre- and post-treatment measurements, p<0.001. The functional class indicator was evaluated by the Pearson Criteria (chi-square test). Statistical accuracy was obtained when analyzing the results after 6 months of treatment (p<0.001).
This article analyzes the results of a 6-month clinical and echocardiographic examination of the patients with chronic heart failure and the effects of the sacubitril/valsartan complex on these results. Because the study was conducted among patients with a reduced fraction of left ventricle, echocardiography examination was used to evaluate the left ventricular ejection fraction before and after treatment. Positive changes were found in the left ventricular ejection fraction as well as in the patient's general condition during the analysis of echocardiography and postoperative treatment of clinical symptoms.
Results
In the evaluation of the results of the echocardiographic examination and clinical indications (complains, functional class and etc.) six months after the use of the sacubitril/ valsartan combination in patients, positive changes were found in the majority of patients compared with the indications of previous 6 months.
Conclusions
In summary, the statistical analysis of the results obtained from the study concluded that the addition of the sacubitril/valsartan complex to the treatment of patients had a positive effect on the overall condition of the patients.
Declarations
Ethics approval and consent to participate: I can only send this document only in the beginning of June. Because of Covid-19 virus, it is impossible to take official documents from institutions. If it is accepted, I can send the official registration code of my study in the Republic of Azerbaijan (BTEB-094, http://bteb.science.gov.az/az/dissertation). It is website of Azerbaijan National Academy of Sciences Division of Biological and Medical Sciences.
Conflict of Interest
There is no conflict of interest.
Funding
There is no funding support.
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