Research Article - Interventional Cardiology (2021) Volume 13, Issue 1
Impact of Sacubitril/Valsartan on Patient Outcomes in Chronic Heart Failure
- Corresponding Author:
- Eyubova UA
Department of III Internal Diseases,
Azerbaijan Medical University;
Baku,
Azerbaijan,
E-mail: eyubovaulviyya@ mail.ru
Received date: December 14, 2020 Accepted date: December 28, 2020 Published date: January 04, 2021
Abstract
Background: Chronic Heart Failure (CHF) remains one of the most important problems in cardiology, despite the availability of various modern diagnostic methods and a number of advances in treatment. This is due to its widespread use, lowering the quality of life of patients, as well as high rates of recurrent decompensation and death. Despite the optimal use of modern treatments based on proven medical principles, the disease still has a high morbidity and mortality rate.
Aim: The aim of our study was to evaluate the conservative treatment which pathogenetic complementarity with the inclusion of a combination of sacubitril/valsartan in the treatment of patients with chronic heart failure with a comparison with device therapy of chronic heart failure.
Materials and Methods: The study included 64 patients over the age of 38 suffering from Chronic Heart Failure (CHF) (45 men, 19 women, 59.5 ± 0.9 years of age). Patients were divided into basic and control groups. 33 patients were included in the main group. In the main group, patients received sacubitril/valsartan twice daily in addition to the classic conservative treatment of CHF. The control group included 31 patients who underwent CRT surgery and classic conservative treatment without of sacubitril/valsartan. During the study, the clinical performance of patients before and after 6 months of treatment, the results of BNP tests, the results of a 6-minute walking test were compared.
Conclusion: Evaluation of the results of examinations of patients after 6 months revealed more positive changes in the indicators of the majority of patients in the main group (especially on functional class) than in 6 months ago.
Keywords
Chronic heart failure • Sacubitril /Valsartan combination • CRT
Background
In the treatment of patients with CHF, our main goal is to improve the clinical condition of patients, increase their functional capacity and quality of life, prevent re-hospitalization and, most importantly, reduce the number of deaths [1-3].
Chronic Heart Failure (CHF) remains one of the most important problems in cardiology, this is due to its widespread use, lowering the quality of life of patients, as well as high rates of recurrent decompensation and death. Despite the optimal use of modern treatments based on proven medical principles, the disease still has a high morbidity and mortality rate [4-9]. Many new drugs and devices are currently being used to treat patients with chronic heart failure [2].
Modern principles of existing pharmacological treatments are based on the pathogenetic concept of CHF, which develops as a result of long-term activation of the neurohumoral system. These include, first of all, renin-angiotensin-aldosterenone and sympathetic-adrenal systems, which are considered pathognomonic in patients with chronic heart failure with poor prognosis. Theoretically, the combined use of different groups of neurohumoral modulators may provide additional benefits in the treatment of patients with chronic heart failure as a result of a more complete blockade of neurohormones. The essence of such a concept is very simple, so the higher the level of different levels of neurohumoral regulation, the better the result [2]. In recent years, a new pharmacological drug has been used in the conservative treatment of patients with chronic heart failure with a reduced emission fraction. This pharmacological drug is a pharmacological agent that can provide simultaneous blockade of both the angiotensin system and neprilisyn. Recently, a number of studies have been conducted on this drug, and a series of studies are ongoing.
In addition to drug treatment, the device is widely used in modern therapies. Of these, resynchron heart therapy is the most widely used treatment in recent years in all countries of the world. In patients with moderate to severe heart failure, CRT treatment may improve quality of life in two-thirds of patients and prolong life in one-third [10]. However, not all patients receiving this treatment respond positively to the CRT method. A number of features can affect the course of the disease after this treatment and the mortality rate. For example, in patients with ischemic etiology, left ventricular function develops less positively after this treatment due to scar tissue of the myocardium. This reduces the likelihood of favorable remodeling during the use of CRT in such patients [3].
Materials and Methods
The study included 64 patients over the age of 38 who were treated at the Eurasia Hospital with a diagnosis of CHF. The diagnosis of CHF was confirmed on the basis of anamnesis, objective and instrumental examination methods.
Eligibility criteria
History of chronic heart failure; circulatory failure (functional class II-IV, NHYA); left ventricular ejection fraction <40%.
Exclusion criteria
Acute myocardial infarction; hypertrophic cardiomyopathy; congenital heart defects; Patients under 25 years of age; heart failure in oncology patients. According to the admission criteria, a total of 64 patients were included in the study, 45 men (70.3% ± 5.7%) and 19 women (29.7% ± 5.7%). The mean age of the patients was 59.5 ± 0.9. During the study, each patient in the main group was given a combination of sacubitril / valsartan twice a day for 6 months in addition to the conservative treatment received for CHF. CRT surgery was performed on patients in the control group. Demographic and clinical characteristics of the patients included in the study are given in Table 1. Thus, no statistically significant differences were obtained during the analysis of the indicators between of patients divided into two groups P>0.05.
| Characteristics | Groups | |
|---|---|---|
| I group (n=33) | II group (n=31) | |
| Age | 59.6 ± 1.3 | 59.5 ± 1.4 |
| (38-70) | (39-73) | |
| Male | 25 | 20 |
| 75.8% ± 7.5% | 64.5% ± 8.6% | |
| Female | 8 | 11 |
| 24.2% ± 7.5% | 35.5% ± 8.6% | |
| BMI | 36.9 ± 0.5 | 35.9 ± 0.3 |
| (31.6-43.6) | (32.1-38.7) | |
| Obesity | ||
| I grade | 8 | 6 |
| 24.2% ± 7.5% | 19.4% ± 7.1% | |
| II grade | 18 | 25 |
| 54.5% ± 8.7% | 80.6% ± 7.1% | |
| III grade | 7 | 0 |
| 21.2% ±7.1% | 0.00% | |
| Action | ||
| Activ | 4 | 4 |
| 12.1% ± 5.7% | 12.9% ± 6.0% | |
| Non-activ | 29 | 27 |
| 87.9% ± 5.7% | 87.1% ± 6.0% | |
| Smoking | ||
| Does not smoke | 8 | 11 |
| 24.2% ± 7.5% | 35.5% ± 8.6% | |
| A few | 8 | 4 |
| 24.2% ± 7.5% | 12.9% ± 6.0% | |
| A lot | 17 | 16 |
| 51.5% ± 8.7% | 51.6% ± 9.0% | |
| Diabetus mellitus | 27 | 26 |
| 81.8% ± 6.7% | 83.9% ± 6.6% | |
| Arterial hypertension | 21 | 20 |
| 63.6% ± 8.4% | 64.5% ± 8.6% | |
| Family | ||
| Mother | 5 | 7 |
| 15.2% ± 6.2% | 22.6 ± 7.5% | |
| Father | 8 | 4 |
| 24.2% ± 7.5% | 12.9% ± 6.0% | |
| Both | 20 | 20 |
| 60.6% ± 8.5% | 64.5% ± 8.6% | |
Table 1: Demographic and clinical characteristics of patients.
Results
During the study, the clinical performance of patients before and 6 months after the start of treatment, the results of a 6-minute walking test were compared. Statistical analyzes included the Wilcoxon Signed Ranks Test (Tables 2 and 3) and the Mann-Whitney Test (Table 4), and the Pearson Chi-Square Tests (Table 5).
| Ranks | n | Mean rank | Sum of ranks | p | |
|---|---|---|---|---|---|
| Shortness of breath a- Shortness of breath | Negative ranks | 30 | 15,50 | 465,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 3 | ||||
| Total | 33 | ||||
| Heartbeat a – Heartbeat | Negative ranks | 28 | 14,50 | 406,00 | |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 5 | ||||
| Total | 33 | ||||
| Cough a–Cough | Negative ranks | 15 | 8,00 | 120,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 18 | ||||
| Total | 33 | ||||
| Pulmonary auscultation a-pulmonary auscultation | Negative ranks | 33 | 17,00 | 561,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 0 | ||||
| Total | 33 | ||||
| Edema in the legs a-edema in the legs | Negative ranks | 33 | 17,00 | 561,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 0 | ||||
| Total | 33 | ||||
| Pulse fullness a - Pulse fullness | Negative ranks | 1 | 1,00 | 1,00 | 0.317 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 32 | ||||
| Total | 33 | ||||
| Pulse rate a - Pulse rate | Negative ranks | 32 | 16,50 | 528,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 1 | ||||
| Total | 33 | ||||
| SaO2 a–SaO2 | Negative ranks | 0 | 0,00 | 0,00 | 0 |
| Positive ranks | 33 | 17,00 | 561,00 | ||
| Ties | 0 | ||||
| Total | 33 | ||||
| Decompentation a-Decompentation | Negative ranks | 26 | 14,29 | 371,50 | 0 |
| Positive ranks | 6,50 | 6,50 | |||
| Ties | 6 | ||||
| Total | 33 | ||||
| 6 min. walk test a-6 min. walk test | Negative ranks | 32 | 16,50 | 528,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 1 | ||||
| Total | 33 | ||||
| FC a–FC | Ties | 0at | 0 | ||
| Total | 33 | ||||
| SPATs - SPAT | Negative Ranks | 21au | 11,00 | ||
| Total | 33 | ||||
| SAH a–SAH | Negative Ranks | 21 | 11,00 | 231,00 | 0 |
| Positive Ranks | 0 | 0,00 | 0,00 | ||
| Ties | 12 | ||||
| Total | 33 | ||||
| DAH a–DAH | Negative Ranks | 21 | 11,00 | 231,00 | 0 |
| Positive Ranks | 0 | 0,00 | 0,00 | ||
| Ties | 12 | ||||
| Total | 33 |
a: after 6-month (after treatment)
Table 2: Wilcoxon Signed ranks testi–Group 1.
| Ranksa | n | Mean Rank | Sum of Ranks | p | |
|---|---|---|---|---|---|
| Shortness of breath a-Shortness of breath | Negative ranks | 18 | 9,50 | 171,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 13 | ||||
| Total | 31 | ||||
| Heartbeat a–Heartbeat | Negative ranks | 27 | 14,00 | 378,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 4 | ||||
| Total | 31 | ||||
| Cough a-Cough | Negative ranks | 12 | 6,50 | 78,00 | 0.001 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 19 | ||||
| Total | 31 | ||||
| pulmonary auscultation a-pulmonary auscultation | Negative ranks | 28 | 14,50 | 406,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 3 | ||||
| Total | 31 | ||||
| edema in the legs a-edema in the legs | Negative ranks | 30 | 15,50 | 465,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 1 | ||||
| Total | 31 | ||||
| Pulse fullness a-Pulse fullness | Negative ranks | 4 | 2,50 | 10,00 | 0.046 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 27 | ||||
| Total | 31 | ||||
| Pulse rate a-Pulse rate | Negative ranks | 31 | 16,00 | 496,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 0 | ||||
| Total | 31 | ||||
| SaO2 a–SaO2 | Negative ranks | 0 | 0,00 | 0,00 | 0 |
| Positive ranks | 31 | 16,00 | 496,00 | ||
| Ties | 0 | ||||
| Total | 31 | ||||
| Decompentation a-Decompentation | Negative ranks | 24 | 14,25 | 342,00 | 0 |
| Positive ranks | 2 | 4,50 | 9,00 | ||
| Ties | 5 | ||||
| Total | 31 | ||||
| 6 min. walk test a-6 min. walk test | Negative ranks | 31 | 16,00 | 496,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 0 | ||||
| Total | 31 | ||||
| FC a-FC | Negative ranks | 18 | 9,50 | 171,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 13 | ||||
| Total | 31 | ||||
| SAH a–SAH | Negative ranks | 24 | 12,50 | 300,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 7 | ||||
| Total | 31 | ||||
| DAH a–DAH | Negative ranks | 22 | 11,50 | 253,00 | 0 |
| Positive ranks | 0 | 0,00 | 0,00 | ||
| Ties | 9 | ||||
| Total | 31 |
Table 3: Wilcoxon Signed ranks testi–Group 2.
| Ranks | ||||
|---|---|---|---|---|
| Gr1 | n | Mean rank | Sum of ranks | |
| Group 1 | 33 | |||
| Group 2 | 31 | |||
| Total | 64 | |||
| Test Statisticsa | ||||
| Mann-Whitney U | Wilcoxon W | Z | Asymp. Sig. (2-tailed) | |
| Shortness of breath | 5,03,000 | 10,64,000 | -0,139 | 0,890 |
| Shortness of breath a | 3,80,000 | 9,41,000 | -2,517 | 0,012 |
| Heartbeat | 4,49,500 | 9,45,500 | -0,985 | 0,325 |
| Heartbeat a | 4,48,000 | 9,44,000 | -1,042 | 0,298 |
| Cough | 4,87,000 | 10,48,000 | -0,368 | 0,713 |
| Cough a | 3,91,500 | 9,52,500 | -2,309 | 0,021 |
| Pulmonary auscultation | 4,07,000 | 9,03,000 | -1,913 | 0,056 |
| Pulmonary auscultation a | 4,92,500 | 9,88,500 | -0,376 | 0,707 |
| Edema in the legs | 4,75,500 | 10,36,500 | -0,844 | 0,399 |
| Edema in the legs a | 2,74,000 | 8,35,000 | -3,521 | 0,000 |
| Pulse fullness | 5,02,500 | 10,63,500 | -0,155 | 0,877 |
| Pulse fullness a | 4,70,000 | 9,66,000 | -0,800 | 0,424 |
| Pulse rate | 4,97,000 | 9,93,000 | -0,195 | 0,845 |
| Pulse rate a | 4,90,000 | 9,86,000 | -0,290 | 0,772 |
| SaO2 | 4,08,000 | 9,69,000 | -1,485 | 0,138 |
| SaO2 a | 4,55,500 | 9,51,500 | -0,775 | 0,439 |
| QRS | 4,82,000 | 9,78,000 | -0,447 | 0,655 |
| Decompentation | 4,46,500 | 10,07,500 | -0,892 | 0,373 |
| Decompentation a | 4,99,500 | 10,60,500 | -0,178 | 0,859 |
| 6 min. walk test | 4,66,000 | 10,27,000 | -1,315 | 0,189 |
| 6 min. walk test a | 3,41,500 | 9,02,500 | -3,105 | 0,002 |
| FC | 5,10,500 | 10,71,500 | -0,021 | 0,983 |
| FC a | 3,49,500 | 9,10,500 | -2,390 | 0,017 |
| Initial compensation period | 3,73,000 | 9,34,000 | -1,958 | 0,050 |
| SAH | 4,75,500 | 10,36,500 | -0,496 | 0,620 |
| SAH a | 5,06,000 | 10,67,000 | -0,079 | 0,937 |
| DAH | 4,86,500 | 10,47,500 | -0,360 | 0,718 |
| DAH a | 4,71,500 | 10,32,500 | -0,564 | 0,573 |
Table 4: Mann-Whitney Test.
| Ranks | Significance | |
|---|---|---|
| Shortness of breath | Chi-square | 0,020 |
| Df | 2 | |
| Sig. | 0,990 | |
| Shortness of breath a | Chi-square | 8,165 |
| Df | 3 | |
| Sig. | 0,043 | |
| Heartbeat | Chi-square | 4,478 |
| Df | 2 | |
| Sig. | 0,107 | |
| Heartbeat a | Chi-square | 5,142 |
| Df | 2 | |
| Sig. | 0,076 | |
| Cough | Chi-square | 5,379 |
| Df | 2 | |
| Sig. | 0,068 | |
| Cough a | Chi-square | 5,531 |
| Df | 2 | |
| Sig. | 0,063 | |
| Pulmonary auscultation | Chi-square | 3,718 |
| df | 1 | |
| Sig. | 0,054 | |
| Pulmonary auscultation a | Chi-square | 3,541 |
| df | 2 | |
| Sig. | 0,170 | |
| edema in the legs | Chi-square | 0,724 |
| df | 1 | |
| Sig. | 0,395 | |
| Edema in the legs a | Chi-square | 16,263 |
| df | 3 | |
| Sig. | 0,001 | |
| Pulse fullness | Chi-square | 0,024 |
| df | 1 | |
| Sig. | 0,876 | |
| Pulse fullness a | Chi-square | 0,650 |
| df | 1 | |
| Sig. | 0,420 | |
| 6 min. walk test | Chi-square | 1,756 |
| df | 1 | |
| Sig. | 0,185 | |
| 6 min. walk test a | Chi-square | 13,706 |
| df | 2 | |
| Sig. | 0,001 | |
| FC | Chi-square | 0,414 |
| df | 2 | |
| Sig. | 0,813 | |
| FCa | Chi-square | 6,687 |
| df | 3 | |
| Sig. | 0,083 | |
| Initial compensation period | Chi-square | 7,212 |
| df | 3 | |
| Sig. | 0,065 | |
Table 5: Pearson chi-square tests.
Discussion
As can be seen from the tables above, during the study, the pulse and blood pressure readings, anamnesis, physical examination results of all patients, as well as the results of the 6-minute walking test were examined in detail by statistical analysis. Both qualitative and quantitative tests were used in statistical analysis. During the Wilxson test, statistical accuracy was obtained in the results of other indicators 6 months later, except for pulse fulness in group 1. p<0.05 Calculation of pulse fullness results 6 months before and after did not give statistically accurate results (p= 0.317). There are also positive changes in the comparison of pre- and post-treatment outcomes of patients in group 2. Thus, statistically accurate results were obtained. That is, positive results were obtained from the treatments carried out separately in both groups. An intergroup analysis of patients’ results was performed with the Mann- Whitney Test. Although statistical accuracy was not obtained in all indicators during this analysis, statistical accuracy was obtained in some indicators (history of shortness of breath, cough complaints, 6-minute walking test) as shown in Table 3. The most important of these is the acivite of patients and functional class indicator. The intergroup 6 minutes’ walk test index gave a statistically accurate result (p=0.000). The intergroup functional class index gave a statistically accurate result (p=0.017). In the Pearson Chi-Square Test, a qualitative analysis, no statistical accuracy was obtained in most indicators, nor in the functional class (p=0.083).
Conclusion
OIn summary, a statistical analysis of the results of our study concluded that the addition of sacubitril/valsartan complex to the treatment of patients had a better effect on the reduction of complaints in the anamnesis of patients, activity of patients and functional class performance than other treatments.
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