We treat the heart without any side effects. Expert on the situation around valsartan

Introduction

Approximately 1–2% of the adult population in developed countries have heart failure (HF), and in patients over the age of 70 years, the risk of developing HF is more than 10% [1–4]. Among people over 65 years of age with new-onset dyspnea on exertion, 1 in 6 people will have unrecognized HF, mostly HF with preserved ejection fraction (EF) [3, 4]. The risk of developing heart failure at age 55 years is 33% for men and 28% for women [5].

Over the past 25 years, since enalapril has been shown to reduce mortality in patients with HF with reduced EF while taking enalapril, inhibitors of the renin-angiotensin-aldosterone system (RAAS) have been the mainstay of treatment for HF. Subsequent studies found that triple neurohormonal blockade: angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers and mineralocorticoid receptor antagonists reduced the risk of death from 30-35 to 22-30%.

In 2016, a new drug appeared in the arsenal of cardiologists - sacubitril/valsartan (Uperio), which is a complex of neprilysin inhibitor and angiotensin-2 receptor blocker. Neprilysin is a membrane enzyme involved in the degradation mainly of natriuretic peptides [1–3]. Inhibition of neprilysin, in turn, causes an increase in the level of these peptides, which counteracts maladaptive neurohormonal activation, which contributes to sodium and water retention in the body, maintaining vasoconstriction and tissue remodeling [6, 7]. Simultaneous inhibition of the RAAS and neprilysin allows one to achieve an optimal level of neurohormonal balance, stabilize and improve the clinical condition of patients with HF with systolic dysfunction, as was demonstrated in the prospective randomized clinical trial PARADIGM-HF.

According to modern recommendations for the diagnosis, prevention and treatment of HF, sacubitril/valsartan is recommended for patients with chronic HF (CHF) functional class II-III with systolic dysfunction, who do not require intravenous or doubling the dose of oral diuretics, and with systolic blood pressure (BP) more than 100 mmHg, if ACE inhibitors or angiotensin receptor antagonists are tolerated, to further reduce the risk of death and subsequent hospitalizations due to worsening CHF (class of recommendation I, level of evidence B) [8].

The place of valsartan in modern cardiology

Today, generally accepted indications for the use of ARBs are: 1) treatment of hypertension, as well as renovascular hypertension and hypertension developing after kidney transplantation; 2) treatment of CHF caused by systolic dysfunction of the left ventricle (though so far only in cases where ACE inhibitors are contraindicated or poorly tolerated); 3) treatment and secondary prevention of diabetic nephropathy. Potential indications for the use of ARBs: 1) treatment of arterial hypertension that develops in the workplace; 2) treatment of CHF with preserved left ventricular systolic function, instead of or together with ACE inhibitors; 3) prevention of post-infarction left ventricular dysfunction; 4) treatment of non-diabetic kidney diseases; 5) prevention of restenosis after coronary angioplasty; 6) primary prevention of hypertension in individuals with high normal blood pressure; 7) primary and secondary prevention of stroke, including in patients with atrial fibrillation; prevention of cardiovascular diseases of atherosclerotic origin in people at high risk; 9) prevention of type 2 diabetes mellitus in people at high risk. Currently, the ARB group is represented by four subgroups that differ in chemical structure: • biphenyl tetrazoles (losartan, irbesartan, candesartan) • non-biphenyl tetrazoles (telmisartan) • non-biphenyl non-tetrazoles (eprosartan) • non-heterocyclic compounds (valsartan) ARBs can be: • pharmacologically active ( telmisartan, irbesartan, eprosartan); • prodrugs (losartan, candesartan); • hydrophilic – losartan is the most hydrophilic drug; • lipophilic (telmisartan is the most lipophilic). According to the degree of antagonism to AT1 receptors, they are divided into: • competitive (eprosartan, losartan); • non-competitive (valsartan, telmisartan, irbesartan, candesartan). The pharmacodynamic effects of ARBs are associated with their ability to block the renin–angiotensin–aldosterone system (RAAS) at the level of angiotensin receptor type 1 (AT1). According to modern concepts, it is through the activation of these receptors that the pathological effect of high concentrations of the main RAAS effector angiotensin II is realized in cardiovascular diseases. It should be recalled that almost all organs and systems of the body are involved in the RAAS. In the liver, there is active synthesis of angiotensinogen, a protein from the globulin class, consisting of 453 amino acids, which, under the influence of renin, turns into angiotensin I. The main amount of renin is synthesized in the juxtaglomerular apparatus (JAA) of cortical nephrons. Renin is synthesized in the form of prorenin, which is found in granules. As the granules enlarge, prorenin becomes renin (the active form). In response to decreased renal perfusion, decreased delivery of sodium and chloride ions, and hypoxia, renin production is activated. Angiotensin I does not have biological pressor activity and is only a precursor of active angiotensin II, which is formed under the influence of angiotensin-converting enzyme (ACE). But the conversion of angiotensin I to angiotensin II under the influence of ACE occurs only in the systemic circulation, while in tissues it is carried out under the influence of chymases. Therefore, the effects of the RAAS, leading to the development of pathological processes (for example, in the myocardium), cannot be completely neutralized only with the use of ACE inhibitors. This may also explain the phenomenon of “escape” of the effect during their long-term use. And the fundamental differences between ACE inhibitors and ARBs are revealed precisely in the mechanism of action at this stage. ARBs have a specific effect and block only the biological effects of ATII without interfering with the kinin system, which improves their tolerability. It is the unique tolerability profile that is the most important feature of ARBs. The results of many randomized clinical trials consistently show that the incidence of side effects when using drugs in this group, even in high dosages, is extremely low and comparable to placebo. For a long time, this served as the basis for considering ARBs as a replacement for ACE inhibitors in case of intolerance to the latter. However, in recent years, a large base has been accumulated proving that ARBs are not inferior to other classes of antihypertensive drugs in terms of both their main pharmacodynamic effects and their impact on endpoints. A drug whose effectiveness has been proven for all generally accepted and a number of additional indications for the use of ARBs in large studies is valsartan. It is rapidly absorbed from the gastrointestinal tract, the maximum concentration in the blood plasma is reached 2-4 hours after oral administration; At the same time, the antihypertensive effect of the drug appears. A long half-life (about 9 hours), as well as a strong connection with AT1 receptors (24 thousand times higher than that with AT2 receptors) ensures 24-hour maintenance of the effect, which allows you to take the drug once a day. Based on an analysis of the results of studies involving more than 140 thousand patients, it was found that the proportion of patients continuing antihypertensive therapy with valsartan for 1 year is significantly higher compared to therapy with other drugs (amlodipine and lisinopril) [3]. Valsartan's selectivity for type 1 angiotensin receptors is 24 thousand times higher than for type 2 receptors. Antihypertensive efficacy In two studies, valsartan at a dose of 80 mg/day. was not inferior in effectiveness to 20 mg enalapril [4,5]. At the same time, the frequency of cough with valsartan was almost 6 times lower than with enalapril. The effectiveness of valsartan in isolated systolic hypertension was studied in the Val-Syst study in comparison with amlodipine [6]. It was shown that both drugs effectively lowered SBP, but with valsartan, the frequency of adverse events was one and a half times lower [7]. More extensive data were obtained during the open multicenter randomized trial Val-MARC to evaluate the effect of lowering blood pressure on the concentration of C-reactive protein in 1668 patients with stage 2 hypertension. [8]. The use of valsartan at a dose of 160–320 mg provided a decrease in systolic blood pressure and diastolic blood pressure by 18 and 9 mm Hg. respectively. Moreover, the antihypertensive effect of valsartan appeared starting with very low dosages (20–40 mg/day) and increased as the dose increased. At the same time, a decrease in blood pressure while taking valsartan at a dosage of 80–320 mg occurs while maintaining a normal circadian rhythm [9]. Later, these data were confirmed by a combined analysis of the results of 9 studies, which included 803 patients with stage 1 hypertension, which showed both an increase in the antihypertensive effect and the frequency of achieving target blood pressure when the dose of valsartan was increased from 80 to 160 mg/day. [10]. Important data were obtained in a trial of valsartan using ambulatory 24-hour blood pressure monitoring. 90 patients had stage 1–2 hypertension. an equal decrease in the average daily values ​​of SBP and DBP was noted with both morning and evening single doses of 160 mg of the drug [11]. Thus, the timing of valsartan administration does not affect the stability of its antihypertensive effect. Also in the Japanese JIKEY HEART study, 3081 patients with hypertension and a high risk of complications (concomitant ischemic heart disease, CHF, diabetes or multiple risk factors, average age 65 years, average body weight 24 kg/m2) joined the basic therapy (67% calcium antagonists ; 35% ACE inhibitors; 32% b-blockers and other drugs) valsartan at a dose of 40–160 mg helped reduce blood pressure from 139/81 to 132/78 mm Hg. Cardioprotective effect A meta-analysis [12], which included 3767 patients from 146 treatment groups and 346 patients from 17 placebo groups, standardized for treatment duration and DBP, showed that ARBs provided the greatest reduction in left ventricular myocardial mass index (LVMI) (–13 %), superior to calcium antagonists (–11%), ACE inhibitors (–10%), diuretics (–8%) and β-blockers (–6%). The ability of valsartan to reduce the severity of LVH in patients with hypertension has been shown in several studies [13,14]. In particular, in a comparative study with amlodipine, it was noted that with the same reduction in blood pressure, the LVMM index in the valsartan group significantly decreased by 16%, and in the amlodipine group - only by 1.2%, and not significantly [15]. Important results were obtained in the Val-PREST and VALVACE studies. Valsartan therapy has been proven to reduce the risk of restenosis and re-interventions in patients who have undergone transluminal balloon angioplasty of the coronary arteries [16,17]. The VALIANT (Valsartan in Acute Myocardial Infarction Trial) study examined the effect of valsartan on the course of acute myocardial infarction. Patients were included in the study within 0.5–10 days after the development of MI. According to this study, monotherapy with valsartan at a dose of 160 mg 2 times / day. turned out to be as effective in the treatment of post-infarction patients with left ventricular dysfunction and/or heart failure as monotherapy with captopril at a dose of 50 mg 3 times a day, the value of which in a similar situation has been proven previously [18]. Antiarrhythmic effect The cardioprotective properties of valsartan are also evidenced by the ability of the drug to reduce the risk of developing new cases of atrial fibrillation in patients with hypertension and CHF, proven in the VALUE [19] and Val-HeFT [20] studies. Atrial fibrillation (AF) is a prognostically unfavorable sign in patients with hypertension and myocardial hypertrophy, which increases the risk of cardiovascular morbidity and mortality. Use for CHF Today, the importance of imbalance of the RAAS in the pathogenesis of the development of CHF is undeniable. Existing recommendations for the treatment of CHF, along with cardiac glycosides, diuretics, beta-blockers, also include drugs that affect the RAAS - ACE inhibitors and sartans. It is also known that with long-term CHF there is a partial change in the pathway of conversion of angiotensin I to angiotensin II from systemic (using ACE) to chymase (occurring directly in the tissues), and therefore the use of ARBs is preferable. Valsartan became the first drug from the BAR class, which was registered for the treatment of patients with CHF. The Valsartan in Heart Failure Trial (Val-HeFT) study included 5010 patients with CHF with NYHA functional class II, III and IV who received recommended therapy [20,21]. In 93% of patients, either valsartan was added to the therapy, including ACE inhibitors, at a starting dose of 40–80 mg, followed by an increase to 160 mg 2 times a day, or placebo. The addition of valsartan led to a reduction in the risk of developing the primary combined endpoint (mortality and cardiovascular morbidity) by 13.2% (p = 0.009), mainly due to a decrease in the number of hospitalizations due to heart failure. The most pronounced clinical effects were observed in a group of 366 patients who did not receive ACE inhibitors due to intolerance: mortality from all causes was 33.1% lower compared to the placebo group. Nephroprotective effect The advantages of ARBs include their proven nephroprotective effect, the most important component of which is the antiproteinuric effect. One of the first studies, the MicroAlbuminuria Reduction with VALsartan (MARVAL), examined the effect of valsartan 80 mg versus amlodipine 5 mg on urinary protein excretion over 24 weeks in 332 patients with type 2 diabetes and MAU [22]. As a result, with the same reduction in blood pressure in both groups, the level of albumin excretion (AEA) in the valsartan group decreased by 44%, and in the amlodipine group - by only 8%. The proportion of patients who reached the level of normoalbuminuria while taking valsartan (29.9%) was significantly higher than that while taking amlodipine (14.5%). Moreover, the decrease in AEA in the valsartan group began already from the first weeks of treatment and at low doses (80 mg/day). On the contrary, in the amlodipine group, the AEA increased in the first 8 weeks, and its decrease began only after doubling the drug dose (to 10 mg/day). Since the reduction in blood pressure was the same in both groups, the antiproteinuric effect of valsartan was blood pressure independent. It is important that valsartan had an effect on AER not only in patients with hypertension, but also in patients with initially normal blood pressure. The antiproteinuric efficacy of valsartan in hypertension and type 2 diabetes was confirmed in the Japanese open comparative study SMART [23]. It was shown that with the same antihypertensive effectiveness, the albumin/creatinine ratio (ACR) in urine in the valsartan treatment group significantly decreased by 32%, and in the amlodipine treatment group it increased by 18%. The proportion of patients who experienced remission or regression of MAU was significantly higher in the valsartan group compared to amlodipine. In this study, while taking valsartan, a continuous progressive decrease in TBC was noted, while in the amlodipine group, a decrease in TBC was detected only in patients who reached target blood pressure values. When the target blood pressure was not achieved in the amlodipine group, the blood pressure increased by 40%. Data on the effect of different dosages of valsartan on the level of proteinuria in patients with hypertension and type 2 diabetes were obtained in the DROP study [24]. Patients were randomized into 3 groups, in which valsartan was prescribed in one of the dosages - 160, 320 or 640 mg per day. A significant decrease in AEA was shown when using the drug at a dose of 160 mg by 36%, and at doses of 320 and 640 mg - by 44 and 48%, respectively. The proportion of patients who achieved normal AEA values ​​(<20 mcg/min) was 12.4% in the group receiving 160 mg of valsartan, 19.2% in the group receiving 320 mg, and 24.3% in the group receiving 640 mg. Metabolic effects It has been proven to reduce the incidence of diabetes mellitus in patients receiving ARBs as an antihypertensive agent or in complex therapy of CHF. This property was shown for valsartan in the previously mentioned VALUE study [25] and in clinical practice [26]. In addition, valsartan improves the sensitivity of peripheral tissues to glucose in patients with hypertension [27]. It has also now been shown that sartans have a distinct hypouricemic effect. Valsartan ranks 2nd in its effect on uric acid levels (80–160 mg/day). It is important that the uricosuric effect persists even when used in combination with diuretics, thereby preventing the increase in uric acid levels in the blood caused by diuretics. Therefore, ARBs are recommended for use in patients with hypertension associated with metabolic syndrome [28]. Among the advantages of ARBs, it is necessary to note the positive impact on such an important aspect of quality of life as sexual function in men and women with hypertension. This has been convincingly demonstrated for valsartan [29]. Impact on endpoints The VALUE study did not reveal significant between-group differences in the prevalence of primary endpoints (cardiac morbidity, mortality and total mortality) between valsartan and amlodipine. In the JIKEY HEART study, over 3.1 years of follow-up, treatment with valsartan was associated with a reduction in the risk of developing the primary summary endpoint, including cardiac, cerebral and renal complications. During therapy with valsartan, a significant reduction in the risk of cardiovascular mortality and morbidity by 39% was noted. In addition, there was a 40% reduction in the risk of primary or recurrent stroke, a 65% reduction in the risk of hospitalization due to angina, a 47% reduction in the risk of hospitalization due to heart failure, and an 81% reduction in the risk of developing a dissecting aortic aneurysm. In the KYOTO HEART study, over 3.3 years of follow-up, the addition of valsartan to the treatment of insufficiently controlled patients with hypertension led to a reduction in the incidence of the primary endpoint by 45% (which was taken as the sum of all fatal and non-fatal cardiovascular events). Thus, today ARBs, and, in particular, valsartan, occupy a leading position in the treatment of many conditions, and valsartan is the most prescribed sartan worldwide [30]. The optimal representative of valsartan on the Russian market in terms of price-quality ratio is Valsacor (pharmaceutical). Valsacor is available in convenient dosages of 40, 80 and 160 mg. References 1. Pals DT, Massucci FD, Sipos F., Dennig Jr GSA specific competitive antagonist of the vascular action of angiotensin II. Cirs Res. 1971; 29: 664–12. 2. Kang PM, Landau AJ, Eberhardt RT, Frishman WH Angiotensin II receptor antagonists: A new approach to blockade of the renin–angiotensin system. Am heart J. 1994; 127:1388–401. 3. Wogen J. et al. Patient adherence with amlodipine, lisinopril, or valsartan therapy in a usual–care setting // J Managed Care Pharm., 2003; 9:424–429. 4. Holwerda et al. J Hypertens 1996;14(9):1147–1151. 5. Mallion et al. Blood Press Monit 1997;2(4):179–184. 6. Malacco et al. Clin Ther 2003;25:2765–2780. 7. Malacco E et al. Am J Hypertens. 2003;16:126A. 8. Ridker et al. Hypertension 2006;48(1):73–79. 9. Neutel et al. Clin Ther 1997;19(3):447–458. 10. Weir et al. J Clin Hypertens 2006;8(5;suppl A):A102 (P–232) 11. Hermida et al. Hypertension 2003;42:283–290. 12. Klingbeil AU, Schneider M, Martus P, Messerli FH, Schmieder RE. A meta–analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med. 2003 Jul;115(1):41–6. 13. Mutlu H, Ozhan H, Okcun B et al. The Efficacy of Valsartan in Essential Hypertension and its Effects on Left Ventricular Hypertrophy. Blood Pressure 2002; 11:53–5. 14. Thurmann PA, Kenedi P, Schmidt A et al. Influence of the angiotensin II antagonist valsartan on left ventricular hypertrophy in patients with essential hypertension. Circulation 1998; 98:2037–42. 15. Yasunari et al. JACC 2004;43:2116–212. 16. Peters S, Gotting B, Trummel M et al. Valsartan for prevention of restenosis after stenting of type B2/C lesions: the VAL–PREST trial. J Invasive Cardiol 2001; 13:93–7. 17. Peters S, Trummel M, Meyners W et al. Valsartan versus ACE inhibition after bare metal stent implantation–results of the VALVACE trial. Int J Cardiol 2005; 98:331–5. 18. McMurray J, Solomon S, Pieper K et al. The Effect of Valsartan, Captopril, Or Both on Atherosclerotic Events After Myocardial Infarction. Analysis of the Valsartan in Acute Myocardial Infarction Trial (Valiant). J Am Coll Cardiol 2006; 47: 726–33. 19. Schmieder R, Hua T. Reduced Incidence of New Onset Attrial Fibrillaration with Angiotensin II Reception Blockade: The Value - Tial. J Hypertens 2006; 24 (SUPPL.): S3. 20. Maggioni Ap, Latini R, Carson Pe et al. VALSARTAN REDUCES The Incidence of Atrial Fibrillaration in Patience with Heart Failure: Results from the Valsart Failure Trial (Val - HEFT). Am Heart J 2005; 149: 548–57. 21. Wong M, Staszewsky L, Latini R et al. VALSARTAN BENEFITS LEFT Ventricular Structure and Function in Heart Failure: Val - Heft Echocardiographic Study. J Am Coll Cardiol 2002; 40: 970–5. 22. Viberti G. Microalbuminuria Reduction with VALSARTAN in PATIENTS WITH TYPE 2 DIABEBETES MELLITUS: A Blood Pressure - Independent Effect. Wheeldon and for the Microalbuminuria Reduction with Valsartan (Marval) Study Investigators.circulation 2002; 106: 672–8. 23. The Shiga Microalbuminuria Reduction Trial (Smart) Group. Reduction of Microalbuminuria in Patients with Type 2 Diabetes. Diabetes Care; 2007: 30.6: 1581–1583. 24. Hollenberg et al. American Heart Association 2006 (Abstract). 25. KJELDSEN SE, Julius S, Mancia G et al. Effects of Valsartan Compared to Amlodipine on Preventing Type 2 Diabetes in High -Risk Hypertensive Patients: The Value Trial. J Hypertens 2006; 24: 1405–12. 26. WeyCker D, Edelsberg J, Vincze G et al. RISK of Diabetes in AL - World Setting Among Patients Initiating Antihypensave Therapy with Valsartan Or Amlodipine. J Hum Hypertens 2007; 21: 374–80. 27. Top C, Cingozbay by, Terekeci H et al. The Effects of Valsartan on Insulin Sensitivity in Patents with Primary Hypertension. J Int med Res 2002; 30: 15–20. 28. Diagnosis and treatment of metabolic syndrome. Russian recommendations. Moscow, 2007. Cardiovascular therapy and prevention 2007; Appendix 2: 3–26. 29. Fogari R, Preti P, Derosa G et al. Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men. EUR J Clin Pharmacol 2002; 58: 177–80. 30. World Sales ims Data, 2007.

Clinical case

Patient B.

, 62 years old, was hospitalized from 08/29/18 to 09/09/18. She was admitted through emergency medical care with decompensated CHF. Upon admission, she complained of shortness of breath at rest, a feeling of lack of air, severe swelling of the lower extremities, general weakness, and pain in the lower extremities.

From the anamnesis it is known that the patient has been suffering from hypertension for a long time with maximum blood pressure values ​​of 200/110 mm Hg, the usual blood pressure figures are 120-130/90 mm Hg. On an outpatient basis I took daily: bisoprolol 5 mg, losartan 50 mg, furosemide 20 mg, clopidogrel 75 mg, aspirin 100 mg. The patient had a history of myocardial infarction (of unknown duration) and a long-term persistent form of atrial fibrillation. I have type 2 diabetes mellitus, insulin dependent. Denies any history of cerebrovascular accident. About 2 years ago, atherosclerosis of peripheral arteries and occlusion of the arteries of the lower extremities were detected. She was repeatedly hospitalized due to S.N.’s decompensation. The condition worsened over the course of a week, when the above complaints began to increase.

The condition at admission was of moderate severity. The patient is conscious, the position is forced - orthopnea. The physique is normosthenic, body weight 60 kg, height 155 cm, BMI 25 kg/m2. The skin and mucous membranes are pale in color and clean. Symmetrical pronounced dense swelling of the legs and feet. The right lower limb is cold to the touch. Trophic ulcers of the right leg. In the lungs, breathing is harsh, fine wheezing on both sides, breathing is not audible in the lower sections. Heart sounds are muffled, irregular, there is no noise. Heart rate (HR) 117 beats/min, blood pressure 120/78 mm Hg. The abdomen is not enlarged, soft, painless. Stool and diuresis are not disturbed.

Data from clinical tests upon admission: hemoglobin 100 g/l, leukocytes 11.5·109/l; ESR 40 mm/h, neutrophils 9.4%. General urine test - without significant pathology, biochemical blood test: creatinine 203.66 mmol/l, urea 17.8, glucose 11.5 mmol/l, AST 33 U/l, ALT 60 U/l, potassium 5.6 mmol /l, sodium 137 mmol/l, natriuretic peptide BNP 3568 pg/ml, cholesterol 3.5 mmol/l. LDL 2.1 mmol/l, HDL 0.56 mmol/l.

Instrumental research data: electrocardiography (ECG) dated 08/29/18 - atrial fibrillation rhythm, heart rate 117 beats/min. The electrical axis of the heart is deviated to the left.

On the chest x-ray dated 08/30/18: bilateral hydrothorax.

Echocardiographic examination of the heart (EchoCG) dated 08/30/18

— aorta: sinus of Valsalva 3.5 cm. Left atrium 4.5×5.0×5.5 cm (4.0×4.0×6.0 cm), interventricular septum 1.0 cm (0.7— 1.1 cm); posterior wall of the left ventricle 0.9 cm (0.7-1.1 cm), end-systolic size 4.4 cm (2.5-4.1 cm), end-diastolic size 5.5 cm (3.5-5 .6 cm). The contractility of the left ventricular (LV) myocardium is diffusely reduced. Pronounced hypokinesia of the septum, anterior wall, akinesia of the apex. LVEF 40%, right atrium 5.0×5.0 cm (4.4×6.0 cm), right ventricle 2.5×4.0 cm (3.0×4.3 cm), additional formations: parietal thrombus 3.0×1.5 cm in the apex of the left vein. Contractility of the right ventricle is not impaired. The aortic valve is tricuspid, the leaflets are thickened, the leaflets are fully opened, the maximum pressure gradient is 3 mm Hg, degree I regurgitation. Mitral valve - multidirectional movement, regurgitation of the second degree. The tricuspid valve is not changed, regurgitation of II-III degree. The average pressure in the pulmonary artery is 50 mm Hg. There is 1.0 cm of fluid in the pericardial cavity. Bilateral hydrothorax.

Clinical diagnosis made:

Basic:

IHD. Post-infarction cardiosclerosis. Atherosclerosis of the aorta and coronary arteries. Atherosclerosis of the arteries of the lower extremities. Chronic arterial insufficiency of the 4th degree according to Fontaine-Pokrovsky. Occlusion of the tibial arteries on the right. Trophic ulcers of the right leg, I, II toes of the right foot. Forming gangrene of the right leg and foot.

Background disease:

stage III hypertension, stage 3 arterial hypertension, the risk of cardiovascular complications is very high.

Complication:

NK 2B, 3rd functional class according to NYHA. Chronic kidney disease - C4 (glomerular filtration rate - GFR - according to CKD-EPI 22 ml/min). Bilateral hydrothorax. Hydropericardium. Permanent form of atrial fibrillation. The risk of thromboembolic complications according to the CHADS2VASC scale is 6 points. The risk of bleeding on the HASBLED scale is 3 points.

Related:

diabetes mellitus type 2, insulin-requiring. Duodenal ulcer, without exacerbation. Chronic mixed gastritis.

Treatment in hospital: due to the presence of tachyform atrial fibrillation, the dose of bisoprolol was increased to 7.5 mg/day; For the first few days, intravenous furosemide was prescribed at a dose of 40 mg/day, followed by a transition to oral torsemide 10 mg/day. There was no significant decrease in creatinine levels after the administration of intravenous furosemide; creatinine clearance according to CKD-EPI was 24 ml/min (creatinine from 08/01/19 - 190 mlmol/l). After transferring the patient to an oral diuretic, it became possible to prescribe the drug sacubitril/valsartan (Uperio) 100 mg/day. Antiplatelet therapy was carried out with rivaroxaban 15 mg/day and clopidogrel 75 mg/day. The patient also received omeprazole 40 mg/day for gastroprotection and amoxiclav 3 g/day due to the presence of trophic ulcers.

After 7 days of therapy

Complaints of general weakness persist, shortness of breath at rest does not bother him, pain in the legs, mainly at night.

Objective status:

the condition is relatively satisfactory. The patient is conscious and moves around within the ward. The skin and mucous membranes are pale in color and clean. Edema of the lower extremities has regressed, some pastiness remains. Breathing in the lungs is harsh, somewhat weakened in the lower sections. Heart sounds are muffled, irregular, there is no noise. Heart rate 80 beats/min. Blood pressure 110/70 mm Hg. The abdomen is not enlarged, soft, painless. Stool and diuresis are not disturbed.

Laboratory tests indicate a decrease in creatinine to 120 mmol/l, urea 15.0, natriuretic peptide BNP 2000.2 pg/ml, glucose 10 mmol/l, potassium 4.9 mmol/l, ALT 9 mmol/l, AST 25 mmol/l.

Instrumental studies: ECG dated 09/05/18 - atrial fibrillation, heart rate 80 beats/min. On a repeat X-ray of the chest organs dated 09/07/18: positive dynamics of stagnant changes. Positive dynamics on EchoCG: improvement in LV myocardial contractility, increase in EF up to 50%, decrease in pressure in the pulmonary artery, resolution of hydropericardium and hydrothorax on the left.

Due to the stabilization of the patient’s condition and a decrease in creatinine levels during treatment, it became possible to conduct angiography of the vessels of the lower extremities. The patient was transferred to the surgery department, where recanalization, balloon angioplasty and stenting of the right superficial femoral artery were performed, Abbott SUPERA 5.0×200 mm stents were implanted distally, Abbott SUPERA 6.0×150 mm proximally. After the operation, the patient noted a decrease in pain.

Valsartan

Light pink, film-coated tablets, round, biconvex, scored on one side; on the fracture, two layers are visible - a white or almost white core and a film shell.

Excipients: microcrystalline cellulose 45.1 mg, croscarmellose sodium 2.75 mg, colloidal silicon dioxide 1.35 mg, magnesium stearate 0.8 mg.

Film shell composition: Opadry Pink 3 mg, including polyvinyl alcohol 1.2 mg, macrogol-3350 - 0.731 mg, red iron oxide dye - 0.012 mg, yellow iron oxide dye - 0.007 mg, talc 0.444 mg, titanium dioxide 0.606 mg .

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Discussion

One subanalysis of the PARADIGM-HF study assessed the effect of sacubitril/valsartan (Uperio) therapy on measures of renal function in patients with HF, particularly creatinine clearance and urinary albumin-to-creatinine ratio. Compared with enalapril, sacubitril/valsartan was found to slow the rate of decline in GFR and have beneficial effects on both cardiovascular and renal outcomes [9]. A slower decline in GFR was observed in a wide range of patients regardless of blood pressure levels, low levels of which are known to worsen kidney function.

Similar nephroprotective effects of sacubitril/valsartan (Uperio) were previously noted in the small 36-week PARAMAUNT-HF trial in patients with preserved EF, in which sacubitril/valsartan (Uperio) also delayed the decline in GFR compared with valsartan [10].

The exact mechanism of preservation of renal function when taking sacubitril/valsartan (Uperio) is unknown, and is currently interpreted as a consequence of restoration of normal perfusion of renal tissue against the background of improved neurohormonal balance due to the protective effect of natriuretic peptides.