RU2425671C1 - Method of correcting kidney malfunction in patients with stable stenocardia in combination with hypertension - Google Patents

Abstract

FIELD: medicine, pharmaceutics. ^ SUBSTANCE: invention relates to field of medicine, namely to cardiology, and can be used for correction of kidney dysfunction in patients with stable stenocardia in combination with hypertension. For this purpose at the background of standard therapy, which includes inhibitor of angiotensin-converting enzyme, beta-adrenoblocker, aspirin and statin, Medicaqtion ivabradin is administered in day dose 5-15 mg in 2 intakes, daily, during 6 months. ^ EFFECT: method makes it possible to increase efficiency of kidney malfunction correction due to positive dynamics of GFR, level of C-terminal telopeptide type I collagen and TIMP-1. ^ 1 tbl, 2 ex

Description

The invention relates to medicine, namely to cardiology, and can be used to correct impaired renal function in patients with stable angina pectoris (SS) in combination with hypertension (GB).

It was found that impaired renal function in patients with cardiovascular disease is an independent risk factor for an unfavorable prognosis and indicates the development of cardiorenal syndrome. A known method of pharmacological correction of renal dysfunction in patients with SS and GB: angiotensin converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor antagonists, calcium antagonists, beta-blockers with a vasodilating effect (National clinical recommendations. Collection / edited by R. G. Oganova . - 2nd edition. - M.: "Silicea-Polygraph", 2009. - 528 p.). The disadvantage of this method: lack of effectiveness.

Effect: improving the correction of renal impairment in patients with SS in combination with GB.

The task is achieved through the use of ivabradine in the complex treatment of patients with SS in combination with GB.

Ivabradine (Coraxan, Servier, France) is a new antianginal and anti-ischemic drug that affects heart rate by inhibiting the I _f channels of the sinus node cells.

The method is as follows. The presence of clinical renal damage in SS patients in combination with GB is determined by the glomerular filtration rate (GFR) determined by the calculation method and the integral indicators of changes in the extracellular collagen matrix of the kidneys and renal arteries: a matrix matrix metalloproteinase inhibitor (TIMP-1) and level C terminal collagen telopeptide type 1 (CITP-1).

GFR was calculated using the MDRD formula (The Modification of Diet in Renal Disease Study, 1999).

GFR = 186 ^* (creatinine / 88, μmol / L) 1,154 * (age, years),

(ml / min / 1.73 m ² ), for women the result was multiplied by 0.742.

GFR of less than 60 ml / min / 1.73 m ^{2 was} regarded as a clinical kidney lesion according to the Recommendations of the Russian Medical Society for Arterial Hypertension and the All-Russian Scientific Society of Cardiology "Diagnosis and treatment of arterial hypertension", 2008.

TIMP-1 was determined by enzyme-linked immunosorbent assay (ELISA) of blood plasma using an original diagnostic kit for enzyme-linked immunosorbent assay company Bio Source EUROPE S.A. (Belgium) on a strip enzyme-linked immunosorbent analyzer Stat Fax 303 (Awareness Technology, USA). The reference value of this indicator is 111-138 ng / ml. An increase in TIMP-1 is regarded as damage to the intercellular collagen matrix of the kidneys and renal arteries. CITP-1 level was determined by enzyme-linked immunosorbent assay using an original diagnostic kit from Nordic Bioscience Diagnostics (Denmark) using a Stat Fax 303 analyzer (Awareness Technology, USA). The reference value of this indicator in men is 0.115-0.748 ng / ml, in fertile women - 0.112-0.738 ng / ml, in postmenopausal women - 0.142-1.351 ng / ml. A decrease in CITP-1 is regarded as damage to the intercellular collagen matrix of the kidneys and renal arteries.

Patients with stable angina pectoris of functional class II-III (FC) in combination with GB on the background of standard therapy, including ACE inhibitors perindopril 4-8 mg per day, beta-blocker bisoprolol 2.5-5 mg per day, aspirin 75 mg per day and simvastatin 20-40 mg per day, ivabradine is additionally prescribed in a daily dose of 5-15 mg (6.21 ± 2.05 mg) in 2 doses, taking into account the initial heart rate (HR) and subsequent dose titration in accordance with the dynamics of heart rate. The duration of ivabradine therapy is 6 months.

The novelty of the method is the use of ivabradine in a daily dose of 5-15 mg (6.214 ± 2.05 mg) in 2 doses daily, against the background of standard therapy for 6 months in patients with coronary artery disease in combination with hypertension. The drug ivabradine for the correction of renal dysfunction in patients with coronary artery disease and GB has not been previously used.

Examples of specific application.

Example 1. Patient S., 60 years old. Diagnosis: ischemic heart disease. Angina pectoris III FC. Hypertension of the III stage, arterial hypertension of 3 degrees with correction to the target level of blood pressure, risk 4. CHF IIA / II FC.

Before treatment, the GFR level according to the MDRD formula was 42 ml / min / 1.73 m ² , the C-terminal telopeptide of type 1 collagen was 0.4 ng / ml, TIMP-1 was 184 ng / ml.

On the background of complex therapy, including perindopril 8 mg per day, bisoprolol 5 mg per day, indapamide 1.5 mg / day, aspirin 75 mg per day, simvastatin 20 mg per day, in combination with ivabradine 5 mg 2 times a day, through For 6 months, the following results were obtained: the GFR level according to the MDRD formula was 49 ml / min / 1.73 m ² , the C-terminal telopeptide of type 1 collagen was 0.8 ng / ml, TIMP-1 was 106 ng / ml.

In addition, against the background of complex therapy with ivabradine, the patient noted a reduction in angina attacks and increased exercise tolerance.

Example 2

Patient P., 60 years old, diagnosis: IHD. Myocardial infarction (2000). Angina pectoris II FC. Hypertension of the III stage, arterial hypertension of 3 degrees with correction to the target level of blood pressure, risk 4. CHF IIA / II FC.

Before treatment, the GFR level according to the MDRD formula was 40 ml / min / 1.73 m ² , the C-terminal telopeptide of type 1 collagen was 0.2 ng / ml, TIMP-1 was 374 ng / ml.

On the background of complex therapy, including perindopril 8 mg per day, bisoprolol 5 mg per day, aspirin 75 mg per day, simvastatin 20 mg per day, in combination with ivabradine 5 mg 2 times a day, after 6 months the following results were obtained: level GFR according to the MDRD formula was 47 ml / min / 1.73 m ² , C-terminal telopeptide of type 1 collagen was 0.4 ng / ml, TIMP-1 was 182 ng / ml.

In addition, against the background of complex therapy with ivabradine, the patient noted a reduction in angina attacks and increased exercise tolerance.

The observation of 15 SS patients in combination with GB during a 6-month treatment with ivabradine in complex therapy showed that when taking the drug, there was a significant positive dynamics in the level of GFR, the level of the C-terminal telopeptide of type 1 collagen and TIMP-1 (Table).

Table Dynamics of GFR level, level of C-terminal telopeptide of collagen type 1 and TIMP-1 in patients with stable angina pectoris in combination with hypertension during treatment with ivabradine (n = 15) Indicator Originally After treatment p GFR, ml / min / 1.73 m ² 50.33 ± 8.67 58.22 ± 9.76 0,027 CITP-1, ng / ml 0.34 ± 0.07 0.49 ± 0.14 0.011 TIMP-1, ng / ml 260.44 ± 89.67 154.55 ± 26.75 0.004

The positive effect of using the proposed method is manifested in increasing the efficiency of correction of renal impairment in patients with SS in combination with GB.

Claims (1)

A method for the correction of renal dysfunction in patients with stable angina pectoris in combination with hypertension using standard medication consisting of an angiotensin converting enzyme inhibitor, beta-blocker, aspirin and statin, characterized in that the patient is additionally prescribed ivabradine in a daily dose of 5-15 mg per 2 doses daily for 6 months.