New the approach in treatment of an arter...
New the approach in treatment of an arterial hypertension
Arterial the hypertension (AG) for today is one
iz the most widespread chronic diseases which are badly giving in to the control and
lecheniju. According to epidemiological researches, an arterial hypertension
stradaet more than third of adult population of Russia. It is in obvious
protivorechii with results of the numerous researches testifying about
tom, that at level arterial pressure (HELL) below 140/90 mm hg
znachitelno the risk of development of a stroke, ischemic illness of heart,
hronicheskoj nephritic and stagnant warm insufficiency, that, in turn,
privodit to decrease in a death rate from cardiovascular diseases decreases.
Ris. 1. FREQUENCY of NORMALIZATION the HELL AT TREATMENT NOLIPRELOM In the CURRENT 12 WEEKS > >>
Ris. 2. PERCENT of the PATIENTS who RESPONDED TO TREATMENT And have REACHED NORMALIZATION the HELL at dlitelnom reception Noliprela > > >
Soglasno to national recommendations about diagnostics and treatment AG (2001) uroven the HELL below 140/90 mm is hg recognised target for patients with AG, at some grupp patients should be even more low. So, for example, at a diabetes level AD should be <130/85 mm hg, and in the presence of nephritic insufficiency - <125/75 mm hg Achievement of such optimum level the HELL is the major zadachej which the doctor observing of the patient with povyshennym the HELL should put before itself. At the same time effective decrease in arterial pressure nabljudaetsja only in 5-10 % of cases. It is connected by that in real practice not vsegda is possible to supervise the HELL at purpose only one antigipertenzivnogo a preparation; there are certain difficulties in selection adekvatnyh doses for decrease the HELL to target values, and, at last, important rol plays adherence of patients to the appointed treatment.
Monotherapy is not always effective
Soglasno to last recommendations, as starting therapy at I and II stepenjah increases the HELL (soft and moderated AG) can be appointed one of preparatov the first row (diuretik, ingibitor angiotenzinprevrashchajushchego enzyme, beta-blokator, the antagonist of calcium, the antagonist of receptors to angiotensin II or alfa-blokator) with the subsequent increase in a dose at insufficient effect snizhenija the HELL. However for today does not raise the doubts that fact, that essentsialnaja AG represents the heterogeneous disease caused nalichiem of a considerable quantity of factors, promoting development vazokonstriktsii and podderzhaniju raised the HELL. In modern representation increase in activity system renin-angiotensin-aldosteronovoj, hyperstimulation sympathetic nervous sistemy and a sodium delay in an organism are the cores pathogenetic mehanizmami developments of an arterial hypertension. Quite often monotherapy directed na correction only of one of numerous pathogenetic links, not pozvoljaet to reach desirable level of decrease the HELL. The role concrete vazokonstriktornogo the mechanism dominating in patogeneze AG, very much variabelna u each patient, and it partly explains low efficiency of treatment odnim a preparation. Results of variety of researches on studying of the basic groups antigipertenzivnyh means as monotherapy have shown, that, despite uvelichenie doses, efficiency of treatment by one preparation makes about 50-60 %.
S dose increase, and achievements tselevogo level the HELL, the major problem frequency of development of by-effects grows in treatment AG, it is possible to achieve far not vsegda. For example, serious by-effects are marked at treatment big dozami diuretikov. The risk of development gipokaliemii, giperurikemii and giperglikemii in rezultate applications of this class of preparations as monotherapy in maksimalnyh doses is great enough, that forces patients to refuse them ispolzovanija. Besides, at therapy only diuretikami are activated kontrreguljatornye nejrogumoralnye the mechanisms weakening gipotenzivnye properties preparatov that demands escalating of a dose and promotes bolshej to expressiveness pobochnyh effects. Dozozavisimymi also such by-effects, as kashel also are at application ingibitorov APF, peripheral hypostases at treatment antagonistami calcium. Selection of adequate doses of preparations is big problemoj at an out-patient stage of treatment when the doctor is deprived possibility regularly kontrolirovat a status of the patient.
Nemalovazhnyj the factor in therapy AG - adherence of the patient to ordered vrachom to treatment. The combination picked up very carefully, no less than monoterapija, can appear inefficient at irregular reception of preparations. Slozhnyj the mode of the treatment which is switching on quantity of accepted tablets or high chastotu and fixed time of reception of preparations, leads to infringement by the patient rekomendatsy the doctor. In this plan not last role such factors, as uhudshenie play also qualities of a life at occurrence of by-effects from spent therapy i, certainly, cost of medicamentous treatment. Infringement of recommendations privodit to considerable reduction of degree of decrease in cardiovascular risk u patients with AG, mainly owing to the unsatisfactory control the HELL. For mnogie years some strategy for interest improvement bolnogo in treatment were offered. It and informing on risk of cardiovascular complications, svjazannyh with AG, and selection of preparations with an optimum parity "efficiency/shipping", and training of patients to independent measurement AD. However the greatest adherence to treatment at the present stage it is possible dostich application rational combined antigipertenzivnyh preparations.
Advantages nizkodozovyh the combined preparations
Lechenie by the combined preparations in last recommendations it is considered kak one of variants of therapy of the first level. Its doubtless advantage javljaetsja big antigipertenzivnaja efficiency. Application nizkodozovyh kombinatsy reduces quantity of by-effects, lowers cost of therapy and tem most undoubtedly improves adherence of patients to treatment. It is supposed, chto more than 50 % of the patients suffering even not complicated, soft and moderated AG, require the combined therapy. In groups, where arterial hypertension soputstvujut a diabetes, chronic nephritic insufficiency, number such bolnyh essentially above as target level the HELL should be lower.
Dlja achievements of adequate target level are necessary for using the HELL various kombinatsii antigipertenzivnyh preparations. Therapy diuretikami and ingibitorami APF as at sochetannom primenenii preparations of these groups decrease the HELL for the bill vzaimodopolnjajushchih effects is more often reached has appreciable advantages komb inirovannaja.
Pri therapies diuretikami, especially in high doses, can To occur kompensatornaja activation the system renin-angiotensin-aldosteronovoj, leading snizheniju them gipotenzivnogo effect. Addition to treatment ingibitora APF niveliruet arising negative nejrogumoralnyj effect, raising verojatnost the answer of the patient to treatment to 80 % in comparison with monotherapy diuretikom. On the contrary, joining to therapy ingibitorami APF diuretikov znachitelno raises sensitivity to them of fabrics that allows a thicket to reach gipotenzivnyj effect. Besides, arising at treatment diuretic preparatami gipokaliemija can be corrected at joining ingibitorov APF which are capable to reduce ekskretsiju kalija. Therefore such sereznoe complication at treatment diuretikami, as gipokaliemija, practically iskljuchaetsja. At last, ingibitory APF in itself are weak natrij-uretikami, that strengthens effect diuretikov at sochetannom application. Takim in the image, addition tiazidnogo or tiazidopodobnogo diuretika to ingibitoru APF allows to achieve target level the HELL reception of smaller doses of preparations vsledstvie them sinergidnogo action.
Est and some negative sides of such combination. It is not necessary to forget, that u the elderly patients receiving treatment diureticheskimi by preparations, addition to terapii ingibitora APF can call sharp falling the HELL as display “effect pervoj doses” in this connection purpose of preparations by such patient should be ochen cautious and in minimum, but effective dosages. Besides, at pozhilyh patients and the patients, suffering stagnant warm insufficiency, funktsija kidneys often it is broken, that influences for the speed ekskretsii ingibitorov APF and trebuet corrections of a dose of an accepted preparation.
Noliprel - the optimum combination of the minimum doses
Sovremennym a preparation with the fixed combination of very low doses tiazidopodobnogo diuretika and ingibitora APF is Noliprel, in which structure vhodjat perindopril and indapamid. In clinical researches by an estimation effektivnosti and the shipping, responding the most strict methodological kriterijam, have taken part about 3 thousand persons. In one of researches were opredeleny necessary doses of the operating substances which are a part of a preparation. Glavnym decrease diastolicheskogo the HELL through 24 ch was considered as criterion of efficiency. After taking the medicine, and leading criterion of shipping - frequency vozniknovenija gipokaliemii. The optimum combination minimalnyh doses of preparations (2 mg - half of therapeutic dose perindoprila and 0,625 mg - a quarter of a therapeutic dose indapamida), completely responding kriterijam "efficiency/shipping" for starting therapy AG has been as a result chosen. Farmakokineticheskie profiles perindoprila and indapamida in combined preparate do not change, that does possible unitary reception of a preparation in sutki. Undoubtedly, it improves adherence of patients to treatment, reducing chislo accepted preparations and frequency rate of their reception. Decrease also material zatraty on treatment that is important for many patients with AG.
Klinicheskaja efficiency Noliprela as preparation of the first choice has been studied pri short-term treatment in double blind platsebokontroliruemom research in parallelnyh groups. Within 12 weeks 362 patients at the age from 65 to 85 let with soft and moderated essentsialnoj an arterial hypertensia after 4 weeks platsebo received on 1 tablet of a preparation a day. In the group accepting Noliprel, k 12th week of treatment on therapy was responded 81 % of patients, thus normalisation by the HELL sostavila 74 % whereas in group platsebo the answer was only at 42 % of patients (fig. 1). Frequency of occurrence gipokaliemii (kaly whey of blood less than 3,4 mmol/l) v to group Noliprela was chrevyzchajno low and comparable to that in group platsebo.
Odnako in practice important preservation of an effective control the HELL is represented at dlitelnom application gipotenzivnogo means. Efficiency Noliprela at dlitelnom application was studied in double blind platsebokontroliruemom issledovanii with participation of 253 patients with essentsialnoj AG at the age from 65 to 85 let, receiving a preparation more than 12 months. In active group it was estimated Noliprel, doza which doubled if necessary. 90 mm hg for sistolodiastolicheskogo and <160 mm hg for sistolicheskogo arterial pressure were considered as criterion of normalisation snizhenie the HELL
K antigipertenzivnyh means for treatment of elderly patients with AG it is necessary for a choice podhodit with special attention. In the numerous researches spent with uchastiem of patients with isolated sistolicheskoj AG, it has been proved, that dostizhenie target level the HELL authentically reduces risk of occurrence not only insultov, but also coronary complications. As in the given group of patients in rezultate monotherapy of an optimum level the HELL is possible to achieve only in small protsente cases, that fact, that is rather indicative at use fiksirovannoj nizkodozovoj combinations at 80 % of the patients which middle age sostavil 73 years, target level the HELL was reached in 12 months of therapy. Udvoenie preparation doses it was required less than in 30 % of cases.
Rezultaty clinical researches have shown, that Noliprel responds all sovremennym to the requirements shown to preparations of the first choice for treatment AG. Noliprel is the first and unique for today in Russia nizkodozovym the combined preparation personifying new therapeutic podhod in treatment of patients with AG. Introduction in clinical practice fixed kombinatsy very low doses antigipertenzivnyh preparations will allow to provide effektivnyj the control the HELL at a considerable quantity of patients with AG and simultaneously svesti to a minimum quantity of by-effects at treatment such heavy and groznogo diseases, as an arterial hypertensia.
Ris. 1. FREQUENCY of NORMALIZATION the HELL AT TREATMENT NOLIPRELOM In the CURRENT 12 WEEKS > >>
Ris. 2. PERCENT of the PATIENTS who RESPONDED TO TREATMENT And have REACHED NORMALIZATION the HELL at dlitelnom reception Noliprela > > >
Soglasno to national recommendations about diagnostics and treatment AG (2001) uroven the HELL below 140/90 mm is hg recognised target for patients with AG, at some grupp patients should be even more low. So, for example, at a diabetes level AD should be <130/85 mm hg, and in the presence of nephritic insufficiency - <125/75 mm hg Achievement of such optimum level the HELL is the major zadachej which the doctor observing of the patient with povyshennym the HELL should put before itself. At the same time effective decrease in arterial pressure nabljudaetsja only in 5-10 % of cases. It is connected by that in real practice not vsegda is possible to supervise the HELL at purpose only one antigipertenzivnogo a preparation; there are certain difficulties in selection adekvatnyh doses for decrease the HELL to target values, and, at last, important rol plays adherence of patients to the appointed treatment.
Monotherapy is not always effective
Soglasno to last recommendations, as starting therapy at I and II stepenjah increases the HELL (soft and moderated AG) can be appointed one of preparatov the first row (diuretik, ingibitor angiotenzinprevrashchajushchego enzyme, beta-blokator, the antagonist of calcium, the antagonist of receptors to angiotensin II or alfa-blokator) with the subsequent increase in a dose at insufficient effect snizhenija the HELL. However for today does not raise the doubts that fact, that essentsialnaja AG represents the heterogeneous disease caused nalichiem of a considerable quantity of factors, promoting development vazokonstriktsii and podderzhaniju raised the HELL. In modern representation increase in activity system renin-angiotensin-aldosteronovoj, hyperstimulation sympathetic nervous sistemy and a sodium delay in an organism are the cores pathogenetic mehanizmami developments of an arterial hypertension. Quite often monotherapy directed na correction only of one of numerous pathogenetic links, not pozvoljaet to reach desirable level of decrease the HELL. The role concrete vazokonstriktornogo the mechanism dominating in patogeneze AG, very much variabelna u each patient, and it partly explains low efficiency of treatment odnim a preparation. Results of variety of researches on studying of the basic groups antigipertenzivnyh means as monotherapy have shown, that, despite uvelichenie doses, efficiency of treatment by one preparation makes about 50-60 %.
S dose increase, and achievements tselevogo level the HELL, the major problem frequency of development of by-effects grows in treatment AG, it is possible to achieve far not vsegda. For example, serious by-effects are marked at treatment big dozami diuretikov. The risk of development gipokaliemii, giperurikemii and giperglikemii in rezultate applications of this class of preparations as monotherapy in maksimalnyh doses is great enough, that forces patients to refuse them ispolzovanija. Besides, at therapy only diuretikami are activated kontrreguljatornye nejrogumoralnye the mechanisms weakening gipotenzivnye properties preparatov that demands escalating of a dose and promotes bolshej to expressiveness pobochnyh effects. Dozozavisimymi also such by-effects, as kashel also are at application ingibitorov APF, peripheral hypostases at treatment antagonistami calcium. Selection of adequate doses of preparations is big problemoj at an out-patient stage of treatment when the doctor is deprived possibility regularly kontrolirovat a status of the patient.
Nemalovazhnyj the factor in therapy AG - adherence of the patient to ordered vrachom to treatment. The combination picked up very carefully, no less than monoterapija, can appear inefficient at irregular reception of preparations. Slozhnyj the mode of the treatment which is switching on quantity of accepted tablets or high chastotu and fixed time of reception of preparations, leads to infringement by the patient rekomendatsy the doctor. In this plan not last role such factors, as uhudshenie play also qualities of a life at occurrence of by-effects from spent therapy i, certainly, cost of medicamentous treatment. Infringement of recommendations privodit to considerable reduction of degree of decrease in cardiovascular risk u patients with AG, mainly owing to the unsatisfactory control the HELL. For mnogie years some strategy for interest improvement bolnogo in treatment were offered. It and informing on risk of cardiovascular complications, svjazannyh with AG, and selection of preparations with an optimum parity "efficiency/shipping", and training of patients to independent measurement AD. However the greatest adherence to treatment at the present stage it is possible dostich application rational combined antigipertenzivnyh preparations.
Advantages nizkodozovyh the combined preparations
Lechenie by the combined preparations in last recommendations it is considered kak one of variants of therapy of the first level. Its doubtless advantage javljaetsja big antigipertenzivnaja efficiency. Application nizkodozovyh kombinatsy reduces quantity of by-effects, lowers cost of therapy and tem most undoubtedly improves adherence of patients to treatment. It is supposed, chto more than 50 % of the patients suffering even not complicated, soft and moderated AG, require the combined therapy. In groups, where arterial hypertension soputstvujut a diabetes, chronic nephritic insufficiency, number such bolnyh essentially above as target level the HELL should be lower.
Dlja achievements of adequate target level are necessary for using the HELL various kombinatsii antigipertenzivnyh preparations. Therapy diuretikami and ingibitorami APF as at sochetannom primenenii preparations of these groups decrease the HELL for the bill vzaimodopolnjajushchih effects is more often reached has appreciable advantages komb inirovannaja.
Pri therapies diuretikami, especially in high doses, can To occur kompensatornaja activation the system renin-angiotensin-aldosteronovoj, leading snizheniju them gipotenzivnogo effect. Addition to treatment ingibitora APF niveliruet arising negative nejrogumoralnyj effect, raising verojatnost the answer of the patient to treatment to 80 % in comparison with monotherapy diuretikom. On the contrary, joining to therapy ingibitorami APF diuretikov znachitelno raises sensitivity to them of fabrics that allows a thicket to reach gipotenzivnyj effect. Besides, arising at treatment diuretic preparatami gipokaliemija can be corrected at joining ingibitorov APF which are capable to reduce ekskretsiju kalija. Therefore such sereznoe complication at treatment diuretikami, as gipokaliemija, practically iskljuchaetsja. At last, ingibitory APF in itself are weak natrij-uretikami, that strengthens effect diuretikov at sochetannom application. Takim in the image, addition tiazidnogo or tiazidopodobnogo diuretika to ingibitoru APF allows to achieve target level the HELL reception of smaller doses of preparations vsledstvie them sinergidnogo action.
Est and some negative sides of such combination. It is not necessary to forget, that u the elderly patients receiving treatment diureticheskimi by preparations, addition to terapii ingibitora APF can call sharp falling the HELL as display “effect pervoj doses” in this connection purpose of preparations by such patient should be ochen cautious and in minimum, but effective dosages. Besides, at pozhilyh patients and the patients, suffering stagnant warm insufficiency, funktsija kidneys often it is broken, that influences for the speed ekskretsii ingibitorov APF and trebuet corrections of a dose of an accepted preparation.
Noliprel - the optimum combination of the minimum doses
Sovremennym a preparation with the fixed combination of very low doses tiazidopodobnogo diuretika and ingibitora APF is Noliprel, in which structure vhodjat perindopril and indapamid. In clinical researches by an estimation effektivnosti and the shipping, responding the most strict methodological kriterijam, have taken part about 3 thousand persons. In one of researches were opredeleny necessary doses of the operating substances which are a part of a preparation. Glavnym decrease diastolicheskogo the HELL through 24 ch was considered as criterion of efficiency. After taking the medicine, and leading criterion of shipping - frequency vozniknovenija gipokaliemii. The optimum combination minimalnyh doses of preparations (2 mg - half of therapeutic dose perindoprila and 0,625 mg - a quarter of a therapeutic dose indapamida), completely responding kriterijam "efficiency/shipping" for starting therapy AG has been as a result chosen. Farmakokineticheskie profiles perindoprila and indapamida in combined preparate do not change, that does possible unitary reception of a preparation in sutki. Undoubtedly, it improves adherence of patients to treatment, reducing chislo accepted preparations and frequency rate of their reception. Decrease also material zatraty on treatment that is important for many patients with AG.
Klinicheskaja efficiency Noliprela as preparation of the first choice has been studied pri short-term treatment in double blind platsebokontroliruemom research in parallelnyh groups. Within 12 weeks 362 patients at the age from 65 to 85 let with soft and moderated essentsialnoj an arterial hypertensia after 4 weeks platsebo received on 1 tablet of a preparation a day. In the group accepting Noliprel, k 12th week of treatment on therapy was responded 81 % of patients, thus normalisation by the HELL sostavila 74 % whereas in group platsebo the answer was only at 42 % of patients (fig. 1). Frequency of occurrence gipokaliemii (kaly whey of blood less than 3,4 mmol/l) v to group Noliprela was chrevyzchajno low and comparable to that in group platsebo.
Odnako in practice important preservation of an effective control the HELL is represented at dlitelnom application gipotenzivnogo means. Efficiency Noliprela at dlitelnom application was studied in double blind platsebokontroliruemom issledovanii with participation of 253 patients with essentsialnoj AG at the age from 65 to 85 let, receiving a preparation more than 12 months. In active group it was estimated Noliprel, doza which doubled if necessary. 90 mm hg for sistolodiastolicheskogo and <160 mm hg for sistolicheskogo arterial pressure were considered as criterion of normalisation snizhenie the HELL
K antigipertenzivnyh means for treatment of elderly patients with AG it is necessary for a choice podhodit with special attention. In the numerous researches spent with uchastiem of patients with isolated sistolicheskoj AG, it has been proved, that dostizhenie target level the HELL authentically reduces risk of occurrence not only insultov, but also coronary complications. As in the given group of patients in rezultate monotherapy of an optimum level the HELL is possible to achieve only in small protsente cases, that fact, that is rather indicative at use fiksirovannoj nizkodozovoj combinations at 80 % of the patients which middle age sostavil 73 years, target level the HELL was reached in 12 months of therapy. Udvoenie preparation doses it was required less than in 30 % of cases.
Rezultaty clinical researches have shown, that Noliprel responds all sovremennym to the requirements shown to preparations of the first choice for treatment AG. Noliprel is the first and unique for today in Russia nizkodozovym the combined preparation personifying new therapeutic podhod in treatment of patients with AG. Introduction in clinical practice fixed kombinatsy very low doses antigipertenzivnyh preparations will allow to provide effektivnyj the control the HELL at a considerable quantity of patients with AG and simultaneously svesti to a minimum quantity of by-effects at treatment such heavy and groznogo diseases, as an arterial hypertensia.