Treatment an arterial hypertension: a cho...
Treatment an arterial hypertension:
After half a century, and this time was marked by the important opening in studying mehanizmov regulation the HELL and formation AG, creation of new classes antigipertenzivnyh prepratov and formation of essentially new approach to otsenke efficiency of treatment - the medicine based on proofs, the choice of an optimum preparation for lechenija the patient with AG became one of trudnyh problems for the doctor - the clinical physician. Complexity consisted that at absence spetsialnyh indications, there are some classes effective antigipertenzivnyh sredstv, any of which can be applied in this situation.
Moreover, come to the end randomizirovannye researches have not found out znachimyh advantages at any of six classes antigipertenzivnyh preparatov concerning expressiveness of decrease the HELL. There is clear that vnimanie which we give abilities of preparations to reduce serdechno-sosudistuju disease and death rate at high quality preservation zhizni.
In methodical recommendations the CART/MOAG (1999) It is expected, that most vazhnymi distinctions between classes antigipertenzivnyh means (diuretiki, b-blokatory, antagonisty calcium, a-blokatory, ingibitory APF and blokatory angiotenzivnyh retseptorov) is presence or absence of proofs received in randomizirovannyh clinical researches on influence of these preparations on uroven diseases and death rates at AG (3). Until recently we raspolagaem similar data about beneficial effect on a current and the forecast bolnyh with AG only for diuretikov and b-blokatorov while about antagonistah calcium (AK) and ingibitorah angiotenzinprevrashchajushchego enzyme (APF) bylo it is not enough data. Come to the end in a current of last several years variety krupnomasshtabnyh their researches with diuretikami and b-blokatorami, in considerable stepeni have met this lack. The given job is devoted the analysis of results osnovnyh researches of this period of time and to their influence on a formulation sovremennyh representations about a choice of medicinal therapy for treatment of patients AG.
Antagonists of calcium
Antagonists of calcium (AK), pojavivshiesja in clinical practice in the early seventies, substantially rasshirili possibilities of treatment of patients with ischemic illness of heart (IBS) and AG. Poetomu it is no wonder, that to the beginning of 90th years this class of preparations has won shirokuju popularity as among practical doctors, and patients with various serdechno-sosudistymi diseases, and well-known by-effects at lechenii AK were quite comprehensible at comparison with reached favorable effektami. Antagonists of calcium were rekomendovanny as preparations of the first line dlja treatments AG and as one of base means in treatment stable stenokardii. Also it was known, that short-range nifedipiny can uhudshat a current of disease at patients with sharp coronary syndromes (a myocardium heart attack (to IT), an astable stenocardia) and their application was supposed tolko in a combination with b-blokatorami, and the verapamil appointed after IT, rendered neblagoprijatnoe influence at patients with clinical displays warm nedostatochnosti.
In this situation message Furberg and soavt. (1995) about possible negative posledstvijah long application AK of short action (to this class pripisyvalis such effects as increase of risk of development of a heart attack of a myocardium, krovotecheny, malignant new growths and it is possible other disasters) at bolnyh AG and IBS at once have appeared in the centre of attention of the medical public. Bolshinstvo publications of that period of time came to an end equally - it is necessary poluchit results large prospektivnyh randomizirovannyh researches for okonchatelnogo decisions of a question on safety AK, how much negative effekty have been noted in retrospective jobs. Further the basic are presented krupnomasshtabnye researches in which AK were base preparations and in mnogih cases were compared to classes of preparations with already proved blagoprijatnymi effects.
Research sistolicheskoj hypertensions in Europe (SYST-EUR) . In issledovanie 4695 patients with isolated sistolicheskoj AG have been switched on is more senior 60 years, average duration of supervision has made 2 years. Active treatment AK nitrendipinom (at insufficient antigipertenzivnom effect joined diuretiki and ingibitory angiotenzinprevrashchajushchego enzyme) against platsebo in gruppe comparisons has led to authentic decrease in frequency of a brain stroke on 44 %, decrease in frequency of development of all fatal and not fatal serdechno-sosudistyh complications on 31 % (p <0,001) also was observed. Any distinctions on otnosheniju to the general death rate and risk of development of new growths it was not marked. In odnom from fragments of research SYST-EUR it has been shown, that antigipertenzivnaja terapija nitrendipinom has reduced frequency dementsii.
Research on optimum treatment AG (NOTES) . One of most krupnyh researches (it is switched on about 19 thousand patients with AG) has shown, that vyzvannoe AK felodipinom (was supposed addition of others antigipertenzivnyh sredstv at insufficient effect) decrease the HELL was accompanied low znachitelnym by reduction of frequency of occurrence of cardiovascular complications. Pri comparison of the data of the general death rate received in this research okazalos, that they were more low, than at lechenyh sick AG other researches and not bylo is defined increases in risk of complications at treatment AK.
Verapamil research at AG and stenocardias (VHAS) . In it issledovanii verapamil and diuretik hlortalidon to the same extent reduced uroven the HELL. Frequency of development of cardiovascular complications was identical in obeih groups. Distinctions in the general death rate also it has not been revealed. However, analiz data repeated ultrozvukovogo researches of carotids has shown, chto in group receiving verapamil the atherosclerosis progressed more slowly, chem in group receiving diuretik.
r the Swedish research at elderly patients with AG - 2 (STOP-Hypertension - 2) . More than six and a half thousand patients with AG of both sexes at the age from 70 till 84 years have been divided on Three groups also received on an extent of 4th years sledujushchie preparations: diuretik/b-blokator (group of usual treatment), AK (felodipin ili isradipin) or ingibitory (enalapril or lizinopril). The estimation of influence noted before therapeutic modes ("new" classes antigipertenzivnyh means against "old") on serdechno-sosudistuju death rate and clinical complications (a brain stroke, infarkt, sudden death) was the Main objective issledovanija. Arterial pressure has decreased equally in all gruppah. The primary combined final point (a fatal stroke, and drugie fatal cardiovascular complications) has been noticed by IT at 221 of 2213 bolnyh in group of usual treatment (19.8 events on 1000) and at 438 of 4401 patients in group of new preparations (19,8 events on 1000), that staticheski nerazlichalos (r = 0,89). The conclusion that "old" and "new" preparations are identical has been drawn are effective in the prevention of complications and death rate pri AG, and the major importance in this plan is given to decrease the HELL. However, at pogruppovom the analysis it has appeared, that risk of development by IT and warm insufficiency byl above at patients receiving AK in comparison with ingibitorami APF while ne was distinctions in comparison with diuretikami/b-blokatorami.
The Scandinavian research diltiazema (NORDIL) . In the form of it randomizirovannogo open research with the ciphered final points bolnye with primary AG (59-69 years, about 11 thousand patients) received treatment or diltiazemom 180-360 mg, either diuretikami or b-blokatorami in a current of 5 years. Tselju researches was to estimate potential preventive effects AK on serdechno-sosudistuju disease and death rate in comparison with traditional lekarstvennymi preparations in treatment AG. Sistolichesky and diastolicheskoe the HELL odinakovo it was effectively supervised in both groups (decrease on 20,3/18,7 protiv 23,3/18,7 mm hg in group diuretiki/b-blokatory, distinction sistolicheskogo the HELL r <0,001). It is primary combined (fatal and not fatal mozgovoj a stroke, to IT and other cardiovascular death) the final point was zafiksirovanna and at 400 patients in group diuretik/b-blokator (16,6 against 16,2 sobytijana 1000, r = 0,95), a fatal and not fatal brain stroke razvitija at 1159 patients in group AK and at 196 patients on 1000, r = 0,04), and fatal and not fatal IT though is is more often noted in group of patients poluchavshih diltiazem (183 and 157 patients, or 7,4 against 6,3 events on 1000, r = 0,17), this distinction was nedostaverno. Thus rezultaty researches NORDIL testifies that diltiazem has appeared takim an effective preparation as diuretiki and b-blokatory in forecast improvement bolnyh AG.
The international research of nifedipine GITS. Intervention as the purpose lechenija AG (INSIGHT) . In this controllable research with use dvojnogo a blind method it has been switched on 6321 patients with AG with presence of one or bolee concomitant factors of risk of cardiovascular diseases. Patients in vozraste from 55 till 80 years randomizirovalis in groups receiving AK nifedipine GITS (gastrointestinalnaja therapeutic system) or a combination gidrohlortiazida and amilorida with joining of other preparations if it was not reached target snizhenija the HELL. The general cardiovascular disease and death rate, and also obshchaja death rate (a total result of primary and final points - an overall objective) sostavila 12,1 % in group AK and 12,5 % in group diuretika (distinction is doubtful). Etot level has appeared almost on 50 % more low, than was predicted on a basis opredelenija cardiovascular risk (use Framingamsky issledovanija for nelechennyh patients) and confirms the big benefits for patients poluchavshih treatment including AK. Besides, for the first time has shown umenshenie frequencies of occurrence of new cases of a gout, peripheral sosudistyh diseases and a diabetes at patients lechennyh AK in comparison with bolnymi receiving diuretiki.
prospektivnaja randomizirovannaja an estimation of vascular effects norvaska (PREVENT) . Osnovnoj the influence estimation amlodipina (duration of treatment 3 year) on atherosclerosis progressing in sleepy and coronary arteries at 825 bolnyh with IBS was a research objective. It has appeared, that amlodipin has authentically slowed down development ateroskleroticheskogo protsesa in carotids in comparison with group platsebo. Vlijanie a preparation on dynamics of defeats of coronary arteries was not authentic po to data quantitative coronary angiografii. By comparison clinical rezultatov such indicators as the general death rate, fatal and not fatal IT amlodipin the general number of all complications IBS was on 31 % more low (r = 0,01), than prodemonstriroval favorable clinical effects.
Thus, in five researches (STOP-2, NORDIL, INSIGHT, VHAS, NICS-EH) po to efficiency comparison antigipertenzivnogo treatments based on ispolzovanii AK against diuretikov/b-blokatorov it was observed in total 23454 patients at whom it is noted 2485 basic cardiovascular complications and 1552 patients have died of all reasons. It has appeared, that at the patients receiving AK znachitelno more low (on13 %) risk of development of a brain stroke in comparison with bolnymi on treatment diuretikami or b-blokatorami. On the other hand, against priema AK on 12 % more, there was a probability of development of complications vsledstvii IBS, vkljuchaja cardiovascular insufficiency. It is the extremely important, that on such pokazateljam as frequency vozniknivenija all cardiovascular complications, serdechno-sosudistaja and the general death rate these groups did not differ, i.e. AK in plane antigipertenzivnogo treatments pomenshej to a measure do not concede influence on these parametres of efficiency until recently to reference classes - diuretikam i b-blokatoram.
Ingibitory APF
Creation ingibitorov APF is ogromnym achievement in treatment AG and other cardiovascular diseases. This klass preparations (now them is about three tens) sochetaet in itself of advantage in respect of high efficiency, low frequency pobochnyh effects, maintenance of high quality of a life with proved kardio, vaskulo - and renoprotektivnym action, and also as it has been shown recently, snizhenija frequencies of cardiovascular complications and duration increase zhizni patients at long application. Our representations about ingibitorah APF in znachitelnoj degrees were generated on the basis of data received in the last tri year in following researches - CAPPP, STOP-2, UKPDS-HDS, ABCD-hyperteusive, HOPE, PART-2, QUIET, SCAT, FACET.
CAPPP . According to this large research (about 11 thousand bolnyh with AG) captopril also was effective, as “traditional therapy” b-blokatorami i diuretikami, in decrease the HELL and the basic cardiovascular complications for iskljucheniem frequencies of a brain stroke. In group of patients receiving ingibitor APF was less cases of development of a diabetes (SD). Besides, captopril prodemonstriroval it is authentic the best efficiency in respect of decrease in death rate and chastoty oslozhneniju patients AG isd in comparison with persons receiving diuretiki ili b-blokatory.
the Estimation of the preventi on of warm outcomes (HOPE) . In research NORE (regarding this research in comparison of effects ramiprila against platsebo nabljudalos about 9300 patients) was has shown, that purpose ingibitorov APF ramipr Silt the patient with high risk of development cardiovascular oslozhneny (IBS, AG, the diabetes, defeat of peripheral arteries, narushenie brain blood circulation) it is authentic on 20-31 % reduces frequency smertelnyh outcomes, to IT and a brain stroke in comparison with platsebo for a long time predpolagaemye antiatherosclerotic effects ingibitorov APF.
the Suitable control of a blood pressure at a diabetes (ÀÂÑD) . Eto prospektivnoe, randomizirovannoe research by a main objective put sravnenie effects moderated (80-89 mm hg) and intensive (75 mm hg) snizhenija diastolicheskogo the HELL on frequency of development and progressing vascular oslozhneny SD. Also in this research have estimated influence nisaldipina (the antagonist of calcium and enalapril (ingibitora APF) as first line antigipertenzivnoj therapies at 470 patients SD in a combination with AG. Frequency IT was dostoverno above (r = 0,001) among patients receiving nisoldipin (n = 25) on sravneniju with group receiving enalapril (n = 5).
the Analysis of other researches allows to assume, that noted distinction mezhdu nisoldipinom and enalaprilom can be faster result more blagoprijatnogo than effect ingibitora APF, than negative action AK. How much dannye this part of research ÀÂÑD are based on results of a secondary problem, neobhodimo their specification in other jobs. Nevertheless it is possible to assume, that ingibitory APF it is necessary to appoint first of all patient AG with SD.
In the meta-analysis presented recently (BPLT Trialists’ Collaborahion 2000) po to comparison of efficiency of modes of medicamentous treatment based on ingibitorah APF against the cores on diuretikah or b-blokatorah (researches CAPPP, STOP-2, UKPDS-HDS; 2022 basic cardiovascular complications and 1257 fatalnyh outcomes from all reasons at the switched on 18357 patients) it is not revealed zametnyh distinctions between randomizirovannymi groups in respect of risk of development of any oslozhneny and a failure. Thereby, also as regarding devoted AK it has been shown, that ingibitory APF at least also are effective v the relation of risk of development of complications and a fatal outcome at AG as well as diuretiki s b-blokatorami.
Celled and e
Thus, summing up vysheizlozhennomu, it is possible to ascertain, that the data obtained recently klinicheskih researches prove ability both AK, and ingibitorov APF umenshat cardiovascular disease and death rate at long primenenii at patients AG. All it is the basis for inclusion AK and ingibitorov APF in the list of preparations, along with diuretikami and beta-blokatorami, naznachaemyh to patients with for the first time revealed not complicated AG.