Необходимость новых исследований

За прошедшие 10–15 лет была закончено несколько исследований антигипертензивной терапии, но они, главным образом. сосредоточены на сравнениях между различными препаратами или сфокусированы на пациентах с высоким сердечно-сосудистым риском, и используемые ими сложные дизайны и многочисленные сопутствующие методы лечения часто делают интерпретацию их результатов

трудными и спорными (Бокс 9). Хотя эти исследования все же добавляют полезную информацию,

некоторые главные проблемы не были исследованы или были недостаточно разъяснены. Как следствие, многие важные решения относительно лечния гипертензии в настоящее время могут быть прияты только на основе post hoc анализа данных исследования о связи сердечно-сосудистых событий с достигнутыми величинами АД, у которого есть печально известные ограничения из-за недостатков дизайна рандомизации и возможных различий исходного риска пациентов, достигающих различных величин АД. Поэтому, очень желательно, что бы рекомендации о пороговом АД для инициирования медикаментозного лечения и о целевом АД в различных группах пациентов были поддержаны информацией от проспективных рандомизированных исследований с дизайном, обращенным к имеющимся пробелам в нынешнем знании.

Следующие проблемы имеют срочную потребность в исследованиях с простым дизайном:

(1) Должы ли антигипертензивные препараты назначаться всем лицам с 1 ст. гипертензии (САД 140–

159 мм рт.ст. или ДАД 90–99 мм рт ст.), даже когда общий сердечно-сосудистый риск относительно низок или умерен? Это очевидно, что рандомизированное исследование активноголечения против плацебо, основанное на твердых сердечно-сосудистых исходах было бы очень трудно выполнить у пациентов с действительно низким сердечно-сосудистым риском с 1 ст. гипертензии, потому что у таких пациентов очень низкий процент сердечно-сосудистых событий делает необходимым планировать исследование нереалистичных размеров и/или продолжительности. Однако, плацебо-контролируемые исследования, используя промежуточные конечные точки, такие как ГЛЖ, микроальбуминурия, или другие признаки

повреждения органов мишеней, признанные прогностически важными, должны быть выполнимыми, этически и клинически релевантными.

(2) Должныли быть назначены антигипертензивные препараты пожилым с 1ст. гипертензии и должно ли антигипертензивное лечение достигать цели ниже 140/90 мм рт.ст. также и у пожилых? Все успешные исследования пожилых гипертензивных пациентов включали пациентов с САД 160 мм рт.ст. или выше, и у большинства из них средняя величина входного АД была выше 170 мм рт.ст. Аналогично, во всех пока проводимых исследованиях достигнутое САД всегда было выше 140 мм рт.ст. Поскольку пожилые гипертензивные пациенты характеризуются большим сердечно-сосудистым риском (и таким образом,

большим числом событий в течение нескольких лет посленачала исследования), эти исследования могли бы использовать твердые сердечно-сосудистые исходы и могли бы быть плацебо-контолируемыми.

(3) Все руководящие принципы предлагают начинать антигипертензивное лечение у диабетических пациентов или у пациентов с предшествующей церебро-васкулярной или сердечно-сосудистой болезнью,

когда АД находится в высоком нормальном уровне (САД 130–139 мм рт.ст. или ДАД 85–89 мм рт.см.), и рекомендуют достигать цели САД ниже 130 мм рт.ст. Хотя эти рекомендации могут быть разумными, они не основаны на данных исследований. Например, нет успешного исследования антигипертензивного лечения диабетических пациентов имеющих величины САД меньше 130 мм рт.ст. В большинстве исследований пациентов с высоким сердечно-сосудистым риском, рандомизированное лечение было начато

на фоне мощного предшествующего антигипертензивного медикаментозного лечения из-за неправильного предположенияе, что все эти пациенты, так или иначе, требуют очень агрессивной снижащей АД терапии (результаты замены доказательств здравым смыслом [71]). В других исследованиях большая часть пациентов попутно лечилась препаратами, к которым относятся вещества, действиекоторых пересекалось с тестируемыми лекарствами. Например, в исследовании I-PRESERVE [259] хронической сердечной недостаточности с сохраненной систолической функцией 39% пациентов, у которых проверялся эффект

антагониста рецептора ангиотензина, одновременно лечились ингибитором АПФ, хотя нет доступных данных, что ингибитор АПФ полезен при этом типе сердечной едостаточности.Здесь, снова, необходимы исследования с относительно простым дизайном специфически нацеленные на ответы на эти вопросы у пациентов с предшествующим инсультом или коронарным случаем или с диастолической сердечной нелостаточностью была.

(4) Идентификация самого низкого безопасного АД при лечении при различных клинических состояниях имеет очевидную клиническую важность, правомерно обращаясь к 'специальным' проспективным исследованиям, которые сравнили бы более интенсивую против менее интенсивной снижающей АД стратегии лечения у пациентов с различными уровнями сердечно-сосудистого риска.

(5) Некоторые типы изменений образа жизни показали способность к снижению АД, но они бездоказательны в уменьшении смертности и заболеваемости при гипертензии.

Хотя исследование заболеваемости/смертности при изменении образа жизни у пациента с АГ 1 ст., возможно, не выполнимая задача, было бы желательно контролируемое рандомизированное исследование, использовавшее промежуточные конечные точки (повреждение органов-мишеней).

Перечень акронимов

ABCD: Appropriate Blood pressure Control in

Diabetes.

ACCESS: Acute Candesartan Cilexetil Therapy in

Stroke Survivals.

ACCOMPLISH: Avoiding Cardiovascular Events in

Combination Therapy in Patients Living with Systolic

Hypertension.

ACCORD: Action to Control Cardiovascular Risk in

Diabetes.

ACTION: A Coronary Disease Trial Investigating

Outcome with Nifedipine gastrointestinal therapeutic

system.

ADVANCE: Action in Diabetes and Vascular disease;

Perterax and Diamicron-MR Controlled Evaluation.

ALLHAT: Antihypertensive and Lipid-Lowering

Treatment to Prevent Heart Attack Trial.

ASCOT: Anglo-Scandinavian Cardiac Outcomes Trial.

AUSTRALIAN: Australian Therapeutic Trial in Mild

Hypertension.

BENEDICT: Bergamo Nephrologic Diabetic Complications

Trial.

CAFE: Conduit Artery Function Evaluation.

CAMELOT: Comparison of Amlodipine versus

Enalapril to Limit Occurrences of Thrombosis.

CAPRAF: Candesartan in the Prevention of Relapsing

Atrial Fibrillation.

CASE-J: Candesartan Antihypertensive Survival

Evaluation in Japan.

CHARM: Candesartan in Heart Failure-Assessment

of Reduction in Mortality and Morbidity.

CHHIPS: Controlling hypertension and hypothension

immediately poststroke.

COMET: Carvedilol or Metoprolol European Trial.

COOPER and WARRENDER: Treatment of Hypertension

in Elderly Patients in Primary Care.

COOPERATE: Combination Treatment of Angiotensin-

II Receptor Blocker and Angiotensin-Converting-

Enzyme Inhibitor in Non-Diabetic Renal Disease.

DIRECT: Diabetic Retinopathy Candesartan Trials.

ELSA: European Lacidipine Study on Atherosclerosis.

EUROPA: European Trial on Reduction of Cardiac

Events with Perindopril in Stable Coronary Artery

Disease.

EWPHE: European Working Party on High Blood

Pressure in the Elderly.

FEVER: Felodipine Event Reduction.

GEMINI: Glycemic Effect in Diabetes Mellitus:

Carvedilol–Metoprolol Comparison in Hypertensives.

GISSI-AF: Gruppo Italiano per lo Studio della Sopravvivenza

nell’Infarto Miocardico–Atrial Fibrillation.

HDFP: Hypertension Detection and Follow-up

Program.

HOPE: Heart Outcomes Prevention Evaluation.

HOT: Hypertension Optimal Treatment Study.

HYVET: Hypertension in the Very Elderly Trial.

IDNT: Irbesartan Diabetic Nephrophaty Trial.

INSIGHT: International Nifedipine GITS Study:

Intervention as a Goal in Hypertension Treatment.

INVEST: International Verapamil SR/Trandolapril

study.

I-PRESERVE: Irbesartan in Heart Failure with

Preserved Systolic Function.

JATOS: Japanese Trial to Assess Optimal Systolic

Blood Pressure in Elderly Hypertensive Patients.

JUPITER: Justification for the Use of Statins in

Primary Prevention: An Intervention Trial Evaluating

Rosuvastatin.

LIFE: Losartan Intervention For Endpoint reduction

in Hypertension.

MDRD: Modification of Diet in Renal Disease.

MICROHOPE: Microalbuminuria, Cardiovascular

and Renal Outcomes in the Heart Outcomes Prevention

Evaluation.

MRC: Medical Research Council Trial of Treatment

of Mild Hypertension.

MRC elderly: Medical Research Council Trial of

Treatment of Hypertension in Older Adults.

ONTARGET: Ongoing Telmisartan Tlone and in

combination with Ramipril Global Endpoint Trial.

OSLO: Oslo Study of Treatment of Mild Hypertension.

PAMELA: Pressioni Arteriose Monitorate E Loro

Associazioni.

PATS: Post-stroke Antihypertensive Treatment Study.

PEACE: Prevention of Events with Angiotensin

Converting Enzyme Inhibition.

PHARAO: prevention of hypertension with the

angiotensin-converting enzyme inhibitor ramipril in

patients with high-normal blood pressure.

PHYLLIS: Plaque Hypertension Lipid Lowering

Italian Study.

PREVEND: Prevention of Renal and Vascular End

Stage Disease.

PREVENT: Prospective Randomized Evaluation of

the Vascular Effects of Norvasc Trial.

PROFESS: Prevention Regimen for Effectively

Avoiding Second Strokes.

PROGRESS: Perindopril Protection against Recurrent

Stroke Study.

RENAAL: Reduction of Endpoints in Noninsulin

dependent diabetes mellitus with the Angiotensin II

Antagonist Losartan.

SCOPE: Study on Congnition and Prognosis in the

Elderly.

SCORE: Systematic Coronary Risk Evaluation.

SENIORS: Study of the Effects of Nebivolol Intervention

on OUtcomes and Rehospitalisation in Seniors

with heart failure.

SHEP: Systolic Hypertension in the Elderly Program.

STOP: Swedish Trial in Old Patients with Hypertension.

Syst-China: Systolic Hypertension in China.

Syst-Eur: Systolic Hypertension in Europe.

TNT: Treating to New Targets.

TRANSCEND: Telmisartan randomized assessment

study in ACE-I intolerant subjects with cardiovascular

disease.

TROPHY: Trial of Preventing Hypertension.

UKPDS: United Kingdom Prospective Diabetes

Study.

VADT: Veterans Affairs Diabetes Trial.

Val-HeFT: Valsartan Heart Failure Trial.

VALIANT: Valsartan In Acute Myocardial Infarction

Trial.

VALUE: Valsartan Antihypertensive Long-term Use

Evaluation.

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