Артериальная гипертония. Это интересно.

[Igor73]

Исследование ONTARGET фактически "похоронило" сартаны как самостоятельный класс препаратов:
1. Телмисартан не лучше рамиприла.
2. Комбинация телмисартан+рамиприл увеличивало риск гипотензии и почечной недостаточности.
3. Сартаны перед этим проиграли иАПФ (каптоприлу) при ХСН, есть данные (мета-анализ), что сартаны увеличивают риск ОНМК при АГ. Теперь ясно, что сартаны не лучше иАПФ у пациентов высокого риска развития ССЗ. Чтобы их "реанимировать", нужно проводить исследование с большим, чем в ONTARGET количеством пациентов (по 8 тыс. в каждой группе), при этом целевая группа пациентов остается под вопросом.
4. В ближайшее время будет закончено исследование TRANSСEND, где при неперносимости иАПФ (кашель, например) пациенты высокго риска принимали телмисартан или плацебо. Если сартан победит плацебо, то тогда у сартанов останется только одна ниша - неперносимость иАПФ (примерно 2-5% пациентов).

[michmed]

Коллеги, простите неосведомленность, а что-то было про сартаны при диабете? В ONTARGET вроде только про высокий риск. Или там имеется ввиду высокий риск у диабетиков?

[Melnichenko]

Были версии и исследования в ходу по ретинопатии как мишени лечения и очевидная версия - непереносимость АПФ
не скажу, чтобы я плакала от горя при мысли о судьбе ныне существующих сартанов - будем искать такие же, но без крыльев ( с)

[Igor73]

Еще одно убедительное исследование, ставящее точки над многими ё у пациентов с реноваскулярной АГ.
The Impact of Renal Artery Revascularisation in Atherosclerotic Renovascular Disease: The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) Trial – Philip A. Kalra
[Ссылки доступны только зарегистрированным пользователям ]

•

•Currently no evidence of a benefit for revascularization on renal function in the ARVD patients entered into ASTRAL – those in whom clinicians ‘uncertain’ of whether to revascularize
•Also no evidence of differences between the arms for any of the secondary endpoints (i.e. blood pressure, major events, mortality)
•No evidence of differences in treatment effect across the various subgroups – for renal functional end-point only
•Minor differences in some parameters at 4 years (Creatinine, SBP, CVS events) but longer follow-up is needed to assess significance

[Igor73]

"Наш" ответ ALLHAT.
Озвучены результаты долгожданного исследования ACCOMPLISH. После ASCOT-BPLA появился "новый" стандарт лечения пациентов с АГ - АКК+иАПФ. Но у этой комбинации оставался мощный конкурент - иАПФ+Диуретик, практически не осталось фиксированной комбинации иАПФ без диуретика (ГХТЗ). В представленном исследовании ГХТЗ 12.5-25 мг "боролся" с амлодипином 5-10 мг (иАПФ был идентичным). Сенсации не получилось: по общей смертности, сердечно-сосудистой смертности, нефатальным ИМ и ОНМК, внезапной смерти и нестабильной стенокардии группы не отличались.
иАПФ+АКК были лучше по влиянию на смешанную СС заболеваемость и смертность в основном за счет большей частоты реваскуляризаций в группе иАПФ+Диуретик. При прочих равных условиях иАПФ/АКК/диуретик хороши при АГ (на мой взгляд, комбинацией эналаприл 20 мг + ГХТЗ 12.5 мг + при неэффективности пролонгированный нифедипин 40 мг при правильном подходе можно у 95% пациентов с АГ достичь целевых цифр АД).

Avoiding Cardiovascular Events Through COMbination Therapy in Patients LIving With Systolic Hypertension (ACCOMPLISH — Presented at SCAI-ACC i2
Description
The goal of this trial was to evaluate the safety and efficacy of the combination of amlodipine/benazapril, compared with hydrochlorothiazide (HCTZ)/benazapril in reducing cardiovascular morbidity and mortality in high-risk patients with systolic hypertension.
Hypothesis
The fixed dose combination of amlodipine/benazapril is superior to HCTZ/benazapril in reducing cardiovascular mortality and morbidity in high-risk patients with hypertension.
Drugs/Procedures Used
After a screening phase, patients with hypertension were randomized to either fixed dose combination of amlodipine 5 mg/benazapril 20 mg or HCTZ 12.5 mg/benazapril 20 mg. After 1 month, benazapril was titrated to 40 mg in both arms. Thereafter, HCTZ was titrated to 25 mg daily, and amlodipine was titrated to 10 mg daily, as tolerated. After 3 months, other antihypertensive agents could be added on as needed to achieve a blood pressure target of <140/90 mm Hg, or <130/80 mm Hg in patients with diabetes or renal insufficiency.
Concomitant Medications
Angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker (78%), lipid-lowering therapy (67%), and antiplatelet therapy (63%)
Principal Findings
A total of 11,462 patients were randomized, 5,741 to the amlodipine/benazapril arm, and 5,721 to the HCTZ/benazapril arm. About 50% of the patients were obese, 60% had diabetes, and 97% were previously being treated for hypertension. Only 37.5% had adequately controlled hypertension (blood pressure <140/90 mm Hg). The prespecified efficacy boundary was crossed with 60% of the expected trial information; therefore, the trial was terminated early.

Systolic blood pressure was significantly reduced by amlodipine/benazapril, compared with HCTZ/benazapril by 0.7 mm Hg (p < 0.05). Target blood pressure was achieved in 78.5% of patients in the HCTZ/benazapril arm, and 81.7% of patients in the amlodipine/benazapril arm. A total of 16.2% of patients in the HCTZ/benazapril arm compared with 15.0% in the amlodipine/benazapril arm were on two or more add-on medications, although about 50% of patients were on one pill only.

There was a 20% reduction in the primary endpoint of cardiovascular mortality, stroke, myocardial infarction (MI), coronary revascularization, unstable angina, and resuscitation from death in the amlodipine/benazapril arm compared with the HCTZ/benazapril arm (p = 0.002). Cardiovascular death, stroke, and MI was also reduced by 20% (p = 0.007). All other endpoints, including cardiovascular mortality, nonfatal MI, nonfatal stroke, and resuscitated sudden death were similar between the two groups.
Interpretation
The results of this large, randomized trial indicate that a single combination therapy of amlodipine/benazapril is superior to HCTZ/benazapril in the reduction in blood pressure as well as cardiovascular endpoints in patients with high-risk hypertension. These findings are very important, and challenge current guidelines, including Joint National Committee-7, which recommend an initial diuretic-based approach to the treatment of hypertension. Cost considerations will also be important.
Conditions
• Hypertension

Therapies
• ACE Inhibitor
• Calcium channel blocker / Amlodipine

Study Design
Randomized. Blinded. Parallel.
Patients Enrolled: 11,462
Mean Follow-Up: 36 months
Mean Patient Age: 68.4 years
% Female: 39

Primary Endpoints
Cardiovascular mortality, stroke, MI, coronary revascularization, unstable angina, and resuscitation from death
Patient Population
• Systolic hypertension ≥160 mm Hg or currently on antihypertensive therapy
• Age ≥55 years
• Evidence of cardiovascular or renal disease or target organ damage
[Ссылки доступны только зарегистрированным пользователям ] | [Ссылки доступны только зарегистрированным пользователям ] [Ссылки доступны только зарегистрированным пользователям ]

[birdname]

Сообщение от Igor73

Если сартан победит плацебо, то тогда у сартанов останется только одна ниша - неперносимость иАПФ (примерно 2-5% пациентов).

Честно говоря, мне кажется, что еще одна реальная ниша для сартанов - популяция исследования TROPHY ([Ссылки доступны только зарегистрированным пользователям ]) и подобные им "начинающие". Думаю, что, поскольку многих относительно молодых людей с невысокими цифрами довольно сложно убедить лечиться в принципе, особенно если у них голова не болит , комплайенс лучше, если возможность кашля и прочих прелестей изначально сведена к минимуму.

[Igor73]

Сообщение от birdname

Честно говоря, мне кажется, что еще одна реальная ниша для сартанов - популяция исследования TROPHY

Спасибо за упоминание TROPHY! Немного незаслуженно забытое исследование. Сартаны там просто первые прозвучали, иАПФ будут прекрасно "работать" для профилактики АГ.
Если интересно, некоторые мысли по поводу предгипертонии (высокого нормального АД) [Ссылки доступны только зарегистрированным пользователям ]
1. Если лечить всех лиц подобных включенным в TROPHY, то мы будем "перелечивать" очень много народу. Надо выделять группу пациентов (ВЭМ, моделировать ментальный стресс и т.д.) с высоким рисом развития АГ.
2. Таких пациентов надо более тщательно наблюдать (измерение АД 1 раз в 3 мес).
3. Модификация образа жизни - ключевой момент. Обычно говорю пациенту, что "Вы находитесь в серой зоне (всем выйти из сумрака!): уже не норма, но еще и не болезнь. Есть все шансы предотвратить развитие АГ и пожизненный прием лекарственных препаратов, немного изменив Ваш образ жизни"

[birdname]

Модификация образа жизни - согласна. Но если это по каким-то причинам не удается?

[Igor73]

Сообщение от birdname

Модификация образа жизни - согласна. Но если это по каким-то причинам не удается?

"Совет за 100$ бросить курить лучше, чем бесплатный" Alex_MD

[Igor73]

Resistant Hypertension: AHA Committee Offers Recommendations

A committee of the American Heart Association has issued a review of resistant hypertension in the journal Hypertension.

The committee advises:

• care in the technique of taking blood pressure, which can itself lead to errant diagnoses;
• ruling out the "white-coat effect" by use of ambulatory monitoring, if necessary;
• looking for secondary causes of hypertension, such as obstructive sleep apnea, renal artery stenosis, and primary aldosteronism;
• encouraging weight loss, moderation in drinking, and salt restriction;
• maximizing diuretic therapy, while considering the addition of a mineralocorticoid receptor antagonist;
• combining agents with different mechanisms of action, such as an ACE inhibitor and a calcium channel blocker.

The article includes a simple, helpful chart that outlines diagnostic and treatment recommendations.
[Ссылки доступны только зарегистрированным пользователям ] (Free PDF)

[Igor73]

Reduction in Blood Pressure With StatinsResults From the UCSD Statin Study, a Randomized Trial
Beatrice A. Golomb, MD, PhD; Joel E. Dimsdale, MD; Halbert L. White, PhD; Janis B. Ritchie, BSN; Michael H. Criqui, MD, MPH

Arch Intern Med. 2008;168(7):721-727.
Background Some studies have suggested reductions in blood pressure (BP)with statin treatment, particularly in persons with hypertension. Randomized trial evidence is limited.
Methods We performed a randomized, double-blind, placebo-controlled trial with equal allocation to simvastatin, 20 mg; pravastatin sodium,40 mg; or placebo for 6 months. Nine hundred seventy-three men and women without known cardiovascular disease or diabetes mellitus, with low-density lipoprotein cholesterol screening levels of 115 to 190mg/dL, had assessment of systolic and diastolic BP (SBP and DBP, respectively). Blood pressure values were compared for placebo vs statins by intention-to-treat (ITT) analysis. Additional analyses were performed that (1) were confined to subjects with neither high baseline BP (SBP >140 mm Hg or DBP >90mm Hg) nor receiving BP medications, to exclude groups in whom BP medications or medication changes may have influenced results, and (2) separately evaluated simvastatin and pravastatin (vs placebo). The time course of BP changes after statin initiation and the effect of stopping statins on BP were examined.
Results Statins modestly but significantly reduced BP relative to placebo,by 2.2 mm Hg for SBP (P = .02) and 2.4mm Hg for DBP (P < .001) in ITT analysis.Blood pressure reductions ranged from 2.4 to 2.8 mm Hg for both SBP and DBP with both simvastatin and pravastatin, in those subjects with full follow-up, and without potential for influence by BP medications (ie, neither receiving nor meriting BP medications).
Conclusions Reductions in SBP and DBP occurred with hydrophilic and lipophilic statins and extended to normotensive subjects. These modest effects may contribute to the reduced risk of stroke and cardiovascular events reported on statins.
Trial Registration clinicaltrials.gov Identifier: [Ссылки доступны только зарегистрированным пользователям ]
[Ссылки доступны только зарегистрированным пользователям ]

[Igor73]

Thomas G. Pickering et al.
This call-to-action article makes the following recommendations: (1) It is recommended that HBPM hould become a routine component of BP measurement in the majority of patients with known or suspected hypertension; (2) Patients should be advised to purchase oscillometric monitors that measure BP on the upper arm with an appropriate cuff size and that have been shown to be accurate according to standard international protocols. They should be shown how to use them by their healthcare
providers; (3) Two to 3 readings should be taken while the subject is resting in the seated position, both in the morning and at night, over a period of 1 week. A total of
12 readings are recommended for making clinical decisions; (4) HBPM is indicated in patients with newly diagnosed or suspected hypertension, in whom it may distinguish between white-coat and sustained hypertension. If the results are equivocal, ambulatory BP monitoring may help to establish the diagnosis; (5) In
patients with prehypertension, HBPM may be useful for detecting masked hypertension; (6) HBPM is recommended for evaluating the response to any type of antihypertensive treatment and may improve adherence; (7) The target HBPM goal for treatment is
135/85 mm Hg or
130/80 mm Hg in high-risk patients; (8) HBPM is useful in the elderly, in whom both BP variability and the white-coat effect are increased; (9) HBPM is of value in patients with diabetes, in whom tight BP control is of paramount importance; (10) Other populations in whom HBPM may be beneficial include pregnant women, children,
and patients with kidney disease; and (11) HBPM has the potential to improve the quality of care while reducing costs and should be reimbursed. (Hypertension. 2008;52)
[Ссылки доступны только зарегистрированным пользователям ]

[Igor73]

Salim Yusuf et al.
Telmisartan to Prevent Recurrent Stroke and Cardiovascular Events.
NEJM 2008 [Ссылки доступны только зарегистрированным пользователям ]
ABSTRACT Background Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin–angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin–angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.
Methods In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes.
Results The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10).
Conclusions Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062 [Ссылки доступны только зарегистрированным пользователям ]).

[Igor73]

Telmisartan in ACE-Inhibitor–Intolerant Patients: A Disappointment

In a placebo-controlled trial, researchers found an unexpectedly low, statistically nonsignificant reduction in clinical outcomes.
ACE inhibitors improve outcomes in patients with or at risk for cardiovascular disease; however, about 20% of patients cannot tolerate these agents. Randomized clinical trials are under way to determine whether angiotensin-receptor blockers are an equivalent — or even superior — alternative to ACE inhibitors.
In this manufacturer-sponsored trial, investigators assessed the effectiveness of telmisartan, an ARB, in patients who are intolerant to ACE inhibitors. After a 3-week run-in period, 5926 such patients who had cardiovascular disease or diabetes with end-organ damage, many of whom were concomitantly taking other proven therapies for their conditions, were randomized to receive telmisartan (80 mg/day) or placebo. The study had a power of 94% to detect a 19% reduction in relative risk for the primary outcome of interest — a composite of cardiovascular death, MI, stroke, or hospitalization for heart failure.
During a median follow-up of 56 months, mean blood pressure was lower in the telmisartan group than in the placebo group (no statistical analysis of this difference was reported). A primary endpoint occurred in 15.7% of patients in the telmisartan group and in 17.0% of those in the placebo group (hazard ratio, 0.92; P=0.216). The rate of permanent discontinuation of study medication was lower in the telmisartan group than in the placebo group (21.6% vs. 23.7%). Hypotensive symptoms were more common in the telmisartan group (0.98%) than in the placebo group (0.54%).
Comment: In this study, telmisartan was well tolerated by patients at high cardiovascular risk who were intolerant to ACE inhibitors, but it had no significant effect on the primary study outcome. Considering that telmisartan was recently shown to be noninferior to ramipril ([Ссылки доступны только зарегистрированным пользователям ]), the 8% relative-risk reduction was surprisingly small, perhaps because this study population received more lipid-lowering therapy, beta-blockers, and antiplatelet drugs than did the subjects in previous clinical trials. These findings suggest that the clinical effects of ARBs are less robust than those of ACE inhibitors and that ARBs should be used to prevent vascular events only in patients who cannot tolerate ACE inhibitors.
— [Ссылки доступны только зарегистрированным пользователям ]
Published in Journal Watch Cardiology September 17, 2008

Citation(s):
The TRANSCEND Investigators. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: A randomised controlled trial. Lancet 2008 August 31; [e-pub ahead of print]. ([Ссылки доступны только зарегистрированным пользователям ])

[Igor73]

Сообщение от Melnichenko

Были версии и исследования в ходу по ретинопатии как мишени лечения и очевидная версия - непереносимость АПФ

Candesartan Has Limited Effectiveness for Diabetic Retinopathy
Candesartan, an angiotensin II receptor blocker, modestly reduces the development of retinopathy in type 1 diabetes and encourages regression of the condition in type 2 diabetes, according to two Lancet reports released online.
In separate studies, industry-funded researchers randomized 3300 patients with type 1 diabetes and 1900 with type 2 diabetes to either daily candesartan or placebo, with follow-up for a median 4.7 years. (Type 1 diabetics were normotensive, and patients with type 2 disease could be either normotensive or receiving treatment for hypertension.)
Type 1 diabetics on candesartan had a modest reduction in the incidence of retinopathy, but there was no effect on progression among those who already had retinopathy.
Among type 2 diabetics with established retinopathy, candesartan lowered the risk for progression of the complication, although not significantly. The drug also prompted regression among those with early retinopathy.
Commentators conclude that candesartan has benefits, but "with some caveats" about their limit.
[Ссылки доступны только зарегистрированным пользователям ] (Free abstract; full text requires subscription)
[Ссылки доступны только зарегистрированным пользователям ] (Free abstract; full text requires subscription)
[Ссылки доступны только зарегистрированным пользователям ] (Subscription required)