Minociclina no Acidente Vascular Cerebral Agudo

Estudos em modelos animais têm mostrado um efeito neuroprotetor da minociclina, um antibiótico de segunda geração derivada da tetraciclina, possivelmente em função das suas propriedades anti-inflamatórias sobre o tecido glial.
O presente estudo randomizado, cego para o avaliador, analisou o efeito de 200mg de minociclina administrada oralmente por 5 dias, iniciando entre 6 e 24hs do quadro de acidente vascular cerebral (AVC).
Os pacientes com AVC agudo tratados com minociclina tiveram significativamente melhor evolução do que aqueles que receberam apenas placebo. Os efeitos adversos foram de pequena monta. Esses achados sugerem um benefício potencial da minociclina nos AVC agudos isquêmicos.

Tibolona diminui fraturas e câncer de mama, mas dobra o risco de Acidente Vascular Cerebral

Cummings SR et al. The Effects of Tibolone in older Postmenopausak Women. NEJM. August 14, 2008; 359(7):697-708.

A Tibolona (Livial(R)) atualmente está aprovada em 90 países para tratar sintomas da menopausa e em 45 países para tratar osteoporose, entretanto, ainda não está aprovada nos EUA. Trata-se de um regulador sintético seletivo da atividade estrogênica tecidual (STEAR) e é sabido que previne perda óssea, entretanto, seus efeitos sobre fraturas, câncer e doença cardiovascular ainda não são conhecidos.
O ensaio clínico Long-Term Intervention on Fractures with Tibolone (LIFT) foi conduzido com 4.538 mulheres, entre 60 e 85 anos de idade, as quais foram randomizadas para receber 1,25mg de tibolona diariamente ou placebo.
Esse estudo teve que ser suspenso prematuramente em função de um claro aumento no risco de Acidentes Vasculares Cerebrais (AVC).
Durante um seguimento médio de 34 meses de tratamento, as mulheres em uso de tibolona tiveram uma redução significativa no risco de fratura vertebral e não vertebral, assim como câncer de cólon e mama. Porém, elas também tiveram um aumento no risco absoluto para AVC de 2,3 por 1.000 pessoa-ano e mais do que o dobro na chance relativa de AVC. Também houve uma tendência para uma maior incidência de câncer de endométrio em mulheres com útero.
Outros efeitos, comuns na combinação hormonal de estrógenos e progesterona como ganho de peso, metrorragia e infecção e desconforto mamário foram similares com a droga.
Atenção, portanto, em mulheres com fatores de risco para AVC ou mesmo para aquelas mais idosas, as quais não deveriam usar tibolona.

57th Annual Scientific Sessions of the American College of Cardiology

Apresentação de vários ensaios clínicos no Encontro Anual do Colégio Americano de Cardiologia em Chicago IL de 30 de Março a 02 de Abril de 2008, incluindo os ensaios ONTARGET, ACCOMPLISH, ENHANCE e (JUPITER).

JUPITER examined the role of rosuvastatin (20 mg/day) in the primary prevention of cardiovascular disease among patients with low levels of LDL-cholesterol and elevated high-sensitivity C-reactive protein.

The trial was stopped early as evidence clearly showed a reduction in cardiovascular morbidity and mortality in patients treated with rosuvastatin compared with placebo.

Full study details to be published once final analysis of data is complete.

STUDY OUTCOMES:

Over 5,000 patients without evidence of cardiovascular disease and low to normal LDL-C, but elevated C-reactive protein were enrolled in the trial. The trial was stopped early based on a recommendation from an independent Data and Safety Monitoring Board due to unequivocal evidence of a reduction in cardiovascular morbidity and mortality in patients treated with rosuvastatin compared with placebo.

ONTARGET enrolled 25,620 high risk subjects aged > 55 with either established vascular disease or DM and end-organ damage into a large international randomized trial of angiotensin modulating therapy. Subjects received either ramipril 10 mg, telmisartan 80 mg or the full dose combination daily. Over a mean follow up of 56 months, telmisartan was found to be statistically non-inferior, clinically equivalent and better tolerated than ramipril while the combination was no better than ramipril alone but with greater side-effects! The results were consistent for all major components of the primary end-point, including myocardial infarction, stroke, heart failure hospitalisation and cardiovascular death and across all pre-defined patient subgroups (age, gender, risk, BP, DM, Hx of CAD). Physicians now have a choice between an ACE inhibitor or an ARB in CVD prevention in the “HOPE-type” patient.

STUDY OUTCOME:

Telmisartan was found to be statistically non-inferior, clinically equivalent and better tolerated than ramipril while the combination was no better than ramipril alone but with greater side-effects.

ACCOMPLISH examined the role of amlodipine/benazapril (5 mg/40 mg), compared with hydrochlorothiazide (HCTZ)/benazapril (12.5 mg/40 mg) in reducing cardiovascular morbidity and mortality in high-risk patients with systolic hypertension.
The trial was stopped early with a finding of a 20% reduction in many of the primary endpoints with amlodipine/benazapril compared with HCTZ/benazapril

STUDY OUTCOME:

Trial was terminated early due to a finding of 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.

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Beta-Bloqueadores no peri-operatório aumentam os riscos após cirurgia não-cardíaca

POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. The Lancet Early Online Publication, 13 May 2008

Beta-bloqueador – especificamente succinato de metoprolol, único usado no estudo – aumenta o risco de acidente vascular cerebral e morte não-cardiovascular.

In an international, double-blind, industry-supported study, some 8350 patients with (or at risk for) atherosclerotic disease were randomized preoperatively to a 30-day regimen of extended-release metoprolol or placebo. Patients already receiving beta-blockers were excluded.

By 30 days, patients on metoprolol showed favorable results for the primary endpoint (a composite of cardiovascular death, nonfatal MI, and nonfatal cardiac arrest) — but they had significantly higher rates of death and stroke.

The authors write that current perioperative guidelines ought to be reconsidered. Commentators agree that the regimen used carries more risk than benefit; however, they recommend a lower-dose long-acting regimen that is "titrated to effect" at least 7 days before surgery. That regimen, they say, "is associated with overall benefit compared to risk."

Asked to comment, Journal Watch Cardiology editor-in-chief Harlan Krumholz says that using extended-release metoprolol to reduce risk in patients undergoing noncardiac surgery "has suddenly become a lot more controversial than it was yesterday. If this strategy is contemplated, then it should be done with the patient's knowledge of the potential trade-offs in outcomes."

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Achados na tomografia computadorizada do crânio pode predizer derrame após isquemia transitória

Sciolla R, Melis F; SINPAC Group. Rapid identification of high-risk transient ischemic attacks: prospective validation of the ABCD score.Stroke. 2008 Feb;39(2):297-302. Epub 2008 Jan 3.

Ataques isquêmicos transitórios (AIT) determinam um alto risco no curto prazo de acidente vascular cerebral (AVC) definido, entretanto, é dificil distinguir entre os pacientes com isquemias transitórias que evoluirão para um AVC definido.
O desenvolvimento de um escore ABCD de 6 pontos parece clarear essa indefinição: (Age (idade) 60 anos = 1 ponto; Blood pressure (pressão arterial ) 140/90 mm Hg = 1 ponto; Clinical features (apresentação clínica): perda de força unilateral = 2 pontos e dificuldade para falar sem perda de força = 1 ponto; e Duration (duração) de 60 minutos = 2 pontos ou 10 a 59 minutos = 1 ponto). Esse escore prediz o risco de AVC em ambos 7 dias e 1 mês. Altos escores (>/=4) progressivamente conferem um alto risco de AVC subsequente, sendo que aqueles que tem escore <4 não tem AVC dentro de um mês. Achados de imagens de CT de crânio (evidência de doença na substância branca ou infarto cerebral = 1 ponto) cria o escore ABCDi o qual reforça as predições: Um escore ABCD de 5 ou 6 confere um aumento em 6x do risco de AVC em 7 dias e 1 mês, enquanto que o escore ABCDi de 5 ou 7 confere um aumento no risco de 11x. Esse escore com a adição de diabetes (ABCD2) aumenta ainda mais a identificação dos pacientes com AIT que necessitam de pronta e intensiva redução do risco vascular.

Placa carotídea: um precursor subclínico de eventos vasculares

Espessura máxima da placa carotídea é um simples e não invasivo marcador de aterosclerose subclínica associada com risco aumentado de eventos vasculares.

Rundek T, ArifMcCord H et al. Carotid plaque, a subclinical precursor of vascular events

The Northern Manhattan Study. NEUROLOGY 2008;70:1200-1207.

Carotid atherosclerosis is a known biomarker associated with future vascular disease. The risk associated with small, nonstenotic carotid plaques is less clear. The objective of this study was to examine the association between maximum carotid plaque thickness and risk of vascular events in an urban multiethnic cohort.

As part of the population-based Northern Manhattan Study, carotid plaque was analyzed among 2,189 subjects. Maximum carotid plaque thickness was evaluated at the cutoff level of 1.9 mm, a prespecified value of the 75th percentile of the plaque thickness distribution. The primary outcome measure was combined vascular events (ischemic stroke, myocardial infarction, or vascular death).

Carotid plaque was present in 1,263 (58%) subjects. After a mean follow-up of 6.9 years, vascular events occurred among 319 subjects; 121 had fatal or nonfatal ischemic stroke, 118 had fatal or nonfatal myocardial infarction, and 166 died of vascular causes. Subjects with maximum carotid plaque thickness greater than 1.9 mm had a 2.8-fold increased risk of combined vascular events in comparison to the subjects without carotid plaque (hazard ratio, 2.80; 95% CI, 2.04–3.84). In fully adjusted models, this association was significant only among Hispanics. Approximately 44% of the low-risk individuals by Framingham risk score had a 10-year vascular risk of 18.3% if having carotid plaque.

Conclusions: Maximum carotid plaque thickness is a simple and noninvasive marker of subclinical atherosclerosis associated with increased risk of vascular outcomes in a multiethnic cohort. Maximum carotid plaque thickness may be a simple and nonexpensive tool to assist with vascular risk stratification in preventive strategies and a surrogate endpoint in clinical trials.