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Просмотр полной версии : SPARCL: atorvastatin 80 after stroke or TIA


Dr.Vad
16.08.2006, 03:47
Уважаемые коллеги, опубликованы результаты SPARCL:

N Engl J Med. 2006 Aug 10;355(6):549-59.

High-dose atorvastatin after stroke or transient ischemic attack.

Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA; Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators.

Denis Diderot University, Paris.

BACKGROUND: Statins reduce the incidence of strokes among patients at increased risk for cardiovascular disease; whether they reduce the risk of stroke after a recent stroke or transient ischemic attack (TIA) remains to be established. METHODS: We randomly assigned 4731 patients who had had a stroke or TIA within one to six months before study entry, had low-density lipoprotein (LDL) cholesterol levels of 100 to 190 mg per deciliter (2.6 to 4.9 mmol per liter), and had no known coronary heart disease to double-blind treatment with 80 mg of atorvastatin per day or placebo. The primary end point was a first nonfatal or fatal stroke. RESULTS: The mean LDL cholesterol level during the trial was 73 mg per deciliter (1.9 mmol per liter) among patients receiving atorvastatin and 129 mg per deciliter (3.3 mmol per liter) among patients receiving placebo. During a median follow-up of 4.9 years, 265 patients (11.2 percent) receiving atorvastatin and 311 patients (13.1 percent) receiving placebo had a fatal or nonfatal stroke (5-year absolute reduction in risk, 2.2 percent; adjusted hazard ratio, 0.84; 95 percent confidence interval, 0.71 to 0.99; P=0.03; unadjusted P=0.05). The atorvastatin group had 218 ischemic strokes and 55 hemorrhagic strokes, whereas the placebo group had 274 ischemic strokes and 33 hemorrhagic strokes. The five-year absolute reduction in the risk of major cardiovascular events was 3.5 percent (hazard ratio, 0.80; 95 percent confidence interval, 0.69 to 0.92; P=0.002). The overall mortality rate was similar, with 216 deaths in the atorvastatin group and 211 deaths in the placebo group (P=0.98), as were the rates of serious adverse events. Elevated liver enzyme values were more common in patients taking atorvastatin. CONCLUSIONS: In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke.

ErickRed
16.08.2006, 07:11
Интересно! Получается, что аторвастатин показан при нормальном холестерине для снижения риска инсульта?

thorn
16.08.2006, 09:18
Почему смертность не отличалась? "A total of 136 patients in the placebo group and 154 patients in the atorvastatin group died from causes other than stroke before they could have a nonfatal stroke." От чего они умирали, интересно? 2 рабдомиолиза в группе аторва и 3 в группе плацебо, печеночной недостаточности не было...


Dr.Vad
16.08.2006, 10:54
Чего-то не живется пациентам дольше на больших дозах статинов, хотя СС инциденты снижаются. Та же тенденция наблюдалась в ТНТ и недавний мета-анализ подверждает это:

J Am Coll Cardiol. 2006 Aug 1;48(3):438-45.

Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy.

Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E.

Thrombolysis In Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

OBJECTIVES: The purpose of this study was to conduct a meta-analysis that compares the reduction of cardiovascular outcomes with high-dose statin therapy versus standard dosing. BACKGROUND: Debate exists regarding the merit of more intensive lipid lowering with high-dose statin therapy as compared with standard-dose therapy. METHODS: We searched PubMed and article references for randomized controlled trials of intensive versus standard-dose statin therapy enrolling more than 1,000 patients with either stable coronary heart disease or acute coronary syndromes. Four trials were identified: the TNT (Treating to New Targets) and the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid-Lowering) trials involved patients with stable cardiovascular disease, and the PROVE IT-TIMI-22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction-22) and A-to-Z (Aggrastat-to-Zocor) trials involved patients with acute coronary syndromes. We carried out a meta-analysis of the relative odds on the basis of a fixed-effects model using the Mantel-Haenszel method for the major outcomes of death and cardiovascular events. RESULTS: A total of 27,548 patients were enrolled in the 4 large trials. The combined analysis yielded a significant 16% odds reduction in coronary death or myocardial infarction (p < 0.00001), as well as a significant 16% odds reduction of coronary death or any cardiovascular event (p < 0.00001). No difference was observed in total or non-cardiovascular mortality, but a trend toward decreased cardiovascular mortality (odds reduction 12%, p = 0.054) was observed. CONCLUSIONS: Intensive lipid lowering with high-dose statin therapy provides a significant benefit over standard-dose therapy for preventing predominantly non-fatal cardiovascular events.

Dr.Vad
18.08.2006, 02:04
Интересно! Получается, что аторвастатин показан при нормальном холестерине для снижения риска инсульта?

Это и раньше было прописано в гайдлайне только с целью снизить все сосудистые катастрофы, а теперь будет еще и для предупреждения рецидива:

Patients with ischemic stroke or TIA presumed to be
due to an atherosclerotic origin but with no preexisting
indications for statins (normal cholesterol
levels, no comorbid coronary artery disease, or no
evidence of atherosclerosis) are reasonable candidates
for treatment with a statin agent to reduce the risk of
vascular events (Class IIa, Level of Evidence B).

Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke. Stroke 2006;37:577-617

Dr.Vad
13.09.2006, 21:48
Уважаемые коллеги,

Дополнения к SPARCL: исследователи обнаружили наиболее вероятную причину повышения частоты геморрагических инсультов на аторвастатине 80: они полагают чо это было связано с приверженностью к лечению (по-простому - кто тщательно лечился и не "забывал" принимать таблетки все это время), другим обьяснением может стать, что даже при условии 100% комплайенса существуют пациенты, у которых холестерин снижается лучше (чувствительные), но и есть с неадекватным ответом (резистентные).

Подробнее:

Despite the positive findings, investigators were unable to explain the slight increase in the risk of hemorrhagic stroke observed, with 2.3% of patients in the atorvastatin-treatment arm and 1.4% of patients in the placebo arm having a hemorrhagic stroke. As noted previously by heartwire, this apparent increased risk of stroke was included in the overall stroke analysis, suggesting a net benefit for statin use. Still, lead investigator Dr Pierre Amarenco (Bichat University Hospital, Paris, France) and colleagues felt further analyses were necessary to identify patients who might be at increased risk, as well as to find reasons for the findings.

Taking advantage of the 55 000 LDL-cholesterol measurements taken during the study, investigators used LDL-cholesterol levels as a surrogate marker for adherence to statin therapy, with more than 11 measurements taken per patient. Of the 4731 patients included in SPARCL, 32.7% had no change or an increase in LDL levels, 39.4% had a less than 50% reduction in LDL, and 27.9% had a greater than 50% decrease in LDL cholesterol levels. Nearly all patients with LDL reductions >50% were taking atorvastatin 80 mg.

Investigators report that patients most adherent to atorvastatin--those with LDL reductions >50%--had a significant 31% reduction in the risk of stroke, a significant 37% reduction in the risk of major coronary events, and a 47% reduction in the risk of revascularization. The risk of hemorrhagic stroke was not increased in patients with the largest reduction in LDL-cholesterol levels.

"Compared with patients who had no change in LDL-cholesterol levels, the group with more than a 50% reduction in LDL cholesterol had the largest stroke risk reduction, more than what was observed in overall SPARCL population," Amarenco told heartwire. "In addition to this, we also wanted to see the effect on the risk of hemorrhagic stroke. This is big news because among the group with the largest reduction in LDL reduction--those with a greater than 50% reduction--there was no risk of hemorrhagic stroke. When this [hemorrhagic-stroke] finding first emerged, we believed it was chance, but that is why this on-treatment analysis was needed. Now I think we can convince clinicians that other factors were involved."

Amarenco P, on behalf of the SPARCL investigators. Stroke Prevention by Aggressive Reduction in Cholesterol Levels. World Congress of Cardiology 2006; September 3, 2006; Barcelona, Spain

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