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Odkazy a zdroje - Studie - ASCOT-LLA



ASCOT-LLA

Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm

Author(s)
(a) Sever PS, Dahlof B, Poulter NR, et al.

Title(s)
(a) Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial

Reference(s)
(a) Sever PS, Dahlof B, Poulter NR, et al.

Disease
Hypertension, hypercholesterolemia (mild)

Purpose
To study the cardiovascular effects of atorvastatin in hypertensive patients with total cholesterol of ≤6.5 mmol/L

Study design
Randomized, 2 x 2 factorial design, double-blind, multicenter. The antihypertensive arm is designed as Prospective Randomized Open Blinded end points (PROBE) trial

Follow-up
Median 3.3 years

Patients
10,305 patients, 40–79 years old, with untreated hypertension ( ≥160/100 mm Hg) or treated hypertension with blood pressure ≥140/90 mm Hg, who had also serum total cholesterol of ≤6.5 mmol/L and were not currently taking a fibrate or a statin. In addition, patients had to have ≥3 of the following risk factors (left ventricular hypertrophy, abnormal ECG, type 2 diabetes, peripheral vascular disease, previous TIA or stroke, male sex, age ≥55 years, microalbuminuria or proteinuria, smoking, total cholesterol/HDL cholesterol ratio of ≥6, or premature family history of coronary heart disease). Patients with previous myocardial infarction, angina, a stroke within the preceding 3 months, serum triglycerides >4.5 mmol/L, congestive heart failure, uncontrolled arrhythmia or any routine laboratory test showing important hematological or biochemical abnormality were excluded

Treatment regimen
After a 4-week run-in phase, 19,342 patients were randomized to b-blockers ± diuretics or to amlodipine ± ACE inhibitor. In addition, the eligible patients for the lipid-lowering arm were randomized to atorvastatin 10 mg/d (n=5168) or placebo (n=5137)

Concomitant therapy
-

Results
The study was terminated prematurely by the Data and Safety Monitoring Board. Compared with placebo, atorvastatin reduced total cholesterol by 1.3 mmol/L, LDL cholesterol by 1.2 mmol/L, and triglycerides by 0.3 mmol/L at 1 year. HDL cholesterol levels were comparable between the groups. The primary end point of the study (nonfatal MI or coronary heart disease death) occurred in 1.9% in the atorvastatin group and in 3.0% in the placebo group (hazard ratio [HR] 0.64; 95% CI= 0.50–0.83; p=0.0005). All-cause mortality was 3.6% and 4.1%, respectively (p=0.165). Cardiovascular mortality was 1.4% and 1.6%, respectively (p=0.51). Stroke occurred in 1.7% and 2.4%, respectively (HR 0.73; 95% CI=0.56–0.96; p=0.024), and MI in 1.7% and 2.7%, respectively (HR 0.62; 95% CI= 0.47–0.81; p=0.0005). Total cardiovascular events and procedures occurred in 7.5% and 9.5% of the patients, respectively (HR 0.79; 95% CI=0.69–0.90; p=0.0005). Coronary events occurred in 3.4% in the atorvastatin and 4.8% in the placebo group (HR 0.71; 95% CI=0.59–0.86; p=0.0005). The rates of serious adverse events and liver-enzyme elevation were comparable between the atorvastatin and placebo groups.
In summary, atorvastatin 10 mg/d reduced major cardiovascular events and stroke in hypertensive patients with high-risk features for cardiovascular disease and normal or only mildly elevated serum cholesterol levels.