Pierre Amarenco

Background and Purpose— The intention-to-treat analysis of data from the placebo-controlled Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial found 80 mg atorvastatin per day reduced the risk of stroke and major coronary events in patients with recent stroke or transient ischemic attack. This benefit was present despite only a 78% net difference in adherence to randomized treatment over the course of the trial. In this exploratory analysis, our aim was to evaluate the benefit and risks associated with achieving a ≥50% low-density lipoprotein cholesterol (LDL-C) reduction from baseline. Methods— This post hoc analysis was based on 55 045 LDL-C measurements among the 4731 patients enrolled in SPARCL (average, 11.6 measurements per patient) during a mean follow-up of 4.9 years. At each postrandomization LDL-C assessment, percent change in LDL-C from baseline for each patient was classified as no change or increase from baseline (32.7% of measurements), Results— Compared with no change or an increase in LDL-C, analysis of time-varying LDL-C change showed that patients with ≥50% LDL-C reduction had a 31% reduction in stroke risk (hazard ratio, 0.69, 95% CI, 0.55 to 0.87, P =0.0016), a 33% reduction in ischemic stroke ( P =0.0018), no statistically significant increase in hemorrhagic stroke ( P =0.8864), and a 37% reduction in major coronary events ( P =0.0323). There was no increase in the incidence of myalgia or rhabdomyolysis. Persistent liver enzyme elevations were more frequent in the group with ≥50% LDL-C reduction. Conclusions— As compared with having no change or an increase in LDL-C, achieving a ≥50% lowering was associated with a greater reduction in the risk of stroke and major coronary events with no increase in brain hemorrhages.

Atrial fibrillation is associated with a risk of cerebral embolism, the only proven effective prevention of which is anticoagulant therapy. There is no known alternative in cases with contra-indications to this treatment. Percutaneous exclusion of the left atrial appendage by the implantation of a prosthesis (PLAATO System, ev3 Inc., Plymouth, Minnesota) is a new approach to the prevention of these complications. The authors report the results observed in a series of 11 consecutive patients (7 men, mean age 72 +/- 9 years) in whom this procedure was proposed. All patients had atrial fibrillation for over 3 months, were at high risk and had contra-indications to oral anticoagulants. The implantation of the prosthesis was performed after treatment with aspirin and clopidogrel, under general anaesthesia radioscopy and transoesophageal echocardiographic guidance with success in 9 cases (1 implantation refused in the catheter laboratory and 1 failure). The only complication observed was transient ST elevation treated by emergency angioplasty. The echographic and angiographic criteria of success of left atrial appendage exclusion were fulfilled in all implanted patients. The hospital course was uncomplicated. One recurrence of stroke was observed at the second month: transoesophageal echocardiography confirmed the absence of thrombosis, of migration of the prosthesis and its impermeability in all the patients. After 7 +/- 5 months' follow-up, no other adverse event was observed. This new procedure is technically feasible. Despite encouraging results, its long-term efficacy in the prevention of thromboembolic complications of atrial fibrillation remains to be demonstrated.

This paper reviews recent studies into the outcomes of clinical trials in which statin therapy has been used in the prevention and treatment of strokes. Epidemiologic studies found no or little association between blood cholesterol levels and stroke. Randomized trials have confirmed that LDL lowering decreased the risk of stroke, in diabetic or hypertensive patients with ‘normal’ LDL cholesterol at baseline, and in patients with coronary artery disease, with respectively 48, 27 and 25% reduction in stroke incidence. A meta-analysis of trials showed that the greater the LDL cholesterol reduction, the greater the intima-media thickness and stroke risk reductions. Even if statins also have ‘pleiotropic’ effects, their main action seems to be through LDL reduction. The Heart Protection Study only included strokes that occurred 4.6 years before – a time when the stroke event rate is low and the cardiac event rate is high, and so may not have had the power to find a true effect of LDL cholesterol lowering in preventing recurrent stroke. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial may give a definite answer because SPARCL investigators included 4732 patients with brain infarction or transient ischemic attacks and no history of myocardial infarction within 6 months of their stroke event, at a time when the expected stroke rate is very high and the myocardial infarction rate is very low. The results should be announced by mid-2006. The positive effect of statins on stroke observed in trials of patients with coronary heart disease depended mainly on between-group LDL reduction, but other mechanisms could be involved. Though effective in prevention of major coronary events after a first stroke, statins have not yet been proven effective in prevention of recurrent stroke.