Natural statins and stroke.

To the Editor: The comprehensive review by Furberg1 of natural statins and stroke raises a number of issues. Stroke was a secondary end point in these studies in patients with cardiovascular disease (CVD). Primary end-point trials in stroke are awaited. Surrogate markers can be valuable guides to the introduction of better therapies before large-scale trials are completed. LDL may be the best surrogate marker of prognosis in CVD. In stroke, the primary role of LDL is less clear, but the subgroup analyses and the association of LDL reduction with mechanisms of plaque stabilization imply the need for effective therapy. The new target of LDL ,100 mg/dL (,2.5 mmol/L) may be difficult to achieve with some natural statins. The extent to which comparative trials between statins are necessary to demonstrate a class effect is debatable, as they seem to share many ancillary actions.2 The effects of statins on fibrinogen are controversial. Epidemiological evidence suggests fibrinogen is an independent risk factor, but it is unnecessary as an additional predictor in models of CVD risk. No clinical trials have demonstrated that a reduction in fibrinogen alone will reduce events or the converse. In contrast to the non–peer-reviewed communication cited with its claimed 50% increase in fibrinogen,1 we have published observational data of 19% to 23% median increases in fibrinogen with atorvastatin in 89 patients with familial hyperlipidemias3 and a subset of 21 patients at high risk of CVD.4 We have extended these observations to 201 patients with familial hyperlipidemias and have found a median increase of 13% (range 225% to 63%) at 12 weeks with atorvastatin 10 to 80 mg. Previously, 98 of the same patients showed a 5% median decrease (range 228% to 28%) in fibrinogen when initially treated with simvastatin 20 to 40 mg. The effects of atorvastatin seen in our studies contrast with data from larger randomized, placebo-controlled trials in different but commoner patient groups.5 Our observations need to be investigated in randomized, placebo-controlled trials in specified patient groups, and any drug specificity or time course needs to be determined.3–5 The consequences of large reductions in LDL as opposed to small rises in fibrinogen are unknown. However, LDL seems to be a stronger predictor of risk than fibrinogen. Until evidence on interventions affecting fibrinogen is available, decisions on drug therapy need to be made in the light of available trial data. Currently, that means the most cost-effective, least side-effect–prone, evidence-based method of achieving LDL, and secondarily HDL and triglyceride, targets.