Lipitor Reduces Risk of Second Stroke
August 21, 2006
The study, by K Michael Welch, MB, ChB, of Rosalind Franklin University of Medicine and Science, and colleagues, was published in the August 10 issue of The New England Journal of Medicine and summarized by MedPage Today on August 9.
Results of the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial showed that participants who took Lipitor (80 mg/day) after stroke or TIA had a 2.2% absolute reduction in the risk of stroke over the next five years. They also had a 16% relative reduction in risk of fatal or non-fatal stroke.
Participants taking Lipitor also fared better with regard to secondary endpoints, with the exception of death, including:
- stroke or TIA
- major coronary events
- nonfatal MI
- major cardiovascular events
- acute coronary events
- any coronary event
- any cardiovascular event.
In the Lipitor group 216 deaths occurred, compared with 211 in the placebo group.
SPARCL was a double-blind trial that randomized 4,731 participants with baseline LDL levels of 100-190 mg/dL and no known history of coronary heart disease to Lipitor (80 mg) or placebo. All participants enrolled in the study within six months of a stroke or TIA.
Patients’ average age was 63 years, and 60% were male. The average baseline LDL level in both groups was about 133 mg/dL, and average follow-up was 4.9 years.
The SPARCL study results are significant, in part because they support the contention that statins can stroke-risk in people with no established heart disease. Statins have long been known to benefit people with established cardiovascular disease, decreasing the likelihood of stroke.
The authors ascribe Lipitor’s benefit in participants with no heart disease to Lipitor’s ability to reduce levels of low-density liporoteins (LDLs), stating that Lipitor reduces the "risk of cerebral infarction, the mechanism of which largely has been attributed in to a reduction in LDL cholesterol levels," they wrote.
The mean LDL level among participants receiving Lipitor was 73 mg/dL, compared with 129 mg/dL among participants on placebo.
However, Lipitor was associated with a higher risk of hemorrhagic stroke: 55 of the 88 patients who experienced one or more hemorrhagic stroke were in the Lipitor group. Despite this effect, however, the SPARCL investigators concluded their data "support the initiation of [Lipitor] treatment soon after a stroke or TIA."
The case for changing prescribing guidelines in lights of the SPARCL trial results is not clear-cut, according to an accompanying editorial, David M Kent, MD, of the Institute for Clinical Research and Health Policy Studies at Tufts-New England Medical Center in Boston.
Dr Kent pointed out that "the relative risk of hemorrhagic stroke was increased by 66% among patients in the [Lipitor arm], an effect that is likely to be of some import among patients presenting with a hemorrhagic stroke."
He also noted the stroke paradox: while little epidemiologic evidence links cholesterol levels to stroke, convincing evidence exists that statins prevent stroke.
"This so-called stroke paradox can be easily explained, either by the heterogeneous effects of cholesterol on different subtypes of stroke in the epidemiologic studies or by the pleiotropic (e.g., antithrombotic, antiinflammatory, and plaque stabilizing) effects of statins in the clinical trials," wrote Dr Kent.
Finally, although the SPARCL results did nto convince Dr Kent that high-dose Lipitor should be prescribed for all stroke or TIA survivors, he predicted they would likely add to the "gathering momentum favoring the promotion of ischemic stroke to a ’coronary heart disease risk equivalent,’ the adoption of statin therapy on discharge as a ’quality indicator,’ and the inclusion of statins in preprinted stroke orders to improve adherence by physicians."
Dr Kent felt this effect would be beneficial, as statins are under-prescribed, even for patients eligible for statin therapy based on current guidelines. He notes, “In one recent study, even among patients who were eligible for statin therapy according to the ATP II guidelines, only one third had discharge medications that included statins.”
Dr Kent concluded that "it does not take a recursive subgroup analysis to show that the greatest current risk to patients with ischemic stroke vis-à-vis statins remains gross under treatment."
High-Dose Atorvastatin after Stroke or Transient Ischemic Attack. Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators, The New England Journal of Medicine, volume 355, pages 549-559, August 10, 2006.
Stroke – an Equal Opportunity for the Initiation of Statin Therapy. Kent DM, The New England Journal of Medicine, volume 355, pages 613-615, August 10, 2006.
Posted: August 2006