High-Dose Statins Should Only Be Used in Atherosclerotic Strokes
Statin therapy should not be initiated in this patient, a young woman free of vascular risk factors and at low risk for atherosclerotic cerebrovascular disease. Unfortunately, this patient has an iatrogenic stroke after a cardiac catheterization performed for symptoms described as “atypical.” There is no evidence that underlying atherosclerotic disease accounted for her cardiac symptoms or stroke. Cardiac catheterization can cause stroke by multiple mechanisms including disruption of aortic arch atheroma, embolization of thrombus from the catheter tip, air emboli, provoked arrhythmias, hemodynamic instability, or cervical artery dissection.1–3 All potential procedure-mediated mechanisms should be considered and explored to the extent possible, but it is not unusual for the precise cause to remain elusive.
The disparate findings of the Medical Research Council/British Heart Foundation Heart Protection Study (HPS) and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trials suggest that careful selection of patients with atherosclerotic stroke is critical for realizing a benefit to statin treatment.4,5 In a retrospective analysis of the HPS, in subjects with a history of stroke, simvastatin did not significantly reduce the risk of recurrence (hazard ratio, 0.98; 95% CI, 0.79–1.22). In contrast, in SPARCL, which targeted patients with an atherosclerotic mechanism of stroke, atorvastatin at 80 mg daily resulted in a 2.2% 5-year absolute reduction in risk (hazard ratio, 0.84; 95% CI, 0.71–0.99; P=0.03). Generalizing the results of SPARCL to individuals with stroke due to nonatherosclerotic mechanisms is unwarranted. Of all the potential mechanisms of stroke complicating cardiac catheterization, only aortic arch atheroma would conceivably be amenable to statin treatment; however, even under this hypothetical scenario, avoiding repeated catheter manipulation and initiating antithrombotic therapy, as opposed to a statin, to inhibit thrombus formation on damaged epithelial surfaces would be the primary interventions for preventing recurrent stroke.
A clinician might be tempted to simply treat the low-density lipoprotein of 106 mg/dL rather than perseverate on the underlying pathophysiology of the procedure-related stroke. However, the threshold for initiating statin therapy for primary prevention of cerebrovascular disease is based on cardiovascular risk. The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (Adult Treatment Panel III) recommends a low-density lipoprotein target of <160 mg/dL in individuals with no risk factors.6 This patient, free of vascular risk factors, would be well within goal with a low-density lipoprotein of 106 mg/dL. Therefore, there is no indication for initiating statin therapy in this patient, at any dose, for low-density lipoprotein reduction.
Finally, despite their seemingly ubiquitous use, it is important to remain cognizant of the substantial costs and potential risks associated with statin treatment. In SPARCL, high-dose atorvastatin caused elevations in liver enzymes and creatine kinase. Rarely, high-dose statin therapy results in catastrophic rhabdomyolysis. In addition, in SPARCL, there was a higher incidence of hemorrhagic stroke in the atorvastatin-treated subjects (2.3% in the atorvastatin arm versus 1.4% in placebo; hazard ratio, 1.66; 95% CI, 1.08–2.55). Therefore, statins should not be used indiscriminately, particularly in conditions in which there is likely to be little or no benefit.
In conclusion, it is reckless and irresponsible to reflexively initiate statin therapy in all patients with stroke without first carefully considering the potential risks and benefits to the individual. Existing evidence supports the use of high-dose statin therapy in patients with an atherosclerotic mechanism of stroke or transient ischemic attack and a low-density lipoprotein >100 mg/dL.7 In the absence of other noncerebrovascular indications for statin therapy such as coronary heart disease or diabetes, in patients with nonatherosclerotic causes of stroke such as cardioembolism, dissection, hypercoagulable state, or vasospasm, until there is evidence of benefit in these subgroups, a statin should not be initiated.
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 2 of a 3-part article. Parts 1 and 3 appear on pages 1992 and 1996, respectively.
- Received December 16, 2011.
- Revision received January 20, 2012.
- Accepted January 24, 2012.
- © 2012 American Heart Association, Inc.
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