Recurrent Stroke Risk Higher in Type 2 Diabetes

Megan Brooks

June 15, 2011

June 14, 2011 — Patients with type 2 diabetes, but without frank cardiovascular disease, are at higher risk for recurrent stroke and cardiovascular events than patients without diabetes or without metabolic syndrome. However, statin therapy appears to cut the risk in both groups and to the same degree as in people without these conditions.

The findings come from a post hoc analysis of the Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) trial published online June 13 in the Archives of Neurology.

"The take-home message from this paper would be that patients with type 2 diabetes and stroke or TIA [transient ischemic attack] without known heart disease have increased risk of future events compared to those without type 2 diabetes or with metabolic syndrome," first author Alfred Callahan, MD, from Vanderbilt University, Nashville, Tennessee, told Medscape Medical News.

Dr. Alfred Callahan

"This increased risk is attenuated by intensive lipid lowering not only in diabetics but also those with metabolic syndrome as well as those without type 2 diabetes or metabolic syndrome," he added.

"Although the possibility of variation in the benefit of statin treatment in subjects with or without type 2 diabetes or MetS [metabolic syndrome] cannot be excluded by this analysis, there was no evidence of a difference in treatment effect," the study team notes in their report.


Until now, little was known about the effect of statins on secondary stroke prevention in patients with type 2 diabetes or metabolic syndrome compared with those without these conditions, the authors note.

The SPARCL trial was the first to specifically look at the effect of atorvastatin in reducing the risk for stroke in patients with a prior stroke or TIA but with no history of coronary artery disease.

A total of 4731 patients with a stroke or TIA within the past 1 to 6 months were randomly assigned to atorvastatin (Lipitor, Pfizer), 80 mg/d, or placebo.

The mean baseline low-density lipoprotein (LDL) cholesterol level in SPARCL participants was 133 mg/dL, which fell to a mean level of 73 mg/dL in the atorvastatin-treated patients during the trial, a 37% reduction. Levels did not decrease significantly in the placebo group.

The reduction in LDL cholesterol levels appeared to translate into a significant reduction in the primary end point of nonfatal or fatal stroke, which occurred in 11.2% of patients in the atorvastatin group and 13.1% of patients in the placebo group, a 5-year absolute reduction in risk of 2.2% and an adjusted hazard ratio of 0.84 (P = .03).

Full results were published in 2006 in the New England Journal of Medicine.

Planned Secondary Analysis

In this current post hoc analysis, SPARCL investigators explored the impact of type 2 diabetes or metabolic syndrome on the effect of statin treatment for secondary stroke prevention.

At baseline, 794 (16.8%) participants had type 2 diabetes, 642 (13.6%) had metabolic syndrome, and 3295 (69.6%) had neither condition (reference group).

Treatment with atorvastatin led to similar reductions in LDL cholesterol regardless of group. Triglycerides were reduced by 11.3% in the type 2 diabetes group, 20.2% in the metabolic syndrome group, and 9.0% in the reference group. High-density lipoprotein cholesterol levels were similar at baseline and during treatment across the 3 groups.

Compared with the reference group, patients with type 2 diabetes were at an increased risk for stroke, major cardiovascular events, and revascularization procedures.

Table 1. Risk for Stroke and Cardiovascular Events With Type 2 Diabetes vs Reference Group

End Point Hazard Ratio (95% CI) P Value
Stroke 1.62 (1.33 - 1.98) < .001
Major cardiovascular events 1.66 (1.39 - 1.97) < .001
Revascularization procedures 2.39 (1.78 - 3.19) < .001

CI = confidence interval

Patients with metabolic syndrome were not at increased risk for stroke (P = .78) or major cardiovascular events (P = .38), but they more often had revascularization procedures (hazard ratio, 1.78; 95% CI, 1.26 - 2.5; P = .001) than those with neither diabetes nor metabolic syndrome.

Table 2. Vascular Event Rates by Group

Outcome Reference Group (%) Metabolic Syndrome Group (%) Diabetes Group (%)
Stroke (primary) 11.0 10.7 18.1
Major coronary event 3.8 4.4 6.2
Major cardiovascular event 14.1 14.5 22.9
Any coronary heart disease event 6.0 7.9 9.8
Any revascularization procedure 4.3 6.9 8.9
Death 8.2 7.3 13.7


Effect of Statin Therapy

There was no difference in the effect of statin treatment in reducing recurrent stroke or cardiovascular events in patients with or without type 2 diabetes or metabolic syndrome.

"Although this was a preplanned secondary analysis, these results should be viewed as exploratory," the study team notes. "It should be recognized that the SPARCL study was not powered to test for subgroup effects and that this analysis is likely underpowered."

However, the researchers point out that their results support those of the Cholesterol Treatment Trialists' Collaborators, who also found that statin's effect on stroke risk was similar in patients with and those without diabetes.

Dr. Callahan said, "It is impressive to look at the reduction in risk of revascularization procedures by intensive lipid lowering given that no patients were enrolled needing those procedures."

Table 3. Effect of Atorvastatin on Revascularization by Group

Study Group Atorvastatin (%) Placebo (%) P Value
Reference 3.5 5.2 .007
Metabolic syndrome 5.5 8.3 .19
Diabetes 4.8 13.0 < .001


Summing up, Dr. Callahan noted that, "While patients may come with manifest risk in one vascular bed, they have accelerated or high risk of future vascular events in other beds — and should be treated aggressively — and SPARCL showed treatment works," for all the patients.

"Our study," he added, "confirms the value of the concept of thinking about vascular risk from a global perspective rather than an organ-specific view and suggests that such a way of thinking can provide the best global benefit in terms of risk reduction when it is incorporated into patient care."

The study was sponsored by Pfizer Inc. Dr. Callahan and several other co-investigators have received grant and research support, honoraria, and consulting and lecture fees from various pharmaceutical manufacturers, including Pfizer Inc. One of the authors is employed by and owns stock in Pfizer.

Arch Neurol. Published online June 13, 2011.


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