MIAMI BEACH—A prestroke combination therapy of antiplatelets, angiotensin-converting enzyme (ACE) inhibitors, and statins had a greater effect in reducing stroke severity and at-risk tissue compared with antiplatelet therapy alone or antiplatelets plus one of the other two agents, according to Magdy Selim, MD, PhD. The triple therapy was associated with significantly lower baseline NIH Stroke Scale scores and with smaller perfusion-diffusion MRI mismatch volumes. In addition, a significantly larger percentage of stroke patients pretreated with the triple therapy were discharged home.

Dr. Selim, an Assistant Professor of Neurology at Harvard Medical School and Codirector of the Stroke Center at the Beth Israel Deaconess Medical Center in Boston, believes that the added protective benefits from the combination therapy are due to the combined multimodal effects of these drugs. He and his colleagues presented their findings at the 57th Annual Meeting of the American Academy of Neurology.

REDUCING STROKE SEVERITY

Prior studies have shown that antiplatelets, ACE inhibitors, and statins can be effective in reducing ischemic stroke incidence and recurrence. Animal studies have suggested that these drugs may have neuroprotective effects. Other research has shown that patients who are taking aspirin, ACE inhibitors, or statins tend to have milder strokes and improved outcomes.

“Nowadays, there is a tendency to prescribe statins, ACE inhibitors, and antiplatelets in combination for stroke patients,” said Dr. Selim. “We hypothesized that if you used the combination therapy, patients would tend to have milder strokes, and it would also have an impact upon their recovery and functional outcome after their stroke. That’s why we embarked on this preliminary study using clinical data and MRI data to see whether the patients on more than one of these therapies would have less severe strokes or better outcomes than the ones who are only taking antiplatelets.”

Dr. Selim retrospectively reviewed data from a two-year period on 210 consecutive ischemic stroke patients who presented within 24 hours of stroke onset. Patients who were diagnosed with transient ischemic attacks were excluded. Demographics, risk factors for stroke, vital signs at presentation, and other medications that subjects were taking on admission were also analyzed, as were hospital stay and discharge status.

ANTIPLATELETS, ACE INHIBITORS, AND STATINS

Patients were assigned to one of three groups—those who were taking only antiplatelets, those taking antiplatelets plus either a statin or an ACE inhibitor, and patients taking antiplatelets plus both a statin and an ACE inhibitor. A total of 110 patients were taking antiplatelets on admission to the hospital. Of those, 18 were treated with thrombolysis or experimental therapy and were excluded from outcome assessment.

Forty-nine patients were on antiplatelet therapy alone prior to stroke onset. Within this group, 92% were taking aspirin (two of the patients were taking both aspirin and warfarin), 4% were on clopidogrel, and 4% were taking ticlopidine. “We didn’t see anyone on dipyridamole, because this study ended around 2000, and at that time there were not a lot of people taking dipyridamole at our institution,” noted Dr. Selim. There were 43 patients on the antiplatelet dual therapy—almost half (49%) were taking an ACE inhibitor, and 15% of them were taking an antiplatelet plus an angiotensin receptor blocker. For statistical analysis, these were combined together as one group. About 36% were taking antiplatelets plus a statin. A total of 18 patients were on the triple therapy.

No significant differences were observed in age, gender, risk-factor profile, or blood pressure between the groups, according to Dr. Selim. “The percentage of patients who were imaged in less than six hours from stroke symptom onset was also not significantly different among the three groups,” he said. Dr. Selim and colleagues then looked specifically at history of transient ischemic attack, as there is evidence to suggest that such patients may develop ischemic tolerance or pre-ischemic conditioning that affects their stroke severity. However, no significant differences were observed between the three groups, nor were there differences in blood glucose level, systolic or diastolic blood pressure, stroke type/mechanism, history of hypertension, diabetes, or coronary artery disease, or smoking status. Furthermore, “When we looked at other medications, there was no difference in the percentage of patients who were using anticoagulants or other antihypertensive agents,” added Dr. Selim.

Regarding stroke severity as indicated by NIH Stroke Scale score, “patients on antiplatelet plus [an ACE inhibitor or a statin] had a lower [score] compared with those on antiplatelets alone,” Dr. Selim continued. “Those who were on the three [drugs] had a significantly lower NIH Stroke Scale [score] on admission. When we looked at the [group] on antiplatelets plus a statin or ACE inhibitor, there was really no difference whether it was a statin or ACE inhibitor.... When we looked at the MRI imaging data, there was no difference in the baseline diffusion-weighted MRI lesion volume. There was a lower volume of perfusion abnormality in the patients on the triple therapy, and the patients on the triple therapy also had a smaller mismatch volume. Again, when looking at the ones on antiplatelets plus another agent, there was no difference between statins and ACE inhibitors. Also, a significantly larger percentage of patients on the triple therapy were discharged home compared with the other two groups.”

Dr. Selim said that his findings have important therapeutic implications but cautioned that they are preliminary and require further validation in larger studies.

NR

—Colby Stong

Suggested Reading
McCabe DJ, Brown MM. Prevention of ischaemic stroke—antiplatelets. Br Med Bull. 2000;56:510-525.
Trubelja N, Vaughan C, Coplan NL. The role of statins in preventing stroke. Prev Cardiol. 2005;8:98-101.
Weber MA. Managing the patient at risk for a second stroke. J Hypertens. 2005;23 (suppl):S41-S47.

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