Smokers With Stroke May Benefit More From tPA

Sue Hughes

Feb 06, 2013

 

New findings suggest that smokers may have a better response to tissue plasminogen activator (tPA) for the treatment of stroke than nonsmokers.

In the study, smokers had a 4-fold greater chance of reperfusion, a 6-fold greater chance of recanalization, and a trend toward better functional outcomes at 3 months compared with nonsmokers.

Similar findings have previously been reported in patients with myocardial infarction (MI) receiving thrombolysis, but this is thought to be the first time this result has been shown in stroke patients with imaging used to verify the results.

"Our results suggest that for smokers having a stroke the chances of recovery if tPA is given quickly are very good," lead researcher, Anna Kufner, MSc, from Charité–Universitätsmedizin Berlin, Germany, commented to Medscape Medical News. "This means it is even more important to seek help quickly if you are a smoker."

Their results were published online January 3 and appear in the February issue of Stroke.

Better Effect of Thrombolysis

Kufner explained that the study came about because she noticed that stroke patients in the clinic where she worked appeared to be having better outcomes, measured by using the Rankin score at 3 months.

"Everybody thought I was crazy at first, or that it was just due to the smokers being younger, but when we found the MI studies suggesting a better effect of thrombolysis in smokers we thought there may be something in it, and we started the current project to look at imaging data on stroke patients receiving tPA and compare smokers with nonsmokers," she said.

The study included 148 consecutive patients with acute ischemic stroke who had MRI before and 1 day after thrombolysis with tPA, which was given within 4.5 hours of stroke symptom onset. Smokers, who made up 21.6% of the population, were significantly younger, were more often male, and had significantly larger mean baseline perfusion deficits.

Results showed that smoking was associated with significantly reduced relative infarct growth and with large increases in the chance of recanalization of the affected vessel and reperfusion.

Table. Response to Thrombolysis Based on Smoking Status in Patients With Proven Vessel Occlusion

Endpoint	Nonsmokers	Smokers	P Value
Recanalization (%)	50	81.1	.02
Reperfusion (%)	30.6	75	.02
Median relative infarct growth (mL)	3.0	1.5	.007
Good outcome at 3 mo (%)	48.1	66.7	.27

After adjustment for confounding factors, including age, sex, hypertension, glucose, and perfusion deficit, smoking was associated with odds ratios of 5.6 for recanalization and 4.3 for reperfusion.

Although smokers had an increased chance of a favorable outcome, as measured by modified Rankin score 3 months after stroke, the researchers note that this was most likely because of their low clinical risk profiles.

"Nonetheless, a favorable functional outcome after stroke was positively associated with reperfusion, suggesting that increased tPA efficacy in smokers may partially contribute to the observed smoking-thrombolysis paradox phenomenon," they write.

A Logical Explanation

But although these findings may appear paradoxical at first, there is a possible scientific explanation. Kufner explained that smokers are believed to have a reduced amount of endogenous tPA released from endothelial cells, which causes them to have a higher risk of clotting. tPA breaks down fibrin, and a few studies have suggested higher fibrin levels in the blood of smokers vs nonsmokers, she noted.

Therefore, clots formed in smokers could well have a higher fibrin content than those in nonsmokers, which would make them more susceptible to be lysed by tPA when it is given as a treatment for stroke.

"This would mean that smokers would be more susceptible to having a stroke in the first place, but also that they have a greater chance of a good outcome after tPA treatment," she added. "And indeed this is what we appear to be seeing."

Kufner noted that a previous study has suggested a better outcome with tPA after stroke in smokers vs nonsmokers, but that study did not use imaging. "Our imaging study gives more information on the possible mechanism behind this effect," she said.

She commented, "We will now integrate these results into the clinic, and we will ask patents more detailed information about smoking behavior to see if we can establish a dose curve; if the amount of smoking correlates with the degree of recanalization and reperfusion."She cautioned that with only 140 patients, this study should be viewed as preliminary. But Kufner's group is now planning further research in this area.

Funding for this research was provided by the Federal Ministry of Education and Research via the Center for Stroke Research Berlin, the Volkswagen Foundation, the European Union, and the German Research Foundation. Kufner has disclosed no relevant financial relationships; she occasionally smokes.

Stroke. 2013;44:407-413. Abstract