To Curb Secondary Event Risk, Go ‘Granular’ With Causes of TIA, Minor Stroke

Precisely pinpointing the triggers behind a TIA or minor ischemic stroke, including the coexistence of different disease factors, is important for understanding the future risk of major vascular events, according to an analysis of TIAregistry.org.

The patients most at risk are those whose cerebrovascular events were related to atherosclerosis, with lower but still elevated hazards seen for those with underlying cardiac pathology, small-vessel disease (SVD), or other rarer causes or dissection, researchers led by Philippa Lavallée, MD (University Paris-Cité, France), report.

Importantly, the study used a more detailed grading system known as ASCOD to check for the presence of coexisting causes, not the more commonly used TOAST classification system that places patients into mutually exclusive categories.

The findings, published online this week in JAMA Neurology, suggest that this more nuanced grading system might be beneficial for future clinical trial design, as well as for secondary stroke prevention. For instance, investigators could use information it provides to enrich clinical trial populations with patients most likely to benefit from a particular intervention.

Moreover, certain modifiable risk factors—like high blood pressure, obesity, low physical activity, and dyslipidemia—are common across the various causes of TIA/stroke. Thus, Lavallée et al say, trials evaluating the effects of interventions to address those factors could group patients with strokes of different origins together.

The bottom line, they write, is that “risk factor control is the mainstay of secondary stroke prevention, regardless of the underlying disease that caused the stroke, while addressing specific thrombotic processes, triggers (eg, inflammation), and causal factors (eg, lipoprotein(a) or low-density lipoprotein cholesterol levels) should preferably be assessed in patients with stroke selected on the presence of an underlying causal disease.”

TIAregistry.org

There are limited data on long-term outcomes of patients with TIA or minor ischemic stroke based on the underlying cause of the cerebrovascular event, the investigators note. To help address that gap, they turned to TIAregistry.org, a prospective cohort of 4,789 patients with a TIA or minor stroke in the week prior to enrollment. The study was conducted at 61 specialized centers across 21 countries in Asia, Europe, and Latin America.

The current analysis focused on 3,847 patients (mean age 66.4 years; 40.3% women) who completed 5-year follow-up at 42 sites. The investigators applied a grading system called ASCOD (atherosclerosis, SVD, cardiac pathology, other cause, or dissection) to categorize the presence of disease and the likelihood that it was causal in the event.

In terms of disease that was possibly or probably causal, 25.9% of patients had atherosclerosis, 20.1% SVD (lacunar stroke or a lacunar syndrome), 20.8% cardiac pathology, and 5.4% another rare cause or dissection.

These diseases often overlapped. For instance, among the patients with atherosclerosis that was possibly or probably causal, 49.0% also had some form of SVD and 27.6% had underlying cardiac pathology.

The risk of major vascular events (a composite of stroke, ACS, or CV death) through 5 years of follow-up varied according to the type of underlying disease present, ranging from 4.4% among patients with no identified causes to 19.8% among those with atherosclerosis. Rates were 11.1%, 13.6%, and 16.6% for those with SVD, other causes/dissection, and cardiac pathology, respectively.

Hazard ratios for major vascular events, compared with patients with no underlying causes, ranged from 3.21 (95% CI 1.79-5.75) for those with other causes/dissection up to 4.86 (95% CI 3.07-7.72) for those with atherosclerosis. Similar relationships were seen for stroke alone.

The 5-year risk of all-cause mortality was highest among those with causal cardiac pathology (HR 3.99; 95% CI 2.49-6.40), and was also significantly elevated for those with causal atherosclerosis (HR 3.43; 95% CI 2.15-5.48) and lacunar stroke (HR 1.96; 95% CI 1.19-3.25).

“This variability of clinical outcome is surprising in the era of intensive secondary prevention management in sophisticated stroke centers, such as stroke centers involved in the TIAregistry.org,” Lavallée et al write. “The results can most likely be generalized to similar centers worldwide, but not to less well-resourced centers where outcomes are likely to be even less favorable.”

Importance of a Detailed Workup

Commenting for TCTMD, David Wang, DO (Barrow Neurological Institute, Phoenix, AZ), noted that TOAST is easy to use but not very detailed. Using the TOAST criteria, for example, a dissection might be categorized as either large-vessel disease or unknown, whereas ASCOD can link an event more precisely to a range of underlying disease conditions.

But the current analysis’ main advantage is the long-term follow-up of a group in which this type of information is not widely available, Wang said. It shows that “if you have clear causes, your risk of stroke is definitely high in the next 5 years, and gives us some notion that, indeed, working patients up for causes and treating these risk factors aggressively will be helpful in preventing future strokes. So I think that’s really the usefulness of this paper.”

Another important take-home message, he said, is that if there are no clear underlying causes identified, the risk of vascular events during follow-up is much lower, but not zero.

Wang also had an important message for patients with a TIA or minor ischemic stroke: “Do not take it lightly. Your future risk of having another stroke is high, so see doctors quickly and let the doctors figure out why you had a TIA or stroke. Adequate prevention and lowering of risk factors can help prevent another stroke or TIA.”