Changing the Future of Stroke Care: The 2021 ASA/AHA Prevention Guidelines

A year after the 2021 ASA/AHA stroke prevention guidelines were released, experts in the field shared some of the most notable changes to care, and the areas that still need to be addressed going forward.

Since 1990, the American Heart Association (AHA)/American Stroke Association (ASA) has translated scientific evidence into clinical practice guidelines for the better care and management of cerebrovascular disorders. Although the focus is on the United States, many of the aspects of these recommendations are relevant to patients around the world. In 2021, the organization released its most recently updated edition of the guidelines, making changes to the previous guidelines that were published in 2014.1

The guideline was divided into 4 sections: diagnostic evaluation for secondary stroke prevention, vascular risk factor management, management by etiology, and systems of care for secondary ischemic stroke prevention. Among the several take-home points, the recommendations stressed on trying to define the ischemic stroke etiology, and thus identifying targets for treatment to reduce the risk of recurrent stroke.

Mitchell S.V. Elkind, MD, MS, MPhil, the immediate past-president of the AHA—and only the second neurologist to hold the title—told NeurologyLive® that :the major change since 2014 is an increased emphasis on fine-tuning the treatment based on the specific subtype of stroke, or what we would consider the cause of the stroke." For example, for intracranial large artery atherosclerosis (ICAS), a common cause of stroke with a high rate of recurrent stroke, therapeutic trials showed that antithrombotic therapy and vascular risk factor control are effective for stroke prevention for these patients. However, there may be a subset of patients—those with low flow or poor collaterals—who have an even higher risk of recurrent stroke despite medical therapy.

The SAMMPRIS trial (NCT00576693) was a major reference point for the new guidelines of this specific patient group, including the use of short-term combination aspirin and clopidogrel. In that study, patients in the medical arm with severe stenosis treated with aspirin and clopidogrel for 90 days, followed by aspirin alone for the rest of follow-up, had lower 1-year recurrent stroke rate (12.2%) compared with similar patients from the pivotal WASID trial on aspirin alone (25%).2

Because the recommendations are still in their infancy, their effects may take some time to see, Elkind noted. From conversations with colleagues at public meetings, Elkind believes thethe true impact could be seen closer to 10-15 years down the road. Despite this, in the short time since they were published, he did express that there has been a noticeable increase in monitoring for atrial fibrillation, an area heavily emphasized throughout the manuscript.

As atrial fibrillation remains a common and high-risk condition for secondary ischemic stroke, the guidelines recommended the use of anticoagulation to treat these patients if they have no contraindications. As Elkind echoed, the recommendations recommend heart rhythm monitoring for occult atrial fibrillation if no other cause of stroke is discovered.

READ MORE: Preventing Secondary Stroke: Practical Application of Updated Guidelines

The 1991 SPAF trial (Stroke Prevention in Atrial Fibrillation Study) also served as a supportive piece for these recommendations. During a mean follow-up of 1.3 years, the rate of primary events (ischemic stroke and systemic embolism) in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; P = .02; 95% CI, 9-63). In the subgroup of those on vitamin K antagonists with warfarin, the primary event rate was reduced by 67% and was superior to aspirin alone.3

"When I see a patient, I always think about 2 main issues as I approach them,” Elkind said. "First, is trying to figure out what the proximate cause was for the stroke. Do they have atrial fibrillation or some other clear source of blood clot from the heart? Do they have a blockage in the carotid artery on the side of the stroke? Those would be clear causes of the stroke. The other thing we’re always doing is going through the potential risk factors to see which of those a patient has, regardless of the cause of stroke, and then addressing those factors."

Risk factor management, noted numerous times throughout the recommendations, includes vascular risk factors such as diabetes, smoking cessation, lipids, and hypertension, but also lifestyle factors, including healthy dieting and physical activity.1 Known diets such as the low-salt and Mediterranean diets were also recommended for stroke risk reduction. Although these are not wildly new concepts, the increased emphasis is comforting to see for some, including Jose Gutierrez, MD, MPH.

"We’ve known that [hypertension and diabetes] are major contributors to stroke in the general population. For hypertension, we were leaning towards 120/80 mm Hg based on SPRINT-MIND data that came out in 2019," Gutierrez, a study investigator of the guidelines, told NeurologyLive®. "In terms of [low-density lipoprotein] guidelines, we were advocating for 70 mm Hg or lower, which I think we just made tighter and tighter based on evidence that was published since then."

Gutierrez, an associate professor of neurology at Columbia University Medical Center, said that though primary care doctors play a critical role in helping keep the general public aware of the risk factors for secondary stroke. "We, as neurologists, tend to see people in the hospital. Some come and go, and then we never see them again. They go back to the primary care doctors with a plan that we give them. My hope is that general practitioners understand that managing risk factors in a tighter, stricter, aggressive manner, will save lives and decrease the risk of stroke,” Gutierrez said, going on to say that although it’s not “sexy” in general, controlling blood pressure is the most important thing.

In the recommendations, cigarette smoking was noted as an independent, potent, and dose-dependent risk factor for ischemic stroke and silent cerebral infarction, and approximately doubles the risk of stroke.4 Even after a life-threatening vascular event, roughly one-third of all smokers continue to smoke. Although there were no randomized controlled trials that examined smoking cessation interventions compared with no intervention, encouraging evidence of increased smoking cessation rates after stroke using multibehavioral interventions has emerged.

“These guidelines are way more parceled out. Now you can go into most of the stroke etiologies and find something about it. Even just to tell you, ‘We don’t know. We know that this mechanism exists, but we don’t know what’s ideal.’ We can say, this is the evidence that’s out there, this is what needs to be done in the future. Because we want to also identify gaps in knowledge that can be hopefully filled by people who read the guidelines and become curious.” – Jose Gutierrez, MD, MPH

A meta-analysis identified that intensive counseling interventions initiated in hospital with supportive contacts for at least 1 month after discharge increase smoking cessation rates compared with usual care (RR, 1.37; 95% CI, 1.27-1.48), with comparable findings in patients with cardiovascular disease (RR, 1.42; 95% CI, 1.29-1.56) and interventions initiated in rehabilitation hospitals (RR, 1.71; 95% CI, 1.37-2.14). Adding nicotine replacement therapy to the intervention also increased cessation rates compared with intensive counseling alone (RR, 1.54; 95% CI, 1.34-1.79).5

"Besides [identifying] the cause, we need to identify the risk factors and begin them [the patient] on appropriate treatment, such as antithrombotic medications, statin therapy, blood pressure control, diabetes treatment when that’s needed, etc,” Elkind said. "In addition, making recommendations about a healthy diet, getting exercise, quitting smoking, and other types of behavioral changes. Again, the focus is on the cause, with the separate focus on the risk factors."

Elkind and Gutierrez also mentioned the increased evidence and emphasis on patent foramen ovale (PFO) closure since the 2014 guidelines. In the updated version, it is now considered reasonable to percutaneously close PFO in patients who are between 18-60 years, have nonlacunar stroke, no other identified cause, and have high risk PFO features.1

Two major trials—CLOSE (NCT00562289) and RESPECT (NCT00465270)—both published in the New England Journal of Medicine in 2017, confirmed that closure of was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up.6,7 In the intention-to-treat population in RESPECT, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (HR, 0.55; 95% CI, 0.31-0.999; P = 0.046, log-rank test).6

In addition to increased evidence on PFO, the recommendations provided more clarity on embolic stroke of undetermined source (ESUS), which was formally introduced in 2014. "The field has moved significantly in this area [ESUS],” Gutierrez said. "It’s not that we have a definitive answer, but we brought it up in those guidelines."

In the recommendations, ESUS was defined as a stroke that appears nonlacunar on neuroimaging without an obvious source after a minimum standard evaluation, including arterial imaging, echocardiography, extended rhythm monitoring, and key laboratory studies such as lipid profile and HbA1c, to rule out known stroke etiologies such as cardioembolic sources and atherosclerosis proximal to the stroke. Individuals with ESUS have cryptogenic stroke, but the converse is not always the case.1

"They [patients with ESUS] look like somebody who has a major risk source of cardiac embolism, like atrial fibrillation, but we can’t find the atrial fibrillation," Elkind said. "The question remains: how do we best evaluate those patients? There are recommendations to consider—long-term cardiac monitoring—but it’s not yet clear how much monitoring should be done. Is it 48 hours? A week? Four weeks? Is it 3 years, or even 4 and a half years, which is how long these devices can last on a single battery?"

Gutierrez added, "the 2014 guidelines were a little denser, clustering mechanisms within each topic, whereas these guidelines are way more parceled out. Now you can go into most of the stroke etiologies and find something about it. Even just to tell you, ‘We don’t know. We know that this mechanism exists, but we don’t know what’s ideal.’ We can say, this is the evidence that’s out there, this is what needs to be done in the future. Because we want to also identify gaps in knowledge that can be hopefully filled by people who read the guidelines and become curious."

1. Kleindorfer DO, Towfighl A, Chaturvedi S, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52:e364-e467. doi:10.1161/STR.0000000000000375
2. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993-1003. doi:10.1056/NEJMoa1105335
3. Anderson DC, Asinger RW, Newburg SM, et al. Stroke Prevention in Atrial Fibrillation Study: final results. Circulation. 1991;84:527-39. doi:10.1161/01.cir.84.2.527.
4. Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:3754-3832. doi:10.1161/STR000000000000046
5. Rigotti NA, Clair C, Monaco MR, Stead LF. Interventions for smoking cessation in hospitalized patients. Cochrane Database Syst Rev. 2012;5:CD001837. doi:10.1002/124651858.CD001837.pub3
6. Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen oval closure or medical therapy after stroke. N Engl J Med. 2017;377:1022-1032. doi:10.1056/NEJMoa1610057
7. Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs anti platelets after stroke. N Engl J Med. 2017;377(11):1011-1021. doi:10.1056/NEJMoa1705915