Are We Failing at Primary Stroke Prevention?

Nearly 25 years ago, Joseph P. Broderick, MD, stroke expert and neurologist at the University of Cincinnati in Cincinnati, reflected on what stroke prevention and management might be like in 2025. At the time, stroke was the third leading cause of disability in the US and a leading cause of disability worldwide.

“To decrease the enormous burden of stroke throughout the world, we first need to know the barriers that we have to overcome,” Broderick wrote in 2003. “The most important barriers to successful prevention and treatment of stroke are similar to the barriers of the last 25 years,” he added.

Today, stroke ranks as the fifth leading cause of death and disability in the US and the second worldwide. The latest data from World Stroke Organization Global Stroke Fact Sheet show that while the absolute number of incident strokes increased by 70% between 1990 and 2019, the age-standardized incidence decreased by 17% for total stroke and by 10% for ischemic stroke.

Although new strategies for stroke prevention have emerged in recent decades, the most effective approach remains reducing primary risk factors at the population level.

Hypertension, type 2 diabetes, dyslipidemia, and atrial fibrillation (AF) remain the most significant modifiable stroke risk factors. In response to the anticipated rise in stroke prevalence, institutions like the World Stroke Organization have called for increased public awareness and stronger prevention efforts.

“We could prevent about half the number of strokes which occur each year if blood pressure [BP] was properly controlled,” Bruce Ovbiagele, MD, MSc, chief of staff at the San Francisco Veterans Affairs Health Care System, told Medscape Medical News.

Just as it was 25 years ago, the major challenge today is raising awareness of stroke risk and the steps needed to modify that risk, he noted.

Ovbiagele said patients are often unaware of these risks, are concerned about medication side effects, and/or may live in areas that make it difficult to exercise or purchase healthy food.

More broadly, while guidelines outline effective strategies for stroke prevention, these recommendations are not consistently implemented across healthcare systems.

Hypertension Treated Too Late

About 80% of strokes are first events and can be prevented, Larry B. Goldstein, MD, chair of the Department of Neurology and co-director of the Kentucky Neuroscience Institute at the University of Kentucky, Lexington, Kentucky, told Medscape Medical News.

One of the major issues associated with stroke prevention is undiagnosed hypertension. The latest data from the National Health and Nutrition Examination Survey show 47.7% of US adults had hypertension. This survey, conducted between August 2021 and August 2023, showed 50.8% of men and 44.6% of women reported hypertension and showed that its prevalence increases with age.

“Hypertension is termed the ‘silent killer’ because it doesn’t cause symptoms until there is other damage such as stroke, heart disease, kidney disease, or vision loss, among other harmful consequences,” Goldstein said.

People may not know they have hypertension unless they have their BP checked. The American Heart Association (AHA) recommends individuals with a history of high BP monitor their BP at home.

The problem with hypertension is threefold, Ovbiagele said. First, people are often unaware they have hypertension because of lack of access to care that would diagnose it, do not know hypertension is linked to serious medical conditions such as stroke, or are generally unaware of what a stroke is.

Clinicians may also be susceptible to “therapeutic inertia” — a scenario in which necessary treatment or treatment escalation is not initiated, often due to patient-related factors or the clinician’s own concerns, such as uncertainty about the diagnosis or discomfort with the treatment approach. “In clinical practice, treatment is often initiated too late and too conservatively to prevent the complications of hypertension, including stroke,” Ovbiagele noted.

To combat this, clinicians should follow “timely and sustained evidence-based/guideline-endorsed treatment of hypertension,” Ovbiagele said. Both the 2017 American College of Cardiology (ACC)/AHA guidelines on hypertension and the 2023 European Society of Hypertension guidelines focus on management of BP, lifestyle factors, and pharmacotherapy for the diagnosis and management of hypertension.

Another issue concerns treatment adherence. “After being prescribed, therapies, especially pharmacological treatments, may not be taking regularly, continuously or at all. The reasons for lack of full adherence include concerns about side effects and pill-taking fatigue,” Ovbiagele added.

Experts who spoke with Medscape Medical News agreed that treatment plans should be individualized. When patients are seen by providers and diagnosed with hypertension, timely treatment is critical to stroke risk reduction.

AF and Direct Oral Anticoagulants (DOACs)

With the advent of DOACs, clinicians now have access to a treatment that is often preferred over other options like vitamin K antagonists for stroke prevention in the presence of AF. However, DOACs are often underused by patients, with one long-term study showing a 70% adherence rate after 5 years.

A growing body of evidence also shows stroke risk among patients with AF may be lower than previously believed, and that not all cases of AF warrant anticoagulation. Recent research from LOOP, NOAH-AFNET 6, and ARTESIA trials, which looked at detection of AF with implantable devices in patients taking DOACs or another anticoagulant, all showed a lower risk for stroke in the placebo arm.

Guidelines for DOAC prescribing provide detailed descriptions outlining the appropriate use of these treatments, yet clinicians can encounter challenges associated with prescribing, such as selecting the right treatment, treatment duration, and the consideration of drug interactions and comorbidities. Due to these challenges, research shows DOAC prescribing is sometimes at odds with guideline recommendations.

There is also the potential for underprescribing of DOACs, which can increase the risk for thromboembolic events, and overprescribing of DOACs, which might increase the risk for both thromboembolic events and bleeding. Taken together, these issues raise concerns about potential treatment gaps for AF.

“It is not inconceivable that there is both an overprescription of anticoagulation in some lower-risk patients and an undertreatment of anticoagulation in some high-risk patients,” Ovbiagele said. “However, my sense is that the latter is much more of an issue, and that treatment gaps are still significant.”

DOACs have been underused in patients with AF, and the availability of DOACs that “generally do not require blood monitoring and may have a bleeding risk similar to aspirin has provided a much-needed alternative to warfarin, the prior usual approach,” Goldstein said.

The 2019 joint AHA/ACC/Heart Rhythm Foundation focused update of 2014 guidelines for the treatment of AF recommend DOACs over warfarin for stroke prevention because of their superiority in prevention and bleeding risk. Although many clinicians continue to use warfarin to treat AF, the tide appears to be turning, with more recent graduates favoring DOACs over warfarin.

To improve adherence to DOACs, clinicians should be educated on the benefits of DOACs compared to warfarin. “[T]he safety profiles of the novel anticoagulants are much better than warfarin, and some have been shown to be superior to warfarin,” Ovbiagele said.

On the patient side, better follow-up is needed, with one study of Veterans Health Administration sites treating patients with nonvalvular AF showing sites that engaged in appropriate patient selection, pharmacist-led education, and pharmacist-led monitoring had better adherence to DOACs than those that did not engage in these practices.

Addressing other reasons for nonadherence, such as cost, bleeding risk, and patient forgetfulness, may require intervention on an individual level.

Lipid-Lowering Therapies, Diabetes Management

Similarly, greater use of lipid-lowering therapies such as statins for appropriately selected patients would also reduce the risk for stroke, experts told Medscape Medical News. Use of statins at a low or moderate dose can reduce the 10-year risk for myocardial infarction or ischemic stroke by at least 10%.

While statins are effective at preventing primary stroke, long-term adherence is a problem, with one study estimating statin therapy adherence ranges between 34.9% and 63.8%, and evidence shows patients with type 2 diabetes are less likely to adhere to statin therapy than other patient subgroups.

Patients may be reluctant to take statins because they have heard from friends, family, or the media about side effects. “The biggest problem with getting patients to try statins are their reputation for muscle aches,” Cheryl D. Bushnell, MD, chair of the American Stroke Association’s primary stroke prevention writing group, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, told Medscape Medical News.

“My personal experience is that patient perception and fear of side effects are the primary reasons for nonadherence,” she said.

Although statins have a reputation for side effects, “these are generally not supported by a review of the available data,” Goldstein said. He cited a study by his own group that showed statin use does not appear to increase the risk for cognitive impairment, dementia, or hemorrhagic stroke.

For patients who do not have an optimal response when receiving statin therapy, using a combination lipid-lowering therapy with a statin and another non-statin treatment such as a PCSK9 inhibitor may present a possible therapeutic option. “For patients with resistant hypercholesterolemia, combination therapy and injectable therapies, such as PCSK9 inhibitors, are very effective at lowering LDL [low-density lipoprotein] cholesterol,” Bushnell said.

A recent retrospective review analyzing the effect of combination lipid-lowering therapy in patients with a history of atherosclerotic cardiovascular disease and hypercholesterolemia found treatment with a moderate- or high-intensity statin with ezetimibe resulted in a greater reduction of LDL cholesterol than stain therapy alone.

While the same issues associated with patient and clinician education and adherence exist for lipid-lowering therapies as they do for antihypertensive agents, the use of combination treatments “could improve compliance and minimize side effects, thereby enhancing long-term adherence,” Ovbiagele said.

Another major risk factor for stroke is the prevalence of type 2 diabetes. Patients with type 2 diabetes have a 20% higher risk for ischemic stroke than individuals without type 2 diabetes. While there is mixed evidence that improving glycemic control improves a patient’s stroke risk, recent evidence has also shown that GLP-1 receptor agonists and SGLT2 inhibitors hold promise as a treatment to reduce the risk for stroke in patients with type 2 diabetes.

Experts told Medscape Medical News that many of the same approaches to use of antihypertensive agents and lipid-lowering therapies also apply to diabetes management. For patients with diabetes, “stroke risk is reduced with adequate blood pressure control and with the use of statins,” Goldstein said.

Lifestyle Modification Remains Important

In addition to preventive treatments, lifestyle modification remains a critical part of primary prevention.

About 80% of strokes could be prevented through adequate BP control, smoking cessation, lowering waist-to-hip ratio, physical activity, and a healthy diet, Bushnell said.

The most important dietary change patients can make on a population level is reducing salt intake, Goldstein said, which can be accomplished by reading food labels and choosing low-sodium products or salt substitutes.

Patients can also avoid tobacco products, environmental tobacco smoke, and alcohol consumption to lower the risk for stroke. However, he noted that busy lifestyles and lack of time and commitment can affect engagement on these fronts.

“What works for one person may not work for another,” he said. Social or economic factors, such as living in a food desert or in an area without sidewalks and parks, can also be barriers to lifestyle change, he added.

“Healthcare systems can’t directly address some of these barriers, but counseling and providing a consistent message can be important,” Goldstein said.

Barriers to Implementation

The factors that influence a patient’s risk for stroke — including stroke risk factors, BP control, medication adherence, management of underlying conditions, and lifestyle interventions — point to the need for a broader, multidisciplinary approach to prevention. However, multiple systemic barriers make implementing such an approach challenging.

For instance, control of hypertension remains suboptimal even though it is a quality measure for hospitals, said Bushnell. Earlier screening could help identify undetected cases of hypertension.

“In the guideline, we recommend screening at age 18, since some individuals may have elevated BP at that age,” she said. For patients with hypertensive disorders during pregnancy, BP should be monitored after delivery and over the next several years, she added.

However, she noted that social determinants of health, including low health literacy, are major barriers.

On the provider side, having access to real-world patient BP data may help diagnose hypertension earlier. Remote BP management can be performed through uploading BP measurements into an electronic health record but may run afoul of security and privacy issues, Bushnell noted.

“If the only data the provider uses to make decisions is the clinic BP, then this is often an inaccurate assessment of where the patient’s true BPs are on a day-to-day basis,” she said. “There can also be clinical inertia to not manage BPs if providers do not keep up with the latest guidelines, and unfortunately, not all guidelines recommend the same target.”

Therapeutic life counseling is another potential solution that could potentially address the need to improve lifestyle factors. Although patient motivation and education are a factor, clinicians are also often not educated on nutrition in medical school. “Health systems could definitely do more with lifestyle change initiatives,” Bushnell said.

The incorporation of evidence-based and guideline-endorsed therapeutic lifestyle counseling would best be implemented in multidisciplinary dedicated care pathways during a window of opportunity, such as an in-person visit, telehealth visit, or phone call, Ovbiagele said.

This encounter would ideally include a discussion of stroke risk factors with the clinician determining whether the patient has the ability to incorporate the lifestyle recommendations emphasized by the clinician.

“Many patients don’t live in safe environments for them to go on walks, or have access to gyms, or the means to buy healthy food on a consistent basis,” he said. “In such situations, practical recommendations and referral to a social worker might be of help for those patients with socioeconomic barriers to complying with recommendations.”

Options for lifestyle coaching include the use of third-party vendors, but trained pharmacists, community health workers, and social workers may be able to help as well.

“Multidisciplinary approaches to prevention after stroke are obviously needed, but the healthcare systems and billing challenges often limit the feasibility of getting these clinics started and sustaining them.” Bushnell said. “Health coaches are also not commonly paid through typical billing approaches currently, either.”

“Much more needs to be done in this arena,” Bushnell said.

Bushnell, Goldstein, and Ovbiagele reported having no relevant financial relationships.