Making Sense of It All

Illustration accompanying article about stroke prevention. Image includes title of the article: "Making Sense of It All, Essentials of secondary stroke prevention for primary care providers"

Essentials of secondary stroke prevention for primary care providers

by Shawn Oberrath

Subject Matter Expert: Dr. Chirantan Banerjee

On completion of this article, readers should be able to:

  • Summarize the most recent guidelines for acute ischemic stroke management
  • Tailor patient care management after stroke based on the state of the art of secondary stroke prevention.

The incidence of stroke in the United States is around 795,000 cases per year, or about the same as the heart attack incidence (790,000 cases per year). Stroke is the fifth leading cause of death and the leading preventable cause of serious long-term disability in the United States. Acute stroke care improved dramatically with advances in tissue plasminogen activator (tPA) treatment and, more recently, mechanical thrombectomy. Unfortunately, stroke recurrence is still a major source of morbidity and mortality—about 25% of all strokes are recurrences. For patients with a history of stroke, the overall risk of another is 6% at 1 year, 16% at 5 years and 25% at 10 years.1,2

Stroke can be caused by ischemia (80% of strokes), intracerebral hemorrhage (15%) or subarachnoid hemorrhage (5%). This article focuses solely on ischemic events, which can be either transient ischemic attacks (TIAs) or ischemic strokes. TIA was traditionally defined in terms of duration, but the contemporary definition of TIA is a “transient episode of neurologic dysfunction caused by focal brain, spinal cord or retinal ischemia without acute infarction.” This definition is based on tissue status, not time, but generally a TIA lasts for less than an hour. In contrast, ischemic stroke is defined as an episode that includes infarction and usually lasts for more than an hour.3,4

In early 2018, the American Heart Association and the American Stroke Association (AHA/ASA) jointly published the 2018 Guidelines for Early Management of Patients with Acute Ischemic Stroke.5 New blood cholesterol management guidelines were released in late 2018, and even more recently, the 2019 guidelines on primary prevention of cardiovascular disease made their debut.6,7 Each of these publications is comprehensive and replete with data, graphs and charts, potentially leaving providers overloaded with information. In addition, there have been numerous advances in secondary stroke prevention since the most recent official guidelines, published in 2014.

This CME article curates the state of the art of secondary stroke prevention for primary care providers, beginning with a broad overview of acute care and then focusing on modifiable risk factor management for stroke prevention after TIA or ischemic stroke.

Don’t delay, use tPA

Although acute ischemic stroke (AIS) management almost always occurs in the hospital, primary care providers should be familiar with modern best practices. According to the 2018 guidelines for AIS management, the goal door-to-needle time for IV alteplase (a recombinant form of tPA) is 45 minutes. Prior to alteplase administration, all patients suspected of AIS should receive brain imaging evaluation, which should occur without hesitation and without waiting for creatinine levels if there is no history of renal disease. Usually a noncontrast CT scan is the only imaging requirement, and the only result that excludes alteplase treatment is intracerebral hemorrhage. The only lab required prior to alteplase treatment is the blood glucose level to exclude stroke mimicry by hyper- or hypoglycemia.5

IV alteplase should be administered to almost all patients with AIS whose onset was less than three hours previous and to eligible patients whose stroke onset was three to four and a half hours previous. This includes patients with sickle cell disease, those already on antiplatelet therapy, and those with end-stage renal disease. IV alteplase administration with telestroke guidance is as safe and beneficial as that at stroke centers.5

Mechanical thrombectomy with a stent retriever should be initiated within six hours of symptom onset for patients meeting all eligibility criteria. For carefully selected patients, mechanical thrombectomy can be initiated within 24 hours of stroke onset.5

All primary care providers should bear in mind that in cases of stroke, time is equivalent to brain tissue; therefore, it is imperative to act quickly, call 911 and utilize stroke center and telestroke resources.

Mitigate risk

Because of the advanced state of modern acute stroke care, stroke patients should be undergoing appropriate pharmaceutical therapy at the time of discharge from the hospital. The challenge is to ensure ongoing medication compliance and management of major modifiable risk factors to lower the risk of recurrence. The following sections highlight the most recent advice regarding these factors.

Pocket Guide to Secondary Stroke Prevention


Arguably the most important measure to address is hypertension. Aim for a blood pressure of less than 130/80 mm Hg. Treatment may include any evidence-based pharmacologic intervention and/or lifestyle modifications, such as weight loss, dietary changes, reducing alcohol consumption and finding ways to move the body regularly.7


The 2018 ACC/AHA Multisociety Guideline on the Management of Blood Cholesterol recommends the following for patients with hyperlipidemia. Initiate or maintain high-intensity statin therapy to manage lipid levels, adding ezetimibe or a PCSK9 inhibitor (PCSK9-I) if needed. Begin by aiming for a 50% or more reduction in LDL-C levels by use of a statin; if the level is still more than 70 mg/dl at the maximally tolerated statin level, it may be time to add ezetimibe. For patients with very high risk and multiple high-risk clinical factors, it may be reasonable to add ezetimibe to statin therapy, and then if the LDL-C level is still greater than 70 mg/dl, consider adding a PCSK9-I.6

Prediabetes/diabetes mellitus

Diseases of glucose metabolism leave stroke survivors at an almost doubled risk of recurrent stroke. Approximately one third of stroke patients have diabetes, and prediabetes rates in patients with recent stroke or TIA range from 23 to 53%. Clinical outcomes for such patients are poorer after either ischemic or hemorrhagic stroke, with higher mortality rates, poorer functional outcomes and longer hospital stays. Thus, all stroke survivors should be screened for diabetes, and those with prediabetes or diabetes should be treated according to standard practice. In addition, pioglitazone added to standard treatment is associated with a 32% reduction in risk of recurrent stroke and a 25% reduction in risk of major cardiovascular events.8–10 Consider adding pioglitazone therapy for supplemental management of stroke patients with prediabetes or diabetes.

Antithrombotic agents

Aspirin is the most well-studied and well-known antithrombotic agent, and it remains an important part of secondary prevention of ischemic stroke because it is very effective and is the most budget-friendly choice. Clopidogrel is also effective and may be used in patients who are allergic to aspirin. The combination of aspirin and clopidogrel for short-term use may prevent recurrent stroke, especially for patients with symptomatic severe intracranial stenosis, but the combination is not appropriate for long-term use because of increased bleeding risk. Finally, aspirin in combination with dipyridamole may provide an even larger risk reduction for stroke, but this combination is expensive and may not be well tolerated, and it should not be used for long-term secondary prevention.11,12

Atrial fibrillation (AFib) is a highly important risk factor for ischemic stroke, as it is associated with a five times greater risk of stroke. For patients with AFib, coronary artery disease, acute coronary syndrome or stent placement, addition of anticoagulant therapy is warranted. According to the most recent update to the guidelines for AFib, non-vitamin K oral anticoagulants (NOACs) are now recommended as the preferred alternative to warfarin. The exceptions to this recommendation are patients with moderate to severe mitral stenosis or a mechanical heart valve. Note that an advantage of some NOACs is that their action may be reversed if needed.13

Lifestyle factors

Work with patients and their families to encourage lifestyle improvements. Patients who are capable of exercise should do so regularly, nutritional guidance should be provided, and heavy drinkers should be counseled to reduce or avoid alcohol consumption. A sleep study and treatment with CPAP should be considered for patients with any symptoms of sleep apnea. It is very important that smokers or those exposed to secondhand smoke find ways to stop smoking or eliminate their exposure: smokers are two to four times likelier to have stroke than their nonsmoking counterparts.1

Patient compliance

One of the difficult realities for primary care providers is that often patients are placed on an optimized medication regimen in hospital but fail to comply with treatment at home. More than one third of patients stop their medications within two years after stroke. In a recent survey of factors that influence adherence to secondary stroke prevention medications, the major barriers were side effects, negative perceptions about medications, physical difficulty with swallowing pills, and drug costs. On the flip side, there were numerous facilitators of patient adherence: adequate side effect management, a belief that medications are important, use of medication storage devices and routines to help with habit formation, and assistance from caregivers.14 Consider focusing efforts on some or all of these facilitators, as well as encouraging patients and caregivers to use mobile health applications with calendars and reminders. See the American Stroke Association website ( for further excellent resources to guide and encourage patients.


To wrap up, hypertension management, antithrombotic medication and smoking cessation are top priorities for secondary prevention of stroke. It is also imperative to remain current on modern standards for acute stroke care, lipid and glucose management and antithrombotic therapies. Provide the best advice possible to patients, and don’t be shy about using known facilitators of patient behavior to assist them.


1. Benjamin EJ. Circulation. Mar 2018. doi:10.1161/CIR.0000000000000558.
2. CDC. MMWR Morb Mortal Wkly Rep. 2009;58:421–426.
3. Bleck TP. Primary care of the stroke patient. Lecture: Pri-Med Midwest. Oct 2015.
4. Easton JD, et al. Stroke. 2009;40(6). doi:10.1161/STROKEAHA.108.192218.
5. Powers WJ, et al. Stroke. 2018;49:e46–e99. doi:10.1161/STR.0000000000000158.
6. Grundy SM, et al. JAMA Cardiology. 10 Nov 2018. doi:10.1001/jamacardio.2019.0911.
7. Arnett DK, et al. Circulation. 17 Mar 2019. doi:10.1161/CIR.0000000000000678.
8. Fonville S, et al. Cerebrovasc Dis. 2014;37(6):393-400. doi:10.1159/000360810.
9. Lau LH, et al. J Diabetes Investig. 2018;10(3):780-792. doi:10.1111/jdi.12932.
10. Lee M, et al. Stroke. 2017;48(2):388-393. doi:10.1161/strokeaha.116.013977.
11. Johnston SC, et al. NEJM. 2018;379(3):215-225. doi:10.1056/nejmoa1800410.
12. Kernan WN. Stroke. July 2014. doi:10.1161/STR.0000000000000024.
13. January CT, et al. J Am Coll Cardiol. Jan 2019. doi:10.1016/j.jacc.2019.01.011.
14. Jamison J, et al. BMJ Open. 2017;7:e016814. doi:10.1136/bmjopen-2017-016814.