Comprehensive Strategies for Secondary Stroke Prevention

Primary care physicians play a pivotal role in preventing recurrent stroke. In this expert-led discussion on his Practical Updates in Primary Care Presentation, "Optimizing Outcomes: Key Updates in AHA Stroke Guidelines", Deepak L. Bhatt, MD, MPH outlines actionable strategies—ranging from dietary and lifestyle counseling to evidence-based pharmacotherapy—that clinicians can implement to reduce cardiovascular risk in patients with prior stroke or TIA. 

Additional Resources: 

• Aggarwal R, Bhatt DL, Szarek M, et al. Effect of sotagliflozin on major adverse cardiovascular events: a prespecified secondary analysis of the SCORED randomised trial. Lancet Diabetes Endocrinol. 2025;13(4):321-332. doi:10.1016/S2213-8587(24)00362-0
• Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22. doi:10.1056/NEJMoa1812792

Consultant360: You are presenting at our PUPC—Practical Updates in Primary Care—virtual meeting this year. Can you talk about the key themes of your presentation?

Deepak L. Bhatt, MD, MPH: Absolutely. I was discussing various ways of preventing stroke. One could say secondary stroke prevention, that is, in patients that already had ischemic stroke or transient ischemic attack (TIA), though the advice would actually also work for primary prevention of stroke or cardiovascular diseases in general. I reviewed the role of diet in terms of trying to reduce the risk of a recurrent ischemic stroke. I talked about diets such as a Mediterranean-type diet or a DASH diet. These are both evidence-based diets that have been associated with lower rates of cardiovascular events. I also talked about a plant-based diet, which I personally think should be the bedrock of any sort of heart-healthy diet—probably also beneficial in terms of reducing cancer and diabetes risk. And by plant-based diet, I really mean a diet that's high in fresh fruit and vegetables, high in whole grain intake, relatively low or absent in things like red meat.

I talked a bit about salt restriction and trying to reduce sodium intake to maybe no more than, say, two or two and a half grams per day. That's not always easy to do, especially if someone's eating out a lot or eating a lot of processed food—there's a lot of hidden salt—but salt is a determinant of high blood pressure. Especially some patients tend to be very salt-sensitive. In addition to speaking about diets in general, I also spoke about salt or sodium restriction, restricting the amount to two and a half grams per day of salt or less. In some patients there's a great sensitivity to salt leading to high blood pressure, and of course, high blood pressure is a potent risk factor for stroke or recurrent stroke, so trying to prevent excess salt consumption is important as well.

Beyond dietary counseling, I also spoke about recommendations for physical activity. Diet and exercise often go hand in hand, and in terms of counseling, it makes sense to mention these things together. In terms of exactly how much physical activity is good, that has long been a controversial area, of course. But in general, the recommendation that I made in my talk was aiming for at least moderate-intensity aerobic activity for a minimum of 10 minutes, four times a week, or vigorous-intensity aerobic activity for a minimum of 20 minutes twice a week. That's actually verbatim out of the stroke guidelines. But as a general principle—going beyond the exact verbiage in guidelines—I tell patients to shoot for about 30 minutes at least of moderate-intensity activity most days of the week. If they want to take a day off, that's okay. But in general, that level of activity. That's not always achievable, and the lower numbers I mentioned are what the guidelines state. In fact, recent data suggests something is better than nothing. So even a few minutes every day of vigorous physical activity—or even moderate-intensity physical activity—seems to be associated with lower rates of cardiovascular events.

I also talked about smoking cessation. That's something that hopefully is pretty obvious, but still there's lots of patients—in particular those that come in with stroke or TIA—that are still active smokers. So of course counsel them on trying to stop smoking, and if needed, various aids that can help with smoking cessation as well.

Important to point out that alcohol actually doesn't have cardiovascular benefits, and to restrict alcohol intake. What the guidelines say is that patients with ischemic stroke or TIA who drink greater than two alcoholic drinks a day for men, or greater than one for women, should be counseled to eliminate or reduce their consumption of alcohol to reduce stroke risk. And I generally speaking agree with that, though again, I emphasize to patients that that old teaching that alcohol is cardioprotective is basically wrong—it's all confounded analyses. The most recent data actually suggest that even a drink a day raises the risk of atrial fibrillation, which of course is a risk factor for stroke.

Beyond alcohol, also patients with stroke or TIA should be counseled not to use substances of abuse. By that I mean things like amphetamines or cocaine, or things like that that raise the risk of stroke and are of course also generally bad for health. So it is important to counsel patients about substance abuse. Don't just assume that the patient in front of you isn't using one of those substances—better to ask and proactively counsel not to use those substances.

Then I also talked about other things, like recommendations for treating high blood pressure. The most recent data as well suggest that lower is better with respect to blood pressure, assuming that there is no side effect that's occurring. The guidelines, specifically in terms of numbers, say that in patients with hypertension who experience stroke or TIA, an office goal of less than 130 over 80 mm Hg is what's recommended for most patients to try to reduce the risk of recurrent stroke and just cardiovascular events in general. And I think that's good advice. I think it's not an unreasonable thing to push that to 120 over 80—the most recent data actually do support that 120 over 80, if it's not inducing side effects, might be a better target for people in general to try to reduce cardiovascular events.

I also discussed hyperlipidemia—the importance of treating LDL cholesterol. And in general, what the guidelines say is that in patients with an ischemic stroke, that if the LDL cholesterol is greater than 100, atorvastatin 80 mg/day is indicated to reduce stroke recurrence. And also, if patients with ischemic stroke or TIA and atherosclerotic disease, their lipid-lowering therapy with a statin, possibly also with ezetimibe if it's necessary to a goal LDL of less than 70 mg/dL, is recommended to reduce cardiovascular events in general. Other guidelines and consensus statements in other parts of the world and by other societies do suggest perhaps even more aggressive LDL control. It's pretty clear that lower is better in general in terms of reducing the risk of recurrent atherosclerotic events.

That’s what the guidelines say. As far as hypertriglyceridemia, that is also an independent risk factor for cardiovascular events, and the guidelines state that in patients with ischemic stroke or TIA with fasting triglycerides between 135 and 499 and well-controlled LDL, the use of icosapent ethyl, 2 g twice a day, is a reasonable thing to reduce the risk of recurrent stroke. That’s based on the REDUCE-IT trial. And I think, having helped lead that trial, that’s good advice. A lot of times doctors forget about the triglycerides, but especially in patients that are statin-treated, on a good diet, if the triglycerides are high, that’s a very potent marker of future cardiovascular risk.

Consultant360: There is plenty of new data on glucose lowering medications. Did this come up in your presentation?

Dr Bhatt: I also discussed briefly glucose management. There’s a lot of new data about new glucose-lowering drugs. The GLP-1 agonists in particular seem—at least some of them—to be associated with significant reductions in ischemic events, including stroke. So something to consider in terms of the new diabetes drugs and making sure patients can benefit from them.

So I discussed that a little bit. The guidelines also talk about recommendations for obesity and ideal body mass index. And once again there are novel drugs—or maybe they're not so novel anymore—with respect to weight loss. In particular, drugs like semaglutide and tirzepatide that also appear to have cardiac benefits and likely also are beneficial in patients with a history of ischemic stroke or TIA.

Now some of that goes beyond what the guidelines per se discuss. I also briefly touched upon antithrombotic therapy. That’s really a talk in its own right, but important in the patient with a history of stroke or TIA to ensure that they're on appropriate antithrombotic therapy. For many patients, that’s going to end up being something like clopidogrel or aspirin. But again, that’s a topic in itself.

And then finally, I just went through a checklist of different things to think about in terms of reducing future stroke risk, namely, thinking about risk factors like high blood pressure, high glucose, high cholesterol, high triglycerides, also thinking about tobacco and alcohol intake, also thinking about diet and exercise.

Consultant360: Earlier you mentioned how the literature might not always agree. And there is plenty of new research on GLP-1s and SGLT2 inhibitors. I assume that is why this presentation topic is so relevant right now, correct?

Dr. Bhatt: There's a lot of new data with respect to reducing the risk of atherosclerotic ischemic complications. Not all of that data is derived specifically from patients with ischemic stroke or TIA only. These are populations that sometimes are broader than that. But I think a lot of the lessons can be applied to patients with ischemic stroke or TIA.

And these advances include our understanding that lower is better for LDL cholesterol. Lower is better for blood pressure as well, assuming that’s not causing side effects. And probably the ideal new target is less than 120 over 80—again, that’s assuming that that’s not inducing side effects.

As well, in terms of glucose control, it’s more than just controlling the glucose. It turns out that certain medicines really do have cardiovascular benefits. The SGLT2 inhibitors, for example, in people with diabetes reduce the risk of things like heart failure. But even in people without diabetes, if they have heart failure—heart failure with reduced or preserved ejection fraction—or if they have certain forms of chronic kidney disease, they seem to benefit from being on an SGLT2 inhibitor.

With respect to reducing stroke, really only one SGLT2 inhibitor—sotagliflozin—has specifically shown a reduction in stroke. Actually, we just published that recently in Lancet Diabetes & Endocrinology. But as a class, the SGLT2 inhibitors are reducing heart failure and kidney endpoints, so in the right patients those can be useful, including those with a history of prior stroke or TIA as well. The GLP-1 agonists—at least some of them—have been clearly linked with reducing ischemic events, including specifically stroke and ischemic stroke. So that’s something to consider in patients with diabetes in particular, and potentially in patients that are really overweight.

So all these different advances in medical therapy are ones that can benefit patients that have a history of ischemic stroke or TIA, or even just patients that are at high risk for those or other cardiovascular events.

Consultant360: Can you briefly touch on the most important takeaways from your presentation for clinicians in practice?

Dr. Bhatt: So I think the real key takeaways are to screen all patients with stroke or TIA and make sure they’re on the correct secondary stroke prevention therapies. I’ll start first with diet and exercise—so important to make sure patients are on the right diet. And I’d say one that’s largely plant-based, where the bedrock is lots of fresh fruits and vegetables and whole grains, and then you can fill in the rest of the diet with other things, but preferably lower or absent in red meat.

That is, in general, the best diet to reduce ischemic events. But also, it turns out it reduces cancer risk and also diabetes risk. So diet is important, and controlling the number of calories is also important—not just what goes in, but the amount that goes in—and that should be coupled with regular physical activity. At least a few minutes every day would be recommended. So at least moderate-intensity aerobic activity. I personally think some degree of weight training is also a good idea so patients maintain muscle mass and balance and so forth as they get older.

Now, the diet and exercise and the weight control—that’s all good. But that’s not instead of medical therapy. If somebody’s already had an ischemic event, well, in some respects the horse is out of the barn, so it’s important to be aggressive about medical therapy. And that means polypharmacy.

Blood pressure should be treated aggressively. The current secondary stroke guidelines say an office blood pressure goal of less than 130 over 80 is recommended for most patients, and I would agree with that myself. I typically shoot for less than 120 over 80 if it can be achieved safely without side effects.

In those who have diabetes, the recommendation is achieving a hemoglobin A1c in most patients of less than or equal to 7%. Although I think it also matters how you get there. That is, a lot of the older diabetes drugs, while cheap and familiar, don’t have as much data in terms of reducing cardiovascular events as more modern drugs like some of the GLP-1 agonists, and dual incretins, and SGLT2 inhibitors.

Cholesterol should be treated aggressively. In most cases, I would say with high-intensity statins if the patient can tolerate it. And if that doesn’t get them to LDL goals, then adding ezetimibe. And an LDL goal of at least less than 70 is what should be strived for. One could argue for even lower in terms of reducing ischemic events in general. But I guess if one is looking only from an ischemic stroke, TIA, and data-driven perspective, at least less than 70. But in high-risk patients these days, I typically shoot for less than 50, if I can get the patient there safely without inducing side effects.

In addition to that, important to talk about smoking cessation. If the patient smokes—same with substance abuse—and stopping use of things like cocaine and amphetamines. As well, alcohol—a lot of misinformation about how alcohol is cardioprotective. It is not. So important to encourage patients who don’t drink not to start, but ones that do drink for pleasure, to try to get them to limit to no more than two drinks a day for men and up to one drink a day for non-pregnant women. Though even that, it’s important to counsel, is associated with an increase in cardiovascular risk—in particular, risk of atrial fibrillation. Even a drink a day. So a lot of that advice in terms of “two for men, one for women”—not really great advice. But if people enjoy drinking, they really shouldn’t exceed those limits. As well as the cardiac risk, of course, alcohol raises the risk of cancer.

Important to screen for atrial fibrillation also, which increases the risk of ischemic stroke. And in patients that do have atrial fibrillation, if there’s no contraindication, they should, of course, receive an oral anticoagulant.

If atrial fibrillation isn’t present and anticoagulation isn’t necessary, then the patient with the history of ischemic stroke or TIA should be on antiplatelet therapy. Agents like clopidogrel or aspirin are reasonable choices. Dual antiplatelet therapy may also have a role. But that’s typically short-term use in very specific subgroups of patients. It’s a decision neurologists would have usually made, less so primary care physicians in terms of that initial management of antithrombotic therapy.

Screening for sleep apnea is another thing that’s important in patients that have stroke. A pretty high percentage—some studies will say even 30 to 40%—can have sleep apnea. So important to screen for that. And then, if it seems like it might be present, testing for it and treating it as well. Not all the patients like putting on a CPAP mask, but that technology has gotten better or smaller. So worth screening patients for sleep apnea.

Those are some of the things that I think are important in terms of takeaways from my lecture.

Consultant360: Perfect. And finally, are there any gaps in our knowledge that remain? Is there any research on the horizon that you are looking forward to reading?

Dr. Bhatt: There’s a lot of research going on in cardiovascular disease, and a good chunk of it will be relevant to patients with a history of ischemic stroke or TIA. Multiple trials are testing whether even lower LDL cholesterol than current targets might provide incremental benefit. This is being tested in the secondary prevention population, also the primary prevention population. In the secondary prevention trials, there are subgroups of patients with prior ischemic stroke or prior TIA. So we’ll have a wealth of information in the next few to several years in both secondary and primary prevention about whether very low LDL cholesterol—I mean with PCSK9 inhibitors—can further reduce the risk of ischemic events.

We already know from some trials that there is a role of the monoclonal antibody PCSK9 inhibitors in reducing ischemic stroke risk. But agents such as siRNAs —I mean, there are a number of trials going on to see if even lower is better, going beyond just things like high-intensity statins. So that’s really interesting to see if even lower LDL than what we’re striving for now reduces stroke risk.

Other avenues of investigation include studying Lp(a)-lowering strategies to see if that class of drugs—that’s being evaluated right now in clinical trials—reduces the risk of ischemic events. That includes stroke, but also things like myocardial infarction. So that’s an interesting line of investigation.

There are also trials that are studying anti-inflammatory agents in cardiovascular disease. So we’ll find out—even though the main aim isn’t just looking at stroke—we’ll find out what the impact is on stroke.

So really, multiple lines of investigation. Novel antithrombotics as well, to see if we can further reduce the risk of recurrent stroke. So I would say it’s an exciting time in the world of stroke and TIA research. That’s just some of what is going on. There are also various devices that are being studied—left atrial appendage occlusion—which is already FDA approved with some devices. But there are other trials going on just to see what the value is in combination, for example, with the novel oral anticoagulants, or direct-acting oral anticoagulants, as they’re sometimes called.

So hopefully we’ll have an even better sense in the future what the optimal antithrombotic/device-based strategies might be for various types of patients, such as those with atrial fibrillation. So a very, very exciting time in stroke in the next few years.

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