20 Years of Progress in Secondary Stroke Prevention

Hans-Christoph Diener, MD, PhD


November 25, 2015

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Dear colleagues, I'm Hans-Christoph Diener, a stroke neurologist from the University of Essen Department of Neurology. My topic today is what has happened in the last 20 years in secondary stroke prevention. Why are we covering this now? Medscape is turning 20 years old, and we wanted to summarize what has been reported in the last 20 years.

Antithrombotic Therapy for Secondary Stroke Prevention

Let me start with antiplatelet therapy. There is no doubt that aspirin is effective in secondary stroke prevention, but the rate of risk reduction is quite small. Now, clopidogrel as monotherapy is not superior to aspirin in efficacy.[1] It has slightly lower risk for bleeding complications. The combination of aspirin and extended-release dipyridamole is superior to aspirin,[2] but in long-term treatment, the combination of aspirin plus clopidogrel is not superior to either aspirin monotherapy or clopidogrel monotherapy and carries a higher bleeding risk.[3,4] At the moment, we want to find out whether the combination of aspirin plus clopidogrel is superior to aspirin for short-term prevention of recurrent stroke (ie, in the first 4-12 weeks after a stroke).

A major breakthrough was the introduction of novel oral anticoagulants for secondary stroke prevention in patients with atrial fibrillation.[5] Overall, these drugs, compared with warfarin, will reduce the risk for recurrent stroke by about 15%, reduce mortality by 15%, reduce the risk for major bleeding events by 10% to 15%, and most importantly will reduce the risk for intracerebral hemorrhage by 55%.

Advances in Treating Symptomatic Carotid and Intracranial Stenosis

Another issue is symptomatic carotid stenosis. These patients benefit from carotid surgery or stenting. Taking all of the evidence together, it seems that surgery is likely superior to stenting, in particular in patients above the age of 75 years and in women. Unfortunately, we do not have recent trials that compare optimal medical treatment with interventional treatment. However, we now have clear evidence from two randomized trials that stenting of intracranial stenosis is not superior to best medical treatment.[6,7]

Controlling Risk Factors for a Second Stroke

In terms of risk-factor control, we have clear evidence that antihypertensive treatment, in particular with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, will reduce the risk for secondary stroke.[8,9] The blood pressure target at the moment is a systolic blood pressure below 140/90 mm Hg, and for patients with diabetes it is below 130/90 mm Hg. We also have evidence that atorvastatin reduces the risk for stroke, irrespective of whether cholesterol is high or not, without increased risk for cerebral bleeding.[10]

With diabetes, we have only negative trials in secondary stroke prevention; this is true for the new antidiabetic drugs and for more aggressive and less aggressive glucose control.[11,12] It seems that even aggressive antidiabetic treatment will increase the risk for vascular events and not decrease it. In addition, if the diabetes is treated too aggressively, this can lead to treatment-induced polyneuropathy.

We have evidence about other risk factors but almost no randomized trials looking at the effect of smoking cessation, reducing alcohol, weight reduction, increasing physical activity, and particular diets on secondary stroke prevention. Now we have more and more evidence, at least from smaller trials, that something that is called multimodal treatment (ie, optimal medical treatment), which includes addressing behavioral risk factors such as smoking and physical activity, and cognitive training will not only reduce the risk for stroke but will also reduce the risk for cognitive decline.

Concluding Thoughts

Ladies and gentlemen, we can do a lot to prevent strokes, but the most important issue is that we have to implement these prevention strategies, and we have to address adherence and compliance in our patients on drug therapy. Twenty years ago, the only thing we had for secondary stroke prevention was aspirin. Now, we have many more modalities to treat the different subgroups of stroke, whether it's large-vessel disease or cardioembolic stroke.

The last 20 years for stroke prevention have been very fruitful, but we have to go a long way from here. I'm Hans-Christoph Diener, a stroke neurologist from the University of Essen in Germany. Thank you for listening.


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