New recommendations on metabolic syndrome treatment and acknowledgement of a place for stenting in the management of symptomatic carotid stenosis are among the changes seen in updated secondary stroke prevention guidelines from the American Heart Association (AHA)/American Stroke Association (ASA).

The new guidelines were published online October 21 in Stroke. The document notes that the American Academy of Neurology “affirms the value” of the guideline as an educational tool for neurologists and that it has been reviewed and the content affirmed by the American Association of Neurological Surgeons and the Congress of Neurological Surgeons.

The aim of the statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack, the authors write.

This and other AHA stroke-related statements are updated on a regular basis, with these secondary stroke prevention guidelines last being updated in 2006, said Robert J. Adams, MD, professor of neuroscience at the Medical University of South Carolina, Charleston, and a member of the review committee.

“We make a continual effort to get the best recommendations we can looking at the evidence, and as you’ll see in some areas, we felt that we couldn’t really make a recommendation because we felt we didn’t have enough data,” Dr. Adams told Medscape Medical News. “Those are basically by default or de facto areas where we think more research is needed.”

This update is also among the first to flag new recommendations within the text of the document, said Dr. Adams. “We decided to point out to the reader what was new.”

New Metabolic Syndrome Recommendations

All 3 recommendations pertaining to metabolic syndrome are new. The syndrome is a confluence of several physiological abnormalities that increase the risk for vascular disease. According to AHA/ASA criteria, metabolic syndrome is recognized when 3 of the following features are present:

  • increased waist circumference (≥102 cm in men; ≥88 cm in women),
  • elevated triglyceride levels (≥150 mg/dL),
  • reduced high-density lipoprotein cholesterol (<40 mg/dL in women; <50 mg/dL in men),
  • elevated blood pressure (systolic ≥130 mm Hg, or diastolic ≥ 85 mm Hg), and
  • elevated fasting glucose (≥100 mg/dL).

To prevent a secondary stroke or transient ischemic attack in patients who have metabolic syndrome, physicians should treat the individual components of the syndrome that are also stroke risk factors, particularly dyslipidemia and hypertension, the new guidelines note.

Management of patients with metabolic syndrome should include counseling on diet, exercise, and weight loss to reduce vascular risks, but the utility of screening patients for metabolic syndrome after stroke has not been established.

There is considerable controversy surrounding this syndrome, largely because of uncertainty regarding its etiology and clinical usefulness, the authors write. The disorder has been related to an increased risk for diabetes, cardiovascular disease, and all-cause mortality.

The association between metabolic syndrome and risk for first ischemic stroke has been examined in several recent studies, with all except 1 confirming the association, but with only 1 study examining the association between metabolic syndrome and risk for stroke recurrence.

In the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial, participants with metabolic syndrome were more likely to have a stroke, myocardial infarction, or vascular death during 1.8 years of follow-up than participants without metabolic syndrome (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1 – 2.4; P = .0097). Patients with the syndrome were also at increased risk for ischemic stroke alone (HR, 1.7; 95% CI, 1.1 – 2.6; P = .012).

Cardiac features of metabolic syndrome improve with weight loss, which has also been shown to improve insulin sensitivity, lower plasma glucose, low plasma low-density lipoprotein cholesterol, lower plasma triglycerides, raise high-density lipoprotein cholesterol, lower blood pressure, reduce inflammation improve fibrinolysis, and improve endothelial function in patients with metabolic syndrome.

Carotid Artery Stenting

Also included in the revised guidelines is updated research pertaining to carotid artery stenting for extracranial symptomatic carotid disease, based on results of large clinical trials, including the Carotid Revascularization Endarterectomy vs Stent Trial (CREST), most recently reported.

Carotid endarterectomy is recommended for these symptomatic patients with high-grade stenosis (70% – 99%) if the perioperative morbidity and mortality risk is estimated at less than 6%, as well as for those with moderate stenosis (50% – 99%); neither stenting nor surgery is recommended for stenoses less than 50%.

However, the writing group notes that carotid artery stenting is indicated as an alternative to surgery for symptomatic patients at average or low risk for complications associated with endovascular intervention when the diameter of the lumen of the internal carotid artery is reduced by more than 70% by noninvasive imaging or more than 50% by catheter angiography.

“The recommendation is that for certain patients with symptomatic high-grade carotid stenosis and factors that make carotid endarterectomy not favorable, such as previous radiation therapy or previous surgery, or certain medical conditions which increase risk for surgery, that carotid artery stenting is a reasonable alternative,” commented Dr. Adams.

Stenting in that setting is “reasonable when performed by operators with established periprocedural morbidity and mortality rates of 4% to 6%,” the authors add — rates similar to those seen in stenting and surgery trials.

Finally, a new recommendation is that all of these patients receive optimal medical therapy, including antiplatelet therapy, statins, and a risk factor modification.

Atrial Fibrillation

New recommendations on the management of atrial fibrillation (AF) are based on data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) study and ACTIVE A, an arm of the study that compared aspirin with clopidogrel plus aspirin in patients with AF who were considered unsuitable for vitamin K antagonist therapy.

Patients were considered “unsuitable” for warfarin based on physician judgment or patient preference — criteria that were somewhat controversial when this study was first presented. Trial results showed less stroke but more bleeding with clopidogrel plus aspirin vs aspirin alone.

In the new guidelines, however, authors write that “on the basis of uncertainty of how to identify patients who are ‘unsuitable’ for anticoagulation, as well as the lack of benefit in the analysis of vascular events plus major hemorrhage, aspirin remains the treatment of choice for AF patients who have a clear contraindication to vitamin K antagonist therapy but are able to tolerate antiplatelet therapy.”

The combination of clopidogrel plus aspirin carries a bleeding risk similar to warfarin and so is not recommended for those with a hemorrhagic contraindication to warfarin, the authors note.

Another new recommendation is that for patients with AF who are at high risk for recurrent stroke, but who require temporary interruption of oral anticoagulation, bridging therapy with a low-molecular-weight heparin is reasonable, said Dr. Adams.

These new AF guidelines were written before regulatory approval earlier this week of the oral thrombin inhibitor dabigatran, based on encouraging results in the previously reported Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study.

[T]he availability of a highly effective oral agent without significant drug or food interactions that does not require coagulation monitoring would represent a major advance for this patient population.

“No recommendation will be provided for dabigatran in the current version of these guidelines because regulatory evaluation and approval has not yet occurred,” the authors note in the document. “However, the availability of a highly effective oral agent without significant drug or food interactions that does not require coagulation monitoring would represent a major advance for this patient population.”

They also discuss the WATCHMAN left atrial appendage occlusion device, studied in the Embolic Protection in Patients with Atrial Fibrillation (PROTECT-AF) trial as an alternative to oral anticoagulants. “This approach is likely to have the greatest clinical utility for AF patients at high stroke risk who are poor candidates for oral anticoagulation; however, more data are required in these populations before a recommendation can be made.”

Intracranial Atherosclerosis

There is also new research in the area of intracranial atherosclerosis. “There is some new information on the use of antiplatelet agents; it actually didn’t substantially change the guidelines, but it makes the choice somewhat easier, and provides additional information that we didn’t have before,” said Dr. Adams.

The new information was from the WASID trial, on which the recommendation for aspirin over warfarin is based. Aspirin doses of 50 to 325 mg/day are recommended, the authors write. Intracranial stenting is considered investigational at this time, and its utility is still unknown, they note.

As well, there is a new recommendation concerning maintenance of blood pressure, suggesting that for patients with stroke or transient ischemic attack caused by 50% to 99% stenosis of a major intracranial artery, long-term maintenance of blood pressure lower than 140/90 mm Hg and total cholesterol level lower than 200 mg/dL may be reasonable, and there is also a new recommendation against bypass surgery in these patients.

Conflict of Interest Scrutiny

Finally, another new element to these guidelines was the “scrutiny” of committee members reviewing the literature to minimize conflicts of interest, said Dr. Adams.

“How that was managed this time was that we were all given assignments in areas that were unrelated to anything we put on the conflict of interest form;” the upshot is that he was reviewing research, “that I have no interest in or ever spoken about.”

All members of the writing group were required to complete and submit a disclosure questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

Stroke. Published online October 21, 2010.

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