The MERITs of Evidence-Based Clinical Practice in Neurology

ABSTRACT

We examine the relevance of evidence-based clinical practice (EBCP) in the field of clinical neurosciences, emphasize feasible methods for neurologists to incorporate EBCP into their practice, draw attention to available EBCP resources for the neurosciences, highlight how EBCP has been incorporated into clinical neuroscience training programs, present other EBCP initiatives in neurology, and describe the Mayo Clinic Evidence-Based Clinical Practice, Research, Informatics, and Training (MERIT) Center EBCP programs.

KEYWORDS

Evidence-based medicine - neurosciences - neurology - medical education - medical informatics

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APPENDIX

TITLE: MIGRAINE WITH AURA IS AN INDEPENDENT RISK FACTOR FOR CARDIOVASCULAR DISEASE AND STROKE

Clinical Problem: A 53 year-old woman with a history of migraine with prominent hemisensory aura suffers a myocardial infarction. She has no known cardiovascular risk factors. Her family history is remarkable for migraine but not cardiovascular disease.

Clinical Question: Migraine with aura is a risk factor for ischemic stroke. Is migraine, with or without aura, an independent risk factor for cardiovascular disease?

Search Strategy: The Medical Subject Heading (MeSH) terms “cardiovascular diseases” and “migraine disorders” were combined with the Ovid saved search “prognosis/comprehensive” and the keyword “prospective”. Twenty-nine article abstracts were retrieved and reviewed. The Kurth et al article was selected as the best primary data addressing our clinical question.

Evidence: Kurth T et al. Migraine and risk of cardiovascular disease in women. JAMA 2006;296:283-291.

This prospective cohort study evaluated the association between migraine with and without aura and later risk of cardiovascular disease (CVD). Women aged ≥ 45 years participating in the Women's Health Study (a randomized, double-blind, placebo-controlled trial of ASA, vitamin E, both, or neither for primary prevention of CVD) were free of CVD and angina when enrolled in 1992-1995.

Baseline self-reported migraine and related symptoms were recorded at entry. Follow-up assessments and study outcomes were obtained with questionnaires twice in the first year and annually afterwards until 2004. Participants were asked whether they had ever had a migraine headache and whether they had experienced one in the past year and were categorized as no migraine history, active migraine (at least one in the past year), or prior migraine (had migraine but not in the past year). Active migraineurs were questioned about attack duration and other features that the investigators used to classify women using 1988 International Headache Society (HIS) criteria and they were asked whether they had an “aura or any indication a migraine is coming”, allowing classification into active migraine with or without aura.

The primary outcome measure was the combined endpoint of major CVD (first instance of nonfatal ischemic stroke, nonfatal myocardial infarction, or death due to ischemic CVD); other measures were first ischemic stroke, myocardial infarction, coronary revascularization, angina, and death due to ischemic CVD. A Cox proportional hazards model evaluated the associations with adjustment for age, systolic blood pressure, use of antihypertensive medication, history of diabetes, body mass index, smoking status, exercise level, postmenopausal status and hormone use, use of oral contraceptives, lipid levels and lipid-lowering therapy use, and randomized treatment assignment.

Clinical Bottom Lines:

1. Compared to women with no migraine history, women with active migraine with aura were at increased risk of the following outcomes (multivariable adjusted hazard ratio with 95% CI):

   • -major CVD: 2.15 (1.58-2.92)

   • -myocardial infarction: 2.08 (1.30-3.31)

   • -ischemic stroke: 1.91 (1.17-3.10)

   • -ischemic CVD death: 2.33 (1.21-4.51)

   Active migraine without aura was not associated with increased risk of any CVD event.

2. Migraine with aura was also associated with increased risk of coronary revascularization and angina.

3. It is reasonable to put additional emphasis on identification and treatment of modifiable CVD risk factors for women with migraine with aura.

Summary of the Evidence: 27,840 women participated in the study; 18.4% reported any migraine history. Of those, 70.4% had active migraine. 39.7% of the active migraine group (n = 1434) had migraine with aura. Mean follow-up duration was 10 years, during which there were 580 major CVD events. In addition to the events noted above, the multivariable-adjusted hazard ratio indicated increased risk for coronary revascularization [1.74 (1.23-2.46)] and angina [1.71 (1.16-2.53)]. After age-adjustment, there were 18 additional major CVD events attributable to migraine with aura per 10,000 women per year. There was no association between active migraine without aura and any CVD event.

Comments:

Strengths of the study include its prospective cohort design that included both ‘hard’ (MI, stroke, death) and ‘soft’ (coronary revascularization, angina) CVD outcomes, large sample size, and reasonably long and complete follow-up, and thorough adjustment for CVD risk factors known and evaluable at study initiation.

Participant classification relied on headache/migraine and aura self-reporting with secondary classification into IHS criteria. This may lead to misclassification errors. because of various biases (e.g., recall) or imprecise definitions (e.g., patients reporting a nonspecific prodromal symptom such as fatigue, which was then classified as an aura).

Despite multivariable adjustment of the primary outcome analyses, residual confounding is possible, including with some now-known CVD risk factors such as the association of migraine with patent foramen ovale.

There was no detailed information on use of migraine medications, including triptans and ergot derivatives, which have coronary vasoconstrictive properties.

The mechanisms by which migraine with aura might result in increased CVD risk are unclear and further study is required with adjustment for known CVD risk factors, including genetic polymorphisms, and in women under age 45 and men.

Further studies might determine whether migraine therapies and antiplatelet therapies reduce CVD risk in patients with migraine with aura

Reference: Kurth T, Gaziano JM, Cook NR, et al. Migraine and risk of cardiovascular disease in women. JAMA 2006;296:283-291.

Key Words: cerebrovascular accident, migraine, aura, risk factors, prognosis[*]

Appraiser:	Rod Spencer, MD
Content Expert:	David Dodick, MD, FRCP(C)
Informatics Expert:	Kay Wellik, MLS, AHIP
Editors:	Dean Wingerchuk, MD, MSc, FRCP(C)
	Bart M. Demaerschalk, MD, MSc, FRCP(C)
Appraisal Date:	November 1, 2006
Re-appraisal Date:	November 1, 2008

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Mayo Clinic Scottsdale Evidence-Based Clinical Practice,

Research, Informatics, and Training (MERIT) Center

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