The phase 3, double-blind, placebo-controlled migraine prevention studies included patients with

• comorbid CV conditions, and
• CV risk.7

However, to minimize confounding at the case level and improve interpretation of the CV data, patients with acute CV events and/or serious CV risk were excluded from the clinical studies.

A patient had a baseline CV disease risk of

• "yes" if they had 1 or more conditions that were part of the patients’ medical history or preexisting conditions using broad and narrow terms from the Medical Dictionary for Regulatory Activities (MedDRA) standardized MedDRA queries (SMQs), or
• "no" if they did not have any of the preferred terms (PTs) in the MedDRA SMQs as a preexisting condition or medical history event.8

Patients were excluded from phase 3, migraine prevention study enrollment if they met any of the following criteria at screening:

• electrocardiograms (ECGs) showing abnormalities compatible with acute CV events or serious CV risk, including, but not limited to a corrected QT (QTcB [Bazett's]) interval >470 ms for women and >450 ms for men
• history of myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft, or deep vein thrombosis/pulmonary embolism within 6 months of screening
• planned CV surgery or percutaneous coronary angioplasty
• stroke within 6 months of screening (EVOLVE-1), or
• a lifetime history of stroke (EVOLVE-2 and REGAIN).7,8

Framingham Risk Score (FRS) was also evaluated in the phase 3, double-blind, placebo-controlled migraine prevention studies. More information on FRS can be found in the Appendix.

The CV safety profile of galcanezumab was evaluated in phase 3 randomized, double-blind, placebo-controlled studies in adult patients for the prevention of

• episodic migraine (EVOLVE-1 and EVOLVE-2; 6 months),9,10 and
• chronic migraine (REGAIN; 3 months).11

This pooled analysis of 2886 adult patients included a total of 1435 patients who received monthly doses of galcanezumab (120 mg or 240 mg) administered subcutaneously.12

The majority of patients were female (>80%) and Caucasian (>75%), with a mean age of 41 to 42 years.12

There were no significant differences in CV treatment-emergent adverse events (TEAEs) observed between the CV disease risk subgroups (CV TEAEs in CVD Risk Group: Phase 3, Double-blind, Placebo-Controlled Migraine Prevention Trials).8,13

There were no significant differences between galcanezumab and placebo in the frequency of CV serious adverse events (SAEs) or discontinuations due to CV TEAEs.7,8,12

There were 3 CV SAEs each in the

• galcanezumab 240 mg (acute myocardial infarction, transient ischemic attack, pulmonary embolism), and
• placebo (pulmonary embolism, deep vein thromboembolism, myocardial infarction) groups.8,12

All the CV SAEs in the galcanezumab-treated patients resolved.12 Based on similarities in the type, frequency, and time of onset of these events from study treatment between patients treated with galcanezumab and placebo, the events were not considered to be related to galcanezumab treatment.7,8 

The 3 patients with CV SAEs in the galcanezumab 240-mg group were in the "no" CV disease-risk group.7

Of the 3 patients in the placebo group with CV SAEs,

• patients who reported myocardial infarction and deep vein thrombosis were in the CV disease-risk "yes" subgroup, and
• the patient who reported pulmonary embolism was in the CV disease-risk "no" subgroup.7

Cardiovascular TEAEs leading to discontinuation in placebo-treated patients were

• myocardial infarction
• deep vein thrombosis, and
• hypertension.

One galcanezumab-treated patient discontinued due to a transient ischemic attack (CV disease-risk "no" subgroup).8,12

The use of CV medications was evaluated including

• antihypertensives
• antiarrhythmics
• antithrombotics, and
• antianginals.8

The proportion of patients taking these medications at baseline and any change in postbaseline use was summarized. Postbaseline change was defined as

• initiation of a new treatment, or
• a dose increase in an existing treatment.8

Any CV medications whose indication for use was "primary study condition" were removed as many of the CV medications are used for migraine treatment (eg, beta blockers and calcium channel blockers).7

There was no difference in the increase of concomitant CV medications between CV disease risk subgroups.7,8

Dose Increase or New Start of CV Concomitant Medications - Phase 3, Double-blind, Placebo-Controlled, Migraine Prevention Analysis Set summarizes the increase in CV concomitant medications during the double-blind treatment phase by CV disease risk group.8

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Exposure-adjusted incidence rates (EAIRs) are a measure of whether TEAEs occur at an increased frequency with increased treatment duration.7

There were no significant differences between any galcanezumab dose group and placebo in the EAIRs across the 9 SMQs and associated PTs that were used to assess baseline CV risk. The EAIRs for SMQs that can be related to ischemic events are provided below: Exposure-Adjusted SMQs for TEAEs Likely CV in Nature per Medical Review – Ischemic-Related Events: Phase 3, Placebo-Controlled, Migraine Prevention Analysis Set.7

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The FRS is a gender-specific algorithm used to estimate the 10-year CV risk of an individual.14