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PREMIUM: PFO closure fails to reduce migraine attacks, adverse events
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Patients with migraine who were treated with medical therapy and patent foramen ovale closure did not have a reduction in responder rate compared with those who were treated with medical therapy and a sham procedure, according to a study published in the Journal of the American College of Cardiology.
Jonathan M. Tobis, MD, professor of medicine at UCLA David Geffen School of Medicine, and colleagues reviewed data from 230 patients who had six to 14 headache days per month, were not successful with three different migraine preventive medications and had a significant right-to-left shunt. Migraine frequency was reported in a diary for 60 days before randomization.
PFO closure vs. control
Patients were assigned medical therapy with PFO closure (Amplatzer PFO Occluder, St. Jude Medical; n = 123; mean age, 43 years; 89% women) or medical therapy with a sham procedure (n = 107; mean age, 44 years; 89% women), which included right heart catherization.
“It used a sham control group, which is important when the endpoint is subjective such as migraine headaches,” Tobis said in an interview with Cardiology Today’s Intervention.
A diary questionnaire on the patients’ migraine duration, quality, symptoms and medications was completed daily. Patients reviewed their diaries with a neurologist periodically for 1 year.
The primary efficacy endpoint of interest was the responder rate, which was defined as a 50% reduction in the monthly number of migraines during the baseline phase and from 10 to 12 months during the treatment phase. The primary safety endpoint of interest was device-related major adverse events during follow-up. Secondary endpoints included a reduction in migraines during treatment vs. baseline, changes in the number of migraine days from baseline to treatment and closure of the defect.
The responder rate did not differ between the PFO closure group (38.5%) and the control group (32%; P = .32).
“The clinical response in the placebo group of 32% was higher than expected,” Tobis said. “Since there was no change in the prophylactic medications in either group, the large placebo effect is presumably due in part to the supervision and care that the subjects received by the neurologists while they were involved with the trial, which lasted 1 year.”
Fewer days with migraines
The mean number of migraine days decreased by 3.4 days in the PFO closure group vs. 2 days in the control group (P = .025).
“The degree in reduction of headache days was similar to that achieved in the recently published articles on calcitonin gene-related peptide antibodies, which are considered to be positive studies,” Tobis told Cardiology Today’s Intervention.
Migraine attacks ceased in 8.5% of patients assigned PFO closure and 1% of those assigned the control procedure (P = .01).
Nonsustained atrial fibrillation occurred in one patient while the device was being deployed.
“Because the trial did not reach its primary endpoint, the FDA would not consider this to be adequate proof that PFO closure is an effective deterrent for migraineurs who have a large right-to-left shunt, so for the present time, the PREMIUM trial should not be used to change clinical practice,” Tobis said. “However, subgroup analysis from the PREMIUM data suggests that patients who have migraine with frequent episodes of aura (> 50% of the time) are more likely to respond to PFO closure. This implies that future clinical trials could look at this patient population as being more likely to have migraines triggered by right-to-left shunting and, therefore, might be more likely to have a positive study.” – by Darlene Dobkowski
For more information:
Jonathan M. Tobis, MD , can be reached at Cardiovascular Center, 100 Medical Plaza, 100 UCLA Medical Plaza, Suite 630, Los Angeles, CA 90095; email: tobis@mednet.ucla.edu.
Disclosures: This study was funded by St. Jude Medical. Tobis reports he serves on the PREMIUM steering committee. Please see the study for all other authors’ relevant financial disclosures.
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