Thienopyridine Agents and Patent Foramen Ovale Closures Reduce Migraines

Investigators reviewed past studies to find evidence that P2Y12 inhibitors effectively improve migraine headache symptoms.

Platelet inhibition using thienopyridine agents provided patients with migraine headache relief, which remained after closing of the patent foramen ovale (PFO) and subsequent discontinuation of the medication, according to the results of a retrospective study published in Neurology.

Researchers analyzed data from patients with migraine headaches and PFO to evaluate the effect P2Y12 platelet inhibition, through clopidogrel or prasugrel and closing of the PFO, had on the number of migraine headache days per month. Patients took clopidogrel daily until a ≥50% reduction of migraine headache days per month was met or they were considered nonresponsive. 

Nonresponders were switched to prasugrel to see if the different activation pathway elicited with this medication effectively reduced the number of migraine headache days per month to ≥50%. Then, all thienopyridine agent responders were offered a PFO closure.

Of the 136 patients included, 86% were female, 62% had episodic migraine headaches, 53% had a moderate-large right-to-left shunt, and the mean age was 37.9±14.6 years old. Clopidogrel was effective in 59% of the study population, with 70% of responders demonstrating a ≥90% reduction in migraine headache days per month. Prasugrel was effective in 62% of the study population who switched medications. In total, 66% of the entire study population responded to either clopidogrel or prasugrel and reached an adequate P2Y12 inhibition with a P2Y12 reaction units value <140.

All responders were offered a PFO closure, and 94% of the patients who opted for the closure had continued migraine headache reductions even after the discontinuation of the thienopyridine agent. The 8 patients who did not undergo the closure and discontinued the medication saw a return of their migraine headaches. The 26 patients who did not undergo the closure but continued medication saw improvements for up to 4 years.

Related Articles

Limitations of this study include relying on medical records of past migraine frequency at baseline, short thienopyridine agents follow-up, and potential for possible placebo effects.

The researchers “observed not only a reduction in [migraine headache] frequency when adequate platelet inhibition was achieved, but also a tight correlation between thienopyridine responsiveness and benefit from subsequent PFO closure, allowing us to speculate on the pathophysiologic mechanism and implications for clinical therapy.”


Sommer RJ, Nazif T, Privitera L, Robbins BT. Retrospective review of thienopyridine therapy in migraineurs with patent foramen ovaleNeurology. 2018;91(22):1002-1009.