A hole between the left and the right side of the heart has been suspected to be the cause of migraines in some people. However, closing this hole has not produced dramatic improvement in several blinded studies that have been conducted in the past few years.

The hole, called atrial septal defect (ASD) is present in utero but begins to close as soon as the baby is born. In about 1.5% of the population (in twice as many women than men) the hole does not close completely. In most people this hole is small and does not cause any symptoms. However, if it is big, it requires intervention because it can lead to heart failure and strokes. Smaller ASD may not cause any symptoms, but has been suspected to be related to migraine headaches, especially migraines preceded by a visual aura.

The closure of ASD is done by threading up through a vein in the groin an umbrella-like device which is positioned and opened inside the heart to close the hole. A recent study looked at the need for different blood thinners to prevent blood clots from forming in the heart after the procedure. Half of the 171 migraine patients in the study were given aspirin and placebo and the other half aspirin and clopidogrel, another blood thinner. Interestingly, those who were given two blood thinners (aspirin and clopidogrel) had less severe migraine attacks than those on one (aspirin and placebo). This suggests, that the benefit seen in some of the previous ASD closure studies was due to the blood thinner rather than the procedure itself.

A trial currently under way at the Columbia University Medical Center is examining whether a different blood thinner, Brilinta will improve migraines in those with an ASD. If you’d like to consider participating and want to learn more about the study, go to this website.

For years researchers have tried to find ways to block various chemicals (neurotransmitters) released during a migraine attack, including serotonin, CGRP, nitric oxide, substance P, glutamate, and other. Triptans (such as IMitrex or sumatriptan), the first “designer” drugs for migraine, which were developed over 20 years ago, bind to a very specific subtype of serotonin receptor and are very effective in stopping a migraine attack.

A very promising new type of migraine medications is being developed by at least four different companies – Alder, Amgen, Eli Lily, and Teva. These drugs are monoclonal antibodies against the CGRP molecule or the CGRP receptor. CGRP (calcitonin gene-related peptide) is widely distributed in the body and is involved in regulating blood vessel opening and in the function of the nervous system. All four companies developing these drugs recently presented the results of their phase II clinical trials and the data looks very promising. The antibody tightly binds to its target (CGRP molecule or receptor) with the effect lasting a month, or in case of the Alder drug, up to 6 months. The Alder drug is given every six months intravenously, while the other three, are given every month by an injection into the muscle.

All four drugs appear to be very effective in preventing migraine attacks when compared to a placebo injection. And fortunately, at least so far, they all look very safe. However, in phase II trials only a couple of hundred patients are treated and we need to await the results of the larger and more definitive phase III trials to confirm the safety and efficacy of this new group of medications. This means that the earliest we will see these drugs approved by the FDA is in about 3 years.

It is possible that these drugs will be effective not only for the prevention of migraines, but also for stopping an acute migraine attack.

An opening between the left and the right side of the heart, called patent foramen ovale (PFO), is found in 25% of the general population. It has been found to be more common in people who suffer from migraines. A large PFOs can cause shortness of breath, heart failure, and strokes and they are usually closed surgically. Several companies developed a device to close this opening without open heart surgery, but rather by inserting an umbrella-like device through a vein in the groin.

The manufacturers of these devices have conducted clinical trials in the hope of preventing migraines by closing the PFO. The results so far have been mixed with some studies showing improvement in migraines and some showing no benefit. A study just presented at the annual meeting of the American Headache Society by Dr. Andrew Charles of UCLA and his colleagues reported on one such trial. This study was blinded, with 107 patients having a sham procedure (the catheter was inserted into the groin vein, but the PFO was not closed) and 123 having their PFO closed. Overall, there was a significant reduction in headache days in the closure group (-3.4 days) compared with the sham group (-2.0 days), however there was no difference in the primary efficacy endpoint of the number of patients with 50% or more reduction in migraine attacks.

A subset of patients did particularly well compared to the sham group – patients who had migraine aura with the majority of their migraine attacks. A significant reduction in migraine days was present in half of patients with aura compared with a quarter in the control group. About 11% (8 out of 74 patients) of those who had migraine with aura had complete elimination of migraine attacks, while this happened to only 1.5% (1 out of 68 patients) in the sham group with auras.

This study suggests that patients who have auras with the majority of their migraine attacks and whose migraines are difficult to control should undergo an echocardiogram to test for the possible presence of a PFO. If PFO is present, it may be reasonable to consider seeing an interventional cardiologist to close the PFO. This is a relatively safe procedure if done by an experienced doctor and that is a very important if. Pick a doctor who has done a hundred or more of these procedures.