Imagine you had a drug that dramatically improved the symptoms or signs of a disease in 70% of the patients who take it, but carried the risk of stroke or death in 1 out of 1000 people taking it. Would you approve it for general consumption?
Atrial fibrillation is an abnormal rhythm of the main collection chamber of the heart, usually the left atrium, which collects oxygenated blood returning from the lungs, and delivers it in a bolus to the main pump of the heart, the left ventricle, which delivers it with a forceful thrust (your heartbeat) throughout the body. Normally this sequence of relaxation/filling followed by contraction/ejection of the atrium and ventricle is coordinated and precisely timed with the valves between these chambers by the pressures in the chambers and the electrical system of the heart so that the atrium and ventricle contract in the periodic, regular rhythm of your heartbeat. However, quite commonly as people age and for a variety of other reasons, the atrium gets erratic and starts vibrating (fibrillating) instead of rhythmically contracting. Normally, this does not transmit to the ventricle which still suboptimally fills normally, but there is a danger of death if this fibrillation does transmit to the ventricle, as essentially, the heart will no longer be pumping blood but just vibrating uselessly (ventricular fibrillation/heart attack).
This is the motivation for Correvio’s Brinavess®. With a minutes-long infusion, certain patients in atrial fibrillation can be converted back to the normal rhythm and reduce the danger of ventricular fibrillation. And indeed, 70% of patients studied in the trial experienced just that, which is spectacular. However, mucking with the heartbeat is, well, mucking with life and death. The system is both precise and unpredictable, so rarely, but consistently, patients receiving the drug would convert to sinus rhythm only to have the resulting heartbeat insufficient to maintain adequate blood pressure or, worse, not convert to sinus rhythm and instead have the potassium channel blockade result in the ventricle going into fibrillation, which is usually fatal unless the heart can be shocked out of it.
This risk was too much for the FDA, which declined to approve the drug, despite the spectacular efficacy. Could a drug that only works on potassium channels in the atrium do better? Unknown, and perhaps unlikely, since the electrical systems between the atrium and ventricle are connected. Still, such a tissue specific approach could yield a new avenue of improvement, which Correvio might need to survive.