Areas of Focus


Angina is chest discomfort caused by an imbalance between the supply of oxygen to and the demand for oxygen by the heart. It can feel like pain, pressure, or squeezing in the chest, with discomfort also possible in the shoulders, arms, neck, jaw, or back.

Angina is primarily, but not always, caused by either narrowing or spasm of the coronary arteries. The coronary arteries sit on the surface of the heart muscle and supply it with oxygen and nutrients.

Narrowing of the coronary arteries is most often caused by lifestyle factors resulting in fatty plaques that build up and reduce blood flow. This is a condition known as coronary artery disease, or CAD, which can lead to a heart attack and is linked to a significant increase in hospitalizations and mortality. Angina from CAD is characterized as one of two forms: stable or unstable.

Stable angina manifests when the heart’s oxygen demand increases but the heart can’t supply it due to reduced blood flow from blockages in the arteries. Stable angina can be triggered by physical exertion, cold weather, or other factors, such as emotional stress. Episodes are typically short-lasting, five minutes or less, and disappear soon after exertion is terminated (or the trigger is removed), or after using anti-anginal medication.

The hallmark of unstable angina is that it usually occurs unexpectedly, typically occurring at rest, during sleep, or with little physical exertion. In addition, it lasts longer than stable angina, may increase in frequency, and may not be relieved by anti-anginal medication (or it takes more medication than previously to achieve relief). Unstable angina is very dangerous and can be a sign of an impending heart attack.

Coronary spasm, also known as variant or Prinzmetal’s angina, is the sudden and involuntary tightening of the muscles within the coronary arteries, which narrows them and reduces blood flow to the heart. It may be due to high blood pressure, high cholesterol, or certain drugs, but in most cases no identifiable etiology is present.

Prevalence Data

Angina from CAD is characterized as one of two forms: stable or unstable. Stable angina is the most common form, affecting approximately 3% of the adult population, or approximately nine million patients in the United States. The coronary spasm form of angina, also known as variant or Prinzmetal’s angina, represents approximately two out of every hundred cases of angina.

Our Approach

Nitrates are prescribed to provide immediate relief of angina. Nitroglycerin is a common form of nitrate that is available primarily in sublingual formulations. In up to 20% of patients, nitroglycerin is not tolerated, and some patients do not respond to treatment with nitroglycerin. It can also cause severe hypotension, circulatory collapse, and death if used together with phosphodiesterase type 5 (PDE5) inhibitor drugs that are prescribed for erectile dysfunction. Calcium channel blockers are used to treat angina associated with coronary spasm; however, they do not provide immediate relief. We are not aware of any approved rapid-onset, short-acting treatments for coronary spasm. We are planning to study whether etripamil could be used to rapidly reduce symptoms in the outpatient setting in patients with angina who cannot tolerate or do not respond to nitrates, and in patients experiencing coronary spasm.

Clinical Trials

Milestone is in the early evaluation and planning stages for proof-of-concept trials to test the efficacy and safety of etripamil in various forms of angina.