During a routine physical examination, physicians diagnose coronary artery disease by looking for changes in blood pressure, noting any rapid weight gain (a possible indication of heart failure), and taking a blood profile. The presence of certain enzymes in a blood profile can suggest evidence of recent or acute damage to heart tissue (heart attack). Although extremely sensitive to heart damage, these enzymes disappear quickly—within a week to ten days after a heart attack. A change in a patient's resting or stress electrocardiogram may also indicate a prior cardiac episode.

The physician should listen for the development of a new heart murmur or rub (the sound of an irritated, inflamed pericardium), or for the emergence of an irregular heartbeat. The addition of a third or fourth heart sound to the normal "lub dub" of the first and second beat may indicate a damaged heart—stiff, under high pressure, or weakened. Among the advanced diagnostic tools, echocardiograms, ultrasounds, nuclear scans, and angiograms are all helpful in identifying patients with artery disease and in determining the impact that the disease has already had on heart muscle and valve function.

Physicians initially treat coronary artery disease by turning to the vast assortment of effective medical options. Beta-blockers interfere with the effect of adrenaline on the heart, thereby reducing the heart rate. The number of beats per minute determines the amount of oxygen—delivered through the coronary arteries—that the heart requires. Arterial disease interferes with the ability of the arteries to supply that oxygen. Decreasing the baseline demand for oxygen, therefore, helps to create a better balance between supply and demand.

Other medical treatments seek to improve arterial flow by either stabilizing or reversing arterial plaque. These therapies include cholesterol-lowering drugs such as statins, aspirin, ACE (angiotensin converting enzyme) inhibitors, and ARBs (angiotensin receptor blockers). Aspirin promotes arterial blood flow by decreasing the stickiness of blood cells called platelets. When platelets clump together, they interact with artery walls to advance disease. ACE inhibitors promote arterial health by interfering with the production of a kidney hormone that interacts with the vascular system. A second-generation class of drugs, ARBs work on the artery wall to reduce resistance to blood flow and have beneficial effects on the heart and kidneys similar to those of ACE inhibitors.