Angiographically normal or near-normal coronary arteries are more common among women, who are more likely than men to have myocardial ischemia due to microvascular dis- ease. The relatively high proportion of patients with ischemia and no significant epicardial stenoses may indicate opportuni- ties to improve patient selection for coronary angiography, or to consider the possibility of syndromes caused by abnormal coronary vasoreactivity. Nevertheless, the exclusion of signifi- cant epicardial CAD with a high level of confidence can be important for high-quality diagnosis and patient management, and therefore the reported frequencies of normal coronary findings should be understood within this context.29,35 37 4.4. Guideline-Directed Medical Therapy 4.4.2. Additional Medical Therapy to Prevent MI and Death: Recommendation 4.4.2.5. Additional Therapy to Reduce Risk of MI and Death See Table 2 for the revised recommendation for chelation ther- apy and Online Data Supplement 2 for evidence supporting the recommendation. 4.4.2.5.4. Chelation Therapy. Chelation therapy, which consists of a series of intravenous infusions of disodium ethylene diamine tetraacetic acid (EDTA) in combination with other substances, has been touted as a putative noninvasive means of improving blood flow in atherosclerotic vessels, treating angina, and preventing cardiac events. EDTA combines with polyvalent cations, such as calcium and cadmium (a constituent of cigarette smoke that is associated with cardiovascular risk),43,44 to form soluble complexes that can be excreted. Advocates maintain that this process can result in both regression of atherosclerotic plaques and relief of angina and that EDTA reduces oxidative stress in the vascular wall.Anecdotal reports have suggested that EDTA chelation therapy can result in relief of angina in patients with SIHD. 