NSAIDs with increasing degrees of relative COX- 2 selectivity should not be administered to patients with NSTE-ACS and chronic musculoskeletal dis- comfort when therapy with acetaminophen, nonac- etylated salicylates, tramadol, small doses of narcot- ics, or nonselective NSAIDs provide acceptable pain (Level of Evidence: B) Selective COX-2 inhibitors and other nonselective NSAIDs have been associated with increased cardiovascular risk, and the risk appears to be amplified in patients with established. In a large Danish observa- tional study of patients with first MI (n=58432), the HR and There were dose-related increases in risk of death and non dose-dependent trends for rehospitaliza- tion for MI for all drugs.234,467 An AHA scientific statement on the use of NSAIDs concluded that the risk of cardiovascular events is proportional to COX-2 selectivity and the underly- ing risk in the patient.237 Non-pharmacological approaches were recommended as the first line of treatment, followed by the stepped-care approach to pharmacological therapy, as shown in Figure 4. 6.3.5. Hormone Therapy: Recommendation Class III: Harm 1. Hormone therapy with estrogen plus progestin, or estrogen alone, should not be given as new drugs for secondary prevention of coronary events to post- menopausal women after NSTE-ACS and should Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e381 not be continued in previous users unless the ben- efits outweigh the estimated risks.17,470 472 (Level of Evidence: A) Although prior observational data suggested a protective effect of hormone therapy for coronary events, a randomized trial of hormone therapy for secondary prevention of death and MI (the HERS [Heart and Estrogen/Progestin Replacement] study) failed to demonstrate a beneficial effect.473 There was an excess risk for death and MI early after initiation of hor- mone therapy. 