Effect of Naltrexone Hydrochloride ER and Bupropion Hydrochloride ER Combination (Contrave®/Mysimba®) on Major Adverse Cardiovascular Events (MACE)

Inclusion Criteria: 1. Patient age ≥18 years at screening 2. Able to understand the key components of the study, as described in the written informed consent document, and willing and able to provide written informed consent 3. BMI ≥30 kg/m2 (obese) or ≥27 kg/m2 (overweight) in the presence of at least 1 weight-related comorbidity (eg, hypertension, type 2 diabetes mellitus, or dyslipidemia) 4. At increased risk of adverse cardiovascular outcomes: In the opinion of the investigator, has a high likelihood of cardiovascular disease with at least 1 of the following: * History of documented MI \>90 days prior to screening * History of coronary revascularization (ie, coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy) \>90 days prior to screening * History of carotid or peripheral revascularization (ie, carotid endarterectomy, lower extremity atherosclerotic disease atherectomy, repair of abdominal aorta aneurysm, femoral or popliteal bypass) \>90 days prior to screening * Angina with ischemic changes (resting echocardiogram (ECHO), ECG changes on a graded exercise test (GXT), or positive cardiac imaging study) * Ankle brachial index \<0.9 (by simple palpation) within prior 2 years or Type 2 diabetes mellitus with at least 2 of the following: * Hypertension (controlled with or without pharmacotherapy at \<145/95 mmHg) * Dyslipidemia requiring pharmacotherapy * Documented low HDL cholesterol (\<50 mg/dL in women or \<40 mg/dL in men) within the prior 12 months * Current tobacco smoker 5. Patients who have completed a washout (2-weeks or 5 half-lives, whichever is longer) of the prohibited concomitant medication(s) at screening 6. Subject willing to comply with daily completion of an eDiary using a mobile smartphone application Exclusion Criteria: 1. Using prescription medications, other than Contrave/Mysimba, or surgical or medical device interventions for weight loss 2. History of MI or stroke within 90 days prior to screening 3. Uncontrolled hypertension, defined as systolic BP ≥160 mmHg and/or \>100 mmHg diastolic BP on the average of 3 seated BP measurements after the patient has been at rest for at least 5 minutes 4. Meets any of the following criteria: * Confirmed end-stage renal disease (ie, a degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate \[\<15 mL/minute/1.73 m2\] and other manifestations including increased serum creatinine), * Severe hepatic impairment (Child-Pugh score 10 to 15 \[Class C\]), * Hemodynamic instability, including patients with severe heart failure (New York Heart Association Class IV) 5. Seizure disorders or history of seizures, not including subjects with a history of pediatric febrile seizures 6. Use of other bupropion-containing products (including but not limited to Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Aplenzin) 7. Active anorexia nervosa or bulimia 8. Chronic opioid or opiate agonist (eg, methadone) or partial agonists (eg, buprenorphine) use, or acute opioid withdrawal or has a positive urine drug result for opioids at screening 9. Undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs 10. Concomitant administration of MAOIs. This also includes use of reversible MAOIs, such as linezolid or intravenous methylene blue. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with Contrave/Mysimba. 11. Subject has any disease or condition, or use of any pharmacological agent to treat the disease/condition, that, in the opinion of the investigator, would contraindicate study participation 12. Known allergy to bupropion, naltrexone, or any other component of Contrave/Mysimba 13. Pregnant or nursing 14. Known life-threatening arrythmias, including Brugada syndrome 15. Participation in any other concurrent investigational trial