Table 3.
Subjects with One or More Cardiovascular-Related Adverse Events.*
| Subject No. | Adverse Event | MedDRA- Classified Cardiac Event |
Cardiovascular- Related Event |
Atherosclerosis- Related Event |
Method of Confirmation† |
|---|---|---|---|---|---|
| no. of events | |||||
| Testosterone group | |||||
| 1 | Acute coronary syndrome and chest pain | 1 | 2 | 1 | Review of medical records |
| 2 | Chest pain | 1 | 1 | Examination by study physician | |
| 3 | Syncope | 1 | Self-report | ||
| 4 | Syncope | 1 | Self-report | ||
| 5 | Myocardial infarction treated with angioplasty and placement of pacemaker | 1 | 1 | 1 | Review of medical records |
| 6 | Myocardial infarction | 1 | 1 | 1 | Review of medical records |
| 7 | Angioplasty and coronary-artery bypass grafting | 1 | 1 | Review of medical records | |
| 8 | Peripheral edema | 1 | Examination by study physician | ||
| 9 | Peripheral edema | 1 | Examination by study physician | ||
| 10 | Ectopy on ECG (premature ventricular contractions, couplets) | 1 | 1 | ECG evaluation by study physician | |
| 11 | Left ventricular strain pattern during exercise testing | 1 | 1 | ECG evaluation by study physician | |
| 12 | ST-segment depression during exercise testing | 1 | 1 | ECG evaluation by study physician | |
| 13 | Elevated blood pressure | 1 | Examination by study physician | ||
| 14 | Atrial fibrillation with rapid ventricular rate and shortness of breath and exacerbation of congestive heart failure, which necessitated hospitalization | 2 | 2 | Examination by study physician (atrial fibrillation) and report of primary care physician (exacerbation of congestive heart failure) | |
| 15 | Stroke | 1 | Review of medical records | ||
| 16 | Elevated blood pressure and atrial fibrillation | 1 | 1 | Review of medical records | |
| 17 | Peripheral edema | 1 | Examination by study physician | ||
| 18 | Peripheral edema | 1 | Examination by study physician | ||
| 19 | Elevated blood pressure | 1 | Examination by study physician | ||
| 20 | Tachycardia with fatigue | 1 | 1 | Self-report | |
| 21 | Death, suspected myocardial infarction | 1 | 1 | 1 | Notification by physician |
| 22‡ | Peripheral edema | 1 | Examination by study physician | ||
| 23 | Congestive heart failure exacerbation | 1 | 1 | Review of medical records | |
| Placebo group | |||||
| 1 | Syncope resulting in hospitalization | 1 | Self-report | ||
| 2 | Tachycardia | 1 | Examination by study physician | ||
| 3 | Elevated blood pressure | 1 | Examination by study physician | ||
| 4 | Arrhythmia–ectopy noted on ECG before exercise testing | 1 | 1 | Examination by study physician | |
| 5 | Carotid bruit and carotid-artery plaque identified on ultrasonography | 1 | 1 | Examination by study physician and review of medical records | |
In addition to an assessment of cardiac events as categorized with the use of the Medical Dictionary for Regulatory Activities (MedDRA) classification, the data and safety monitoring board requested two analyses. The first included MedDRA-classified cardiac events plus events that the data and safety monitoring board considered to be cardiovascular in nature but that were included in other MedDRA System Organ Class categories: stenting and bypass procedures (included in the MedDRA category of surgical and medical procedures); peripheral edema (included in the category of general disorders); elevated blood pressure, arrhythmias, and electrocardiographic changes (included in the investigations category); and stroke and syncope (included in the category of nervous system disorders). For clarity, these adverse events are listed as cardiovascular-related events. The second analysis included atherosclerosis-related events, which were events that were directly related to atherosclerotic vascular disease, such as myocardial infarction, sudden death, angioplasty, coronary-artery bypass grafting, and stroke. ECG denotes electrocardiogram.
Medical records were reviewed if an adverse event was reported and records were available to document that event.
Two men, both in the testosterone group, underwent elective vascular procedures during treatment that were not included in these analyses since they were deemed to have been related to preexisting conditions: Subject 22 underwent elective surgery to repair an aortic aneurysm, and another participant, not listed in this table, underwent prescheduled elective angioplasty and placement of a stent in his leg owing to peripheral vascular disease. The results of the analyses did not change when these two events were included.