TABLE 2.
Serious adverse events,a conditions of interest, and monitored clinical measures, according to treatment group and gender
| Standard treatment | Intensive treatment | Hazard ratio (95% Cl) for intensive to standard treatment | |||||
|---|---|---|---|---|---|---|---|
| Description | Women, N (%) with events | Men, N (%) with events | Women, N (%) with events | Men, N (%) with events | Women, hazard ratio (95% Cl) | Men, hazard ratio (95% Cl) | P value for interaction between treatment arm and gender |
| A: total serious adverse eventsa | 576 (35) | 1166 (38.4) | 637 (37.8) | 1162 (38.8) | 1.11 (0.99, 1.25) | 1.01 (0.93, 1.10) | 0.24 |
| Conditions of interest | |||||||
| B: serious adverse event only | |||||||
| Hypotension | 18 (1.1) | 40 (1.3) | 30 (1.8) | 69 (2.3) | 1.64 (0.91, 2.94) | 1.74 (1.18, 2.57) | 0.87 |
| Syncope | 27 (1.6) | 46 (1.5) | 40 (2.4) | 57 (1.9) | 1.48 (0.90, 2.43) | 1.25 (0.85, 1.84) | 0.62 |
| Bradycardia | 23 (1.4) | 45 (1.5) | 22 (1.3) | 56 (1.9) | 0.98 (0.54, 1.77) | 1.25 (0.85, 1.86) | 0.42 |
| Electrolyte abnormality | 56 (3.4) | 48 (1.6) | 76 (4.5) | 62 (2.1) | 1.29 (0.91, 1.84) | 1.30 (0.90, 1.90) | 0.91 |
| Injurious fallb | 46 (2.8) | 55 (1.8) | 49 (2.9) | 53 (1.8) | 1.05 (0.69, 1.58) | 0.97 (0.66, 1.41) | 0.78 |
| Acute kidney injury (AKI) or acute renal failure (ARF)c | 28 (1.7) | 87 (2.9) | 55 (3.3) | 138 (4.6) | 2.01 (1.26, 3.21) | 1.61 (1.23, 2.11) | 0.49 |
| C: emergency room visit or SAE | |||||||
| Hypotension | 25 (1.5) | 54 (1.8) | 41 (2.4) | 103 (3.4) | 1.60 (0.97, 2.63) | 1.93 (1.39, 2.68) | 0.56 |
| Syncope | 36 (2.2) | 64 (2.1) | 58 (3.4) | 90 (3) | 1.61 (1.06, 2.45) | 1.42 (1.03, 1.95) | 0.66 |
| Bradycardia | 27 (1.6) | 49 (1.6) | 28 (1.7) | 66 (2.2) | 1.05 (0.62, 1.80) | 1.36 (0.94, 1.97) | 0.38 |
| Electrolyte abnormality | 61 (3.7) | 66 (2.2) | 94 (5.6) | 76 (2.5) | 1.49 (1.07, 2.06) | 1.16 (0.84, 1.62) | 0.24 |
| Injurious fallb | 135 (8.2) | 182 (6) | 165 (9.8) | 170 (5.7) | 1.21 (0.96, 1.53) | 0.94 (0.76, 1.15) | 0.10 |
| AKI or ARFc | 31 (1.9) | 89 (2.9) | 56 (3.3) | 145 (4.8) | 1.83 (1.17, 2.88) | 1.66 (1.27, 2.16) | 0.78 |
| D: monitored clinical events | |||||||
| Laboratory measured | |||||||
| Serum sodium less than 130 mmol/l | 50 (3) | 53 (1.7) | 95 (5.6) | 94 (3.1) | 1.83 (1.29, 2.58) | 1.80 (1.29, 2.52) | 0.84 |
| Serum sodium more than 150 mmol/l | 0 (0) | 0 (0) | 1 (0.1) | 5 (0.2) | — | — | — |
| Serum potassium less than 3 mmol/l | 37 (2.2) | 38 (1.3) | 65 (3.9) | 52 (1.7) | 1.70 (1.14, 2.56) | 1.38 (0.91, 2.10) | 0.43 |
| Serum potassium greater than 5.5 mmol/l | 67 (4.1) | 106 (3.5) | 71 (4.2) | 113 (3.8) | 1.01 (0.72, 1.42) | 1.08 (0.83, 1.40) | 0.89 |
| Orthostatic hypotensione | |||||||
| Alone | 347 (21.1) | 510 (16.8) | 301 (17.9) | 476 (15.9) | 0.84 (0.72, 0.98) | 0.93 (0.82, 1.06) | 0.30 |
| With dizziness | 30 (1.8) | 41 (1.4) | 35 (2.1) | 27 (0.9) | 1.18 (0.72, 1.93) | 0.66 (0.41, 1.08) | 0.12 |
A serious adverse event was defined as an event that was fatal or life-threatening, which resulted in clinically significant or persistent disability, which required or prolonged a hospitalization, or that was judged by the investigator to represent a clinically significant hazard or harm to the participant that might require medical or surgical intervention to prevent one of the other events listed above.
An injurious fall was defined as a fall that resulted in evaluation in an emergency department or that resulted in hospitalization.
Acute kidney injury or acute renal failure were coded if the diagnosis was listed in the hospital discharge summary and was believed by the safety officer to be one of the top three reasons for admission or continued hospitalization. A few cases of acute kidney injury were noted in an emergency department if the participant presented for one of the other conditions of interest.
Adverse laboratory measures were detected on routine or unscheduled tests; routine laboratory tests were performed at 1 month, then quarterly during the first year, then every 6 months.
Orthostatic hypertension was defined as a drop in SBP of at least 20mmHg or in DBP of at least 10mmHg at 1 min after the participant stood up, as compared with the value obtained whenever the participant was seated. Standing blood pressures were measured at screening, baseline, 1 month, 6 months, 12 months, and yearly thereafter. Participants were asked if they felt dizzy at the time the orthostatic measure was taken.