Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease: The TEAM-AD VA Cooperative Randomized Trial

doi:10.1001/jama.2013.282834

Table 3

Adverse Events and Serious Adverse Events

Event	Vitamin E (n = 152)	Memantine (n = 155)	Vitamin E + Memantine (n = 154)	Placebo (n = 152)
Adverse events
Patients with event, No. (%)	91 (60)	97 (63)	90 (58)	89 (59)
Adverse event, No. of events	198	196	211	202
Event attributed to study medications, No. of events^a	35	29	33	24
Adverse event >5% and ≥placebo, No. of events (% of patients with event)^b
Falls	58 (20)	38 (17)	64 (23)	48 (20)
Bleeding^c	6 (4)	5 (3)	11 (6)	5 (3)
Serious adverse events
Patients with event, No. (%)	82 (54)	84 (54)	83 (54)	95 (63)
Serious adverse event, No. of events	180	187	179	170
Event attributed to study medications, No. of events^a	19	18	13	19
Type of event, No. of events^d
Hospitalization	152	143	146	128
Other	14	20	41	28
Death	26	39	32	31
Annual mortality rate, %^e	7.3	11.3	9.0	9.4
Cause of death^f
Cardiac disorders	5	10	8	10
Nervous system disorders	4	6	6	5
Infections or infestations	4	4	3	2
Neoplasms	4	5	3	1
Respiratory disorders	2	4	5	3
Other	5	6	6	8
Unknown	2	4	1	2
Serious adverse event >5% and ≥placebo, No. of events (% of patients with an event)^b
Falls	16 (10)	16 (10)	14 (8)	18 (10)
Bleeding^c	7 (5)	10 (5)	7 (5)	10 (5)
Pneumonia	11 (5)	9 (5)	15 (10)	5 (3)
Urinary tract infection	8 (5)	8 (5)	13 (5)	5 (3)
All infections or infestations^g	29 (13)	31 (15)	44 (20)	13 (7)

^aThe principal investigator at each clinical site determined whether an adverse event or serious adverse event was attributed to study therapy.

^bAdverse events and serious adverse events are listed according to the preferred term used in the Medical Dictionary for Regulatory Activities (MedDRA).

^cBleeding events are calculated by combining preferred terms from MedDRA and other events that involved bleeding.

^dMore than 1 event type permitted for serious adverse events.

^eCox proportional hazard ratio for vitamin E relative to placebo = 0.87; 95% CI, 0.67-1.13; P = .31.

^fCause of death is based on the organ class system used in MedDRA.

^gInfections or infestations are based on the organ class system used in MedDRA;

χ23 $χ_{3}^{2}$ test of a difference across treatment groups P = .01;

χ21 $χ_{1}^{2}$ test for vitamin E vs placebo P = .12, for memantine vs placebo P = .03, and for vitamin E + memantine vs placebo P = .001.