Table 4

Detailed assessment of adverse events

Placebo (n = 184)DFMO/sulindac (n = 191)
Aspirin (n = 69)Non-aspirin (n = 115)Aspirin (n = 77)Non-aspirin (n = 114)
Cardiovascular
CAD, prior Hx*0130
CAD, new0110
MI, prior Hx1010
MI, new0031
CVA, prior Hx0000
CVA, new0111
CHF, prior Hx1010
Chest pain, new0404
Subtotal, prior Hx2150
Subtotal, new0656
 Total9 (4.9)16 (8.4)
 Risk ratio (95% CI)1.71 (0.78-3.78)
P0.17
Hearing
Audiometric evaluations at end of study, no. patients with adverse events / no. patients in cohort (%)
 Hearing loss at least 15 dB at ≥2 frequencies24/123 (19.5)35/136 (25.7)
  Risk ratio (95% CI)1.32 (0.83-2.09)
  P0.23
 Hearing loss at least 15 dB at ≥2 consecutive frequencies12/123 (9.8)25/136 (18.4)
  Risk ratio (95% CI)1.88 (0.99-3.59)
  P0.05
 Hearing loss at least 15 dB at ≥2 consecutive frequencies in the normal range (500-3,000 Hz)7/123 (5.7)14/136 (10.3)
  Risk ratio (95% CI)1.81 (0.75-4.33)
  P0.17
Bilateral audiometric changes at 36 mo or at least 6 mo off-study
 End of study, no. with bilateral changes (%)§2/9 (22.2)10/21 (47.6)
  Risk ratio (95% CI)2.14 (0.58-7.88)
  P0.18
 At 6 mo posttreatment
  Improved1/2 (50.0)3/10 (30.0)
  Persistent0/2 (0.0)1/10 (10.0)
  Unilateral hearing loss with development of bilateral hearing loss1/2 (50.0)2/10 (20.0)
  Pending0/2 (0.0)4/10 (40.0)
  • *Prior Hx, subjects had prior history.

  • Relative risk estimation by log-binomial regression. Likelihood ratio test P values are reported.

  • All self-reported hearing complaints were recorded. Hearing thresholds were assessed for 259 patients with follow-up audiograms measured from 18 to 36 mo after beginning of therapy.

  • §Unilateral or bilateral change from baseline at 36 mo (n = 30; placebo, n = 9; DFMO/sulindac, n = 21).

  • Bilateral changes at 36 mo or at least 6 mo off-study (n = 12; placebo, n = 2; DFMO/sulindac, n = 10).