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Table 5 Adverse event summary

From: Response by sex to statin plus ezetimibe or statin monotherapy: A pooled analysis of 22,231 hyperlipidemic patients

  Full Cohort Male Female  
Adverse events, n (%) Statin Statin/EZ Between treatment p-value P-value for effect of sex Statin statin/EZ Between
Treatment
p-value
Statin Statin/EZ Between
treatment
p-value
  N = 10517 N = 11714    N = 5380 N = 6129   N = 5137 N = 5585  
≥1 3455 (32.9) 3717 (31.7) 0.849 < 0.001 1537 (28.6) 1779 (29.0) 0.173 1918 (37.3) 1938 (34.7) 0.114
Drug related* 833 (7.9) 961 (8.2) 0.181 < 0.001 349 (6.5) 456 (7.4) 0.025 484 (9.4) 505 (9.0) 0.819
Serious 145 (1.4) 187 (1.6) 0.220 0.370 74 (1.4) 107 (1.7) 0.122 71 (1.4) 80 (1.4) 0.091
Serious drug related 6 (0.1) 13 (0.1) 0.148 0.908 2 (0.0) 8 (0.1) 0.075 4 (0.1) 5 (0.1) 0.784
Discontinuations due to AEs 219 (2.1) 263 (2.2) 0.286 < 0.001 91 (1.7) 105 (1.7) 0.828 128 (2.5) 158 (2.8) 0.229
Drug related* 136 (1.3) 177 (1.5) 0.117 < 0.001 49 (0.9) 69 (1.1) 0.234 87 (1.7) 108 (1.9) 0.288
Serious 34 (0.3) 38 (0.3) 0.906 0.320 18 (0.3) 23 (0.4) 0.659 16 (0.3) 15 (0.3) 0.746
Serious drug related 6 (0.1) 7 (0.1) 0.864 0.749 2 (0.0) 4 (0.1) 0.485 4 (0.1) 3 (0.1) 0.689
   Deaths 5 (0.0) 7 (0.1) 0.702 0.655 4 (0.1) 3 (0.0) 0.582 1 (0.0) 4 (0.1) 0.197
   Gastrointestinal-related 861 (8.2) 889 (7.6) 0.367 < 0.001 339 (6.3) 390 (6.4) 0.636 522 (10.2) 499 (8.9) 0.113
   Gallbladder-related§ 9 (0.1) 11 (0.1) 0.824 0.014 2 (0.0) 3 (0.0) 0.754 7 (0.1) 8 (0.1) 0.940
   Allergic reaction or rash 175 (1.7) 213 (1.8) 0.194 < 0.001 70 (1.3) 90 (1.5) 0.326 105 (2.0) 123 (2.2) 0.382
   Hepatitis-related 24 (0.2) 39 (0.3) 0.079 0.030 13 (0.2) 27 (0.4) 0.038 11 (0.2) 12 (0.2) 0.858
ALT ≥ 3 × ULN, consecutive, m/n (%) 31/10341
(0.3)
50/11512
(0.4)
0.519 0.241 15/5289
(0.3)
34/6031
(0.6)
0.111 16/5052
(0.3)
16/5481
(0.3)
0.611
AST ≥ 3 × ULN, consecutive, m/n (%) 23/10342
(0.2)
30/11512
(0.3)
0.087 0.100 7/5290
(0.1)
16/6031
(0.3)
0.018 16/5052
(0.3)
14/5481
(0.3)
0.873
ALT or AST ≥3 × ULN, consecutive, m/n (%) 36/10342
(0.3)
64/11512
(0.6)
0.018 0.185 17/5290
(0.3)
41/6031
(0.7)
0.006 19/5052
(0.4)
23/5481
(0.4)
0.649
CK ≥ 10 × ULN, m/n (%) 13/10342
(0.1)
9/11514
(0.1)
0.337 0.028 9/5290
(0.2)
7/6033
(0.1)
0.543 4/5052
(0.1)
2/5481
(0.0)
0.395
Myopathy#, m/n (%) 4/10342
(0.04)
3/11512
(0.03)
0.667 0.699 2/5290
(0.04)
2/6031
(0.02)
0.985 2/5052
(0.04)
1/5481
(0.02)
0.517
Rhabdomyolysis^, m/n (%) 0/10342
(0.00)
0/11512
(0.00)
N/A N/A 0/5290
(0.00)
0/6031
(0.00)
N/A 0/5052
(0.00)
0/5481
(0.00)
N/A
  1. ALT = alanine aminotransferase, ALT = aspartate aminotransferase, CK = creatine kinase ULN = upper limit of normal
  2. % = m/n × 100 = (number of patients within the AE category/number of treated patients) × 100
  3. *Determined by the investigator to be related to the drug
  4. Study medication withdrawn
  5. For gastrointestinal-related clinical adverse events, the preferred terms (preferred Medra terms) were pre-identified for collective review, including e.g. abdominal discomfort, abdominal distension, abdominal pain, abdominal tenderness, colitis, colonic polyp, constipation, dental caries, dental discomfort, diarrhoea, diverticulum, duodenitis, dyspepsiea, dysphagia, erosive duodenitis, faeces discolored, flatulence, flood poisoning, gastitis, gastoesophageal reflux disease, gingival pain, haemorrhoids, hiatus hernia, nausea, oesophageal stenosis, rectal haemorrhage, tooth loss, toothache, and vomiting.
  6. §For gallbladder-related clinical adverse events the preferred terms (preferred Medra terms) were pre-identified for collective review, including e.g. bile duct obstruction, bile duct stenosis, bile duct stone, biliary colic, cholangitis, cholecystectomy, cholecystitis, cholelithiasis, gallbladder disorder, and gallbladder perforation
  7. For allergic reaction or rash the preferred terms (preferred Medra terms) were pre-identified for collective review, including e.g. analphylaxis, angioedema, dermatitis, dermagraphism, drug hypersensitivity, eczema, eosinophilia, erythema, face oedema, hypersensitivity, palmar erythema, periorbital oedema, photodermatosis, photosensitivity, pigmentation disorder, pruritis, rash, rosacea, skin disorder, skin exfoliation, skin hyperpigmentation, skin inflammation, skin lesion, subcutaneious nodule, systemic lups erythematosus rash, and urticaria
  8. In addition to review of the effects of ezetimibe + statin on laboratory parameters associated with liver function, potentially "hepatitis-related" clinical adverse event terms (preferred Medra terms) were pre-identified for collective review, e.g., cholestasis, hepatic necrosis, hepatocellular injury, cytolytic hepatitis, hepatitis, hepatomegaly, hepatic cyst, hepatitis cholestatic, jaundice, hepatic failure, hepatitis fulminant, jaundice cholestatic, hepatic lesion, and, hepatitis infectious.
  9. #Myopathy is defined as CK elevation > 10XULN with associated muscle symptoms with no other explanatory cause.
  10. ^Rhabdomyolysis is defined as myopathy with associated evidence of renal damage.