Table 2:

Efficacy and safety outcomes of patients according to homocysteine level and treatment

OutcomeHomocysteine ≤ 12.9 μmol/L
n = 2650
Homocysteine > 12.9 μmol/L
n = 2790
p value for interaction
No. (%) of patientsHR (95% CI)p valueNo. (%) of patientsHR (95% CI)p value
Ticagrelor–ASA event rate*
n = 1349
Clopidogrel–ASA event rate*
n = 1301
Ticagrelor–ASA event rate*
n = 1391
Clopidogrel–ASA event rate*
n = 1399
Primary outcome
Stroke86 (6.4)87 (6.7)0.97 (0.71–1.32)0.874 (5.3)119 (8.5)0.60 (0.45–0.81)< 0.0010.04
Secondary outcome
Stroke within 30 days72 (5.3)74 (5.7)0.95 (0.68–1.33)0.858 (4.2)98 (7.0)0.57 (0.41–0.79)< 0.0010.06
Composite vascular events96 (7.1)114 (8.8)0.84 (0.63–1.11)0.295 (6.8)134 (9.6)0.69 (0.53–0.90)0.010.5
Ischemic stroke86 (6.4)85 (6.5)0.99 (0.73–1.35)> 0.972 (5.2)116 (8.3)0.60 (0.45–0.81)< 0.0010.04
 Disabling stroke44 (3.3)33 (2.5)1.30 (0.82–2.05)0.336 (2.6)43 (3.1)0.83 (0.53–1.30)0.40.2
 Ordinal stroke or TIA§0.81 (0.61–1.08)0.20.71 (0.54–0.93)0.010.5
  Fatal stroke (MRS score 6)2 (0.2)3 (0.2)1 (0.1)3 (0.2)
  Severe stroke (MRS score 4–5)14 (1.0)7 (0.5)11 (0.8)8 (0.6)
  Moderate stroke (MRS score 2–3)28 (2.1)23 (1.8)24 (1.7)32 (2.3)
  Mild stroke (MRS score 0–1)42 (3.1)54 (4.2)38 (2.7)76 (5.4)
  TIA9 (0.6)25 (1.9)20 (1.4)11 (0.8)
  No stroke or TIA1255 (93.0)1189 (91.4)1297 (93.2)1269 (90.7)
Primary safety outcome
Severe or moderate bleeding3 (0.2)2 (0.2)1.59 (0.27–9.58)0.66 (0.4)6 (0.4)0.82 (0.25–2.71)0.70.7
 Fatal bleeding1 (0.1)0 (0.0)NANA2 (0.1)3 (0.2)0.72 (0.12–4.34)0.7> 0.9
 Intracranial hemorrhage0 (0.0)2 (0.2)NANA3 (0.2)4 (0.3)0.70 (0.15–3.22)0.6> 0.9
Secondary safety outcome
Any bleeding76 (5.6)34 (2.6)2.61 (1.69–4.03)< 0.00177 (5.5)32 (2.3)2.38 (1.56–3.63)< 0.0010.7
Mild bleeding 73 (5.4)32 (2.5)2.70 (1.73–4.24)< 0.00171 (5.1)26 (1.9)2.75 (1.73–4.35)< 0.0010.9
Death3 (0.2)4 (0.3)0.68 (0.15–3.03)0.64 (0.3)10 (0.7)0.45 (0.14–1.48)0.20.6
  • Note: ASA = acetylsalicylic acid, CI = confidence interval, HR = hazard ratio, MRS = Modified Rankin Scale, NA = not applicable, TIA = transient ischemic attack.

  • * Event rates for ordinal stroke or TIA are raw estimates, whereas event rates for other outcomes are Kaplan–Meier estimates of the percentage of patients with events at 90 days.

  • Composite vascular events include ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction, and vascular death.

  • A stroke was defined as disabling if the patient had a subsequent score on the MRS of greater than 1 (indicating death or any degree of disability).

  • § Severity measured using a 6-level ordered categorical scale that incorporates subsequent stroke or TIA events and MRS score at 3 months. The common odds ratio is shown rather than the hazard ratio.

  • Severe or moderate bleeding and mild bleeding were defined according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria.