Figures
- FIGURE 1
CONSORT (Consolidated Standards of Reporting Trials) diagram. COPD: chronic obstructive pulmonary disease; DAPT: dual antiplatelet therapy; ITT: intention-to-treat; PP: per-protocol. #: there was one administrative error, so there were 121 randomisations, of which 120 were related to patients; ¶: one patient attended visit but the lab samples were not suitable for analysis.
- FIGURE 2
Primary outcome measure intention-to-treat (ITT) analysis. Boxplots of the a) ASPI test split by no-aspirin and aspirin comparative groups over time; b) adenosine diphosphate (ADP) test split by no-ticagrelor and ticagrelor comparative groups over time (ITT analysis set). i) Baseline; ii) 1 month; iii) 6 months. The green dashed line indicates the threshold below which patients are considered to be responders.
- FIGURE 3
Primary outcome measure per-protocol analysis. Boxplots of the a) ASPI test split by no-aspirin and aspirin comparative groups over time; b) adenosine diphosphate (ADP) test split by no-ticagrelor and ticagrelor comparative groups over time with patients who withdrew, discontinued treatment or lost to follow-up by the timepoint of interest removed (per-protocol analysis set). i) Baseline; ii) 1 month; iii) 6 months. The green dashed line indicates the threshold below which patients are considered to be responders.
- FIGURE 4
Secondary outcome measure St George's Respiratory Questionnaire for chronic obstructive pulmonary disease patients (SGRQ-C). Boxplots of SGRQ-C total score over time by comparative groups split by a) no aspirin and aspirin and b) no ticagrelor and ticagrelor (intention-to-treat analysis set). i) Baseline; ii) 1 month; iii) 6 months.
- FIGURE 5
Secondary outcome measure Euroqol five-dimensions (EQ5D) health score over time by comparative groups split by a) no aspirin and aspirin and b) no ticagrelor and ticagrelor (intention-to-treat analysis set). i) Baseline; ii) 1 month; iii) 6 months.
Tables
- TABLE 1
Baseline characteristics
Placebo Aspirin Ticagrelor DAPT Total Subjects 31 31 29 29 120 Age at randomisation 66.3±9.2 68.5±7.2 66.5±7.7 69.0±10.6 67.5±8.7 Male 15 (48) 12 (39) 15 (52) 15 (52) 57 (47.5) QRISK2 score % 20 (12–28) 19 (17–27) 22 (14–27) 24 (20–35) 22.0 (15.5–28.0) Smoking status Nonsmoker 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Ex-smoker 21 (68) 20 (65) 21 (72) 21 (72) 83 (69.2) Light smoker (<10 pack-years) 3 (10) 0 (0) 1 (3) 3 (10) 7 (5.8) Moderate smoker (10–19 pack-years) 5 (16) 9 (29) 5 (17) 4 (14) 23 (19.2) Heavy smoker (≥20 pack-years) 2 (6) 2 (6) 2 (7) 1 (3) 7 (5.8) Diabetes status Type 1 0 (0) (0) 2 (7) 3 (10) 5 (4.2) Type 2 2 (6) 3 (10) 2 (7) 3 (10) 10 (8.3) Angina or heart attack in a first-degree relative aged <60 years? Yes 10 (32) 6 (19) 7 (24) 9 (31) 32 (26.7) On blood pressure treatment? Yes 10 (32) 9 (29) 12 (41) 13 (45) 44 (36.7) Rheumatoid arthritis? Yes 0 (0) 1 (3) 3 (10) 1 (3) 5 (4.2) Cholesterol/HDL ratio 3.0 (2.2–4.0) 2.8 (2.4–4.1) 3.0 (2.6–3.6) 3.1 (2.4–3.6) 2.9 (2.4–3.8) Systolic blood pressure mmHg 145.7 (16.1) 144.6 (18.2) 143.1 (14.7) 144.5 (22.1) 144.5 (17.7) Height cm 167.5 (9.9) 163.0 (10.5) 164.6 (11.3) 166.9 (10.9) 165.5 (10.7) Weight cm 74.7 (18.2) 73.1 (17.4) 72.2 (18.7) 79.9 (18.5) 74.9 (18.2) BMI kg·m−2 26.5 (5.4) 27.4 (5.6) 26.5 (5.7) 28.9 (7.0) 27.3 (6.0) COPD disease category# Severe (FEV1 <30% pred) 8 (27) 6 (19) 6 (21) 5 (17) 25 (21.0) Moderate (FEV1 30–49% pred) 10 (33) 14 (45) 7 (24) 11 (38) 42 (35.3) Mild (FEV1 50–79% pred) 12 (40) 11 (35) 16 (55) 13 (45) 52 (43.7) Daily sputum producer >3 months in each of last 2 year? Yes 22 (71) 15 (48) 18 (62) 15 (52) 70 (58.3) Number of acute exacerbations of COPD treated in past 12 months 4.2 (4.5) 3.4 (3.1) 2.6 (3.1) 2.5 (2.0) 3.2 (3.3) Number of hospitalisation in past 12 months for COPD 0.6 (1.2) 0.4 (1.6) 0.4 (0.9) 0.2 (1.0) 0.4 (1.2) Data are presented as n, mean±sd, n (%) or median (interquartile range). DAPT: dual antiplatelet therapy; HDL: high-density cholesterol; BMI: body mass index; COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in 1 s. #: National Institute for Health and Care Excellence Clinical guideline (June 2010).
- TABLE 2
Laboratory and other secondary outcomes data
Placebo Aspirin Ticagrelor DAPT Total Subjects 31 31 29 29 120 Haemoglobin g·L−1 146.4±13.3 145.4±14.5 146.1±13.0 141.8±16.6 144.9±14.4 White blood cell count ×109 cells·L−1 8.6±2.6 8.6±2.3 8.8±2.2 8.3±1.9 8.6±2.2 Platelet count ×109 cells·L−1 284.3±77.2 280.6±61.0 284.9±65.7 281.6±71.8 282.9±68.4 Neutrophil count ×109 cells·L−1 5.7±2.3 5.6±2.0 5.6±1.8 5.3±1.8 5.2 (4.3–6.4) Monocytes ×109 cells·L−1 0.73±0.42 0.64±0.21 0.70±0.19 0.67±0.23 0.60 (0.50–0.80) Eosinophil count ×109 cells·L−1 0.24±0.17 0.20±0.15 0.18±0.12 0.24±0.19 0.19 (0.11–0.31) Urea mmol·L−1 4.7±1.2 5.4±2.1 5.0±2.3 5.9±1.8 5.2±1.9 Creatinine µmol·L−1 76.1±14.9 71.4±14.0 76.1±20.0 86.9±19.2 77.5±17.9 Fibrinogen g·L−1 3.9±0.8 3.7±0.7 3.9±0.8 3.7±0.9 4.0 (3.0–4.0) hsCRP mg·L−1 7.8±15.4 3.6±3.5 8.2±16.5 3.8±3.8 2.5 (1.2–5.6) TNF-α pg·mL−1 2.38±2.73 2.35±2.59 1.52±1.23 1.44±1.50 1.00 (0.70–2.14) IL-6 pg·mL−1 5.81±5.64 5.96±6.18 3.82±3.04 3.39±1.61 3.43 (2.26–5.20) MPO ng·mL−1 814.38±480.4 1013.17±578.5 785.53±453.5 702.53±324.3 773.63 (420.40–1173.66) Vascular stiffness m·s−1 9.74±1.90 9.91±2.49 9.23±1.23 9.87±2.58 9.69±2.11 CIMT maximum mm 1.0±0.2 1.0±0.3 1.0±0.2 1.0±0.2 1.0±0.2 MRC dyspnoea scale 3.6±1.0 3.7±1.1 3.4±1.3 3.3±1.2 3.5±1.1 1 0 (0) 1 (3) 3 (10) 2 (7) 6 (5.0) 2 7 (23) 4 (13) 4 (14) 7 (24) 22 (18.3) 3 4 (13) 6 (19) 6 (21) 4 (14) 20 (16.7) 4 15 (48) 13 (42) 10 (34) 12 (41) 50 (41.7) 5 5 (16) 7 (23) 6 (21) 4 (14) 22 (18.3) EQ5D-5L index 0.619±0.261 0.676±0.222 0.662±0.221 0.675±0.253 0.658±0.238 EQ5D health score 61.8±20.4 59.3±16.6 66.6±18.1 60.9±17.5 62.1±18.2 SGRQ-C current health Very good 2 (6) 0 (0) 0 (0) 0 (0) 2 (1.7) Good 4 (13) 5 (17) 10 (34) 8 (28) 27 (22.7) Fair 18 (58) 18 (60) 12 (41) 14 (48) 62 (52.1) Poor 4 (13) 7 (23) 6 (21) 6 (21) 23 (19.3) Very poor 3 (10) 0 (0) 1 (3) 1 (3) 5 (4.2) SGRQ-C symptom score 73.6±22.2 72.3±18.4 60.2±24.8 67.3±19.7 68.5±21.8 SGRQ-C activity score 74.2±27.3 74.8±24.6 67.7±24.2 62.8±30.8 70.1±27.0 SGRQ-C impact score 45.2±26.7 42.5±20.1 40.0±25.2 42.2±27.2 42.5±24.7 SGRQ-C total 59.1±23.9 57.7±19.1 53.0±21.8 53.0±25.2 55.8±22.5 Data are presented as n, mean±sd, median (interquartile range) or n (%). DAPT: dual antiplatelet therapy; hsCRP: high-sensitivity C-reactive protein; TNF: tumour necrosis factor; IL: interleukin; MPO: myeloperoxidase; CIMT: carotid intima media thickness; MRC: Medical Research Council; SGQR-C: St George's Respiratory Questionnaire for COPD patients.
- TABLE 3
Primary outcome measures
Aspirin No aspirin Ticagrelor No ticagrelor ITT analysis set# 60 60 58 62 Baseline 1 6 4 1 1.7 (0.2–11.3) 10 (4.5–20.8) 6.9 (2.6–17.3) 1.6 (0.2–10.9) 6 months 29 7 24 2 48.3 (35.8–61) 11.7 (5.6–22.8) 41.4 (29.3–54.6) 3.2 (0.8–12.3) PP analysis set¶ 41 45 32 54 6 months 28 7 22 2 68.3 (52.3–80.9) 15.6 (7.5–29.6) 68.8 (50.4–82.6) 3.7 (0.9–14.0) Data are presented as n or % (95% CI). ITT: intention-to-treat; PP: per-protocol. #: descriptive statistics for the primary outcome of response for the comparative groups at baseline and 6 months for the ITT analysis set; ¶: response is ASPI response in the aspirin and no-aspirin columns and adenosine diphosphate response in the ticagrelor and no-ticagrelor columns.
Supplementary Material
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Supplementary material 00110-2019.supp
