Article Figures & Tables
Tables
- Table 1:
Characteristics of 130 325 patients who started allopurinol during the study period, by presence of heart disease
Characteristic No. (%) of patients* Standardized mean difference† Heart disease
n = 28 176No heart disease
n = 102 149Age, yr 0.80 Mean ± SD 70.2 ± 11.6 59.9 ± 14.0 < 60 5401 (19.2) 48 494 (47.5) 60–70 7301 (25.9) 27 271 (26.7) ≥ 70 15 454 (54.9) 26 384 (25.8) Sex, female 9328 (33.1) 27 870 (27.3) 0.13 Region‡ 0.21 Richmond 1010 (3.6) 4574 (4.5) Vancouver and Fraser North 9414 (33.4) 24 994 (24.5) North Shore and Fraser South 5687 (20.2) 20 998 (20.6) Remainder 12 065 (42.8) 51 583 (50.5) Comorbidities Ischemic heart disease 24 537 (87.1) 0 3.67 Heart failure 10 076 (35.8) 0 1.06 Chronic kidney disease 7138 (25.3) 8736 (8.6) 0.46 Diabetes 12 111 (43.0) 20 759 (20.3) 0.50 Gout 18 104 (64.3) 61 660 (60.4) 0.08 Medications Diuretics 16 415 (58.3) 26 124 (25.6) 0.70 Initial allopurinol dosage > 100 mg/d 16 333 (58.0) 66 520 (65.1) 0.15 Note: SD = standard deviation.
↵* Unless stated otherwise.
↵† Standardized mean differences > 0.1 are considered meaningful.
↵‡ Regions are grouped by proportion of Asian people in the population according to data from the 2016 Canadian Census (Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.190339/-/DC1) and are used here as a surrogate for Asian race, which has the highest prevalence of the HLA-B*5801 polymorphism.
- Table 2:
Risk of hospital admission for allopurinol-associated severe cutaneous adverse reactions, by purported risk factor
Risk factor No. (%) Risk of hospital admission for allopurinol-associated severe cutaneous adverse reactions per 1000 patients (95% CI) Relative risk (95% CI) Allopurinol initiators Hospital admissions for severe cutaneous adverse reactions Age- and sex-adjusted Primary multivariable* Secondary multivariable† All 130 325 (100) 109 0.84 (0.69–1.01) – – – Sex Male 93 127 (71.5) 49 (45.0) 0.53 (0.39–0.70) 1.0 1.0 1.0 Female 37 198 (28.5) 60 (55.0) 1.61 (1.23–2.08) 2.45 (1.67–3.61) 2.48 (1.67–3.70) 2.45 (1.65–3.65) Age, yr Continuous, 1-year age increase – – – – 1.02 (1.00–1.04) – < 60 53 895 (41.4) 23 (21.1) 0.43 (0.27–0.64) 1.0 – 1.0 60–70 34 572 (26.5) 21 (19.3) 0.61 (0.38–0.93) 1.76 (1.37–2.25) – 2.24 (1.33–3.78) ≥70 41 858 (32.1) 65 (59.6) 1.55 (1.20–1.98) 3.09 (1.89–5.06) – 5.04 (1.77–14.30) Region‡ Continuous, per 1% Asian increase – – – – 1.03 (1.02–1.04) – Richmond 5584 (4.3) 8 (7.3) 1.43 (0.62–2.82) 4.66 (2.66–8.15) – 4.67 (2.65–8.25) Vancouver and Fraser North 34 408 (26.4) 54 (49.5) 1.57 (1.18–2.05) 2.79 (1.92–4.05) – 2.80 (1.92–4.08) North Shore and Fraser South 26 685 (20.5) 15 (13.8) 0.56 (0.31–0.93) 1.67 (1.39–2.01) – 1.67 (1.38–2.02) Remainder 63 648 (48.8) 32 (29.4) 0.50 (0.34–0.71) 1.0 – 1.0 Heart disease Yes 28 176 (21.6) 43 (39.4) 1.53 (1.10–2.06) 1.84 (1.23–2.76) 1.60 (1.04–2.44) 1.55 (1.01–2.37) No 102 149 (78.4) 66 (60.6) 0.65 (0.50–0.82) 1.0 1.0 1.0 Chronic kidney disease Yes 15 874 (12.2) 26 (23.9) 1.64 (1.07–2.40) 1.70 (1.08–2.67) 1.86 (1.16–2.99) 1.88 (1.17–3.02) No 114 451 (87.8) 83 (76.1) 0.73 (0.58–0.90) 1.0 1.0 1.0 Diabetes Yes 32 870 (25.2) 36 (33.0) 1.10 (0.77–1.52) 1.12 (0.75–1.68) 0.96 (0.63–1.46) 0.95 (0.62–1.45) No 97 455 (74.8) 73 (67.0) 0.75 (0.59–0.94) 1.0 1.0 1.0 Gout Yes 79 764 (61.2) 57 (52.3) 0.71 (0.54–0.93) 0.80 (0.55–1.16) 0.80 (0.54–1.16) 0.80 (0.55–1.17) No 50 561 (38.8) 52 (47.7) 1.03 (0.77–1.35) 1.0 1.0 1.0 Diuretic use Yes 42 539 (32.6) 55 (50.5) 1.29 (0.97–1.68) 1.32 (0.88–1.98) 1.27 (0.84–1.94) 1.26 (0.83–1.92) No 87 786 (67.4) 54 (49.5) 0.62 (0.46–0.80) 1.0 1.0 1.0 Initial allopurinol dosage > 100 mg/d 82 853 (63.6) 86 (78.9) 1.04 (0.83–1.28) 2.53 (1.59–4.02) 2.79 (1.75–4.45) 2.78 (1.75–4.43) ≤100 mg/d 47 472 (36.4) 23 (21.1) 0.48 (0.31–0.73) 1.0 1.0 1.0 Note: CI = confidence interval
↵* Adjusted for sex, age (continuous), % Asian (continuous), heart disease, chronic kidney disease, diabetes, gout, diuretic use and initial allopurinol dosage.
↵† Adjusted for sex, age, region, heart disease, chronic kidney disease, diabetes, gout, diuretic use and initial allopurinol dosage.
↵‡ Regions are grouped by proportion of Asian people in the population according to data from the 2016 Canadian Census (Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.190339/-/DC1) and are used here as a surrogate for Asian race, which has the highest prevalence of the HLA-B*5801 polymorphism.
- Table 3:
Heart disease and risk of hospital admission for allopurinol-associated severe cutaneous adverse reactions, by presence of chronic kidney disease and initial allopurinol dosage
Variable Initial allopurinol dosage (+) Heart disease (−) Heart disease Risk of hospital admission for allopurinol-associated severe cutaneous adverse reactions per 1000 patients (95% CI) Multivariable relative risk* (95% CI) Risk of hospital admission for allopurinol-associated severe cutaneous adverse reactions per 1000 patients (95% CI) Multivariable relative risk* (95% CI) (+) Chronic kidney disease > 100 mg/d 4.45 (2.44–7.47) 11.13 (4.66–26.58) 1.41 (0.52–3.06) 4.52 (1.60–12.78) ≤100 mg/d 1.00 (0.27–2.56) 2.28 (0.68–7.58) 0.45 (0.05–1.61) 1.24 (0.27–5.80) (−) Chronic kidney disease > 100 mg/d 1.29 (0.75–2.06) 3.44 (1.52–7.81) 0.79 (0.58–1.04) 3.06 (1.50–6.23) ≤100 mg/d 1.02 (0.44–2.01) 2.41 (0.92–6.64) 0.29 (0.13–0.55) 1.00 (Ref.) Note: CI = confidence interval, Ref. = reference category
↵* Adjusted for age, sex, region, diabetes, diuretics and gout.
- Table 4:
Heart disease and risk of hospital admission for allopurinol-associated severe cutaneous adverse reactions, by demographic profiles
Variable (+) Heart disease (−) Heart disease Risk of hospital admission for allopurinol-associated severe cutaneous adverse reactions per 1000 patients (95% CI) Multivariable relative risk* (95% CI) Risk of hospital admission for allopurinol-associated severe cutaneous adverse reactions per 1000 patients (95% CI) Multivariable relative risk* (95% CI) Female sex, region with high Asian population†; age, yr ≥70 3.65 (1.57–7.19) 22.61 (7.57–67.60) 3.12 (1.49–5.73) 20.61 (7.69–57.46) < 70 1.44 (0.17–5.21) 9.13 (1.82–45.83) 2.60 (1.35–4.55) 17.52 (6.53–47.01) Female sex, region with low Asian population†; age, yr ≥ 70 2.30 (1.05–4.37) 13.76 (4.67–40.55) 0.99 (0.43–1.95) 6.42 (2.18–18.87) < 70 1.63 (0.34–4.78) 9.68 (2.35–39.80) 0.67 (0.29–1.32) 4.38 (1.51–12.73) Male sex, region with high Asian population†; age, yr ≥ 70 2.72 (1.17–5.36) 17.10 (5.78–50.55) 2.77 (1.38–4.96) 18.28 (6.73–49.68) < 70 1.28 (0.42–2.99) 8.43 (2.56–27.77) 0.34 (0.12–0.73) 2.33 (0.75–7.24) Male sex, region with low Asian population†; age, yr ≥70 0.93 (0.34–2.03) 5.48 (1.70–17.56) 0.45 (0.15–1.05) 2.92 (0.89–9.63) < 70 0.36 (0.04–1.30) 2.27 (0.45–11.34) 0.14 (0.05–0.32) 1.00 (Ref.) Note: CI = confidence interval, Ref. = reference category.
↵* Adjusted for chronic kidney disease, initial allopurinol dosage, diabetes, diuretics and gout.
↵† Proportion of Asian people in the population by region, according to data from the 2016 Canadian Census, is used here as a surrogate for Asian race, which has the highest prevalence of the HLA-B*5801 polymorphism.