Impact of Allopurinol on Risk of Myocardial Infarction
Impact of Allopurinol on Risk of Myocardial Infarction
The 2277 cases with first-ever MI and their 4849 matched controls had a mean age of 59.3 years (SD: 11.6), 76.4% were men and 56.3% were hypertensive. Prevalence of gout, as reported by the physicians, was 0.9% and 0.6% in controls and cases, respectively. MI cases showed classical vascular risk profile (Table 1). High BMI, diabetes, smoking (ever) and minimal physical activity were more frequent for cases than controls. On multivariate analysis, all factors were independently associated with MI (p<0.05 for all adjusted ORs).
Allopurinol was by far the most frequent ULT taken by participants. Indeed, no case and only 0.1% of controls reported use of febuxostat, and no participant took uricosurics. In all, 3.1% of cases and 3.8% of matched controls reported allopurinol use during at least one period within the two preceding years. Among allopurinol users, most (90% of cases and 92% of controls) had taken the drug regularly (at least 5 days per week) during the preceding 2 years. About two-thirds of cases and controls took a daily dose ≥200 mg, whereas 19% of cases and 25% of controls took ≥300 mg.
When adding all vascular risk factors to the conditional logistic regression model, the adjusted OR (aOR) for MI was at the limit of the significance: aOR=0.80 (0.59 to 1.09) (Table 2). When the number of visits to the GP was excluded from the matching criteria in order to use the whole cases pool (n=2593) and their 5185 matched controls, the aOR was 0.73 (0.54 to 0.99). We then categorised allopurinol use by dosage (no use, <200, ≥200 mg) and found no association of allopurinol dose and MI risk (<200 mg: aOR=0.63 (0.37 to 1.09); ≥200 mg: aOR=0.74 (0.51 to 1.08)) Table 3.
Stratified analysis showed that the adjusted ORs were similar for hypertensive and non-hypertensive patients and for both sexes (figure 2). Next, we examined whether the relation between allopurinol use and MI risk was similar by type of MI (STEMI and NSTEMI). Allopurinol use was associated with a significantly decreased risk of STEMI (aOR: 0.65 (0.44 to 0.96)) but not of NSTEMI (aOR: 1.17 (0.69 to 1.98)). Polytomous logistic regression revealed significant aORs after stratification on STEMI/NSTEMI cases (p=0.01).
(Enlarge Image)
Figure 2.
Forest plot of adjusted ORs by type of myocardial infarction (ST-elevated (STEMI) and non-ST-elevated (NSTEMI)), sex and hypertension status (HTA− and HTA+). The number of cases who had STEMI and NSTEMI was n=1710 and n=540, respectively.
Among the 56 MI presented with a resuscitated cardiac arrest ('near-deaths'), previous allopurinol use was 0% (95% CI (0.0% to 6.2%)), which is not statistically different from that of non-near-death MI patients (3.1%). Previous allopurinol use in the 115 matched controls to near-death patients was 3.8%, which is similar to the proportion of users in the whole control population.
Finally, we investigated the association of colchicine use and risk of MI. Cases and controls had taken colchicine in the same proportion: 1.1% (see online supplementary table S1 http://ard.bmj.com/content/74/5/836/suppl/DC1). Colchicine use in the previous 2 years was not associated with decreased MI risk. When cases were compared with their matched controls, the aOR was 1.17 (0.70 to 1.93).
Results
Characteristics of Participants
The 2277 cases with first-ever MI and their 4849 matched controls had a mean age of 59.3 years (SD: 11.6), 76.4% were men and 56.3% were hypertensive. Prevalence of gout, as reported by the physicians, was 0.9% and 0.6% in controls and cases, respectively. MI cases showed classical vascular risk profile (Table 1). High BMI, diabetes, smoking (ever) and minimal physical activity were more frequent for cases than controls. On multivariate analysis, all factors were independently associated with MI (p<0.05 for all adjusted ORs).
Association of Allopurinol use and MI
Allopurinol was by far the most frequent ULT taken by participants. Indeed, no case and only 0.1% of controls reported use of febuxostat, and no participant took uricosurics. In all, 3.1% of cases and 3.8% of matched controls reported allopurinol use during at least one period within the two preceding years. Among allopurinol users, most (90% of cases and 92% of controls) had taken the drug regularly (at least 5 days per week) during the preceding 2 years. About two-thirds of cases and controls took a daily dose ≥200 mg, whereas 19% of cases and 25% of controls took ≥300 mg.
When adding all vascular risk factors to the conditional logistic regression model, the adjusted OR (aOR) for MI was at the limit of the significance: aOR=0.80 (0.59 to 1.09) (Table 2). When the number of visits to the GP was excluded from the matching criteria in order to use the whole cases pool (n=2593) and their 5185 matched controls, the aOR was 0.73 (0.54 to 0.99). We then categorised allopurinol use by dosage (no use, <200, ≥200 mg) and found no association of allopurinol dose and MI risk (<200 mg: aOR=0.63 (0.37 to 1.09); ≥200 mg: aOR=0.74 (0.51 to 1.08)) Table 3.
Association of Allopurinol use With MI Risk by Subgroup
Stratified analysis showed that the adjusted ORs were similar for hypertensive and non-hypertensive patients and for both sexes (figure 2). Next, we examined whether the relation between allopurinol use and MI risk was similar by type of MI (STEMI and NSTEMI). Allopurinol use was associated with a significantly decreased risk of STEMI (aOR: 0.65 (0.44 to 0.96)) but not of NSTEMI (aOR: 1.17 (0.69 to 1.98)). Polytomous logistic regression revealed significant aORs after stratification on STEMI/NSTEMI cases (p=0.01).
(Enlarge Image)
Figure 2.
Forest plot of adjusted ORs by type of myocardial infarction (ST-elevated (STEMI) and non-ST-elevated (NSTEMI)), sex and hypertension status (HTA− and HTA+). The number of cases who had STEMI and NSTEMI was n=1710 and n=540, respectively.
Among the 56 MI presented with a resuscitated cardiac arrest ('near-deaths'), previous allopurinol use was 0% (95% CI (0.0% to 6.2%)), which is not statistically different from that of non-near-death MI patients (3.1%). Previous allopurinol use in the 115 matched controls to near-death patients was 3.8%, which is similar to the proportion of users in the whole control population.
Association of Colchicine use and MI
Finally, we investigated the association of colchicine use and risk of MI. Cases and controls had taken colchicine in the same proportion: 1.1% (see online supplementary table S1 http://ard.bmj.com/content/74/5/836/suppl/DC1). Colchicine use in the previous 2 years was not associated with decreased MI risk. When cases were compared with their matched controls, the aOR was 1.17 (0.70 to 1.93).
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