Post by Admin on Dec 12, 2023 20:57:44 GMT
Neither refers to participants who weighed <70 kg and did not smoke, either refers to participants who weighed ≥70 kg or smoked, and both refers to participants who weighed ≥70 kg and smoked. Numbers of events are four fewer than listed in table 1 because of missing data on smoking status for four individuals. HR=hazard ratio.
The weight dependence of the effect of low-dose aspirin on cardiovascular events was observed for all tablet formulations (appendix pp 8,9), but loss of effect in participants weighing 70 kg or more was more evident for enteric-coated or delayed-release aspirin and alternate-day, standard-release aspirin than for daily, standard-release aspirin.
In participants weighing 70 kg or more, low-dose aspirin (75–100 mg) was associated with an increase in case fatality of first cardiovascular events (OR 1·33 [95% CI 1·08–1·64], p=0·0082; appendix p 10), particularly for myocardial infarction (1·73 [1·20–2·49], p=0·0035), with an overall increase in fatal first cardiovascular events in participants aged 70 years or older (HR 1·45 [95% CI 1·01–2·10], p=0·04).
The increased risk of major bleeding on low-dose aspirin versus control was lost in participants weighing 90 kg or more (pinteraction=0·024; figure 1; appendix p 11).
Modification by weight of the effect of low-dose aspirin on cardiovascular events remained when stratifying by BMI (appendix p 5), and the effect was also modified by height (appendix p 12). Effect modification was similar for body surface area, lean body mass, and fat mass, but bodyweight was most informative (appendix pp 13, 14). When modelled together, effect modification by weight (pinteraction=0·0026) and smoking (pinteraction=0·0027) exceeded that by BMI (pinteraction=0·30).
In secondary prevention of stroke in the ESPS-2 trial,28 aspirin (25 mg twice daily vs placebo) reduced cardiovascular events in participants weighing less than 70 kg (HR 0·74 [95% CI 0·63–0·87], p=0·0003; appendix p 15). Some benefit was also evident in participants weighing 70 kg or more, but only in the acute phase of treatment (appendix p 15). Effect modification by weight during all follow-up of that trial was similar to that in the primary prevention trials of 75–100 mg aspirin, particularly in women (HR for cardiovascular events or death was 0·68 [95% CI 0·56–0·83, p=0·0001] in women weighing <70 kg and 1·02 [0·77–1·35, p=0·90] in those weighing ≥70 kg; pinteraction=0·022; figure 2; appendix p 15). However, benefit was also seen in women who weighed less than 50 kg (HR 0·50 [95% CI 0·29–0·84, p=0·0094] for all cardiovascular events or death; appendix p 15). In the Dutch-TIA trial (aspirin 30 mg vs 283 mg),31 30 mg aspirin also tended to be more effective than 283 mg in women weighing less than 70 kg (23 of 253 women treated with 30 mg had a cardiovascular event vs 47 of 319 women treated with 283 mg), although the difference was not significant (HR 0·64 [95% CI 0·39–1·06], p=0·081).
The weight dependence of the effect of low-dose aspirin on cardiovascular events was observed for all tablet formulations (appendix pp 8,9), but loss of effect in participants weighing 70 kg or more was more evident for enteric-coated or delayed-release aspirin and alternate-day, standard-release aspirin than for daily, standard-release aspirin.
In participants weighing 70 kg or more, low-dose aspirin (75–100 mg) was associated with an increase in case fatality of first cardiovascular events (OR 1·33 [95% CI 1·08–1·64], p=0·0082; appendix p 10), particularly for myocardial infarction (1·73 [1·20–2·49], p=0·0035), with an overall increase in fatal first cardiovascular events in participants aged 70 years or older (HR 1·45 [95% CI 1·01–2·10], p=0·04).
The increased risk of major bleeding on low-dose aspirin versus control was lost in participants weighing 90 kg or more (pinteraction=0·024; figure 1; appendix p 11).
Modification by weight of the effect of low-dose aspirin on cardiovascular events remained when stratifying by BMI (appendix p 5), and the effect was also modified by height (appendix p 12). Effect modification was similar for body surface area, lean body mass, and fat mass, but bodyweight was most informative (appendix pp 13, 14). When modelled together, effect modification by weight (pinteraction=0·0026) and smoking (pinteraction=0·0027) exceeded that by BMI (pinteraction=0·30).
In secondary prevention of stroke in the ESPS-2 trial,28 aspirin (25 mg twice daily vs placebo) reduced cardiovascular events in participants weighing less than 70 kg (HR 0·74 [95% CI 0·63–0·87], p=0·0003; appendix p 15). Some benefit was also evident in participants weighing 70 kg or more, but only in the acute phase of treatment (appendix p 15). Effect modification by weight during all follow-up of that trial was similar to that in the primary prevention trials of 75–100 mg aspirin, particularly in women (HR for cardiovascular events or death was 0·68 [95% CI 0·56–0·83, p=0·0001] in women weighing <70 kg and 1·02 [0·77–1·35, p=0·90] in those weighing ≥70 kg; pinteraction=0·022; figure 2; appendix p 15). However, benefit was also seen in women who weighed less than 50 kg (HR 0·50 [95% CI 0·29–0·84, p=0·0094] for all cardiovascular events or death; appendix p 15). In the Dutch-TIA trial (aspirin 30 mg vs 283 mg),31 30 mg aspirin also tended to be more effective than 283 mg in women weighing less than 70 kg (23 of 253 women treated with 30 mg had a cardiovascular event vs 47 of 319 women treated with 283 mg), although the difference was not significant (HR 0·64 [95% CI 0·39–1·06], p=0·081).
