4.5.0.0 As­pirin Dos­ing

Av­er­age daily dosages used in most clin­i­cal tri­als in­volv­ing pa­tients with di­a­betes ranged from 50 mg to 650 mg but were most­ly in the range of 100–325 mg/‍day. There is lit­tle ev­i­dence to ­sup­port any specific dose, but using the low­est pos­si­ble dose may help to re­duce side ef­fects (132). In the U.S., the most com­mon low-‍dose tablet is 81 mg. Al­though platelets from pa­tients with di­a­betes have al­tered func­tion, it is un­clear what, if any, ef­fect that finding has on the re­quired dose of as­pirin for car­dio­pro­tec­tive ef­fects in the pa­tient with di­a­betes. Many al­ter­nate path­ways for platelet ac­ti­va­tion exist that are in­de­pen­dent of throm­box­ane A2 and thus are not sen­si­tive to the ef­fects of as­pirin (133). “As­pirin re­sis­tance” has been de­scribed in pa­tients with di­a­betes when mea­sured by a va­ri­ety of ex vivo and in vitro meth­ods (platelet ag­gre­gom­e­try, mea­sure­ment of throm­box­ane B2) (134), but other stud­ies sug­gest no im­pair­ment in as­pirin re­sponse among pa­tients with di­a­betes (135). A re­cent trial sug­gest­ed that more fre­quent dos­ing reg­i­mens of as­pirin may re­duce platelet reac­tiv­i­ty in in­di­vid­u­als with di­a­betes (136); how­ev­er, these ob­ser­va­tions alone are insufficient to em­pir­i­cal­ly rec­om­mend that high­er doses of as­pirin be used in this group at this time. An­oth­er re­cent metaanal­y­sis raised the hy­poth­e­sis that low-‍dose as­pirin efficacy is re­duced in those weigh­ing more than 70kg (137); how­ev­er, the AS­CEND trial found benefit of low dose as­pirin in those in this weight range, which would thus not val­i­date this sug­gest­ed hy­poth­e­sis (121). It ap­pears that 75–162 mg/‍day is op­ti­mal.