Cerebrovascular disease Defined from diagnosis ICD10: I60-69, ICD8:

Transcription

1 Supplmntary Tabl 1: ICD cods Diagnoss, surgical procdurs, and pharmacothrapy usd for dfining th study population, comorbidity, and outcoms Study population Myocardial Infarction ICD8: 430 ICD10: I21-22 Comorbidity Crbrovascular disas ICD10: I60-69, ICD8: Diabts with complications ICD10: E10-E14 ICD8: 250 Cardiac dysrhythmias ICD10: I47-49, I460,I469, R001 ICD8:427 Acut rnal failur Chronic rnal failur Hart failur of chronic glomrulonphritis, chronic tubul intstinal nphropathy, non-nd-stag chronic kidny disas, and diabtic and hyprtnsiv nphropathy. plus tratmnt ICD10: N17, N19, R34 ICD8: 584 ICD10: E102, E112, E132, E142, I120, M200, M313, M319, M321B, N02-N08, N11-N12, N14, N18-N19, N26, N158-N160, N162-N164, N168, Q612-Q613, Q615, Q619 ICD8: 403, 404, 580-4, 590, 223, 25002, 40039, 59009, 59320, , ICD10: I110, I42, I50, J819 ICD8: 425, Tratmnt: Loop-diurtics Malignancy Dfind from diagnoss of cancr (non-bnign) ICD10: C00-C97 ICD8: Shock ICD10: R57 ICD8: 7855 Pulmonary odma ICD10: J81.J182 ICD8: 514 Prvious Blding of gastrointstinal, ICD10: I60-I62, I690-I692, J942, K250, K254, K260,

2 Pptic Ulcrs Livr Alcohol intracranial, rspiratory, and urinary tract bldings; and anmia causd by blding. K264, K270, K280, K920-K922, N02, R04, R31, S064-S066 ICD8: ICD10: K25, K26, K27, K29 ICD10: B15-19, C22, K70-77, DZ944, DD684C, DI982B, DQ618A, ICD8: 571-3,155,070 ICD10: K70, T52, K860, E52, E244, G312, O354, Z714, Z721, G621,G721, K292,L278, I 426 Prcutanous coronary NSCP: KFN (includs graft implantation and othr Dfind from procdur procdur coronary intrvntions) ICD8: 8 th rvision of th Intrnational Classification of Disass systm ICD10: 10 th rvision of th Intrnational Classification of Disass systm NCSP: Th Nordic Mdical Statistics Committs Classification of Surgical Procdurs Outcoms Gastrointstinal blding Dath from or diagnosis of gastrointstinal blding. ICD10: K250, K254, K260, K264, K270, K280, K920-K922, Supplmntary Tabl 2: ATC cods Tratmnt Oral anticoagulants ATC: BO11AA03-4 Vitamin K antagonists including warfarin and phnprocoumon Aspirin ATC: BO1AC06, NO2BA01 Actylsalicylic acid Clopidogrl ATC: BO1AC04 Non-stroidal anti-inflammatory drugs ATC: M01A but xcluding glucosamin (M01AX05) Including rofcoxib (M01AH02), clcoxib (M01AH01), naproxn (M01AE02), diclofnac (M01AB05), ibuprofn (M01AE01) Statins ATC: C10A Bta-blockrs ATC: C07 Rnin angiotnsin systm inhibitors ATC: C09 Including: angiotnsin-convrting-nzym

3 inhibitors, angiotnsin-ii rcptor blockrs Loop-diurtics ATC: C03C Thiazids ATC: C03A Proton-pump inhibitors ATC: A02BC Oral glucos-lowring drugs ATC: A10 Glucocorticoids ATC: H02AB Including: prdnisolon ATC: Anatomical Thraputic Chmical (ATC) systm Supplmntary Tabl 3: Risk of blding according to antithrombotic tratmnt Monothrapy (Aspirin or clopidogrl) + Dual Thrapy + NSAID NSAID No PPI PPI No PPI PPI Evnts n Risk tim in prson yars Crud rats* Adjustd HR Rfrnc 0.77 [ ] Rfrnc 0.41 [ ] *Crud rats ar vnts pr 100 prson yars. Supplmntary Tabl 4: Risk of blding according to th individual NSAIDs Rofcoxib Clcoxib Diclofnac Ibuprofn Naproxn No PPI PPI No PPI PPI No PPI PPI No PPI PPI No PPI PPI Evnts n Risk tim in prson yars Crud rats*

4 Adjustd HR Rfrnc 0.50[ ] Rfrnc *Crud rats ar vnts pr 100 prson yars. 0.30[ ] Rfrnc 0.68[ ] Rfrnc 0.88[ ] Rfrnc 1.57[ ] Appndix: Snsitivity analyss Rstricting th study priod to yars (1997 to 2001) whn NSAIDs wr not availabl ovr th countr did not chang th rsults apprciably (Supplmntal Tabl 5). Using a Wald tst, w xamind intractions btwn us of NSAID, antithrombotic tratmnt, PPI and availabl covariats. No clinically important intractions wr found. Sinc dabigatran was availabl in Dnmark for prvntion of thrombombolic vnts in patints with atrial fibrillation from August 2011, w prformd a snsitivity analysis with th follow-up priod nding in Dcmbr 2010, which yildd rsults similar to th main analysis (Supplmntal Tabl 6). W found no dcrasd risk adding PPI to NSAID and antithrombotic tratmnt rgarding th cardiovascular dath ndpoint (Supplmntal Tabl 7). Th rsults wr unchangd whn th cohort was stratifid for ag ovr 65 yars. W mad a snsitivity analysis adjusting for th variabls in th HAS- BLED scor. Th rsults rmain th sam (Supplmntal Tabl 8). Whn accounting for accumulation of risk factors during follow-up, our rsults wr unaffctd - HR 0.63(0.48 to 0.84). W stratifid patints into high risk of gastrointstinal blding (prvious blding n=5511, vnts=420) and low risk (no prvious blding n=77,444 vnts=2,809) groups. Th HR stimat was similar to th main analysis for high risk patints and - HR 0.53 (0.24 to 1.33, p-valu 0.188) and low risk patints HR 0.75 (0.56 to 1.00, p-valu 0.056). Howvr du to a low numbr of vnts, th rsult was insignificantly. Ticagrlor was mad availabl in Dnmark August 2011; w thrfor undrtook a snsitivity analysis with th follow-up priod nding in Dcmbr Th rsults wr similar to th main analysis (not shown). This was also th cas for th analyss of patints with rhumatoid arthritis (Supplmntal Tabl 9) and for thos xamining duration of NSAID tratmnt (Supplmntal Tabl 10) Supplmntary Tabl 5: Ending follow-up 2001 Adjustd HR prsons (992 vnts) Adjustd HR Rfrnc 0.96 [ ]

5 Supplmntary Tabl 6: Ending follow-up Dcmbr 2010 Adjustd HR prsons (3181) vnts) Adjustd HR Rfrnc 0.73 [ ] Supplmntary Tabl 7: cardiovascular risk Adjustd HR prsons (27349 vnts) Adjustd HR Rfrnc 1.50( ) Supplmntary Tabl 8: Adjustmnt of HAS-BLED Adjustd HR prsons (3229) vnts) Adjustd HR Rfrnc 0.71 [ ] Supplmntal Tabl 9: Rhumatic patints (n=4556, vnts=246) Hazard ratio p-valu Confidnc intrvals NSAID without PPI 1.0 Rfrnc PPI+NSAID Supplmntal Tabl 10: Duration of tratmnt Tim intrvals aftr tratmnt initiatd NSAID Evnts Incidnc rats HR (CI 95%) NSAID+PPI Evnts Incidnc rats HR (CI 95 %) 0-14days Rfrnc ( ) >14 days Rfrnc ( )

6 Supplmntary Figur: Cohort dsign