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ration published an individual patient –\nlevel meta-analysis (161) of the six largetrials of aspirin for primary preventionin the general population. These trials\ncollectively enrolled over 95,000 partici-\npants, including almost 4,000 with dia-betes. Overall, they found that aspirinreduced the risk of serious vascu... | [
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events by 12% (relative risk 0.88 [95%\nCI 0.82 –0.94]). The largest reductionwas for nonfatal MI, with little effect on\nCHD death (relative risk 0.95 [95% CI0.78–1.15]) or total stroke.\nMost recently, the ASCEND (A Study\nof Cardiovascular Events iN Diabetes)\ntrial randomized 15,480 people with diabe- | [
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trial randomized 15,480 people with diabe-\ntes but no evident cardiovascular diseaseto aspirin 100 mg daily or placebo (162).The primary ef ficacy end point was vascu- | [
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lar death, MI, stroke, or transient ischemicattack. The primary safety outcome wasmajor bleeding (i.e., intracranial hemor-rhage, sight-threatening bleeding in theeye, gastrointestinal bleeding, or other\nserious bleeding). During a mean follow-\nup of 7.4 years, there was a signi ficant\n12% reduction in the primary ef... | [
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12% reduction in the primary effi cacy\nend point (8.5% vs. 9.6%; P=0 . 0 1 ) .I n\ncontrast, major bleeding was signi ficantly\nincreased from 3.2 to 4.1% in the aspiringroup (rate ratio 1.29; P=0 . 0 0 3 ) ,w i t h\nmost of the excess being gastrointestinal\nbleeding and other extracranial bleeding.\nT h e r ew e r en ... | [
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T h e r ew e r en os i g n i ficant differences by\nsex, weight, or duration of diabetes orother baseline factors, including ASCVD\nrisk score.\nTwo other large, randomized trials of\naspirin for primary prevention, in peo-\nple without diabetes (ARRIVE [Aspirin toReduce Risk of Initial Vascular Events])\n(163) and in t... | [
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(163) and in the elderly (ASPREE [Aspi-\nrin in Reducing Events in the Elderly])(164), which included 11% with diabe-tes, found no benefi t of aspirin on the\nprimary ef ficacy end point and an in- | [
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primary ef ficacy end point and an in-\ncreased risk of bleeding. In ARRIVE, with12,546 individuals over a period of60 months of follow-up, the primary endpoint occurred in 4.29% vs. 4.48% of indi-\nviduals in the aspirin versus placebo groups\n(HR 0.96 [95% CI 0.81– 1.13]; P=0 . 6 0 ) . | [
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(HR 0.96 [95% CI 0.81– 1.13]; P=0 . 6 0 ) .\nGastrointestinal bleeding events (char-acterized as mild) occurred in 0.97% of\nindividuals in the aspirin group vs.\n0.46% in the placebo group (HR 2.11[95% CI 1.36– 3.28]; P= 0.0007). In\nASPREE, including 19,114 individuals, for\ncardiovascular disease (fatal CHD, MI, | [
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cardiovascular disease (fatal CHD, MI,\nstroke, or hospitalization for heart failure)after a median of 4.7 years of follow-up,the rates per 1,000 person-years were10.7 vs. 11.3 events in aspirin vs. placebo\ngroups (HR 0.95 [95% CI 0.83 –1.08]). The\nrate of major hemorrhage per 1,000 per- | [
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rate of major hemorrhage per 1,000 per-\nson-years was 8.6 events vs. 6.2 events,respectively (HR 1.38 [95% CI 1.18 –1.62];\nP<0.001).\nThus, aspirin appears to have a mod-\nest effect on ischemic vascular events,with the absolute decrease in events de-\npending on the underlying ASCVD risk. | [
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pending on the underlying ASCVD risk.\nThe main adverse effect is an increasedrisk of gastrointestinal bleeding. The ex-cess risk may be as high as 5 per 1,000per year in real-world settings. However,for adults with ASCVD risk >1% per year, | [
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the number of ASCVD events preventedwill be similar to the number of episodesof bleeding induced, although these com-\nplications do not have equal effects on\nlong-term health (165).\nRecommendations for using aspirin\nas primary prevention include both menand women aged $50 years with diabe- | [
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tes and at least one additional majorrisk factor (family history of prematureASCVD, hypertension, dyslipidemia, smok-ing, or CKD/albuminuria) who are not atincreased risk of bleeding (e.g., older age,anemia, or renal disease) (166 –169). Non- | [
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invasive imaging techniques such as coro-nary calcium scoring may help furthertailor aspirin therapy, particularly in thoseat low risk (170,171). For people >70 years\nof age (with or without diabetes), the bal-ance appears to have greater risk thanbenefit (162,164). Thus, for primary pre- | [
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vention, the use of aspirin needs to becarefully considered and may generally not\nbe recommended. Aspirin may be consid- | [
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be recommended. Aspirin may be consid-\nered in the context of high cardiovascularrisk with low bleeding risk but generallynot in older adults. Aspirin therapy for pri-mary prevention may be considered in thecontext of shared decision-making, whichcarefully weighs the cardiovascular bene fits\nwith the fairly comparable... | [
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with the fairly comparable increase in riskof bleeding.\nFor people with documented ASCVD,\nuse of aspirin for secondary prevention\nhas far greater bene fit than risk; for this\nindication, aspirin is still recommended\n(157).\nAspirin Use in People <50 Years of Age | [
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(157).\nAspirin Use in People <50 Years of Age\nAspirin is not recommended for thoseat low risk of ASCVD (such as men andwomen aged <50 years with diabetes\nwith no other major ASCVD risk factors),as the low bene fit is likely to be out-\nweighed by the risk of bleeding. Clinicaljudgment should be used for those at inte... | [
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mediate risk (younger individuals with one\nor more risk factors or older individualswith no risk factors) until further research isavailable. Individuals ’willingness to undergo\nlong-term aspirin therapy should also beconsidered in shared decision-making (172).diabetesjournals.org/care Cardiovascular Disease and Risk... | [
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©AmericanDiabetesAssociation | [
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Aspirin use in individuals aged <21 years is\ngenerally contraindicated due to the associ-\nated risk of Reye syndrome.\nAspirin Dosing\nAverage daily dosages used in most clini-cal trials involving people with diabetes\nranged from 50 to 650 mg but were\nmostly in the range of 100 –325 mg/day. | [
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mostly in the range of 100 –325 mg/day.\nT h e r ei sl i t t l ee v i d e n c et os u p p o r ta n yspecifi c dose, but using the lowest possi-\nble dose may help to reduce side effects(173). In the ADAPTABLE (Aspirin Dosing:A Patient-Centric Trial Assessing Bene fits\nand Long-term Effectiveness) trial of indi-viduals w... | [
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disease, 38% of whom had diabetes,\nt h e r ew e r en os i g n i ficant differences in\ncardiovascular events or major bleedingbetween individuals assigned to 81 mg\nand those assigned to 325 mg of aspirin\ndaily (174). In the U.S., the most com-mon low-dose tablet is 81 mg. Althoughplatelets from people with diabetes h... | [
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altered function, it is unclear what, if any,\neffect that finding has on the required\ndose of aspirin for cardioprotective ef-fects in people with diabetes. Many alter-\nnate pathways for platelet activation\nexist that are independent of thrombox-ane A\n2and thus are not sensitive to the\neffects of aspirin (175). “A... | [
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effects of aspirin (175). “Aspirin re-\nsistance ”has been described in people\nwith diabetes when measured by a vari-ety of ex vivo and in vitro methods(platelet aggregometry and measurement\nof thromboxane B\n2) (176), but other\nstudies suggest no impairment in aspirin | [
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2) (176), but other\nstudies suggest no impairment in aspirin\nresponse among people with diabetes(177). A trial suggested that more fre-quent dosing of aspirin may reduce plate-\nlet reactivity in individuals with diabetes\n(178); however, these observations aloneare insuf ficient to empirically recommend\nthat higher ... | [
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that higher doses of aspirin be used in\nthis group at this time. Another meta-\nanalysis raised the hypothesis that low-dose aspirin ef ficacy is reduced in those\nweighing >70 kg (179); however, the\nASCEND trial found bene fit of low-dose | [
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ASCEND trial found bene fit of low-dose\naspirin in those in this weight range,which would thus not validate this sug-gested hypothesis (162). It appears that\n75–162 mg/day is optimal.\nIndications for P2Y12 Receptor\nAntagonist Use\nCombination dual antiplatelet therapy\nwith aspirin and a P2Y12 receptor antag- | [
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with aspirin and a P2Y12 receptor antag-\nonist is indicated after acute coronarysyndromes and coronary revasculariza-tion with stenting (180). In addition, cur-rent guidelines recommend short-term\ndual antiplatelet therapy after high-risk\ntransient ischemic attack and minorstroke (181). The indications for dual anti... | [
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platelet therapy and length of treatment\nare rapidly evolving and should be deter-\nmined by an interprofessional team ap-\nproach that includes a cardiovascular orneurological specialist, respectively. Evi-\ndence supports use of either ticagrelor or\nclopidogrel if no percutaneous coronary\nintervention was performe... | [
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intervention was performed and clopidog-\nrel, ticagrelor, or prasugrel if a percutane-ous coronary intervention was performed\n( 1 8 2 ) .I np e o p l ew i t hd i a b e t e sa n dp r i o r\nMI (1 –3 years before), adding ticagrelor\nto aspirin signi ficantly reduces the risk of | [
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to aspirin signi ficantly reduces the risk of\nrecurrent ischemic events, including car-diovascular and CHD death (183). Simi-\nlarly, the addition of ticagrelor to aspirin\nreduced the risk of ischemic cardiovascu-\nlar events compared with aspirin alone\nin people with diabetes and stable coro-nary artery disease (184... | [
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0.02646188624203205,
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a higher incidence of major bleeding,\nincluding intracranial hemorrhage, wasnoted with dual antiplatelet therapy. The\nnet clinical bene fit (ischemic bene fitv s .\nbleeding risk) was improved with ticagre-lor therapy in the large prespeci fied\nsubgroup of individuals with history of\npercutaneous coronary intervention... | [
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percutaneous coronary intervention, while\nno net bene fit was seen in individuals\nwithout prior percutaneous coronary in-tervention (185). However, early aspirin\ndiscontinuation compared with continueddual antiplatelet therapy after coronary\nstenting may reduce the risk of bleeding\nwithout a corresponding increase ... | [
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without a corresponding increase in the\nrisks of mortality and ischemic events, as\nshown in a prespeci fied analysis of people\nwith diabetes enrolled in the TWILIGHT\n(Ticagrelor With Aspirin or Alone in High-\nRisk Patients After Coronary Intervention)trial and a recent meta-analysis (186,187).\nCombination Antiplat... | [
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Combination Antiplatelet and\nAnticoagulation Therapy\nCombination therapy with aspirin plus\nlow-dose rivaroxaban may be consid-\nered for people with stable coronary\nand/or PAD to prevent major adverse\nlimb and cardiovascular complications.In the COMPASS (Cardiovascular Out-\ncomes for People Using Anticoagulation | [
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comes for People Using Anticoagulation\nStrategies) trial of 27,395 individualswith established coronary artery disease\nand/or PAD, aspirin plus rivaroxaban2.5 mg twice daily was superior to aspi-\nrin plus placebo in the reduction of car-diovascular ischemic events, including\nmajor adverse limb events. The absolute | [
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-0.... |
major adverse limb events. The absolute\nbene fits of combination therapy ap-\npeared larger in people with diabetes,who comprised 10,341 of the trial par-\nticipants (188,189). A similar treatment\nstrategy was evaluated in the Vascular\nOutcomes Study of ASA (acetylsalicylic\nacid) Along with Rivaroxaban in Endovas- | [
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-0.0127... |
acid) Along with Rivaroxaban in Endovas-\ncular or Surgical Limb Revascularization\nfor Peripheral Artery Disease (VOYAGER\nPAD) trial (190), in which 6,564 individu-\nals with PAD who had undergone revas-\ncularization were randomly assigned to\nreceive rivaroxaban 2.5 mg twice daily\nplus aspirin or placebo plus aspi... | [
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0.01... |
plus aspirin or placebo plus aspirin. Ri-\nvaroxaban treatment in this group ofindividuals was also associated with a\nsignificantly lower incidence of ischemic\ncardiovascular events, including majoradverse limb events. However, an in-\ncreased risk of major bleeding was noted\nwith rivaroxaban added to aspirin treat-\... | [
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ment in both COMPASS and VOYAGER\nPAD.\nThe risks and bene fits of dual antipla-\ntelet or antiplatelet plus anticoagulanttreatment strategies should be thor-\noughly discussed with eligible individu-\nals, and shared decision-making should\nbe used to determine an individually ap-\npropriate treatment approach. This fie... | [
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propriate treatment approach. This field\nof cardiovascular risk reduction is evolv-ing rapidly, as are the de finitions of op-\ntimal care for individuals with differingtypes and circumstances of cardiovascu-\nlar complications.\nCARDIOVASCULAR DISEASE\nScreening\nRecommendations\n10.38a In asymptomatic individuals,\nro... | [
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routine screening for coronary artery\ndisease is not recommended, as it\ndoes not improve outcomes as long\nas ASCVD risk factors are treated. A\n10.38b Consider investigations for\ncoronary artery disease in the pres-ence of any of the following: atypicalcardiac symptoms; signs or symp-\ntoms of associated vascular d... | [
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... |
toms of associated vascular disease,\nincluding carotid bruits, transient is-chemic attack, stroke, claudication,\nor PAD; or electrocardiogram abnor-\nmalities (e.g., Q waves). E\n10.39a Adults with diabetes are at\nincreased risk for the developmentS194 Cardiovascular Disease and Risk Management Diabetes Care Volume ... | [
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-0.0... |
©AmericanDiabetesAssociation | [
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0.0... |
of asymptomatic cardiac structural\nor functional abnormalities (stage Bheart failure) or symptomatic (stage C)\nheart failure. Consider screening adults\nwith diabetes by measuring a natri-uretic peptide (B-type natriuretic pep-\ntide [BNP] or N-terminal pro-BNP [NT-\nproBNP]) to facilitate prevention ofstage C heart ... | [
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proBNP]) to facilitate prevention ofstage C heart failure. B\n10.39b In asymptomatic individuals\nwith diabetes and abnormal natriuretic\npeptide levels, echocardiography is\nrecommended to identify stage Bheart failure. A\n10.40 In asymptomatic individuals\nwith diabetes and age $50 years, mi- | [
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0.... |
with diabetes and age $50 years, mi-\ncrovascular disease in any location, orfoot complications or any end-organ\ndamage from diabetes, screening for\nPAD with ankle-brachial index testingis recommended to guide treatmentfor cardiovascular disease prevention\nand limb preservation. AIn individu-\nals with diabetes dura... | [
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-0.040642619132995605,
0.06814... |
als with diabetes duration $10 years,\nscreening for PAD should be consid-\nered. B\nTreatment\nRecommendations\n10.41 Among people with type 2 di-\nabetes who have established ASCVD\nor established kidney disease, asodium –glucose cotransporter 2 (SGLT2)\ninhibitor or glucagon-like peptide 1(GLP-1) receptor agonist wi... | [
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0.00... |
onstrated cardiovascular disease\nbene fit(Table 10.3B and Table\n10.3C ) is recommended as part of\nthe comprehensive cardiovascularrisk reduction and/or glucose-loweringtreatment plans. A\n10.41a In people with type 2 diabe-\ntes and established ASCVD, multipleASCVD risk factors, or diabetic kid-ney disease, an SGLT2 ... | [
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0.023572638630867004,
-0.07803995907306671,
0.017393... |
demonstrated cardiovascular bene-\nfit is recommended to reduce the\nrisk of major adverse cardiovascularevents and/or heart failure hospital-ization. A\n10.41b In people with type 2 diabetes\nand established ASCVD or multiplerisk factors for ASCVD, a GLP-1 recep-tor agonist with demonstrated cardio-\nvascular bene fit i... | [
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0.006044568028301001,
-0.04010438919067383,
0.0256... |
vascular bene fit is recommended to\nreduce the risk of major adverse car-\ndiovascular events. A10.41c In people with type 2 diabetes\nand established ASCVD or multiple\nrisk factors for ASCVD, combinedtherapy with an SGLT2 inhibitor withdemonstrated cardiovascular bene fit\nand a GLP-1 receptor agonist withdemonstrated... | [
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0.023... |
and a GLP-1 receptor agonist withdemonstrated cardiovascular bene fit\nmay be considered for additive re-\nduction of the risk of adverse cardio-\nvascular and kidney events. A\n10.42a In people with type 2 diabe-\ntes and established heart failure\nwith either preserved or reduced | [
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0.04... |
tes and established heart failure\nwith either preserved or reduced\nejection fraction, an SGLT2 inhibitor(including SGLT1/2 inhibitor) withproven bene fit in this patient popu-\nlation is recommended to reducethe risk of worsening heart failureand cardiovascular death. A\n10.42b In people with type 2 diabe- | [
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0.03... |
10.42b In people with type 2 diabe-\ntes and established heart failurewith either preserved or reducedejection fraction, an SGLT2 inhibitorwith proven bene fit in this patient\npopulation is recommended to im-prove symptoms, physical limitations,and quality of life. A\n10.43 For individuals with type 2 di- | [
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0.0004669046320486814,
-0.03793778643012047,... |
10.43 For individuals with type 2 di-\nabetes and chronic kidney diseasewith albuminuria treated with maxi-mum tolerated doses of ACE inhibitoror ARB, addition of finerenone is rec-\nommended to improve cardiovascularoutcomes and reduce the risk ofchronic kidney disease progression. A\n10.44 In individuals with diabetes | [
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10.44 In individuals with diabetes\nwith established ASCVD or aged$55 years with additional cardio-vascular risk factors, ACE inhibitoror ARB therapy is recommended toreduce the risk of cardiovascularevents and mortality. A\n10.45a In individuals with diabetes | [
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10.45a In individuals with diabetes\nand asymptomatic stage B heart failure,an interprofessional approach to opti-mize guideline-directed medical therapy,which should include a cardiovasculardisease specialist, is recommended toreduce the risk for progression to symp-tomatic (stage C) heart failure. A\n10.45b In indivi... | [
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10.45b In individuals with diabetes\nand asymptomatic stage B heart failure,ACE inhibitors/ARBs and b-blockers are\nrecommended to reduce the risk forprogression to symptomatic (stage C)heart failure. A\n10.45c In individuals with type 2 di-\nabetes and asymptomatic stage Bheart failure or with high risk of orestablish... | [
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treatment with an SGLT inhibitor (in-\ncluding SGLT2 or SGLT1/2 inhibitors)\nis recommended to reduce the risk ofhospitalization for heart failure. A\n10.45d In individuals with type 2 di-\nabetes and diabetic kidney disease, fi-\nnerenone is recommended to reducethe risk of hospitalization for heartfailure. A\n10.45e I... | [
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10.45e In individuals with diabetes,\nguideline-directed medical therapy for\nmyocardial infarction and symptomatic\nstage C heart failure is recommendedwith ACE inhibitors/ARBs, MRAs, an-giotensin receptor/neprilysin inhibitor,\nb-blockers, and SGLT2 inhibitors, simi-\nlar to guideline-directed medical ther-\napy for ... | [
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apy for people without diabetes. A\n10.46 In people with type 2 diabe-\ntes with stable heart failure, metfor-\nmin may be continued for glucose\nlowering if estimated glomerular fil-\ntration rate remains >30 mL/min/\n1.73 m\n2but should be avoided in un-\nstable or hospitalized individuals withheart failure. B\n10.47 ... | [
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0.0... |
10.47 Individuals with type 1 diabe-\ntes and those with type 2 diabetes\nwho are ketosis prone and/or thoseconsuming ketogenic diets who are\ntreated with SGLT inhibition should\nbe educated on the risks and signsof ketoacidosis and methods of riskmanagement and provided with\nappropriate tools for accurate ke- | [
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-0.08665041625499725,
-0.0259... |
appropriate tools for accurate ke-\ntone measurement (i.e., serumb-hydroxybutyrate). E\nCardiac Testing\nCandidates for advanced or invasive car-\ndiac testing include those with 1)t y p i c a l\nor atypical cardiac symptoms and 2)\nan abnormal resting electrocardiogram(ECG). Exercise ECG testing without orwith echocar... | [
-0.006545881740748882,
0.023430000990629196,
0.02580016478896141,
-0.002416846342384815,
-0.05401911213994026,
-0.04966259002685547,
-0.049250196665525436,
0.01809554360806942,
-0.009594076313078403,
-0.04768366739153862,
0.04749619588255882,
-0.13035082817077637,
-0.05435246601700783,
0.0... |
the initial test. In adults with diabetes\n$40 years of age, measurement of cor-onary artery calcium is also reasonablefor cardiovascular risk assessment. Phar-macologic stress echocardiography or\nnuclear imaging should be considered in | [
0.026473496109247208,
0.07164822518825531,
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0.021947700530290604,
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0.05180702358484268,
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0.0... |
nuclear imaging should be considered in\nindividuals with diabetes in whom rest-ing ECG abnormalities preclude exercisestress testing (e.g., left bundle branch\nblock or ST-T abnormalities). In addition,\nindividuals who require stress testingand are unable to exercise shoulddiabetesjournals.org/care Cardiovascular Dis... | [
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0.05493440106511116,
-0.06285284459590912,
0.03159283101558685,
-0.014270933344960213,
-0.018824514001607895,
-0.007291336078196764,
0.06608887761831284,
-0.0537739098072052,
-0.01706160046160221,
0.002948661334812641,
0.0731574296951294,
-0.04816232994198799,
0.035997... |
©AmericanDiabetesAssociation | [
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0.043682683259248734,
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-0.005912777967751026,
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0.0628901943564415,
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0.0067015099339187145,
0.0... |
Table 10.3 A—Cardiovascular and cardiorenal outcomes trials of available antihyperglycemic medications completed after\nthe issuance of the FDA 2008 guidelines: DPP-4 inhibitors\nSAVOR-TIMI 53 (289)\n(n= 16,492)EXAMINE (311)\n(n= 5,380)TECOS (291)\n(n= 14,671)CARMELINA (292,312)\n(n= 6,979)CAROLINA (246)\n(n= 6,042) | [
0.013149701058864594,
-0.009040012024343014,
-0.011890925467014313,
0.03901445120573044,
-0.03498462960124016,
0.005925626028329134,
-0.06705781817436218,
0.1529534012079239,
0.008395268581807613,
0.028559565544128418,
-0.019183222204446793,
0.012854860164225101,
-0.06704355031251907,
-0.0... |
(n= 14,671)CARMELINA (292,312)\n(n= 6,979)CAROLINA (246)\n(n= 6,042)\nIntervention Saxagliptin/placebo Alogliptin/placebo Sitagliptin/placebo Linagliptin/placebo Linagliptin/glimepiride\nMain inclusion\ncriteriaType 2 diabetes and\nhistory of or\nmultiple risk\nfactors for CVDType 2 diabetes and\nACS within 15 –90 | [
0.003123085480183363,
-0.007943512871861458,
-0.05789433419704437,
0.0579393096268177,
-0.07912807166576385,
0.07357243448495865,
0.015861844643950462,
0.09796921908855438,
-0.05240438133478165,
-0.08335784822702408,
-0.02045765332877636,
-0.04187580570578575,
-0.07885363698005676,
-0.0856... |
multiple risk\nfactors for CVDType 2 diabetes and\nACS within 15 –90\ndays beforerandomizationType 2 diabetes and\npreexisting CVDType 2 diabetes and\nhigh CV and renal\nriskType 2 diabetes and\nhigh CV risk\nA1C inclusion\ncriteria (%)$6.5 6.5–11.0 6.5–8.0 6.5–10.0 6.5–8.5\nAge (years)* 65.1 61.0 65.4 65.8 64.0\nRace ... | [
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0.011384144425392151,
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0.02192210964858532,
0.03476112708449364,
0.04771418496966362,
-0.0063734701834619045,
0.08655878901481628,
-0.07723525911569595,
-0.047757942229509354,
0.0015931000234559178,
-0.06735260039567947,
-0.017077727243304253,
-0... |
Race (% White) 75.2 72.7 67.9 80.2 73.0\nSex (% male) 66.9 67.9 70.7 62.9 60.0\nDiabetes duration\n(years)*10.3 7.1 11.6 14.7 6.2\nMedian follow-up\n(years)2.1 1.5 3.0 2.2 6.3\nStatin use (%) 78 91 80 71.8 64.1\nMetformin use (%) 70 66 82 54.8 82.5\nPrior CVD/CHF (%) 78/13 100/28 74/18 57/26.8 34.5/4.5\nMean baseline\n... | [
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0.041723623871803284,
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0.02227053791284561,
-0.02129647135734558,
0.022608155384659767,
-0.07827199995517731,
0.06958238780498505,
-0.04664837568998337,
-0.05722930654883385,
-0.10576548427343369,
-0.04186250641942024,
-0.07321509718894958,
-0.036... |
Mean baseline\nA1C (%)8.0 8.0 7.2 7.9 7.2\nMean difference in\nA1C between\ngroups at end oftreatment (%)/C00.3† /C00.3† /C00.3† /C00.36† 0\nYear started/\nreported2010/2013 2009/2013 2008/2015 2013/2018 2010/2019\nPrimary outcome ‡ 3-point MACE 1.00\n(0.89 –1.12)3-point MACE 0.96\n(95% UL #1.16)4-point MACE 0.98\n(0.8... | [
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0.028169363737106323,
0.0376775749027729,
0.05559580400586128,
-0.01188273448497057,
0.1519956886768341,
0.015341849066317081,
-0.009819278493523598,
0.030636457726359367,
-0.006056004669517279,
-0.018525736406445503,
-0.0... |
(95% UL #1.16)4-point MACE 0.98\n(0.89 –1.08)3-point MACE 1.02\n(0.89 –1.17)3-point MACE 0.98\n(0.84 –1.14)\nKey secondary\noutcome ‡Expanded MACE 1.02\n(0.94 –1.11)4-point MACE 0.95\n(95% UL #1.14)3-point MACE 0.99\n(0.89 –1.10)Kidney composite\n(ESRD, sustained$40% decrease in\neGFR, or renaldeath) 1.04(0.89 –1.22)4-... | [
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0.030913136899471283,
0.023211510851979256,
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-0.007736538536846638,
0.007171317934989929,
0.18372055888175964,
0.026808343827724457,
-0.031305618584156036,
0.0034842416644096375,
0.0298516433686018,
-0.026115477085113525,
0... |
eGFR, or renaldeath) 1.04(0.89 –1.22)4-point MACE 0.99\n(0.86 –1.14)\nCardiovascular\ndeath ‡1.03 (0.87 –1.22) 0.85 (0.66 –1.10) 1.03 (0.89 –1.19) 0.96 (0.81 –1.14) 1.00 (0.81 –1.24)\nMI‡ 0.95 (0.80 –1.12) 1.08 (0.88 –1.33) 0.95 (0.81 –1.11) 1.12 (0.90 –1.40) 1.03 (0.82 –1.29) | [
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-0.021897420287132263,
-0.04440940544009209,
-0.06682261824607849,
0.005286673549562693,
0.1509559005498886,
0.006782824639230967,
0.013967391103506088,
0.003020717529579997,
-0.03599131852388382,
-0.05872627720236778,
0.077... |
Stroke ‡ 1.11 (0.88 –1.39) 0.91 (0.55 –1.50) 0.97 (0.79 –1.19) 0.91 (0.67 –1.23) 0.86 (0.66 –1.12)\nHF hospitalization ‡ 1.27 (1.07 –1.51) 1.19 (0.90 –1.58) 1.00 (0.83 –1.20) 0.90 (0.74 –1.08) 1.21 (0.92 –1.59)\nUnstable angina\nhospitalization ‡1.19 (0.89 –1.60) 0.90 (0.60 –1.37) 0.90 (0.70 –1.16) 0.87 (0.57 –1.31) 1.... | [
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-0.007506246212869883,
0.03769614174962044,
-0.07079172879457474,
-0.004441027995198965,
-0.07722841203212738,
0.021561862900853157,
0.03325045853853226,
-0.01718159392476082,
-0.026803484186530113,
0.006503037642687559,
-0.044136498123407364,
-0... |
All-cause mortality ‡1.11 (0.96 –1.27) 0.88 (0.71 –1.09) 1.01 (0.90 –1.14) 0.98 (0.84 –1.13) 0.91 (0.78 –1.06)\nWorsening\nnephropathy ‡§1.08 (0.88 –1.32) ——Kidney composite\n(see above)—\n—, not assessed/reported; ACS, acute coronary syndrome; CHF, congestive heart failure; CV, cardiovascular; CVD, cardiovascular dise... | [
0.005677964072674513,
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0.018169423565268517,
-0.011738988570868969,
-0.010399756953120232,
-0.008621900342404842,
-0.05638280138373375,
0.12906934320926666,
-0.036286816000938416,
-0.0019940175116062164,
-0.03876188397407532,
0.0476609542965889,
0.006394281052052975,
-... |
DPP-4, dipeptidyl peptidase 4; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; GLP-1, glucagon-like peptide 1; HF, | [
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0.01466321386396885,
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0.00019254452490713447,
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0.1466728001832962,
0.04802706465125084,
0.020061861723661423,
0.023817628622055054,
-0.018344711512327194,
-0.0457526333630085,
0.08... |
heart failure; MACE, major adverse cardiovascular event; MI, myocardial infarction; UL, upper limit. Data in this table were adapted fromCefalu et al. (313). *Age was reported as means in all trials except EXAMINE, which reported medians; diabetes duration was reported asmeans in all trials except SAVOR-TIMI 53 and EXA... | [
0.037010032683610916,
0.015494492836296558,
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0.11355513334274292,
0.0061210147105157375,
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0.14719760417938232,
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-0.010745869018137455,
-0.0035254608374089003,
0.006143033038824797,
-0.022492345422506332,
-0... |
all trials except SAVOR-TIMI 53 and EXAMINE, which reported medians. †Significant difference in A1C between groups ( P<0.05). | [
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0.021240750327706337,
0.0030594286508858204,
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0.12836387753486633,
0.005966146010905504,
0.04725700989365578,
0.016962861642241478,
-0.008625215850770473,
-0.007308966480195522,
-0... |
‡Outcomes reported as hazard ratio (95% CI). §Worsening nephropathy is de fined as a doubling of creatinine level, initiation of dialysis, renal\ntransplantation, or creatinine >6.0 mg/dL ( >530 mmol/L) in SAVOR-TIMI 53. Worsening nephropathy was a prespeci fied exploratory adjudi- | [
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0.04981580376625061,
0.037142492830753326,
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-0.05234859511256218,
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0.1564985066652298,
-0.002812691731378436,
-0.04650745913386345,
-0.04099433496594429,
0.01993453875184059,
0.03571933135390282,
0.0... |
cated outcome in SAVOR-TIMI 53.S196 Cardiovascular Disease and Risk Management Diabetes Care Volume 47, Supplement 1, January 2024\n©AmericanDiabetesAssociation | [
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0.018598493188619614,
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0.0917578712105751,
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0.05188455060124397,
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0.07277384400367737,
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0.0033516946714371443,
0.026852445676922798,
-0.004206570331007242,
-0.0... |
undergo pharmacologic stress echocar-\ndiography or nuclear imaging.\nScreening Asymptomatic Individuals\nfor Atherosclerotic CardiovascularDisease\nThe screening of asymptomatic individu-\nals with high ASCVD risk is not recom-\nmended (191), in part because thesehigh-risk people should already be re-ceiving intensive... | [
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0.014551287516951561,
-0.08257076889276505,
0.032661665230989456,
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0.005210955627262592,
-0.0602475143969059,
0.09927918761968613,
-0.06550390273332596,
-0.030850589275360107,
0.005221476778388023,
0.006633531302213669,
-0.024860991165041924,
... |
approach that provides bene fits similar\nto those of invasive revascularization(192,193). There is also some evidence\nthat silent ischemia may reverse over\ntime, adding to the controversy con-cerning aggressive screening strategies(194). In prospective studies, coronary\nartery calcium has been established as | [
0.03350584954023361,
0.057126544415950775,
0.009885622188448906,
0.05896250903606415,
-0.017611486837267876,
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-0.01862914301455021,
0.07922274619340897,
-0.000463509262772277,
0.06373390555381775,
0.012614567764103413,
0.029244501143693924,
-0.03618382290005684,
0.07714... |
artery calcium has been established as\nan independent predictor of futureASCVD events in people with diabetes\nand is consistently superior to both the\nUK Prospective Diabetes Study (UKPDS)risk engine and the Framingham RiskScore in predicting risk in this population\n(195–197). However, a randomized ob-\nservational... | [
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0.018758058547973633,
-0.03690868243575096,
0.05455198884010315,
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0.04390202462673187,
0.056290965527296066,
0.04964795336127281,
-0.03970704600214958,
0.01362346950918436,
-0.019673172384500504,
0.0325... |
servational trial demonstrated no clinical\nbenefit to routine screening of asymp-\ntomatic people with type 2 diabetes and\nnormal ECGs (198). Despite abnormal\nmyocardial perfusion imaging in morethan one in five individuals, cardiac out- | [
0.062093839049339294,
0.11242477595806122,
-0.03730729594826698,
0.03272585570812225,
-0.021279605105519295,
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-0.0917736142873764,
0.10193942487239838,
0.014744637534022331,
-0.07930121570825577,
-0.01854017935693264,
0.058343641459941864,
-0.0805550068616867,
-0.00909... |
comes were essentially equal (and verylow) in screened versus unscreened indi-viduals. Accordingly, indiscriminate screen-ing is not considered cost-effective. Studies\nhave found that a risk factor –based ap-\nproach to the initial diagnostic evaluation\nand subsequent follow-up for coronaryartery disease fails to ide... | [
0.021450074389576912,
0.04649878293275833,
-0.02325805090367794,
-0.07615765184164047,
0.019006168469786644,
0.008394460193812847,
0.002865771995857358,
0.16121743619441986,
0.040059588849544525,
0.009925109334290028,
0.06167830526828766,
-0.014122086577117443,
0.013710251078009605,
0.0780... |
ple with type 2 diabetes will have silent\nischemia on screening tests (199,200).\nAny bene fit of newer noninvasive coro-\nnary artery disease screening methods,such as computed tomography calcium\nscoring and computed tomography angi-\nography, to identify patient subgroups fordifferent treatment strategies remains un... | [
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0.014239304699003696,
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0.07409028708934784,
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0.013020815327763557,
-0.1038886308670044,
0.0... |
proven in asymptomatic people with dia-\nbetes, though research is ongoing. Sinceasymptomatic people with diabetes withhigher coronary disease burden have more\nfuture cardiac events (195,201,202), these\nadditional imaging tests may provide rea-soning for treatment intensi fication and/or\nguide informed individual dec... | [
0.04405730590224266,
0.06166495010256767,
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0.013675094582140446,
-0.017089594155550003,
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0.028889743611216545,
0.07843759655952454,
0.015234986320137978,
-0.029067497700452805,
-0.060619253665208817,
0.04107595980167389,
-0.04253493621945381,
0.06... |
guide informed individual decision-making\nand willingness for medication initiation\nand participation.\nWhile coronary artery screening meth-\nods, such as calcium scoring, may improvecardiovascular risk assessment in people\nwith type 2 diabetes (203), their routineuse leads to radiation exposure and may\nresult in ... | [
0.03200581297278404,
0.0782012864947319,
-0.012314104475080967,
0.00822494924068451,
0.041618283838033676,
0.011702919378876686,
0.03854138404130936,
0.11422985047101974,
-0.0450715608894825,
-0.005621344316750765,
-0.015180225484073162,
0.02134152688086033,
-0.0356181263923645,
0.06626678... |
result in unnecessary invasive testing,\nsuch as coronary angiography and revas-\ncularization procedures. The ultimate bal-\nance of bene fit, cost, and risk of such an\napproach in asymptomatic individuals re-\nmains controversial, particularly in the\nmodern setting of aggressive ASCVD risk\nfactor control.\nScreenin... | [
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0.1004004254937172,
-0.046180058270692825,
0.03981972113251686,
-0.015509863384068012,
0.0008566459873691201,
-0.0377880334854126,
0.1365523785352707,
-0.01394514087587595,
0.006308236625045538,
0.03354433923959732,
0.019335996359586716,
-0.016093997284770012,
0.01876... |
factor control.\nScreening for Asymptomatic Heart\nFailure in People With Diabetes\nPeople with diabetes are at an increased\nrisk for developing heart failure, as shown\nin multiple longitudinal, observational stud-\nies (9,204– 206). This association is not only\nobserved in people with type 2 diabetes\nbut also evid... | [
0.046255312860012054,
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0.05944536626338959,
0.03905636817216873,
0.06523685902357101,
0.03214887157082558,
0.05057511106133461,
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-0.036255624145269394,
0.012184183113276958,
0.05255218222737312,
-0.052903153002262115,
0.015214... |
but also evident in people with type 1 dia-\nbetes (9,207,208). In a large multinational\ncohort of 750,000 people with diabetes\nwithout established cardiovascular disease,\nheart failure and CKD were the most fre-quent first cardiovascular disease manifes-\ntations (209). For a detailed review ofscreening, diagnosis, ... | [
0.001612192834727466,
0.008112997747957706,
-0.040875256061553955,
-0.001679817447438836,
-0.06898912042379379,
-0.034102264791727066,
0.0707230344414711,
0.1018398106098175,
-0.044731806963682175,
-0.01983175054192543,
-0.05336792394518852,
0.029145199805498123,
-0.05628660321235657,
0.01... |
mendations of heart failure in people with\ndiabetes, the reader is further referred tothe ADA consensus report “Heart Failure:\nAn Underappreciated Complication of Dia-betes. A Consensus Report of the American\nDiabetes Association ”(7).\nThe increased risk for heart failure in\npeople with diabetes is classi fied as t... | [
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0.044767942279577255,
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0.030393579974770546,
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0.059230390936136246,
0.010149885900318623,
-0.037807710468769073,
-0.04150696471333504,
-0.08224526047706604,
0.07373074442148209,
-0.051899638026952744,
-... |
people with diabetes is classi fied as the\npresence of stage A heart failure, i.e.,\nan increased risk for heart failure butwithout symptoms, structural heart dis-\nease, or biomarker evidence of myocar-\ndial strain (210). Similar to those with\nstage A heart failure, people with stage B | [
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0.04069766402244568,
-0.05722805857658386,
0.003908801823854446,
-0.016184119507670403,
0.009525277651846409,
0.038681793957948685,
0.06141059845685959,
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0.022708097472786903,
-0.02974879741668701,
0.0... |
stage A heart failure, people with stage B\nheart failure are asymptomatic but haveevidence of structural heart disease or\nfunctional cardiac abnormalities, including\nelevated biomarkers of myocardial strain\nor increased filling pressures. During\nthese asymptomatic stages of heart\nfailure, people with diabetes are ... | [
0.009666507132351398,
0.027798421680927277,
-0.03733271732926369,
0.03190285712480545,
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-0.013712689280509949,
... |
failure, people with diabetes are at par-\nticularly high risk for progression to\nsymptomatic stage C and D heart fail-\nure (211,212).\nIdenti fication, risk strati fication, and\nearly treatment of risk factors in people\nwith diabetes and asymptomatic stages of\nheart failure reduce the risk for progres-\nsion to sym... | [
0.011505593545734882,
0.02454131841659546,
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sion to symptomatic heart failure (213,\n214). In people with type 2 diabetes, mea-\nsurement of natriuretic peptides, includ-ing B-type natriuretic peptide (BNP) or\nN-terminal pro-BNP (NT-proBNP), identi fiespeople at risk for heart failure develop-\nment, progression of symptoms, and heartfailure –related mortality. ... | [
0.0019591720774769783,
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0.024... |
the Canagli flozin Cardiovascular Assess-\nment Study (CANVAS), a baseline NT-\nproBNP level $125 pg/mL predicted heart\nfailure hospitalization and all-cause mor-\ntality (215). In the Examination of Cardio-vascular Outcomes with Alogliptin versus\nStandard of Care (EXAMINE) trial, in- | [
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0... |
Standard of Care (EXAMINE) trial, in-\ncreased baseline NT-proBNP levels or anincrease after a repeated measurementat 6 months was associated with an in-\ncreased risk for symptomatic heart failure | [
-0.028226597234606743,
-0.03510076552629471,
-0.014698098413646221,
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-0.025575874373316765,
-0.002067107241600752,
-0.0009027806227095425,
-0.03498918563127518,... |
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