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for the Prevention and Treatment ofType 2 Diabetes ”), at least 150 min of mod-\nerate-intensity aerobic activity per week(see Section 3, “Prevention or Delay of\nDiabetes and Associated Comorbidities ”), re-\nstricting sodium intake ( <2,300 mg/day),\nincreasing consumption of fruits and veg-etables (8 –10 servings pe... | [
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dairy products (2 –3s e r v i n g sp e rd a y ) ,\navoiding excessive alcohol consumption(no more than 2 servings per day in menand no more than 1 serving per day inwomen) (52), and increasing activity lev-\nels (53) (see Section 5, “Facilitating\nPositive Health Behaviors and Well-beingto Improve Health Outcomes ”). | [
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These lifestyle interventions are reason-\nable for individuals with diabetes and\nmildly elevated blood pressure (systolic\n>120 mmHg or diastolic >80 mmHg) and\nshould be initiated along with pharmaco-logic therapy when hypertension is diag-\nnosed (Fig. 10.2) (53). A lifestyle therapy | [
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nosed (Fig. 10.2) (53). A lifestyle therapy\nplan should be developed in collaborationwith the person with diabetes and dis-cussed as part of diabetes management.\nUse of internet or mobile-based digital\nplatforms to reinforce healthy behaviors\nmay be considered as a component of | [
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may be considered as a component of\ncare, as these interventions have beenfound to enhance the ef ficacy of medical\ntherapy for hypertension (54,55).\nPharmacologic Interventions\nRecommendations\n10.7 Individuals with confi rmed of fice-\nbased blood pressure $130/80 mmHg\nqualify for initiation and titration of | [
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qualify for initiation and titration of\npharmacologic therapy to achieve therecommended blood pressure goal of\n<130/80 mmHg. A\n10.8 Individuals with confi rmed offi ce-\nbased blood pressure $150/90 mmHg\nshould, in addition to lifestyle therapy,\nhave prompt initiation and timely titra-\ntion of two drugs or a single... | [
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tion of two drugs or a single-pill com-\nbination of drugs demonstrated toreduce cardiovascular events in peoplewith diabetes. A\n10.9 Treatment for hypertension should\ninclude drug classes demonstrated toreduce cardiovascular events in peoplewith diabetes. AACE inhibitors or an- | [
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giotensin receptor blockers (ARBs) arerecommended first-line therapy for hy-\npertension in people with diabetes andcoronary artery disease. A\n10.10 Multiple-drug therapy is gener-\nally required to achieve blood pres-sure targets. However, combinationsof ACE inhibitors and ARBs and com-\nbinations of ACE inhibitors or... | [
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binations of ACE inhibitors or ARBs\n(including ARBs/neprilysin inhibitors)with direct renin inhibitors should notbe used. A\n10.11 An ACE inhibitor or ARB, at the\nmaximum tolerated dose indicated forblood pressure treatment, is the recom-mended first-line treatment for hyperten- | [
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sion in people with diabetes and urinaryalbumin-to-creatinine ratio $300 mg/gS184 Cardiovascular Disease and Risk Management Diabetes Care Volume 47, Supplement 1, January 2024\n©AmericanDiabetesAssociation | [
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creatinine Aor 30 –299 mg/g creatinine. B\nIf one class is not tolerated, the other\nshould be substituted. B\n10.12 For adults treated with an ACE\ninhibitor, ARB, mineralocorticoid recep-t o ra n t a g o n i s t( M R A ) ,o rd i u r e t i c ,s e r u mcreatinine/estimated glomerular filtra- | [
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tion rate and serum potassium levelsshould be monitored within 7 –14 days\nafter initiation of therapy and at least\nannually. B\nInitial Number of Antihypertensive Medi-\ncations. Initial treatment for people with\ndiabetes depends on the severity of hyper-\ntension ( Fig. 10.2 ). Those with bloodpressure between 130/... | [
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90 mmHg may begin with a single drug.\nFor individuals with blood pressure $150/\n90 mmHg, initial pharmacologic treat-\nment with two antihypertensive medica-\ntions is recommended in order to moreeffectively achieve adequate blood pres-\nsure control (56 –58). Single-pill antihy- | [
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sure control (56 –58). Single-pill antihy-\npertensive combinations may improveRecommendations for the Treatment of Confirmed\nHypertension in Nonpregnant People With Diabetes\nInitial BP ≥ 130/80 and\n<150/90 mmHg\nAlbuminuria or CAD *\nNo No Yes YesAlbuminuria or CAD *Initial BP ≥ 150/90 mmHg\nStart one agent\nContin... | [
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Start one agent\nContinue therapy\nContinue therapyLifestyle management Start two agents\nAssess BP Control and Adverse Effects\nAssess BP Control and Adverse Effects\nConsider Addition of Mineralocorticoid Receptor Antagonist;\nRefer to Specialist With Expertise in BP ManagementStart:\nACEi or ARB\nand\nCCB† or Diuret... | [
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ACEi or ARB\nand\nCCB† or Diuretic ‡\nTreatment tolerated\nand target achieved\nNot meeting target\non two agents\nTreatment tolerated\nand target achievedAdverse\neffectsNot meeting target Adverse effects\nNot meeting target or\nadverse effects using a drug\nfrom each of three classesStart one drug:\nACEi or ARB\nCCB†... | [
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ACEi or ARB\nCCB†\nDiuretic ‡Start:\nACEi or ARBStart drug from\n2 of 3 options:\nACEi or ARB\nCCB†\nDiuretic ‡\nAdd agent from\ncomplementary drug class:\nACEi or ARB\nCCB†\nDiuretic ‡Consider change toalternative medication:\nACEi or ARB\nCCB†\nDiuretic ‡REASSESS \nREGULARLY \n(3-6 MONTHS) | [
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ACEi or ARB\nCCB†\nDiuretic ‡REASSESS \nREGULARLY \n(3-6 MONTHS)\nFigure 10.2— Recommendations for the treatment of con firmed hypertension in nonpregnant people with diabetes. *An ACE inhibitor (ACEi) or an-\ngiotensin receptor blocker (ARB) is suggested to treat hypertension for people with coronary artery disease (CA... | [
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ratio 30 –299 mg/g creatinine and strongly recommended for individuals with urine albumin-to-creatinine ratio $300 mg/g creatinine.\n†Dihydropyridine calcium channel blocker (CCB). ‡Thiazide-like diuretic; long-acting agents shown to reduce cardiovascular events, such as chlor- | [
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thalidone and indapamide, are preferred. BP, blood pressure. Adapted from de Boer et al. (18).diabetesjournals.org/care Cardiovascular Disease and Risk Management S185\n©AmericanDiabetesAssociation | [
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medication taking in some individuals\n(59).\nClasses of Antihypertensive Medications.\nInitial treatment for hypertension should in-clude any of the drug classes demonstratedto reduce cardiovascular events in peoplewith diabetes: ACE inhibitors (60,61), ARBs\n(60,61), thiazide-like diuretics (62), or dihy- | [
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(60,61), thiazide-like diuretics (62), or dihy-\ndropyridine calcium channel blockers (63).In people with diabetes and establishedcoronary artery disease, ACE inhibitors orARBs are recommended first-line therapy\nfor hypertension (64 –66). For individu-\nals with albuminuria (urine albumin-to-creatinine ratio [UACR] $30... | [
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initial treatment should include an ACEinhibitor or ARB to reduce the risk of pro-gressive kidney disease (18) ( Fig. 10.2). In in-\ndividuals receiving ACE inhibitor or ARBtherapy, continuation of those medicationsas kidney function declines to estimated glo-merular filtration rate (eGFR) <30 mL/min/\n1.73 m\n2may prov... | [
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1.73 m\n2may provide cardiovascular bene fit\nwithout signifi cantly increasing the risk of | [
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without signifi cantly increasing the risk of\nend-stage kidney disease (67). In the ab-sence of albuminuria, risk of progressivekidney disease is low, and ACE inhibitorsand ARBs have not been found to affordsuperior cardioprotection compared withthiazide-like diuretics or dihydropyridinecalcium channel blockers (68). b... | [
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are indicated in the setting of prior MI, ac-tive angina, or HFrEF but have not been\nshown to reduce mortality as blood pres-\nsure–lowering agents in the absence of\nthese conditions (27,69,70).\nMultiple-Drug Therapy. Multiple-drug ther-\napy is often required to achieve bloodpressure targets ( Fig. 10.2 ), particul... | [
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the setting of diabetic kidney disease.However, the use of both ACE inhibitorsand ARBs in combination, or the combina-tion of an ACE inhibitor or ARB and a directrenin inhibitor, is contraindicated given thelack of added ASCVD bene fita n di n c r e a s e d\nrate of adverse events —namely, hyperka-\nlemia, syncope, and ... | [
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lemia, syncope, and AKI (71– 73). Titration\nof and/or addition of further blood pres-\nsure medications should be made in a\ntimely fashion to overcome therapeutic in-ertia in achieving blood pressure targets.\nBedtime Dosing. Although prior analyses\nof randomized clinical trials found a bene-fit to evening versus mor... | [
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tihypertensive medications (74,75), theseresults have not been reproduced in sub-sequent trials. Therefore, preferential useof antihypertensives at bedtime is not rec-ommended (76).\nHyperkalemia and Acute Kidney Injury.\nTreatment with ACE inhibitors/ARBs ormineralocorticoid receptor antagonists(MRAs) can cause AKI an... | [
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while diuretics can cause AKI and either hy-\npokalemia or hyperkalemia (depending on\nmechanism of action) (77,78). Detection\nand management of these abnormalities isimportant because AKI and hyperkalemia\neach increase the risks of cardiovascular\nevents and death (79). Therefore, serum\ncreatinine and potassium sho... | [
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creatinine and potassium should be moni-\ntored after initiation of treatment with anACE inhibitor/ARB, MRA, or diuretic and\nmonitored during treatment and following\nuptitration of these medications, particu-larly among individuals with reduced glo-\nmerular filtration who are at increased risk\nof hyperkalemia and AK... | [
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of hyperkalemia and AKI (77,78,80).\nResistant Hypertension\nRecommendation\n10.13 Individuals with hypertension\nwho are not meeting blood pressure\nt a r g e t so nt h r e ec l a s s e so fa n t i h y p e r -tensive medications (including a di-uretic) should be considered for MRAtherapy. A\nResistant hypertension is ... | [
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-0.07090010493993759,
-0.026316413655877113,
-0.009327142499387264,
-0.01617347076535225,
0.0... |
Resistant hypertension is de fined as blood\npressure $140/90 mmHg despite a thera-\npeutic strategy that includes appropriatelifestyle management plus a diuretic and\ntwo other antihypertensive drugs with\ncomplementary mechanisms of action atadequate doses. Prior to diagnosing resis-\ntant hypertension, a number of ot... | [
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-0.0... |
tant hypertension, a number of other\nconditions should be excluded, includingmissed doses of antihypertensive medi-\ncations, white coat hypertension, and\nsecondary hypertension. People with dia-\nbetes and con firmed resistant hyperten-\nsion should be evaluated for secondary\ncauses of hypertension, including primar... | [
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0.07810011506080627,
-0.014013869687914848,
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0.0159160103648901,
0.007883959449827671,
0.05134604498744011,
0.08023037016391754,
-0.0600956492125988,
-0.06251715123653412,
0.03921988978981972,
-0.030455194413661957,
-0.08606939762830734,
0.0280421... |
causes of hypertension, including primary\nhyperaldosteroism, renal artery stenosis,\ndiabetic kidney disease, and obstructive\nsleep apnea. In general, barriers to medi-\ncation taking (such as cost and side effects)should be identifi ed and addressed ( Fig. | [
0.024225763976573944,
0.03705086186528206,
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-0.03932003676891327,
0.00850587710738182,
-0.006226757541298866,
-0.02219829149544239,
0.07614903151988983,
0.00287770782597363,
-0.019550299271941185,
-0.053863123059272766,
0.004349857568740845,
-0.029426192864775658,
-0.0... |
10.2). MRAs, including spironolactone andeplerenone, are effective for managementof resistant hypertension in people with\ntype 2 diabetes when added to existing\ntreatment with an ACE inhibitor or ARB,\nthiazide-like diuretic, or dihydropyridine\ncalcium channel blocker (81). In addition,MRAs reduce albuminuria in peo... | [
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0.003343825228512287,
-0.06497688591480255,
-0.006723036058247089,
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0.03591474890708923,
0.11030992865562439,
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-0.012938566505908966,
0.0886949822306633,
-0.03621092811226845,
0.0420... |
diabetic nephropathy (82 –84). However,\nadding an MRA to a treatment plan thatincludes an ACE inhibitor or ARB mayincrease the risk for hyperkalemia, em-phasizing the importance of regularmonitoring for serum creatinine and po-\ntassium in these individuals, and long- | [
-0.02417270839214325,
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0.03807809203863144,
-0.06370511651039124,
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0.0498780757188797,
0.06080048531293869,
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-0.06137637421488762,
-0.057665374130010605,
0.05683598294854164,
-0.04721427708864212,
0.0346... |
tassium in these individuals, and long-\nterm outcome studies are needed tobetter evaluate the role of MRAs inblood pressure management.\nLIPID MANAGEMENT\nLifestyle Intervention\nRecommendations\n10.14 Lifestyle modi fication focusing\non weight loss (if indicated); application | [
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0.03163491562008858,
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0.05546711012721062,
-0.05980735272169113,
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-0.034331969916820526,
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0.... |
on weight loss (if indicated); application\nof a Mediterranean or DASH eatingpattern; reduction of saturated fat andtrans fat; increase of dietary n-3 fatty\nacids, viscous fiber, and plant stanol/\nsterol intake; and increased physical ac-tivity should be recommended to im-prove the lipid pro file and reduce the | [
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-0.021016402170062065,
-0.07803975045681,
0.041798196732997894,
-0.04389004781842232,
0.07389166951179504,
-0.06413836777210236,
-0.021648993715643883,
0.06538524478673935,
-0.05340633913874626,
-0.04787523299455643,
-0.06775... |
risk of developing atherosclerotic car-diovascular disease (ASCVD) in peoplewith diabetes. A\n10.15 Intensify lifestyle therapy and op-\ntimize glycemic control for people withdiabetes with elevated triglyceride levels($150 mg/dL [ $1.7 mmol/L]) and/or\nlow HDL cholesterol ( <40 mg/dL\n[<1.0 mmol/L] for men and <50 mg/... | [
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-0.019878903403878212,
-0.08989006280899048,
0.07597745954990387,
-0.03913682699203491,
0.007794277276843786,
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0.13320499658584595,
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0.029955687001347542,
0.023237647488713264,
-0.044347938150167465,
-... |
[<1.0 mmol/L] for men and <50 mg/dL\n[<1.3 mmol/L] for women). C\nLifestyle intervention, including weight\nloss in people with overweight or obe-sity (when appropriate) (85), increased\nphysical activity, and medical nutrition | [
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0.02036125399172306,
0.1352713257074356,
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-0.04230674356222153,
0.05120709538459778,
-0.01082566473633051,
0.002333851996809244,
-0.0234... |
physical activity, and medical nutrition\ntherapy, allows some individuals to reduceASCVD risk factors. Nutrition interventionshould be tailored according to each per-son’s age, pharmacologic treatment, lipid\nlevels, and medical conditions.\nRecommendations should focus on ap-\nplication of a Mediterranean (83) or Die... | [
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0.01455505657941103,
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0.00045253144344314933,
0.075143963098526,
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0.03126... |
plication of a Mediterranean (83) or Dietary\nApproaches to Stop Hypertension (DASH)eating pattern, reducing saturated and\ntrans fat intake, and increasing plant sta-\nnol/sterol, n-3 fatty acid, and viscous fiber\n(such as in oats, legumes, and citrus) intake\n(86,87). Glycemic control may also bene fi- | [
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0.021974200382828712,
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0.06239273026585579,
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-0.1... |
(86,87). Glycemic control may also bene fi-\ncially modify plasma lipid levels, particularlyin people with very high triglycerides andpoor glycemic control. See Section 5,\n“Facilitating Positive Health Behaviors and\nWell-being to Improve Health Outcomes, ” | [
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0.015489794313907623,
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-0.1... |
Well-being to Improve Health Outcomes, ”\nfor additional nutrition information.S186 Cardiovascular Disease and Risk Management Diabetes Care Volume 47, Supplement 1, January 2024\n©AmericanDiabetesAssociation | [
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-0.057993438094854355,
-0.09... |
Ongoing Therapy and Monitoring\nWith Lipid Panel\nRecommendations\n10.16 In adults with prediabetes or\ndiabetes not taking statins or other\nlipid-lowering therapy, it is reasonable\nto obtain a lipid pro file at the time of\ndiagnosis, at an initial medical evalua-\ntion, annually thereafter, or more fre-quently if in... | [
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0.024012934416532516,
0.017830779775977135,
0.11899906396865845,
-0.009974922053515911,
-0.020139988511800766,
0.003783829277381301,
0.01168141607195139,
-0.11173392832279205,
0.01... |
tion, annually thereafter, or more fre-quently if indicated. E\n10.17 Obtain a lipid pro file at initiation\nof statins or other lipid-lowering ther-apy, 4 –12 weeks after initiation or a\nchange in dose, and annually there-after, as it may help to monitor theresponse to therapy and informmedication taking. A | [
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-0.0061324951238930225,
0.11266930401325226,
0.007304378319531679,
-0.027482492849230766,
0.0894218161702156,
0.002926736604422331,
-0.02155819535255432,
0.08... |
In adults with diabetes, it is reasonable to\nobtain a lipid pro file (total cholesterol,\nLDL cholesterol, HDL cholesterol, and tri-glycerides) at the time of diagnosis, atthe initial medical evaluation, and at leastevery 5 years thereafter in individuals<40 years of age. In younger people with\nlonger duration of dise... | [
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-0.029491057619452477,
-0.0664043053984642,
0.008606309071183205,
0.0060271406546235085,
0.09151273965835571,
-0.01289104763418436,
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0.033607736229896545,
0.04929453879594803,
-0.06817237287759781,
-0.... |
longer duration of disease (such as those\nwith youth-onset type 1 diabetes), more\nfrequent lipid pro files may be reasonable.\nA lipid panel should also be obtained im-mediately before initiating statin therapy.Once an individual is taking a statin, LDLcholesterol levels should be assessed 4 –12 | [
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0.12168406695127487,
-0.043788664042949677,
-0.02739948220551014,
0.04618106037378311,
0.04757248982787132,
-0.07545337080955505,
0.0... |
weeks after initiation of statin therapy, af-ter any change in dose, and annually (e.g.,to monitor for medication taking and ef fi-\ncacy). Monitoring lipid pro files after initia-\ntion of statin therapy and during therapyincreases dose titration and statin adher-ence (88 –90). If LDL cholesterol levels are | [
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0.005484763532876968,
0.006601013243198395,
0.02684292197227478,
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0.09512950479984283,
-0.018746966496109962,
0.0030929413624107838,
0.04610053077340126,
0.020143955945968628,
-0.04950467124581337,
0.04... |
not responding in spite of medication tak-ing, clinical judgment is recommended todetermine the need for and timing of lipidpanels. In individual patients, the highlyvariable LDL cholesterol –lowering response\nseen with statins is poorly understood\n(91). Clinicians should attempt to find a\ndose or alternative statin ... | [
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-0.044772371649742126,
-0.07690174877643585,
0.034902844578027725,
-0.022608758881688118,
0.0206026379019022,
0.01553295273333788,
0.12281802296638489,
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-0.019564051181077957,
0.055026523768901825,
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0.0... |
dose or alternative statin that is tolerable\nif side effects occur. There is evidence forbenefit from even extremely low, less\nthan daily statin doses (92).\nSTATIN TREATMENT\nPrimary Prevention\nRecommendations\n10.18 For people with diabetes aged\n40–75 years without ASCVD, use | [
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0.018709663301706314,
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0.06189113110303879,
0.04441266879439354,
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0.041529685258865356,
0.1990053504705429,
-0.060671932995319366,
0.021315990015864372,
0.010996089316904545,
0.059954505413770676,
-0.032906923443078995,
0.035810... |
10.18 For people with diabetes aged\n40–75 years without ASCVD, use\nmoderate-intensity statin therapy inaddition to lifestyle therapy. A10.19 For people with diabetes\naged 20– 39 years with additional\nASCVD risk factors, it may be rea-\nsonable to initiate statin therapy in\naddition to lifestyle therapy. C\n10.20 F... | [
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0.0687420591711998,
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0.03791157156229019,
0.03408738970756531,
-0.050569087266922,
0.0364705... |
addition to lifestyle therapy. C\n10.20 For people with diabetes aged\n40–75 years at higher cardiovascular\nrisk, including those with one or more\nASCVD risk factors, it is recommended\nto use high-intensity statin therapy\nto reduce LDL cholesterol by $50%\nof baseline and to target an LDL\ncholesterol goal of <70 m... | [
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0.11778147518634796,
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0.03123367764055729,
-0.08294028043746948,
0.01233... |
cholesterol goal of <70 mg/dL\n(<1.8 mmol/L). A\n10.21 For people with diabetes aged\n40–75 years at higher cardiovascular\nrisk, especially those with multiple\nASCVD risk factors and an LDL cho-lesterol $70 mg/dL ( $1.8 mmol/L),\nit may be reasonable to add ezetimibeor a PCSK9 inhibitor to maximum tol-erated statin t... | [
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0.05139549821615219,
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0.05178389698266983,
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0.15516279637813568,
-0.04674416035413742,
-0.00502307852730155,
-0.048863448202610016,
0.0040086740627884865,
-0.041816722601652145,
-0... |
10.22 In adults with diabetes aged\n>75 years already on statin therapy,\nit is reasonable to continue statintreatment. B\n10.23 In adults with diabetes aged\n>75 years, it may be reasonable to\ninitiate moderate-intensity statin ther-apy after discussion of potential ben-\nefits and risks. C\n10.24 In people with diabe... | [
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0.07279876619577408,
-0.0065135592594742775,
0.06395490... |
efits and risks. C\n10.24 In people with diabetes intol-\nerant to statin therapy, treatment\nwith bempedoic acid is recommendedto reduce cardiovascular event rates\nas an alternative cholesterol-lowering\nplan. A\n10.25 Statin therapy is contraindi-\ncated in pregnancy. B\nSecondary Prevention\nRecommendations\n10.26 F... | [
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0.030121050775051117,
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0.032912418246269226,
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0.00146... |
Recommendations\n10.26 For people of all ages with di-\nabetes and ASCVD, high-intensity\nstatin therapy should be added tolifestyle therapy. A\n10.27 For people with diabetes and\nASCVD, treatment with high-intensitystatin therapy is recommended totarget an LDL cholesterol reductionof$50% from baseline and an\nLDL cho... | [
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0.003697140607982874,
0.13043831288814545,
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0.025173136964440346,
0.059588316828012466,
-0.11685717850923538,
-0.0044... |
LDL cholesterol goal of <55 mg/dL\n(<1.4 mmol/L). Addition of ezetimibe\nor a PCSK9 inhibitor with proven ben-efit in this population is recom-\nmended if this goal is not achieved onmaximum tolerated statin therapy. B10.28a For individuals who do not\ntolerate the intended statin inten-\nsity, the maximum tolerated sta... | [
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0.012384059838950634,
0.006303336471319199,
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... |
sity, the maximum tolerated statindose should be used. E\n10.28b For people with diabetes\nand ASCVD intolerant to statin ther-apy, PCSK9 inhibitor therapy with\nmonoclonal antibody treatment, A\nbempedoic acid therapy, Aor\nPCSK9 inhibitor therapy with incli-siran siRNA Eshould be considered\nas an alternative cholest... | [
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0.0014545874437317252,
0.06406140327453613,
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0.02... |
as an alternative cholesterol-lower-ing therapy.\nInitiating Statin Therapy Based on Risk\nPeople with type 2 diabetes have an in-\ncreased prevalence of lipid abnormali-ties, contributing to their high risk ofASCVD. Multiple clinical trials have dem-onstrated the bene ficial effects of statin | [
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0.03329859673976898,
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0.16191022098064423,
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0.07229887694120407,
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0.... |
therapy on ASCVD outcomes in subjectswith and without CHD (93,94). Sub-group analyses of people with diabetesin larger trials (95 –99) and trials in\npeople with diabetes (100,101) showedsignifi cant primary and secondary preven- | [
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tion of ASCVD events and CHD death inpeople with diabetes. Meta-analyses in-cluding data from over 18,000 people withdiabetes from 14 randomized trials ofstatin therapy (mean follow-up 4.3 years)demonstrated a 9% proportional reductionin all-cause mortality and 13% reductionin vascular mortality for each 1 mmol/L(39 mg... | [
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0.016563361510634422,
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0.04796341806650162,
-0.06301077455282211,
-0.01... |
vascular mortality for each 1 mmol/L(39 mg/dL) reduction in LDL cholesterol(102). The cardiovascular bene fiti nt h i s | [
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large meta-analysis did not depend onbaseline LDL cholesterol levels and was lin-early related to the LDL cholesterol reduc-tion without a low threshold beyondwhich there was no bene fito b s e r v e d\n(102).\nAccordingly, statins are the drugs of\nchoice for LDL cholesterol lowering andcardioprotection. Table 10.2 sho... | [
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two statin dosing intensities that arerecommended for use in clinical prac-tice: high-intensity statin therapy willachieve an approximately $50% reduc-\ntion in LDL cholesterol, and moderate-intensity statin plans achieve 30 –49% | [
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reductions in LDL cholesterol. Low-dosestatin therapy is generally not recom-mended in people with diabetes but issometimes the only dose of statin thatan individual can tolerate. For individu-als who do not tolerate the intendedintensity of statin, the maximum toler-ated statin dose should be used.diabetesjournals.org... | [
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dose should be used.diabetesjournals.org/care Cardiovascular Disease and Risk Management S187 | [
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©AmericanDiabetesAssociation | [
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As in those without diabetes, abso-\nlute reductions in ASCVD outcomes\n(CHD death and nonfatal MI) are great-est in people with high baseline ASCVDrisk (known ASCVD and/or very highLDL cholesterol levels), but the overallbene fits of statin therapy in people with | [
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diabetes at moderate or even low riskfor ASCVD are convincing (103,104). Therelative bene fito fl i p i d - l o w e r i n gt h e r a p y\nhas been uniform across most sub-groups tested (94,102), including sub-groups that varied with respect to ageand other risk factors.\nPrimary Prevention (People Without ASCVD) | [
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Primary Prevention (People Without ASCVD)\nFor primary prevention, moderate-dosestatin therapy is recommended forthose aged $40 years (96,103,104), al-\nthough high-intensity therapy should beconsidered in the context of additionalASCVD risk factors. The evidence is strongfor people with diabetes aged 40 –75 | [
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years, an age-group well represented instatin trials showing bene fit. Since cardio- | [
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vascular risk is enhanced in people withdiabetes, as noted above, individuals whoalso have multiple other coronary risk fac-tors have increased risk, equivalent tothat of those with ASCVD. Therefore, cur-rent guidelines recommend that in peo-ple with diabetes who are at highercardiovascular risk, especially those witho... | [
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risk, especially those withone or more ASCVD risk factors, high-intensity statin therapy should be pre-scribed to reduce LDL cholesterol by$50% from baseline and to target an LDLcholesterol of <70 mg/dL ( <1.8 mmol/L) | [
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(105– 107). Since, in clinical practice, it is\nfrequently dif ficult to ascertain the base-\nline LDL cholesterol level prior to statintherapy initiation, in those individuals, a fo-cus on an LDL cholesterol target level of<70 mg/dL ( <1.8 mmol/L) rather than | [
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the percent reduction in LDL cholesterolis recommended. In those individuals, itmay also be reasonable to add ezetimibeor proprotein convertase subtilisin/kexin\ntype 9 (PCSK9) inhibitor therapy to maxi-\nmum tolerated statin therapy if neededto reduce LDL cholesterol levels by$50% and to achieve the recommendedLDL cho... | [
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(<1.8 mmol/L) (108). While there are no\nrandomized controlled trials speci fically as-\nsessing cardiovascular outcomes of addingezetimibe or PCSK9 inhibitors to statin\ntherapy in primary prevention, the Open-\nLabel Study of Long-term EvaluationAgainst LDL Cholesterol (OSLER) study in-cluded /C2480% of study particip... | [
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out established cardiovascular disease. In\nthe treatment group, LDL cholesterol was\nreduced by 61%, and, although explor-atory and not a primary outcome, cardio-vascular events were reduced by 18% in\nthe standard-therapy group to 0.95% in\nt h ee v o l o c u m a bg r o u p( H Ri nt h ee v o l o -cumab group 0.47 [95... | [
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P= 0.003) (109). Similarly, the Long-term\nSafety and Tolerability of Alirocumab in\nHigh Cardiovascular Risk Patients With\nHypercholesterolemia Not AdequatelyControlled With Their Lipid-ModifyingTherapy (ODYSSEY LONG TERM) included\n/C2430% of study participants without es-\ntablished cardiovascular disease and 33% | [
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tablished cardiovascular disease and 33%\nof people with diabetes. Alirocumabadded to statin therapy reduced LDLcholesterol by 62% and major adverse\ncardiovascular events in a post hoc anal-\nysis (1.7% vs. 3.3% compared with pla-cebo; HR 0.52 [95% CI 0.31 –0.90];\nnominal P= 0.02) (110). In addition, a | [
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nominal P= 0.02) (110). In addition, a\nmeta-analysis suggests that there is a car-diovascular benefi t of adding ezetimibe\nor PCSK9 inhibitors to treatment forhigh-risk people (111). The evidence islesser for individuals aged >75 years; rel- | [
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atively few older people with diabeteshave been enrolled in primary preventiontrials. However, heterogeneity by age hasnot been seen in the relative benefi to f\nlipid-lowering therapy in trials that in-\ncluded older participants (94,101,102),and because older age confers higherrisk, the absolute bene fits are actually | [
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greater (94,112). Moderate-intensitystatin therapy is recommended in peoplewith diabetes who are $75 years of age.\nHowever, the risk-bene fitp r o file should\nbe routinely evaluated in this population,\nwith downward titration of dose per-\nformed as needed. See Section 13,“Older Adults,” for more details on clini- | [
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cal considerations for this population.\nAge<40 Years and/or Type 1 Diabetes. Very\nlittle clinical trial evidence exists forpeople with type 2 diabetes under thea g eo f4 0y e a r so rf o rp e o p l ew i t ht y p e1diabetes of any age. For pediatric recom-\nmendations, see Section 14, “Children\nand Adolescents. ”In t... | [
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and Adolescents. ”In the Heart Protection\nStudy (lower age limit 40 years), the\nsubgroup of /C24600 people with type 1\ndiabetes had a reduction in risk propor-\ntionately similar, although not statistically\nsignifi cant, to that in people with type 2\ndiabetes (96). Even though the data arenot de finitive, similar st... | [
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approaches should be considered for\npeople with type 1 or type 2 diabetes, par-\nticularly in the presence of other cardiovas-cular risk factors. Individuals <40 years\nof age have lower risk of developing a car-diovascular event over a 10-year horizon;\nhowever, their lifetime risk of developing | [
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however, their lifetime risk of developing\ncardiovascular disease and suffering an MI,stroke, or cardiovascular death is high. Forpeople who are <40 years of age and/or\nhave type 1 diabetes with other ASCVD\nrisk factors, it is recommended that the in-\ndividual and health care professional dis-c u s st h er e l a t ... | [
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consider the use of moderate-intensitystatin therapy. Please refer to “Type 1 Dia-\nbetes Mellitus and Cardiovascular Disease:AS c i e n t i fic Statement From the American\nHeart Association and American DiabetesAssociation ”(113) for additional discussion.\nSecondary Prevention (People With ASCVD)\nBecause cardiovascu... | [
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Because cardiovascular event rates are\nincreased in people with diabetes and\nestablished ASCVD, intensive therapy isindicated and has been shown to be ofbene fit in multiple large meta-analyses\nand randomized cardiovascular outcomes\ntrials (94,102,112,114,115). High-intensity | [
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trials (94,102,112,114,115). High-intensity\nstatin therapy is recommended for all peo-ple with diabetes and ASCVD to target anTable 10.2 —High-intensity and moderate-intensity statin therapy\nHigh-intensity statin therapy\n(lowers LDL cholesterol by $50%)Moderate-intensity statin therapy(lowers LDL cholesterol by 30 –... | [
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Atorvastatin 40 –80 mg Atorvastatin 10 –20 mg\nRosuvastatin 20 –40 mg Rosuvastatin 5 –10 mg\nSimvastatin 20 –40 mg\nPravastatin 40 –80 mg\nLovastatin 40 mg\nFluvastatin XL 80 mgPitavastatin 1 –4m g\nOnce-daily dosing. XL, extended release.S188 Cardiovascular Disease and Risk Management Diabetes Care Volume 47, Suppleme... | [
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©AmericanDiabetesAssociation | [
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LDL cholesterol reduction of $50% from\nbaseline and an LDL cholesterol goal of\n<55 mg/dL ( <1.4 mmol/L). Based on\nthe evidence discussed below, additionof ezetimibe or a PCSK9 inhibitor is rec-\nommended if this goal is not achieved\non maximum tolerated statin therapy.These recommendations are based onthe observati... | [
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sus moderate-intensity statin therapy\nreduces cardiovascular event rates inhigh-risk individuals with established car-diovascular disease in randomized trials\n(98,114). In addition, the Cholesterol\nTreatment Trialists’ Collaboration, involv-\ning 26 statin trials, of which 5 comparedhigh-intensity versus moderate-in... | [
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statins (102), showed a 21% reduction in\nmajor cardiovascular events in people withdiabetes for every 39 mg/dL (1 mmol/L) ofLDL cholesterol lowering, irrespective ofbaseline LDL cholesterol or individual char-\nacteristics (102). However, the best evi- | [
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acteristics (102). However, the best evi-\ndence to support lower LDL cholesteroltargets in people with diabetes and estab-lished cardiovascular disease derives from\nmultiple large randomized trials investigat-\ning the bene fits of adding nonstatin agents\nto statin therapy. As discussed in detail be-low, these includ... | [
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with statins and ezetimibe (112,116) or\nPCSK9 inhibitors (115,117– 119). Each trial\nfound a signi ficant bene fit in the reduction\nof ASCVD events that was directly related\nto the degree of further LDL cholesterol\nlowering. These large trials included asignificant number of participants with dia-\nbetes and prespeci ... | [
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0.06157650426030159,
-0.056770071387290955,
-0.03... |
betes and prespeci fied analyses on cardio-\nvascular outcomes in people with and\nwithout diabetes (116,118,119). The deci-\nsion to add a nonstatin agent should bemade following a discussion between aclinician and a person with diabetes about\nthe net bene fit, safety, and cost of combi-\nnation therapy.\nCombination T... | [
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nation therapy.\nCombination Therapy for LDL\nCholesterol Lowering\nStatins and Ezetimibe\nThe IMProved Reduction of Outcomes: Vy-\ntorin Ef ficacy International Trial (IMPROVE-\nIT) was a randomized controlled trial in\n18,144 individuals comparing the additionof ezetimibe to simvastatin therapy ver-\nsus simvastatin a... | [
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0.059003058820962906,
-0.11628277599811554,
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0.002396038733422756,
0.05221802368760109,
0.053281672298908234,
-0.04337595775723457,
-0.... |
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