KP National Cardiovascular Risk and Dyslipidemia Management Guideline

Transcription

1 KP Natinal Cardivascular Risk and Dyslipidemia Management Guideline CLINICIAN GUIDE OCTOBER 2014 Intrductin This Clinician Guide was develped t assist Primary Care physicians and ther clinicians in the utpatient management f chlesterl fr primary and secndary preventin f athersclertic cardivascular disease (ASCVD). The KP Natinal Risk Assessment and Chlesterl Management Guideline adpted the 2013 recmmendatins develped by the American Cllege f Cardilgy Fundatin (ACCF)/American Heart Assciatin (AHA), with minr mdificatins. It is nt intended r designed as a substitute fr the reasnable exercise f independent clinical judgment by practitiners. Definitins Clinical athersclertic cardivascular disease (ASCVD) includes acute crnary syndrmes, histry f MI, stable r unstable angina, crnary r ther arterial revascularizatin, strke, TIA, cartid stensis 50%, repaired abdminal artic aneurysm (AAA), r symptmatic peripheral arterial disease presumed t be f athersclertic rigin. Subclinical ASCVD includes asymptmatic crnary artery disease r peripheral artery disease, e.g., artic athersclersis, unrepaired abdminal artic aneurysm (AAA), r abnrmal ankle brachial index (ABI) detected n screening. Terminlgy: Belw is a brief guide t the wrding, strength and actins assciated with the recmmendatins in this Clinician Guide. Recmmendatin Strength* Actin Start, initiate, prescribe, treat,, etc. Strng Mst individuals shuld receive the recmmended curse f actin; nly a small prprtin will nt want the interventin. Cnsider Weak The majrity f individuals in this situatin will want the curse f actin, but many will nt. Different chices will be apprpriate fr different patients. Assist each patient t arrive at a management decisin cnsistent with her r his values and preferences. Cnsider discussing Very Weak Sme patients will want this curse f actin, but the majrity will nt. A discussin f the interventin may be useful t assist selected patients arrive at a management decisin cnsistent with her r his values and preferences. *Refers t the extent t which ne can be cnfident that the desirable effects f an interventin utweigh its undesirable effects. Key Pints Fr all adults, encurage a heart-healthy lifestyle t reduce the risk f ASCVD. This includes regular physical activity, weight reductin and maintenance, smking cessatin, and cntrlling bld pressure and diabetes. Fcus n treatment f bld chlesterl t reduce ASCVD risk in adults. Identify adults mst likely t benefit frm chlesterl-lwering therapy, i.e., the 4 statin benefit grups. Identify and address safety issues related t chlesterl treatment ptins. Chlesterl Treatment FOUR STATIN BENEFIT GROUPS Recmmend statin therapy fr adults in risk grups fr which a demnstrated ASCVD risk reductin benefit has been shwn t utweigh the risks. See Table 1 fr the fur grups in which statins have been shwn t reduce ASCVD. There is n recmmendatin fr r against specific LDL C r nn-hdl C targets fr the primary r secndary preventin f ASCVD. There is n recmmendatin fr r against the initiatin r discntinuatin f statins in patients with NYHA class II-IV ischemic systlic heart failure r in patients n maintenance hemdialysis. TABLE 1. Fur Statin Benefit Grups Secndary Preventin Adults with clinical ASCVD Primary Preventin Adults aged 21 and lder with primary elevatins f LCL-C 190 mg/dl Adults with diabetes aged years wh have LDL-C 70 t 189 mg/dl Adults withut diabetes aged years with estimated 10-year ASCVD risk 7.5% and LDL-C 70 t 189 g/dl

2 2 KP Natinal Cardivascular Risk and Dyslipidemia Management Guideline Clinician Guide Chlesterl Treatment Recmmendatins, By Risk Grup SECONDARY PREVENTION: ADULTS WITH CLINICAL ASCVD PRIMARY PREVENTION: AGED 21 AND OLDER WITH LDL-C 190 MG/DL PRIMARY PREVENTION: DIABETES, AGED AND LDL-C MG/DL PRIMARY PREVENTION: NO DIABETES, AGED AND LDL-C MG/DL PRIMARY PREVENTION: SUBCLINICAL ASCVD OR NO IDENTIFIED STATIN BENEFIT GROUP Aged 75: Initiate r cntinue a high-intensity statin as first-line therapy, unless cntraindicated. If cntraindicated r characteristics predispsing t statin-assciated adverse effects are present, use a mderate-intensity statin as the secnd ptin, if tlerated. If unable t tlerate high-intensity statin therapy, use the maximum tlerated statin intensity. Aged >75: Evaluate the ptential ASCVD risk-reductin benefits, adverse effects and drug-drug interactins, and cnsider patient preferences when initiating a mderate- r high-intensity statin. Cntinue statin therapy in thse wh are tlerating it. Evaluate fr secndary causes f hyperlipidemia Initiate r cntinue high-intensity statin therapy, unless cntraindicated. 10-year ASCVD risk estimatin nt required. If unable t tlerate high-intensity statin therapy, use the maximum tlerated statin intensity. Cnsider intensifying statin therapy t achieve at least a 50% LDL-C reductin. After the maximum intensity f statin therapy has been achieved, cnsider additin f a nnstatin drug t further lwer LDL-C. Evaluate the ptential fr ASCVD risk reductin benefits, adverse effects and drug-drug interactins, and cnsider patient preferences. Initiate r cntinue mderate-intensity statin therapy. Cnsider high-intensity statin therapy fr adults with diabetes and a 7.5% estimated 10-year ASCVD risk. If aged under 40 r ver 75, evaluate the ptential fr ASCVD benefits, adverse effects and drug-drug interactins, and cnsider patient preferences when deciding t initiate, cntinue, r intensify statin therapy. Use The Pled Chrt Equatins (AHA/ACC CV Risk Calculatr) r ther risk calculatr t estimate 10-year ASCVD risk and t guide initiatin f statin therapy. If using The Pled Chrt Equatins fr ppulatins ther than n-hispanic Whites r African Americans, use the equatins fr n-hispanic Whites. NOTE: Because n cardivascular risk calculatr has been studied prspectively and cmpared t anther risk calculatr, sme clinicians may chse a different risk calculatr t estimate cardivascular risk. Clinicians selecting a different risk calculatr may decide t apply different treatment threshlds than thse prpsed in the Pled Chrt Equatins. Fr adults at elevated risk (e.g., %), cnsider treatment with a mderate- t highintensity statin, after a discussin which cnsiders the ptential fr ASCVD risk reductin benefits, adverse effects, drug-drug interactins, and patient preferences fr treatment. Fr adults with a very elevated estimated 10-year ASCVD risk (e.g. 15% by the AHA/ACC Pled Chrt Equatins), initiate r cntinue treatment with a mderate- t high-intensity statin. Cnsider discussing treatment with a mderate-intensity statin with adults wh have a slightly elevated estimated 10-year ASCVD risk (e.g. 5% t 7.4%). In patients with asymptmatic (subclinical) nncrnary athersclersis (including asymptmatic peripheral arterial disease (PAD), cartid stensis and artic athersclersis) r unrepaired abdminal artic aneurysm (AAA), assess ASCVD risk and cnsider a mderate- t high-intensity statin t reduce the risk f develping symptmatic cardivascular disease r cardivascular disease prgressin. Cnsider additinal factrs fr thse nt therwise identified in a statin benefit grup, r in whm a risk-based treatment decisin is uncertain after quantitative risk assessment. Additinal risk factrs include baseline LDL-C 160 r ther evidence f genetic hyperlipidemias, lifetime risk f ASCVD, family histry f premature ASCVD with nset <55 years in a first-degree male relative, r <65 in a first-degree female relative, testing fr hscrp, Ankle-Brachial Index (ABI), r Crnary Artery Calcium (CAC). Order testing fr additinal risk factrs nly if the result will prmpt a therapeutic decisin, and the clinician and patient agree t initiate statin therapy if the result is abnrmal, and t frg statin therapy if the result is nrmal. Use shared decisin making t discuss significant differences in cnvenience, cst, invasiveness, and radiatin expsure.

3 3 KP Natinal Cardivascular Risk and Dyslipidemia Management Guideline Clinician Guide Figure 1. Chlesterl Treatment Recmmendatins, By Risk Grup ASCVD Statin Benefit Grups Encurage a heart-healthy lifestyle t reduce the risk f ASCVD (e.g., regular physical activity, weight reductin and maintenance, smking cessatin, and cntrlling bld pressure and diabetes) Clinical ASCVD Age <75 years? Clinical ASCVD: Initiate r cntinue high-intensity statin (e.g., Atrvastatin mg daily) If nt a candidate fr high-intensity, initiate r cntinue mderate intensity statin (e.g., Simvastatin mg daily r Atrvastatin mg daily) Cnsider mderateintensity statin Subclinical ASCVD*: Cnsider initiating a mderate- t highintensity statin LDL-C 190 mg/dl Initiate r cntinue high-intensity statin If nt a candidate fr high-intensity statin, initiate r cntinue mderate-intensity statin Diabetes (DM), aged & LDL-C mg/dl 10y ASCVD Risk 7.5% Initiate r cntinue mderate-intensity statin Initiate r cntinue mderate-intensity statin Cnsider high-intensity statin NOTE: If under age 40 r ver age 75, evaluate ptential fr ASCVD benefits, adverse effects and drugdrug interactins, and cnsider patient preferences when deciding t initiate, cntinue, r intensify statin therapy. clinical ASCVD r DM, aged and LDL-C mg/dl 10y ASCVD Risk 15% Initiate r cntinue mderate intensity statin Cnsider high-intensity statin *Subclinical ASCVD includes asymptmatic crnary artery disease r peripheral artery disease, e.g., artic athersclersis, unrepaired abdminal artic aneurysm (AAA), r abnrmal ankle brachial index (ABI) detected n screening. ** identified statin benefit grup: Cnsider additinal factrs fr thse nt therwise identified in a statin benefit grup, r in whm a risk-based treatment decisin is uncertain after quantitative risk assessment. See guideline sectin n additinal risk factrs and testing. 10y ASCVD Risk 7.5 t 14.9% 10y ASCVD Risk 5.0 t 7.4% identified statin benefit grup** Cnsider mderate- t high-intensity statin NOTE: Fr 10-year ASCVD risk f %, discuss the benefits and risks f statin therapy with patients. At this risk level, there is mre incrpratin f patient preferences. Cnsider discussing mderate-intensity statin (ptinal)

4 4 KP Natinal Cardivascular Risk and Dyslipidemia Management Guideline Clinician Guide Optimizing Statin Therapy Insufficient Respnse t Statin Therapy Use the maximum tlerated intensity f statin in individuals fr whm a high- r mderateintensity statin is recmmended, but nt tlerated. Fcus n treatment f bld chlesterl t reduce ASCVD risk in adults. In individuals wh have a less-than-anticipated therapeutic respnse r are intlerant f the recmmended intensity f statin therapy: Reinfrce medicatin adherence Reinfrce adherence t intensive lifestyle changes Exclude secndary causes f hyperlipidemia The fllwing are indicatrs f anticipated therapeutic respnse t the recmmended intensity f statin therapy. Fcus is n the intensity f the statin therapy. As an aid t mnitring: High-intensity statin therapy generally results in an average LDL C reductin f 50% frm the untreated baseline; Mderate-intensity statin therapy generally results in an average LDL C reductin f 30 t <50% frm the untreated baseline; LDL C levels and percent reductin are t be used nly t assess respnse t therapy and adherence. They are nt t be used as perfrmance standards. In individuals at higher ASCVD risk receiving the maximum tlerated intensity f statin therapy wh cntinue t have a less than-anticipated therapeutic respnse, cnsider adding a nnstatin chlesterl-lwering drug(s) if the ASCVD risk-reductin benefits utweigh the ptential fr adverse effects. Higher-risk individuals include: Individuals with clinical ASCVD <75 years f age. Individuals with baseline LDL C 190 mg/dl. Individuals 40 t 75 years f age with diabetes mellitus. In individuals wh are candidates fr statin treatment but are cmpletely statin intlerant, cnsider nnstatin chlesterl lwering drugs that have been shwn t reduce ASCVD events in RCTs (i.e., niacin, bile acid resins and fibrates) if the ASCVD risk-reductin benefits utweigh the ptential fr adverse effects. Give preference t nnstatin chlesterl-lwering drugs shwn t reduce ASCVD events in RCTs (i.e., niacin and bile acid resins). Risk Assessment The cntributin t risk assessment fr a first ASCVD event using ApB, CKD, albuminuria, r cardirespiratry fitness is uncertain at present. The Cartid Intima-Media Thickness Test (CIMT) is nt recmmended fr rutine measurement fr risk assessment fr a first ASCVD event. Assess traditinal ASCVD risk factrs every 4 t 6 years in adults aged wh are free frm ASCVD and t estimate 10-year ASCVD risk every 4 t 6 years in adults aged years withut ASCVD. Cnsider assessing 30-year r lifetime ASCVD risk based n traditinal risk factrs in adults 20 t 59 years f age withut ASCVD and wh are nt at high shrt-term risk. A risk calculatr fr this assessment is available at: Triglyceride Treatment There is evidence that elevated TG is independently assciated with increased risk f athersclersis. Hwever, nt all peple with high TGs are at increased risk, and neither the threshld fr initiatin f therapy, nr the gal f therapy, is knwn. Althugh there is direct evidence that lwering LDL C reduces the risk f CAD events, there are n clinical trials t demnstrate that reducing TG levels will reduce CAD events. There is expert pinin that a desirable TG level is <150 mg/dl, but there are n studies t supprt the benefit f btaining this level. When making treatment decisins, cnsider a persn's ther lipid levels and nnlipid CAD risk factrs. Althugh there is n direct evidence, there is cnsensus that TG 500 mg/dl warrants treatment t prevent pancreatitis. Specific recmmendatins fr treating high TG level are presented

5 5 KP Natinal Cardivascular Risk and Dyslipidemia Management Guideline Clinician Guide in the Triglyceride Algrithm (see Figure 2). Figure 2. Triglyceride (TG) Treatment Algrithm TG 200 Assess fr and address secndary causes f hypertriglyceridemia: hyperglycemia hypthyridism renal disease excessive alchl intake besity medicatins (e.g., ral estrgens and ral retinids) Statin indicated? Start Statin Assess TG TG <500 TG TG 1000 Cntinue t ptimize lifestyle factrs Cnsider adding DHA/ EPA 2-4 g daily Cnsider switching t atrvastatin Add DHA/ EPA 2-4 g daily Cnsider switching t atrvastatin Repeat TG 4 weeks Repeat TG 2 weeks TG <500 TG 500 NOTE: clinical trials have prspectively evaluated the pharmaclgic treatment f hypertriglyceridemia and demnstrated reductin in the incidence f pancreatitis. Observatinal data, hwever, suggest the risk f pancreatitis is related t the degree f hypertriglyceridemia. Fr patients n lwer ptency r dse statins, with a TG 500, cnsider switching t high dse atrvastatin mg. Fr example, if histry f pancreatitis r if TG 1000 D nt use gemfibrzil with statins Limit statins t half maximal dse with either niacin r fenfibrate D nt use fenfibrate with GFR <30 Cntinue current treatment and ptimize lifestyle TG <500 Cntinue current treatment and ptimize lifestyle Cnsider adding fibrate r niacin if clinically apprpriate Repeat TG 4 weeks TG 500 Cnsult lipid specialist

6 6 KP Natinal Cardivascular Risk and Dyslipidemia Management Guideline Clinician Guide Statin Safety Recmmendatins Wmen f Childbearing Ptential Statins are classified as pregnancy categry X and are cntraindicated during pregnancy and lactatin. Discuss the ptential risks t the fetus shuld they becme pregnant Discuss practicing effective cntraceptive measures cnsistently while taking statins Advise wmen using stains t stp statins and cntact their OB/GYN prvider immediately if they becme pregnant In wmen planning a pregnancy, discntinue statins prir t cnceptin T maximize the safety f statins, select the apprpriate statin and dse in men and nnpregnant/nnnursing wmen based n patient characteristics, level f ASCVD risk*, and ptential fr adverse effects. ASCVD risk is based n the presence f clinical ASCVD, diabetes mellitus, LDL C 190 mg/dl, r level f estimated 10-year ASCVD risk. Use mderate-intensity statin therapy in individuals in whm high-intensity statin therapy wuld therwise be recmmended when characteristics predispsing them t statin-assciated adverse effects are present. Characteristics predispsing individuals t statin adverse effects include, but are nt limited t: Multiple r serius cmrbidities, including impaired renal r hepatic functin Histry f previus statin intlerance r muscle disrders Unexplained ALT elevatins >3 times ULN Patient characteristics r cncmitant use f drugs affecting statin metablism >75 years f age Additinal characteristics that may mdify the decisin t use higher statin intensities may include, but are nt limited t: Histry f hemrrhagic strke Asian ancestry Evaluate adults receiving statin therapy fr new-nset diabetes mellitus accrding t current diabetes screening guidelines. Encurage thse wh develp diabetes mellitus during statin therapy t adhere t a heart healthy dietary pattern, engage in physical activity, achieve and maintain a healthy bdy weight, cease tbacc use, and cntinue statin therapy t reduce their risk f ASCVD events. Fr adults taking any dse f statins, use cautin in thse >75 years f age, as well as in adults taking cncmitant medicatins that alter drug metablism, taking multiple drugs, r taking drugs fr cnditins that require cmplex medicatin regimens (e.g., thse wh have undergne slid rgan transplantatin r are receiving treatment fr HIV). A review f the manufacturer s prescribing infrmatin may be useful befre initiating any chlesterl-lwering drug. Cnsider decreasing the statin dse when 2 cnsecutive values f LDL C levels are <40 mg/dl. Initiating simvastatin at 80 mg daily r increasing the simvastatin dse t 80 mg daily may be harmful. CK Measurement D nt rutinely measure CK in individuals receiving statin therapy. Cnsider baseline measurement f CK fr individuals believed t be at increased risk fr adverse muscle events based n a persnal r family histry f statin intlerance r muscle disease, clinical presentatin, r cncmitant drug therapy that might increase the risk fr mypathy. During statin therapy, measure CK in individuals with muscle symptms, including pain, tenderness, stiffness, cramping, weakness, r generalized fatigue. Hepatic Functin Perfrm baseline measurement f hepatic transaminase levels (ALT) befre initiating statin therapy. During statin therapy, measure hepatic functin if symptms suggesting hepattxicity arise (e.g., unusual fatigue r weakness, lss f appetite, abdminal pain, dark clred urine r yellwing f the skin r sclera). Table 2: Statin Therapy Optins, By Intensity HIGH INTENSITY* Daily dse lwers LDL-C by apprx. 50% Atrvastatin mg Rsuvastatin mg MODERATE INTENSITY Daily dse lwers LDL-C by apprx % Simvastatin mg Atrvastatin mg Lvastatin mg Pravastatin mg Rsuvastatin 5-10 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2-4 mg LOW INTENSITY Daily dse lwers LDL-C by <30% Simvastatin 10 mg Lvastatin 20 mg Pravastatin mg Fluvastatin mg Pitavastatin 1 mg *Initiating simvastatin 80 mg is n lnger recmmend. Fr thse peple wh are already taking and tlerating simvastatin 80 gm daily, it can be cnsidered a high-intensity statin.

7 7 KP Natinal Cardivascular Risk and Dyslipidemia Management Guideline Clinician Guide Assessing/Managing Muscle Symptms during Statin Treatment Evaluate and treat muscle symptms, including pain, tenderness, stiffness, cramping, weakness, r fatigue, in statin-treated patient: T avid unnecessary discntinuatin, btain a histry f prir r current muscle symptms t establish a baseline befre initiating statin therapy. If unexplained severe muscle symptms r fatigue develp during statin therapy, prmptly discntinue the statin and address the pssibility f rhabdmylysis by evaluating CK, creatinine, and a urinalysis fr myglbinuria. If mild-t-mderate muscle symptms develp during statin therapy: Discntinue the statin until the symptms can be evaluated. Evaluate fr ther cnditins that might increase risk fr muscle symptms (e.g., hypthyridism, reduced renal r hepatic functin, rheumatlgic disrders (plymyalgia rheumatic), sterid mypathy, vitamin D deficiency, r primary muscle diseases.) If muscle symptms reslve and n cntraindicatin exists, give patient the riginal r a lwer dse f the same statin t establish a causal relatinship between the muscle symptms and statin therapy. If a causal relatinship exists, then discntinue the riginal statin. Once muscle symptms reslve, use a lw dse f a different statin. Once a lw dse f a statin is tlerated, gradually increase the dse as tlerated. If muscle symptms r elevated CK levels d nt reslve cmpletely, after 2 mnths withut statin treatment, cnsider ther causes f muscle symptms listed abve. If persistent muscle symptms are determined t arise frm a cnditin unrelated t statin therapy, r if the predispsing cnditin has been treated, resume statin therapy at the riginal dse. If presenting with a cnfusinal state r memry impairment while n statins, cnsider evaluatin fr nnstatin causes (e.g., expsure t ther drugs, systemic and neurpsychiatric causes, etc.), as well as adverse effects assciated with statin therapy. nstatin Safety Recmmendatins Niacin Order baseline hepatic transaminases, fasting bld glucse r hemglbin A1C, and uric acid befre initiating niacin, and again during up-titratin t a maintenance dse and peridically thereafter. D nt use niacin if: Hepatic transaminase elevatins are higher than 2 t 3 times ULN. Persistent severe cutaneus symptms, persistent hyperglycemia, acute gut r unexplained abdminal pain r gastrintestinal symptms ccur. New-nset atrial fibrillatin r weight lss ccurs. If adverse effects frm niacin, recnsider ptential fr ASCVD benefits and adverse effects befre reinitiating niacin therapy. T reduce the frequency and severity f adverse cutaneus symptms: Start niacin at a lw dse and titrate t a higher dse ver a perid f weeks as tlerated. Take niacin with fd r premedicating with aspirin 325 mg 30 minutes befre niacin dsing t alleviate flushing symptms. If an extended-release preparatin is used, increase the dse f extended-release niacin frm 500 mg t a maximum f 2,000 mg/day ver 4 t 8 weeks, with the dse f extended release niacin increasing nt mre than weekly. If immediate-release niacin is chsen, start at a dse f 100 mg 3 times daily and up-titrate t 3 g/day, divided int 2-3 dses. Bile Acid Sequestrants (BAS) D nt use BAS in individuals with baseline fasting triglyceride levels 300 mg/dl r type III hyperlipprteinemia, because severe triglyceride elevatins might ccur. (A fasting lipid panel shuld be btained befre BAS is initiated, 3 mnths after initiatin, and every 6 t 12 mnths thereafter.) Use BAS with cautin if baseline triglyceride levels are 250 t 299 mg/dl, and evaluate a fasting lipid panel in 4 t 6 weeks after initiatin. Discntinue the BAS if triglycerides exceed 400 mg/dl. Chlesterl-Absrptin Inhibitrs Obtain baseline hepatic transaminases befre initiating ezetimibe. When ezetimibe is cadministered with a statin, mnitr transaminase levels as clinically indicated, and discntinue ezetimibe if persistent ALT elevatins >3 times ULN. Fibrates D nt use gemfibrzil in patients n statin therapy due t an increased risk fr muscle symptms and rhabdmylysis. Cnsider fenfibrate cncmitantly with a lw- r mderate-intensity statin nly if the benefits frm ASCVD risk reductin r triglyceride lwering when triglycerides are 500 mg/dl, are judged t utweigh the ptential risk fr adverse effects. Evaluate renal status befre fenfibrate initiatin, within 3 mnths after initiatin, and peridically thereafter. Assess renal safety with bth a serum creatinine level and an egfr based n creatinine. If egfr is between 30 and 59 ml/min per 1.73 m2, d nt exceed a dse f 54 mg/day f fenfibrate. D nt use fenfibrate if mderate r severe renal impairment, defined as egfr <30 ml/min per 1.73 m2, is present. If during fllw-up the egfr decreases persistently t 30 ml/min per 1.73 m2, then discntinue fenfibrate. Omega-3 Fatty Acids If using EPA and/r DHA fr severe hypertriglyceridemia (TG 500 mg/dl), evaluate fr GI disturbance, skin change, and bleeding.

8 8 KP Natinal Cardivascular Risk and Dyslipidemia Management Guideline Clinician Guide DISCLAIMER Kaiser Permanente Clinical Practice Guidelines, Clinician Guides, and Practice Tls/Resurces have been develped t assist clinicians by prviding an analytical framewrk fr the evaluatin and treatment f selected cmmn prblems encuntered in patients. They are nt intended t establish a prtcl fr all patients with a particular cnditin. While the guidelines prvide ne apprach t evaluating a prblem, clinical cnditins may vary significantly frm individual t individual. Therefre, the clinician must exercise independent judgment and make decisins based upn the situatin presented. While great care has been taken t assure the accuracy f the infrmatin presented, the reader is advised that KP cannt be respnsible fr cntinued currency f the infrmatin, fr any errrs r missins in this guideline, r fr any cnsequences arising frm its use. These recmmendatins are nt used t make utilizatin management determinatins regarding the medical necessity f a member s care.