UPDATES IN AMBULATORY MEDICINE ERIK RIESSEN, MD, FACP INTERMOUNTAIN MEDICAL CENTER OUTPATIENT INTERNAL MEDICINE RESIDENCY CLINIC

DISCLOSURES: I have no conflict-of-interest disclosures

UPDATES: THE STRUGGLE TO KEEP UP-TO-DATE Global ScienGfic Output Growth Rate: 8% per year (doubling rate: 9 years) Nature; 10/14; 514:535

Cholesterol: brief review PCSK-9 Inhibitors IMPROVE-IT (ezegmibe) Hypertension SPRINT Trial Pathway-II Trial OUTLINE NutriGon: brief review of upcoming 2015 Dietary Guidelines for Americans Diabetes Post-trial monitoring: DPP Trial, VADT, ADVANCE EMPA-REG Outcome Trial

PCSK-9 INHIBITORS FDA-approved: alirocumab 7/24/15, evolocumab 8/27/15 Meta-analysis of 24 RCTs 1 : phase II and III Reduce LDL~50%, raise HDL~6%, reduce Lp(a)~25% Outcomes: MI reducgon 50%, all-cause mortality 50% Adverse events: serious =placebo; Odyssey Long-Term 2 : 1/3 (~600) LDL<25 1 Annals of Internal Medicine 7/15; 163:40 2 NEJM 4/15; 372:1489

EZETIMIBE Improve-It Trial: RCT ~18,000 pagents x ~7years PaGents age 50+ who just had ACS with high LDL SimvastaGn 40mg vs. SimvastaGn 40+ezeGmibe 10mg Primary outcome: MACE composite: 6% RRR (NNT for 7yrs = 50) AE: ~ none NEJM 615; 372:2387

HYPERTENSION 2/3 adults>60yo 1/3 hypertensives remain undiagnosed 1/3 CAD, 2/3 stroke burden alributable to HTN ½ burden in SBP<145; associated risk down to 115/75 AssociaGon CausaGon. What is goal bp? How much Alributable risk from BP itself vs. confounding risk? Where is asymptote on bp treatment J-shaped curve? How much RCT risk reducgon from bp itself vs. medicagon pleiotropy? JAMA 2014; 311:1424 Annals of Internal Medicine 10/15 e-pub ahead of print

SYSTOLIC BLOOD PRESSURE INTERVENTION TRIAL EFFECTS ON CV OUTCOMES AND TOTAL MORTALITY RCT comparing goal SBP<140 (std care arm) vs. <120 (intensive arm) Inclusion: SBP 130 180, age 50+ with AddiGonal CVD risk (1+): clinical or subclinical CVD (not stroke), GFR 20-59, 10-year FRS 15%, age 75 Exclusion: Previously studied: DM/stroke/CHF/EF<35%/PCKDz/Uprot>1g/d, Risk: GFR<20/CV event<3mths/pregnancy Protocol: unblinded, ALLHAT drugs, forced GtraGon

Dependent variable: Realized BP 121/69 vs. 136/76 ~3meds vs. 2meds OUTCOMES, 3.3 years: Primary MACE composite AND allcause mortality both HR~0.75 NEJM, e-pub 11/9/15

Primary outcome subgroup analysis NEJM, e-pub 11/9/15

Adverse Events: NEJM, e-pub 11/9/15

Adverse Events >75

Landmark trial, but my personal reservagons: Methodologic concerns: un-blinded, protocol driven by in-office bps; no diastolic Hypotension endpoint Trial stopped prematurely Adverse Events factored into net benefit Generalizability

Outcomes Data from SPRINT and ACCORD Trials PERKOVIC V, RODGERS A. N ENGL J MED 2015. DOI: 10.1056/NEJME1513301

UNCONTROLLED HYPERTENSION 30-50% Hypertensives not at goal 10% of treated Hypertensives = Resistant Hypertension PATHWAY-2 Trial: randomized crossover study Inclusion: >3mth 3drugs, office SBP>140 + home SBP>130 12 week sequengal: placebo, doxazosin, bisoprolol, spironolactone Outcomes: spironolactone superior 14.5mm Hg drop in SBP vs. placebo: -8.7; bisoprolol: -4.5; doxazosin: -4.0; JAMA 2014; 311:1424 Lancet 9/15 e-pub ahead of print

PLACEBO EFFECT Network meta-analysis 1 : 149 RCTs of knee OA Placebo effect: intra-argcular>topical>oral Network meta-analysis 2 : treagng OA pain oral placebo<apap<ia placebo<nsaid<ia steroid Annals of Internal Medicine 2015; 163:365 Annals of Internal Medicine 2015; 162:46

NUTRITION 2015 DIETARY GUIDELINE HIGHLIGHTS: Cholesterol: not a nutrient of concern hlp://health.gov/dietaryguidelines/2015

NUTRITION 2015 DIETARY GUIDELINE HIGHLIGHTS: Cholesterol: not a nutrient of concern Remove limit on total fat Saturated fat<10% calories Focus on dietary palerns more than components Carbohydrates: Added sugar<10% calories (<50g/day) Whole grains>50% of all grains hlp://health.gov/dietaryguidelines/2015

DIABETES EPIDEMIOLOGY NHANES 2011-12 Data 1 : Diabetes Prevalence=14%; Increasing 13%/decade 2/3 diagnosed, 1/3 undiagnosed Pre-diabetes Prevalence=38% 90% undiagnosed Minority groups (black, Hispanic, Asian): 2x prevalence, 50% undiagnosed 1 JAMA 9/15; 314:1021 2 NEJM 10/29/15; 373:1720

DIABETES PREVENTION DPP Trial 1 : decrease diabetes with meyormin by ~1/3, lifestyle by ~2/3 Meyormin effect related to baseline risk 2 1 NEJM 2002; 346:393 2 BMJ 2015; 350:h454

DIABETES PREVENTION DPP Post-trial observagons 3 : 15yrs, usual care incident diabetes: 62% Lifestyle: RR 0.73 Meyormin: RR 0.82 Microvasc: no DM RR 0.72 USPSTF Diabetes Screening 4 : Adults 40-70 with BMI>25 1 NEJM 2002; 346:393 2 BMJ 2015; 350:h454 3 Lancet Diabetes and Endocrinology 9/15 e-pub 4 Annals of Internal Medicine; 10/27/15 e-pub

GLP-1 AGONISTS Meta-analysis: GLP1 agonist + Basal Insulin vs. Basal-Bolus Insulin No stagsgcally-significant difference in A1c Lower risk of Hypoglycemia: RR=0.67 Mean weight loss 5.7kg over Basal-Bolus regimens LiragluGde: FDA-approved for weight loss 12/14 Lancet 12/14; 384:2228 NEJM 7/15; 373:11

FDA WARNINGS: DIABETES MEDICINES LixisenaGde and DPP4 s: CV neutrality SaxaglipGn: increased risk CHF Meta-analysis: DPP4s 25% increased risk DPP4 Blockers: risk for arthralgias SGLT2 Inhibitors: canagliflozin: bone density/fractures euglycemic DKA Lancet 5/15;3:356

SGLT2 INHIBITORS EMPA-REG-OUTCOME Trial: RCT ~7000 subjects with DM2 and CVDz: Empagliflozin vs. standard care Trial stopped early at 3 years: decreased CV mortality (HR~0.6), all-cause mortality (HR~0.7) Concerns: Industry-sponsored Secondary endpoints Reproducibility NEJM; 9/17/15 e-pub ahead of print

JAMA 9/15; 314:1052 JAMA 10/15; 314:1509 LONG-TERM DIABETES TREATMENT

AN APPLE A DAY TO KEEP THE DR. AWAY? Cross-secGonal study Dietary recall associagon with healthcare uglizagon Fewer prescripgon medicines JAMA Internal Medicine 5/15; 175:777

THANK YOU. BE GOOD, BUT NOT TOO GOOD