leadership weekend 2020 presentation-use weekend 2020...criteria median follow up (years) primary...

1/9/2020

1

Pearls of Practice: Managing Common Conditions in Pharmacy

Presented by:Lindsay Sheehan, PharmD, CDE, CPP

Kayla Morgan, PharmD, CDE, CPP, BCACPKristy Brittain, PharmD, BCPS, CDE

Disclosure

The speakers have no relevant financial relationships to disclose.

1

2

3

1/9/2020

2

Pharmacist Objectives

Upon completion of this activity, the pharmacist will be able to:1. Describe a pharmacist and pharmacy technician’s role in

chronic disease state management 2. Identify updates in diabetes care including current guidelines,

new medications, and continuous glucose monitors3. Summarize changes in the anticoagulation landscape with the

increasing role of Direct Oral Anticoagulants (DOACs)4. Identify updates in asthma care including current guidelines

and new medications5. Apply therapeutic updates to patient case scenarios

Technician Objectives

Upon completion of this activity, the pharmacy technician will be able to:1. Describe a pharmacist and pharmacy technician’s role in

chronic disease state management 2. Identify new medications and devices for use in diabetes,

anticoagulation, and asthma

Type 2 Diabetes Update

4

5

6

1/9/2020

3

9. Pharmacologic Approaches to Glycemic Treatment

› Treatment decisions for Type 2 Diabetes should consider:› Efficacy› comorbidities such as ASCVD, CKD, and heart failure› hypoglycemia risk› effect on body weight› side effects› cost› patient preference

ADA’s Standards of Medical care in Diabetes‐2020

Diabetes Medications Drug/route Efficacy Weight

changeCV effect

ASCVD CHF

Renal Clinical Pearls

Metformin High

↓ hepatic glucose output

Neutral or modest ↓

Potential benefit

Neutral -CI with GFR < 30-If GFR < 45, don’t start-If on metformin and GFR falls to 30-45 consider decreasing dose.

GI side effects common (ER formulation and taking with meals may help)B12 deficiency

SGLT-2 Inhibitors

empagliflozin*canagliflozin*dapagliflozinertugliflozin

Intermediate

↓ glucose reabsorption in kidneys

Loss Benefit*

empa-gliflozin FDA approved for CVD benefit

Benefit

empa-gliflozin, cana-gliflozin, and dapa-gliflozin

Progression of Diabetic Kidney disease: Benefit (canagliflozin, empagliflozin, dapagliflozin)

Renal dose adjustments required. Don't start if GFR < 45 (< 60 for ertugliflozin)

-BBW: Amputation (canagliflozin)-Bone Fractures (canagliflozin)-DKA-Genitourinary infections-Volume depletion, hypotension-increased LDL-Fournier's gangrene

Am erican Diabetes Association. 9. Pharm acologic approaches to glycem ic treatm ent: Standards of M edical Care in Diabetes—2019 [web annotation]. Diabetes Care 2019;42(Suppl. 1):S90–S102.

SGLT2 inhibitors trialsTrial Intervention Main

inclusion Criteria

Median follow up

(years)

Primary outcome

Results/Conclusion

Intervention Placebo

EMPA-REG OUTCOME(n=7,020)

empagliflozin/placebo

Type 2 diabetes and preexisting CVD

3.1 CV death, MI, and stroke

490 patients (10.5%) 282 patients (12.1%)

HR 0.86 [95% CI 0.74-0.99], P=0.04 for superiority. Lower rates of death from CV cause (38% relative risk reduction), hospitalization for HF (35% relative risk reduction, and death from any cause (32% relative risk reduction).

DECLARE-TIMI 58(n=17,160)

dapagliflozin/ placebo

Type 2 DM and established ASCVD or multiple ASCVD risk factors

4.2 CV death, MI, and stroke, or hospital-ization for HF

8.8% 9.4%

Primary safety outcome: noninferiority to placebo with respect to MACE (p<0.001).Primary efficacy outcome: did not lower rate of MACE; HR 0.93 (95% CI 0.84-1.03) P=0.17.Decreased rate of CV death or hospitalization for HF (4.9% vs 5.8% HR 0.83 (95% CI 0.73-0.95) p=0.005).27% reduction in hospitalization for HF

References 7,8. Abbreviations: CV= cardiovascular disease, ASCVD=atherosclerotic cardiovascular disease, MI=myocardial infarction, HF=heart failure, HR=Hazard ratio, CI=confidence interval, MACE=Major Adverse Cardiac Event

7

8

9

1/9/2020

4

SGLT2 inhibitor trials

Trial Intervention Main inclusion Criteria

Median follow up

(years)

Primary outcome

Results/Conclusion


CANVASandCANVAS-R(n=10,142)

canagliflozin/ placebo

Type 2 diabetes and preexisting CVD at >30 years of age or > 2 CVD risk factors at >50 years of age

3.6 CV death, MI, and stroke

26.9 participants/1000

patient-years

31.5 participants/1000 patient-

years

HR 0.86 [95% CI 0.75–0.97]. Canagliflozin significantly reduced the composite outcome.Increased risk of lower limb amputation (6.3 vs 3.4 participants/1000 patient-years, HR 1.97 [95% CI 1.41-2.75].

CREDENCE(n=4,401)

canagliflozin/ placebo

Type 2 DM and chronic diabetes related kidney disease

2.62

trial ended early

End stage kidney disease, doubling of Scr or death from renal or CV causes

43.2 per 1000 patient-years

61.2 per 1000 patient-years

HR 0.70 [95% CI 0.59-0.82], P=0.00001.Relative risk of the primary outcome 30% lower in the canagliflozin arm. Lower risk of CV death, MI, or stroke (HR 0.80 [CI 0.67-0.95] P=0.01) Lower risk of hospitalization for HF (HR 0.61 [CI 0.47-0.80] P<0.001).No difference in rates of amputation or fracture.

References 10, 11.


changeCV effect

ASCVD CHF


GLP-1 analogs

BID: exenatide Daily: liraglutide, lixisenatideWeekly: exenatide ER, dulaglutide, semaglutide

High

↑ insulin release with foodSlows gastric emptyingPromotes satietySuppresses glucagon

Loss Benefit: liraglutide, sema-glutide, and dula-glutide

Neutral Liraglutide has shown to decrease progression of diabetic kidney disease

-FDA BBW: Thyroid C-cell tumors -GI side effects (nausea, diarrhea, vomiting)-Injection site reactions-possibly acute pancreatitis risk?

DPP-4 inhibitors

alogliptinlinagliptinsaxagliptinsitagliptin

Intermediate

Prolong gut hormone↑ insulin secretionDelay gastric emptying

Neutral Neutral Potential risk with saxagliptin and alogliptin

Renal dose adjustments for all except linagliptin

-Potential risk for pancreatitis -Low risk for hypoglycemia-SE: headache, joint pain, flu-like symptoms

Am erican Diabetes Association. 9. Pharm acologic approaches to glycem ic treatm ent: Standards of M edical Care in Diabetes—2019 [web annotation]. Diabetes Care 2019;42(Suppl. 1):S90–S102.

GLP‐1 analogs and cardiovascular disease trialsTrial Intervention Main

inclusion Criteria

Median follow up

(years)

Primary outcome

Results/Conclusion


LEADER(n=9,340)

Liraglutide/placebo

Type 2 DM, preexisting CVD, CKD, or HF at >50 y/o, or CVD risk at > 60 y/o

3.8 CV death, MI, or stroke

608 patients (13%) 694 patients (14.9%)

HR 0.87 [95% CI 0.78-0.97], P<0.001 for noninferiority, P=0.01 for superiority. 15% reduction in all-cause mortality

SUSTAIN-6(n=3,297)

Semaglutide/placebo

Type 2 DM, preexisting CVD, CKD, or HF at >50 y/o, or CVD risk at > 60 y/o

2.1 CV death, non fatal MI, and nonfatal stroke


HR 0.74 [95% CI 0.58-0.95], P<0.001 for non-inferiority, P=0.02 for superiority. Powered to test noninferiority. No significant difference in CV mortality.

References 2,3

10

11

12

1/9/2020

5

GLP‐1 analogs and cardiovascular disease trialsTrial Intervention Main

inclusion Criteria

Median follow up

(years)

Primary outcome

Results/Conclusion


EXSCEL(n=14,752)

Exenatide ER/placebo

Type 2 DM with or w/o preexisting CVD

3.2 CV death, MI, or stroke


HR 0.91 [95% CI 0.83– 1.00], P< 0.001 for noninferiority. Not superior to placebo P=0.06. All-cause mortality was lower in the exenatide arm.

ELIXA(n=6,068)

lixisenatide/ placebo

Type 2 DM, ACS within 180 days

2.1 CV death, MI, stroke, or hospital-ization for unstable angina


HR 1.2 [95% CI 0.89–1.17]. P<0.001 for non-inferiority, but did not show superiority (P=0.81).

REWIND(n=9,091)

dulaglutide/ placebo

Type 2 DM with preexisting CVD or risk CV risk factors

5.4 CV death (including unknown cause), MI, or stroke

594 patients (12%) 663 patients (13.4%)

HR 0.88 [95% CI 0.79-0.99], P=0.026. All cause mortality did not different between the groups P=0.067.

References 4,5,6. Abbreviation ACS=Acute Coronary Syndrome


changeCV effect

ASCVD CHF


Thiazolidinediones

pioglitazonerosiglitazone

High

↑ insulin sensitivity

Gain Potential benefit

Increased risk

No dose adjustments, but caution in renal impairment due to fluid retention.

-Avoid in patients with heart failure-monitor weight gain and edema-Bone fractures-Bladder cancer (pioglitazone)

Sulfonylurea

glipizide (XL), glimepiride, glyburide

High

Stimulates insulin release

Gain Neutral Neutral Renal impairment can increase risk of lows. Avoid glyburide, initiate glipizide and glimepiride at lower doses.

-Increased risk of hypoglycemia. Especially with longer acting products.-Cheap

Diabetes Care 2019 Jan; 42 (Supplement 1): S103‐S123. https://doi.org/10.2337/dc19‐S010

Standards of Medical Care in Diabetes Section 9

Pharmacologic Therapy for Type 2 Diabetes

13

14

15

1/9/2020

6

Pharmacologic

Approaches to Glycemic Management:Standards of Medical Care

in Diabetes ‐ 2020. Diabetes Care 2020;43(Suppl. 1):S98-S110

Pharmacologic



Pharmacologic



16

17

18

1/9/2020

7

Intensifying to Injectable Therapies

Pharmacologic Approaches to Glycemic

Management:Standards of Medical Care in Diabetes ‐ 2020.

Diabetes Care 2020;43(Suppl. 1):S98-S110



Management:Standards of Medical Care in Diabetes ‐

2020. Diabetes Care 2020;43(Suppl. 1):S98-S110



Management:Standards of Medical Care in Diabetes ‐ 2020.

Diabetes Care 2020;43(Suppl. 1):S98-S110

19

20

21

1/9/2020

8

› First oral GLP‐1 receptor agonist › Indicated in adjunct to diet and exercise to improve BG in

adults with type 2 diabetes› Co‐formulated with salcaprozate sodium which facilitates

absorption in the stomach› Administration:

– Empty stomach and no more than 4 ounces of plain water– > 30 minutes before food, drink, or other medications– Recommend eating 30‐60 minutes after the dose – Do not split, crush, or chew

› Dosing:– 3 mg PO daily x 30 days (not a therapeutic dose)– Then increase to 7 mg PO daily for at least 30 days– If further glycemic control needed can increase to 14 mg PO daily

Oral Semaglutide (RybelsusⓇ)

› Max concentration reached in 1 hour› Steady state achieved in 4‐5 weeks› Precautions:

– not to be used for type 1 DM, pregnancy/lactation, patients < 18 y/o, h/o pancreatitis

› Drug interactions:– insulin and sulfonylureas– levothyroxine

› Patient counseling:– nausea, vomiting, diarrhea most common side effects– thyroid C‐cell tumors seen in rats – stop medication if suspect pancreatitis – worsening renal failure with dehydration

Oral Semaglutide (RybelsusⓇ)

› Efficacy and safety of oral semaglutide 14 mg (n=412) and empagliflozin 25 mg (n=410) compared in patients uncontrolled on metformin

› GI side effects more common with oral semaglutide

Oral Semaglutide vs. Empagliflozin in Patients with Type 2 DM uncontrolled on Metformin: The PIONEER 2 trial

Treatment Policy Estimand

sema empa

Trial Product Estimand

sema empa

Results/conclusion

Change in A1C baseline to week 26 baseline to week 52

-1.3%* -0.9%*-1.3%* -0.9%*

-1.4%* -0.9%*-1.3%* -0.8%

estimated treatment difference -0.4% [95% CI -0.6, -0.3]; *P<0.0001

Change in weight baseline to week 26baseline to week 52

-3.8 kg -3.7 kg-3.8 kg -3.6 kg

-4.2 kg -4.8 kg-4.7 kg** -3.8 kg** **P=0.0114 at week 52

22

23

24

1/9/2020

9

Continuous Glucose Monitors (CGMs)

› Commonly used for diagnosis and assessment of glycemic control

› Cons– Correlates to an average blood sugar– May be inaccurate in some cases

Hemoglobin A1c

› Traditional method for patients and providers to monitor blood sugars on a day‐by‐day basis

› Cons– Painful and cumbersome for patients– Variety of testing supplies required– Checks blood sugar in that specific moment– May require multiple checks throughout the day to get an idea of

trends

Fingerstick Blood Glucose Monitoring

25

26

27

1/9/2020

10

› Typically consists of a sensor, transmitter, and reader/receiver– Sensor is inserted under the skin (usually abdomen or back of arm)– Sensor measures interstitial glucose– Transmitter sends information wirelessly to a reader/monitor

› Allows for continuous feedback on glucose› Data can be downloaded to computer or smart device

Continuous Glucose Monitoring (CGM)

› Takes time for glucose to diffuse from the capillary to the interstitial space– Interstitial glucose tends to lag behind if blood sugars are rapidly

changing

Interstitial Glucose vs. Blood Glucose

› Shows glucose trends and provides dynamic data about direction blood sugar is heading

› Continuous feedback of impact of medications, diet, and exercise on sugars

› Some products alert users to hypoglycemia– Safer for patients with hypoglycemia unawareness

› Requires fewer fingersticks› May improve glycemic control and reduce glycemic

variability

Benefits of CGM

28

29

30

1/9/2020

11

Available Personal CGM SystemsCGM System Details

Sensor Duration

Warm-Up Time

Calibration

Abbott FreeStyle Libre Personal® ▪ Records data every 15 minutes

▪ Does not communicate continuously with reader; Must scan every 8 hours

▪ Reader has built-in blood glucose meter▪ Compatible with iPhone 7 and later through the LibreLinkTM

app▪ Displays current sensor glucose reading, visual alerts, and

trend arrows▪ Has text-to-speech option when enabled

14 days 1 hour Not required

Dexcom G6®

▪ Collects glucose readings every 5 minutes▪ Transmitter battery lasts 3 months▪ Receiver can include a touch-screen receiver, smartphone,

smartwatch, or Tandem X2 insulin pump▪ Application available in Apple App Store and Google Play

Store▪ Displays current sensor glucose reading, trend arrows, and

customizable alerts/alarms

Up to 10 days

2 hours

Not required

Can choose to calibrate

American Diabetes Association. Continuous glucose monitors- Consumer Guide 2018. Diabetes Forecast. http://main.diabetes.org/dforg/pdfs/2018/2018-cg-continuous-glucose-monitors.pdf (accessed Jan. 6, 2019).FreeStyle LibreLink App. Freestyle Libre. https://www.freestylelibre.us/system-overview/continous-glucose-monitor-app.html (accessed Jan. 19, 2019).Abbott’s Freestyle Libre 14 day flash glucose monitoring system now approved in U.S. Abbott. https://abbott.mediaroom.com/2018-07-27-Abbotts-FreeStyle-R-Libre-14-Day-Flash-Glucose-Monitoring-System-Now-Approved-in-U-S (accessed Jan. 19, 2019). Dexcom G6 continuous glucose monitoring system user guide. Dexcom, Inc. https://s3-us-west-2.amazonaws.com/dexcompdf/G6-CGM-Users-Guide.pdf?_ga=2.61291948.1830682920.1549243176-1258106527.1549243176 (accessed Jan. 19, 2019).Images: Continuous glucose monitoring system. Freestyle Libre. https://www.freestylelibre.us/ (accessed Jan. 19, 2019).Make knowledge your superpower with the new Dexcom G6® CGM. Dexcom, Inc. https://www.dexcom.com/get-started-cgm/40?sfc=701f30000018vibAAA&gclid=EAIaIQobChMIw-2n_IbV4AIV0pCfCh2HJwTQEAAYASAAEgLAsvD_BwE (accessed Jan. 19, 2019).

Available Personal CGM Systems

CGM System DetailsSensor

DurationWarm-Up

TimeCalibration

Medtronic Guardian Connect 3®▪ Collects glucose readings every 5 minutes▪ Compatible with Apple devices▪ Does not require purchase of extra device▪ Uses rechargeable transmitter which must be recharged

weekly▪ Displays sensor glucose data, trends, and

customizable/predictive alerts▪ Determines glucose patterns using Sugar.IQTM Diabetes

Assistant ▪ Data automatically uploads to CareLinkTM Personal software

Up to 7 days 2 hoursAt least twice

daily; Every 12 hours

Senseonics Eversense XL®

▪ Sensor is professionally inserted under skin▪ Transmitter with rechargeable battery is placed on top of

sensor placement site▪ Automatically sends glucose reading to mobile app every 5

minutes▪ Provides on-body vibrating alerts when glucose is low or high▪ Displays sensor glucose data, trends, and

customizable/predictive alerts

Up to 90 days

24 hours2-4 times daily depending on

calibration phase

Guardian Connect vs. Freestyle Libre. Medtronic Diabetes. https://guardianconnect.medtronic-diabetes.co.uk/guardian-connect-vs-freestyle-libre# (accessed January 19, 2019).American Diabetes Association. Continuous glucose monitors- Consumer Guide 2018. Diabetes Forecast. http://main.diabetes.org/dforg/pdfs/2018/2018-cg-continuous-glucose-monitors.pdf (accessed January 6, 2019).Eversense User Guide. Food and Drug Administration. https://www.accessdata.fda.gov/cdrh_docs/pdf16/P160048c.pdf (accessed February 6, 2019).Images: Guardian Connect CGM System. Medtronic Diabetes. https://www.medtronicdiabetes.com/products/guardian-connect-continuous-glucose-monitoring-system (accessed January 19, 2019).Eversense: the only long-term continuous glucose monitoring (CGM) system. Senseonics, Inc. https://www.eversensediabetes.com/products/ (accessed February 6, 2019).

Comparing Personal CGM Features

FeaturesAbbott FreeStyle Libre Personal®

Dexcom G6® Medtronic Guardian Connect 3®

Senseonics Eversense XL®

No Calibration Required X X

Ability to Share Data X X X X

Customizable Alerts X X X

Predictive Alerts X X X

Handheld Reader/ Receiver Available

X X

Compatible with Apple Products X X X X

Compatible with Android Products X X X

Equipped with Data Analysis System

X

Location of Sensor Placement Back of Upper ArmAbdomen,

Upper Buttocks*Abdomen Upper Arm

Mean Absolute Relative Difference

9.4% 9.0% 9.1% 8.5%

*Only for patients 2-17 years old

Continuous glucose monitoring system. Freestyle Libre. https://www.freestylelibre.us/ (accessed Jan. 19, 2019).Abbott’s Freestyle Libre 14 day flash glucose monitoring system now approved in U.S. Abbott. https://abbott.mediaroom.com/2018-07-27-Abbotts-FreeStyle-R-Libre-14-Day-Flash-Glucose-Monitoring-System-Now-Approved-in-U-S (accessed Jan. 19, 2019). Dexcom G6 continuous glucose monitoring system user guide. Dexcom, Inc. https://s3-us-west-2.amazonaws.com/dexcompdf/G6-CGM-Users-Guide.pdf?_ga=2.61291948.1830682920.1549243176-1258106527.1549243176 (accessed Jan. 19, 2019).Guardian Connect CGM System. Medtronic Diabetes. https://www.medtronicdiabetes.com/products/guardian-connect-continuous-glucose-monitoring-system (accessed January 19, 2019).Eversense User Guide. Food and Drug Administration. https://www.accessdata.fda.gov/cdrh_docs/pdf16/P160048c.pdf (accessed February 6, 2019).

31

32

33

1/9/2020

12

› Sensor is placed by healthcare professional› Results are usually blinded to patient› Patients follows usual routine for blood sugar monitoring,

medications, diet, exercise, etc.› Sensor data is downloaded at provider’s office

Professional CGM

Abbott FreeStyle Libre Pro

Medtronic iPro 2Dexcom G4

Platinum Pro

Sensor collects data for up to 14 days



Can choose blinded or unblinded mode

› Summary of time in, above, and below range› Sensory usage data› Mealtime and glucose patterns› Hyper‐ and hypoglycemia statistics› Daily logbook› Weekly or monthly summaries with averages

CGM Reports

Clinical Targets for Continuous

Glucose Monitoring

Data Interpretation

Recommendations From the International

Consensus on Time in Range

Diabetes Care 2019;42:1593–1603 |

https://doi.org/10.2337/dci19-0028

34

35

36

1/9/2020

13

Example CGM report: Glucose Pattern Summary

37

Example CGM report

38

Monthly Summary

37

38

39

1/9/2020

14

Example CGM report: Daily summary

40

Example Personal CGM report: Daily summary

41

Anticoagulation Update

40

41

42

1/9/2020

15

› Atrial fibrillation

› Venous thromboembolism

› Cerebrovascular accident

› Myocardial infarction

› Prosthetic heart valves

› Hypercoagulable states

Common Indications for Anticoagulation

› Changing prescribing landscape

› Expanded indications

› Expanded contraindications/precautions

› Atrial fibrillation guideline update

› National patient safety goals

So what is new?

› Vitamin K antagonists (VKA), such as warfarin, have been the mainstay of oral anticoagulation therapy for many years

› Direct oral anticoagulants (DOACs) are now commonly prescribed alternatives

› DOACs may serve as more appealing therapy choices than warfarin

Changing Anticoagulation Landscape

Shehab N, Lovegrove MC, Geller AI. US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014.JAMA. 2016 Nov 22;316(20):2115-2125.

43

44

45

1/9/2020

16

DOAC Pros

› Less frequent monitoring› Fixed dosing› Fewer drug interactions› Fewer diet interactions› Rapid onset› Short half‐life› Improved safety profile in

trials

What’s the big deal?

DOAC Cons

› Monitoring still requires› Dose adjustments› Drug interactions still exist› Strict adherence needed› Cost› Less frequent contact with

healthcare professionals› False perception of safety

Burnett AE, Mahan CE, Vazquez SR, et. al. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016 Jan;41(1):206-32.

› Most common prescribing errors: dosing, administration, duration

› Several studies suggest inappropriate DOAC dosing occurs in 12.8‐34% of patients

Appropriateness of DOAC Prescribing

Whitworth MM, Haase KK, Fike DS, et. al. Utilization and prescribing patterns of direct oral anticoagulants. Int J Gen Med. 2017. 10: 87–94.Moudallel S, Steurbaut S, Cornu P, Dupont A. Appropriateness of DOAC Prescribing Before and During Hospital Admission and Analysis of Determinants

for Inappropriate Prescribing. Front Pharmacol. 2018; 9:1220.

Commercial

› Copay assistance cards› Deductible issue

Medicare

› Deductible up to $415› Copay $25‐45› Coverage gap after $3,820› Catastrophic coverages after $8,139

Manufacturers Patient Assistance Programs

Medicare’s Extra Help Program

CostDOAC AWP

per 30 days

Copay Card

per 30 days*

apixaban $533 $10

rivaroxaban $540 $10

dabigatran $519 $0

edoxaban $436 $4

betrixaban $540 $50 first fill

$0 after

*Eligibility and restrictions apply

46

47

48

1/9/2020

17

Centers for Disease Control and Prevention (CDC) study (2016):

› Oral anticoagulants caused more emergency department visits than any other class of drugs

› >50% of these visits led to hospitalization

Anticoagulants and ER Visits/Hospitalizations

Shehab N, Lovegrove MC, Geller AI. US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014.JAMA. 2016 Nov 22;316(20):2115-2125.

Vitamin K Antagonist and Direct Oral Anticoagulants (DOACs)

Anticoagulants

Anticoagulants: Vitamin K Antagonist

Drug Indication Dose Dose Adjustments Clinical Pearls

warfarin -Atrial fibrillation-Venous thromboembolism prevention and treatment-Embolism prophylaxis and treatment in setting of prosthetic cardiac valves-Reduce risk of embolism following MI

Individualized based on patient specific factors and INR

Renal: No adjustments

Hepatic: Monitor closely and adjust based on INR

Drug Interactions: Monitor closely and adjust based on INR

-Consistency from week to week and open communication with managing providers is key

Coumadin (warfarin) [package insert].Princeton, New Jersey: Bristol-Myers Squibb Company; 2011.

49

50

51

1/9/2020

18

Anticoagulants: Direct Thrombin Inhibitors

Drug FDA Approved Indications

Dose Dose Adjustments Clinical Pearls

dabigatran Atrial fibrillation 150mg BID Renal:Atrial fibrillation:

CrCl 15-30mL/min: 75mg BIDDVT/PE:

CrCl <30mL/min: No recommendationVTE Prevention Post-hip:

CrCl <30mL/min: Avoid use

Hepatic:Mod impairment (Child-Pugh B):

No adjustmentSevere impairment:

Use not recommended

Drug Interactions:P-gp inhibitors

Afib with CrCl 30-50 mL/min: 75mg BIDVTE or CrCl < 30 mL/min: avoid use

Take 2 hours before verapamil, H2 blockers, PPIs

-Cannot be given via tube

-60% dialyzed out

-Store in original container; use open bottle within 4 months

-Discontinuation prior to surgery

- CrCl ≥50: 1-2 days- CrCl <50: 3-5 days

DVT/PE treatment and prevention of recurrence

150mg BID after 5-10 days or parenteral anticoagulant

VTE prevention post-hip replacement

110mg x 1, then 220mg daily x 28-35 days post-op

Pradaxa (dabigatran) [package insert].Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2019.

Anticoagulants: Factor Xa Inhibitors



rivaroxaban Atrial fibrillation 20mg daily with evening meal

Renal:Atrial fibrillation:

CrCl 15-50mL/min: 15mg dailyCrCl <15mL/min: Avoid use

DVT/PE:CrCl <30mL/min: Avoid use

VTE Prevention Post-hip:CrCl <30mL/min: Avoid use

Hepatic:Child-Pugh B or C: Avoid use

Drug Interactions:P-gp inhibitors + strong CYP3A4 Inhibitors (ketoconazole, itranzonazole, ritonavir, conivaptan): Avoid useP-gp inducers + strong CYP3A4 Inducers (carbamazepine, phenytoin, rifampin, St John’s wort): Avoid use

-Can be crushed and given via G-tube; not J-tubes

-Not dialyzable


- 24hr low risk bleed- 48hr high risk bleed

DVT/PE treatment

15mg BID with food x 21 days, then 20mg daily with evening meal

DT/PE prevention of recurrence

After 6 months of treatment: 10mg daily

VTE prevention post-hip or knee replacement

10mg dailyx12 days kneex 35 days hip

Xarelto (rivaroxaban) [package insert].Titusville, NJ: Janssen Pharmaceuticals, Inc; 2019.




rivaroxaban Reduction of CV death, MI, stroke in chronic CAD or PAD

2.5mg BID + aspirin 75-100 mg daily

Xarelto (rivaroxaban) [package insert].Titusville, NJ: Janssen Pharmaceuticals, Inc; 2019.

52

53

54

1/9/2020

19

› Randomized 27,395 patients with stable CAD or PAD to rivaroxaban 2.5mg BID + aspirin, rivaroxaban 5mg BID, or aspirin 100mg daily

COMPASS Trial

Major bleeding events more common in rivaroxaban + aspirin group vs aspirin alone (3.1% vs. 1.9%, HR 1.7; 95% CI 1.40‐2.05; P<0.001)‐ Mostly GI bleeds‐ No difference in fatal bleeding,

intracranial bleeding, or critical organ bleeding

Eikelboom JW, Connolly SJ, Bosch K, et. al. N Engl J Med. 2017 Oct 5; 377(14): 1319-1330.




apixaban Atrial fibrillation 5mg BID Renal:Atrial fibrillation:

At least 2 of : Age ≥80, Wt <60kg, SCr ≥1.5: 2.5mg BID

DVT/PE:No adjustment

VTE Prevention Post-hip:No adjustment

Hepatic:Severe: Avoid use

Drug Interactions:P-gp inhibitors + strong CYP3A4 Inhibitors (ketoconazole, itranconazole, ritonavir, conivaptan): 2.5mg BID or Avoid useP-gp inducers + strong CYP3A4 Inducers (carbamazepine, phenytoin, rifampin, St John’s wort): Avoid use

-Can be crushed and given via tubes

-Not dialyzable



DVT/PE treatment

10mg BID x 7 days, then 5mg BID

DT/PE prevention of recurrence

After 6 months of treatment: 2.5mg BID

VTE prevention post-hip or knee replacement

2.5mg BIDx12 days kneex 35 days hip

Eliquis (apixaban) [package insert].Princeton, NJ: Bristol-Myers Squibb Company. New York, NY: Pfizer Inc; 2019.

55

56

57

1/9/2020

20




edoxaban Atrial fibrillation 60mg once daily

Renal:Atrial fibrillation:

CrCl >95 mL/min: Avoid useCrCl 15-50 mL/min: 30mg dailyCrCl <15 mL/min: Avoid use

DVT/PE:CrCl 15-50 mL/min: 30mg dailyCrCl <15 mL/min: Avoid use

Hepatic:Moderate or severe: Avoid use

Drug Interactions:Strong P-gp inhibitors in DVT/PE patients (quinidine, verapamil, azithromycin, clarithromycin, erythromycin, itraconazole, ketoconazole): 30mg daily Rifampin: Avoid use

-Can be crushed and given via tubes

-Not dialyzable



DVT/PE treatment

60mg once daily after 5-10 days of parenteral anticoagulant

Savaysa (edoxaban) [package insert].Basking Ridge, NJ: Daiichi Sankyo, Inc; 2019.




betrixaban Prophylaxis of VTE in patients hospitalized for acute medical illness who are at risk for VTE complications due to moderate or severe restricted mobility and other risk factors

160mg x 1, then 80mg daily with food x 35-42 days

Renal:CrCl 15-30 mL/min: 80mg x 1, 40mg daily x 35-42 days

Hepatic:Not recommended

Drug Interactions:Strong P-gp inhibitors (amiodarone, azithromycin, verapamil, ketoconazole, clarithromycin): 80mg x 1, 40mg daily

-Unknown if dialyzable

Bevyxxa (betrixaban) [package insert].South San Francisco, CA: Portola Pharmaceuticals, Inc; 2019.

58

59

60

1/9/2020

21

2019 AHA/ACC/HRS Focused Update on 2014 Guideline for Management of Patients with Atrial Fibrillation

January CT, Wann LS, Calkins H, et al. Circulation. 2019; 140: e125-e151.

Section 4.1.1: Selection of Anticoagulant Regimen

› Oral anticoagulants recommended for high risk patients – Now includes edoxaban

› Exclusion criteria for CHA2DS2‐VASc and use of DOACs– Defined as moderate to severe mitral stenosis or mechanical

heart valves› Based on RE‐ALIGN trial, mechanical heart valves are a

contraindication to all DOACs

Atrial Fibrillation Guideline Update


› Patients with aortic or mitral valve replacement were assigned 2:1 to either dabigatran or warfarin

› Terminated prematurely due to excess off thromboembolic and bleeding events with dabigatran– Ischemic stroke: 5% with dabigatran vs 0% with warfarin– Major bleeding: 4% with dagibatran vs 2% with warfarin

RE‐ALIGN: Dabigatran versus Warfarin in Patients with Mechanical Heart Valves

Eikelboom JW, Connolly SJ, Brueckmann M, et. al. N Engl J Med. 2013; 369: 1206-1214.

61

62

63

1/9/2020

22

Section 4.1.1: Selection of Anticoagulant Regimen

› DOACS in patients with renal/hepatic impairment– All DOACs have FDA approval for use in some degree of renal

dysfunction– Dabigatran, rivaroxaban, and edoxaban NOT recommended in

end‐stage CKD– Use of warfarin or apixaban may be reasonable in

dialysis‐dependent patients – DOACs not recommended in severe hepatic impairment



Section 6.1.1: Prevent on Thromboembolism

› Atrial fibrillation or flutter >= 48 hr (or when duration unknown) anticoagulation is recommended for at least 3 weeks prior and 4 weeks after cardioversion– Upgraded to Class I Recommendation

› Atrial fibrillation or flutter <48 hr with CHA2DS2‐VASc >= 2 in mean and >= 3 in women, administration of heparin or DOAC is reasonable as soon as possible before cardioversion– Downgraded to Class IIa



NEW RECOMMENDATIONS

› DOACS recommended over warfarin where eligible except in those with moderate‐severe mitral stenosis or mechanical heart valve

› Weight loss and risk factor modification is recommended for overweight/obese patients



64

65

66

1/9/2020

23

› 4 RCT comparing DOACs to warfarin– Consistent non‐inferiority evidence for combined end

point of stroke or systemic embolism– Superior safety profile

› DOACS recommended as first line therapy for eligible patients

DOACs vs. warfarin

Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.

Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.

https://medium.com/@rajeetsingh/once-you-see-a-bandwagon-its-too-late-e067c94529c4https://engagevideomarketing.com/case-study/why-you-cant-just-jump-on-the-online-id b d /

› Autoimmune disorder where antibodies attack phospholipids

› Increased risk for venous and arterial embolism › May never have signs or symptoms until experience a

thrombotic event› Diagnosis requires antibody testing

Antiphospholipid Syndrome (APS)

Meroni PL, Borghi MO, Raschi E, Tedesco F. Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nature Reviews Rheumatology. 2011. 7: 330-339.

67

68

69

1/9/2020

24

› Increased rate of recurrent thrombotic events when treated with DOAC compared to warfarin– APS triple positive (lupus anticoagulant, anticardiolipin, and anti‐

beta‐2 glycoprotein I antibodies) are at highest risk for treatment failure

› Consider switching patients with APS to warfarin

Anticoagulant Choice with APS

Pengo V, Denas G, Zoppellaro G, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018. 132(13): 1365–71.

NPSG.03.05.01: Reduce the likelihood of patient harm associated with the use of anticoagulant therapy.

› Revised July 2019 to include DOAC management› Acknowledges rise in adverse drug events associated with

DOACs

National Patient Safety Goal (NPSG)

The Joint Commission on Accreditation of HealthCare Organizations. National Patient Safety Goal for Anticoagulant Therapy. Retrieved from: https://www.jointcommission.org/assets/1/18/R3_19_Anticoagulant_therapy_FINAL2.PDF

EP 1: Approved protocols and evidence‐based practice guidelines for the initiation and maintenance of anticoagulant therapy that address:

› Medication selection› Dosing› Drug‐drug interactions› Drug‐food interactions

NPSG Elements of Performance


70

71

72

1/9/2020

25

EP 4: Written policy addressing the need for baseline and ongoing laboratory tests to monitor and adjust anticoagulant therapy

EP6: Provides education to patients and families specific to the anticoagulant medication prescribed

NPSG Elements of Performance


› Ensure appropriate indication› Ensure appropriate dose› Manage drug interactions› Address barriers

– cost– adherence

› Monitoring› Patient education› Perioperative management› Transitions of care

Role of Pharmacists

› Indication› Dosing and administration› Adherence› Importance of monitoring and follow ups› Potential adverse events

– Signs/symptoms of thrombosis– Signs/symptoms of bleeding

› Potential drug interactions› Periprocedural management

Education

73

74

75

1/9/2020

26

Available studies suggest pharmacist‐run DOAC education and monitoring services may reduce medication related adverse drug events

Reduce expenses through avoided complications

› ADEs› Emergency room visits› Hospital admissions

Pharmacist Impact

Shore S, Carey EP, Turakhia MP, et. al. Adherence to dabigatran therapy and longitudinal patient outcomes: Insights from the Veterans Health Administration. Am Heart J. 2014 Jun. 167(6): 810–817.

Erikson AK. Pharmacist management improves dabigatran adherence. PharmacyToday. 2015 Jun. 21 (6): 12.Ashjian E, Kurtz B, Renner E, et. al. Evaluation of a pharmacist-led outpatient direct oral anticoagulant service. Am J Health Syst Pharm. 2017 Apr 1;74(7):483-489.

› Extremes of body weight

› Age

› Renal dysfunction

› Hepatic dysfunction

Dosing in Special Populations

Weight > 120 kg and/or BMI > 40 kg/m2

› Concern for inadequate dosing/thrombosis› Limited clinical date› International Society of Thrombosis and Hemostasis and

Anticoagulation Forum recommend against use of DOACS in this population

Weight < 49 kg

› Concern for drug accumulation and toxicity

Extremes of Body Weight

Atrium Health. November 2018. Direct Oral Anticoagulants (DOACs) Pharmacy Dosing Guideline. Unpublished internal document.Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J

Thromb Haemost 2016; 14:1308-1313.

76

77

78

1/9/2020

27

› Increasing age can increase risk of bleeding› Close attention to renal function› Fall risk

Age

Atrium Health. November 2018. Direct Oral Anticoagulants (DOACs) Pharmacy Dosing Guideline. Unpublished internal document.Benedetti G, Neccia M, Agati L. Direct oral anticoagulants in elderly patients with non valvular atrial fibrillation: state of evidence. Minerva Cardioangiol. 2018 Jun; 66 (3):301-313.

DOAC Elimination

Qamar A, Vaduganathan M, Greenberger NJ, Giugliano RP. Oral anticoagulation in patients with liver disease. J Am Coll Cardiol 2018; 71: 2162.

› Safe and effective with mild‐to‐moderate impairment

› Insufficient evidence to predict safety and efficacy with CrCl

<30 mL/min

› Severe/end‐stage CKD (non‐hemodialysis with CrCl <15)

– <20 mL/min mostly excluded from trials

› End‐Stage CKD on diaylsis

– Apixaban: no dose adjustment necessary if

treatment/ppx DVT/PE or if afib and not >= 80yo with

body wt <= 60kg

– Recommendation based on a SINGLE PK/PD study

Renal Dysfunction

Atrium Health. November 2018. Direct Oral Anticoagulants (DOACs) Pharmacy Dosing Guideline. Unpublished internal document.Ha JT, et al. Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ann Intern Med. 2019; 171(3):181-189.

79

80

81

1/9/2020

28

› Increased risk for thrombosis

– Decreased production of endogenous anticoagulants

(Protein C, antithrombin)

– High circulating levels of procoagulants

– Increased platelet aggregation

– High risk of VTE even with increased INR

› Increased risk for bleeding

– Decreased production of coagulation factors

– Thrombocytopenia

– Increased fibrinolysis

Hepatic Dysfunction

Qamar A, Vaduganathan M, Greenberger NJ, Giugliano RP. Oral anticoagulation in patients with liver disease. J Am Coll Cardiol 2018; 71: 2162.

› Consider for– Extremes of body weight– Drug interactions– Renal impairment– Elderly– Treatment failure– Acute bleeding

› Issues/Concerns– High interpatient variability– No defined therapeutic ranges– Availability of drug‐specific assays

Lab Monitoring: Anti‐Xa Levels

Goddelin RC, Adcock DM, Douxfils J. An update on laboratory assessment for direct oral anticoagulants (DOACs). Int J Lab Hematol. 2019 May;41 Suppl 1:33-39.Connors JM. Testing and monitoring direct oral anticoagulants. Blood. 2018 Nov 8;132(19):2009-2015

82

83

84

1/9/2020

29

› Renal and Hepatic Function› Hemoglobin/Hematocrit

› Frequency?– Limited evidence– Facility/provider specific– Rule of Thumb

› Baseline› Repeat at least yearly

Other Monitoring

Atrium Health. November 2018. Direct Oral Anticoagulants (DOACs) Pharmacy Dosing Guideline. Unpublished internal document.January CT, Wann LS, Calkins H, etal. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With

Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019;Jan 28:[Epub ahead of print].

Conway SE, Hwang AY, Ponte CD et al. Laboratory and Clinical Monitoring of Direct Oral Anticoagulants: What Clinicians Need to Know. Pharmacotherapy 2017; 37(2)236-248

› Changing prescribing landscape

› Expanded indications

› Expanded contraindications/precautions

› Atrial fibrillation guideline update

› National patient safety goals

So what is new?

Asthma Update

85

86

87

1/9/2020

30

● 25.7 million people in the United States (8.4% of the population)○ Globally 1‐18% of the population○ Most common chronic disease among children (highest 0‐17 years)

● Accounts for 1.6% of all ambulatory care visits○ 10.6 million physician office visits○ 1.2 million hospital outpatient visits

● Leading case of preventable hospitalizations in the US○ 479,000 hospitalizations○ 2.1 million ED visits

Asthma

● “Pediatric” disease as most are diagnosed by 5 years of age○ Up to 50% of patients have symptoms by the age of 2 ○ 30‐40% of cases persist into adulthood

● Low mortality rate (80‐90% are preventable)○ Most deaths occur out of the hospital○ Deaths due to (1) inadequate assessment OR (2) inadequate

therapy○ EDUCATION AND ACCESS ARE KEY!

Asthma

Genetic predisposition and environmental interactions

● Socioeconomic status● Family size● Exposure to second‐hand smoke● Allergen exposure● Ambient air pollution● Urbanization● Viral respiratory infections (RSV, rhinovirus)

Risk Factors for Asthma

88

89

90

1/9/2020

31

Genetic predisposition and environmental interactions

● Socioeconomic status● Family size● Exposure to second‐hand smoke● Allergen exposure● Ambient air pollution● Urbanization● Viral respiratory infections (RSV, rhinovirus)

Lower risk of asthma: children exposed to bacteria, those with large number of older siblings, early enrollment in childcare, exposure to cats/dogs/farm animals, low antibiotic exposure

Risk Factors for Asthma

● Atophy● Onset during school age● Presence of bronchial hyper‐responsiveness (BHR)

Predictors of Adult Asthma

● Airflow obstruction● BHR● Airway inflammation

● Disease of exacerbation and remission

Characteristics of Asthma

91

92

93

1/9/2020

32

● Shortness of breath● Chest tightness● Coughing (particularly at night)● Wheezing● Whistling sound while breathing

*Occur in association with exercise/allergens or spontaneously

● Expiratory wheezing on auscultation, dry hacking cough, or signs of atophy

● Laboratory: spirometry, peak expiratory flow

Clinical Presentation of Asthma

● Poor inhaler technique● Poor medication adherence● Incorrect diagnosis of asthma● Comorbid/complication factors/conditions● Ongoing exposure to sensitizing or irritant agents

Contributors to Poor Control of Asthma

94

95

96

1/9/2020

33

● Poor inhaler technique● Poor medication adherence● Incorrect diagnosis of asthma● Comorbid/complication factors/conditions● Ongoing exposure to sensitizing or irritant agents

Contributors to Poor Control of Asthma

● Watch the patient use their inhaler.○ Watch pa ent → Show correct method → Watch again

● Discuss adherence and barriers to use.○ Ask about beliefs, cost of medications and refill frequency.○ Empathetic discussion.

● If possible, remove potential risk factors○ Smoking, beta‐blockers, NSAIDs, allergen exposure

● Assess/manage comorbidities○ Rhinitis, obesity, GERD, obstructive sleep apnea,

depression/anxiety● Consider step‐up treatment

Investigating Poor Symptoms Control

● Aerosol therapy: site specific and enhances therapeutic ratio○ Short‐acting beta agonists: rapid bronchodilation○ Inhaled corticosteroids: enhanced lung activity with minimal

systemic activity

Treatment of Asthma

97

98

99

1/9/2020

34

Short acting beta‐agonists (SABA)

Long acting beta‐agonists (LABA)

Inhaled corticosteroids (ICS)

LABA/ICS Combinations

Common Products in Use Today

100

101

102

1/9/2020

35

SABAs and LABAs

SABA

Albuterol HFA MDI or Respiclick ProAir HFA, Proventil HFA, Ventolin HFA

Albuterol Nebulizer Solution AccuNeb

Levalbuterol HFA MDI Xopenex HFA

Levalbuterol Nebulizer Solution Xopenex

LABA

Formoterol DPI Foradil Aerolizer

Salmeterol DPI Serevent Diskus

Vilanterol In combination products only

ICSs

Beclamethasone HFA MDI Qvar

Budesonide DPI Pulmicort Flexhaler

Budesonide Nebulizer Solution Pulmicort Respules

Ciclesonide HFA MDI Alvesco

Fluticasone HFA MDI Flovent HFA

Fluticasone DPI Flovent Diskus

Fluticasone DPI Arnuity Ellipta

Mometasone DPI Asmanex Twisthaler

ICS/LABA Combos

Budesonide / Formoterol HFA MDI Symbicort

Mometasone / Formoterol HFA MDI Dulera

Fluticasone / Salmeterol DPI Advair Diskus

Fluticasone / Salmeterol HFA Advair HFA MDI

Fluticasone / Vilanterol DPI Breo Ellipta

103

104

105

1/9/2020

36

Global Initiative for Asthma (GINA)

● Not a guideline but an evidence‐based strategy focused on translation into clinical practice

● Recently update in mid 2019

Summary Points:

● Inhaled SABA has been first‐line treatment for over 50 years● Regular or frequent use of SABA is associated with adverse

effects● Higher use of SABA is associated with adverse clinical

outcomes

GINA Updates for Asthma

Major Changes:

● For safety, no longer recommends SABA‐only treatment for Step 1

● Now recommends all adults and adolescents should receive symptom‐driven or regular low dose ICS‐containing controller treatment to reduce the risk of serious exacerbations

New guidance for adults/adolescents and children 6‐11 years.

GINA Updates for Asthma

Adults and Adolescents

GINA Update

106

107

108

1/9/2020

37

No evidence to support SABA‐only

Low dose formoterol/budesonide prn avoids severe exacerbations in 1 in 16 patients with mild asthma versus albuterol alone

GINA Update: Step 1

109

110

111

1/9/2020

38

GINA Update: Step 1

Low dose ICS plus prn SABA

● Reduces risk of severe exacerbations, hospitalizations and death

● Serious exacerbations halved even in patients with symptoms 0‐1 days per week

As‐needed low dose ICS‐formoterol

● Direct evidence from 2 large studies (non‐inferiority) for severe exacerbations versus low dose ICS with prn SABA

● 64% reduction in severe exacerbations versus SABA‐only treatment

GINA Update: Step 2

112

113

114

1/9/2020

39

Other Controller Options

● Low dose ICS taken whenever SABA taken○ Reduced exacerbations compared to SABA‐only

■ ICS/SABA combination (adults)■ Separate inhalers (children/adolescents)

○ Similar ot fewer exacerbations compared with maintenance ICS● Leukotriene receptor antagonists

○ Allergic component of allergy

GINA Update: Step 2

115

116

117

1/9/2020

40

Children 6‐11 years

GINA Update

118

119

120

1/9/2020

41

121

122

123

1/9/2020

42

Inhaler Technique: MDI

124

125

126

1/9/2020

43

Inhaler Technique: MDI with Spacer

Inhaler Technique: Diskus Inhaler

Inhaler Technique: Diskus Inhaler

127

128

129

1/9/2020

44

Inhaler Technique: Respiclick

Questions?

CE CODE:

130

131

132

1/9/2020

45

1. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2019 [web annotation]. Diabetes Care 2019;42(Suppl. 1):S90–S102.

2. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375:1834‐44.

3. Marso SP, Daniels GH, Brown‐Frandsen K, et al. Liraglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375:311‐22.

4. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome5. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double blind,

randomised placebo‐controlled trial. Lancet 2019. 6. Holman RR, Bethel MA, Mentz RJ, et al.; EXSCEL Study Group. Effects of once‐weekly exenatide on cardiovascular outcomes in type 2 diabetes.

N Engl J Med 2017;377:1228–12397. Zinman B, Wanner C, Lachin JM, et al.; EMPAREG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2

diabetes. N Engl J Med 2015;373:2117– 2128.8. Fitchett D, Butler J, van de Borne P, et al.; EMPA‐REG OUTCOME trial investigators. Effects of empagliflozin on risk for cardiovascular death

and heart failure hospitalization across the spectrum of heart failure risk in the EMPAREG OUTCOME trial. Eur Heart J 2018;39:363– 370.9. Wiviott SD, Raz I, Bonaca MP, MOsenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire

DK, Wilding JPH, Ruff CT, Gause‐Nilsson IAM, Fredrisksson M, Johansson PA, Langkilde AM, Sabatine MS; for the DECLARE‐TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347‐357

10. Neal B, Perkovic V, Mahaffey KW, et al.; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644–657 10.

11. Perkovic V, Jardine MJ, Neal B, et al., on behalf of the CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med 2019;380:2295‐306

12. RYBELSUS [package insert]. Plansboro, NJ: Novo Nordisk Inc; September 201913. Helena W. Rodbard, Julio Rosenstock, Luis H. Canani, Chaicharn Deerochanawong, Janusz Gumprecht, Soren Ostergaard Lindberg, Ildiko

Lingvay, Anette Luther Sondergaard, Marianne Bach Treppendahl, Eduard Montanya for the PIONEER 2 Investigators. Oral Semaglutide versus Empagliflozin in Patients with Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 trial. Diabetes Care 2019 Sep;dc190833

14. Pharmacologic Approaches to Glycemic Management: Standards of Medical Care in Diabetes - 2020. Diabetes Care 2020;43(Suppl. 1):S98-S110

Diabetes Updates References

1. American Diabetes Association. Continuous glucose monitors- Consumer Guide 2018. Diabetes Forecast. http://main.diabetes.org/dforg/pdfs/2018/2018-cg-continuous-glucose-monitors.pdf (accessed Jan. 6, 2019).

2. FreeStyle LibreLink App. Freestyle Libre. https://www.freestylelibre.us/system-overview/continous-glucose-monitor-app.html (accessed Jan. 19, 2019).3. Abbott’s Freestyle Libre 14 day flash glucose monitoring system now approved in U.S. Abbott. https://abbott.mediaroom.com/2018-07-27-Abbotts-FreeStyle-

R-Libre-14-Day-Flash-Glucose-Monitoring-System-Now-Approved-in-U-S (accessed Jan. 19, 2019). 4. Dexcom G6 continuous glucose monitoring system user guide. Dexcom, Inc. https://s3-us-west-2.amazonaws.com/dexcompdf/G6-CGM-Users-

Guide.pdf?_ga=2.61291948.1830682920.1549243176-1258106527.1549243176 (accessed Jan. 19, 2019).Images: Continuous glucose monitoring system. Freestyle Libre. https://www.freestylelibre.us/ (accessed Jan. 19, 2019).

5. Make knowledge your superpower with the new Dexcom G6® CGM. Dexcom, Inc. https://www.dexcom.com/get-started-cgm/40?sfc=701f30000018vibAAA&gclid=EAIaIQobChMIw-2n_IbV4AIV0pCfCh2HJwTQEAAYASAAEgLAsvD_BwE

6. Guardian Connect vs. Freestyle Libre. Medtronic Diabetes. https://guardianconnect.medtronic-diabetes.co.uk/guardian-connect-vs-freestyle-libre# (accessed January 19, 2019).

7. American Diabetes Association. Continuous glucose monitors- Consumer Guide 2018. Diabetes Forecast. http://main.diabetes.org/dforg/pdfs/2018/2018-cg-continuous-glucose-monitors.pdf (accessed January 6, 2019).

8. Eversense User Guide. Food and Drug Administration. https://www.accessdata.fda.gov/cdrh_docs/pdf16/P160048c.pdf (accessed February 6, 2019).9. Images: Guardian Connect CGM System. Medtronic Diabetes. https://www.medtronicdiabetes.com/products/guardian-connect-continuous-glucose-

monitoring-system (accessed January 19, 2019).10. Eversense: the only long-term continuous glucose monitoring (CGM) system. Senseonics, Inc. https://www.eversensediabetes.com/products/ (accessed

February 6, 2019).11. Continuous glucose monitoring system. Freestyle Libre. https://www.freestylelibre.us/ (accessed Jan. 19, 2019).12. Abbott’s Freestyle Libre 14 day flash glucose monitoring system now approved in U.S. Abbott. https://abbott.mediaroom.com/2018-07-27-Abbotts-FreeStyle-

R-Libre-14-Day-Flash-Glucose-Monitoring-System-Now-Approved-in-U-S (accessed Jan. 19, 2019). 13. Dexcom G6 continuous glucose monitoring system user guide. Dexcom, Inc. https://s3-us-west-2.amazonaws.com/dexcompdf/G6-CGM-Users-

Guide.pdf?_ga=2.61291948.1830682920.1549243176-1258106527.1549243176 (accessed Jan. 19, 2019).14. Guardian Connect CGM System. Medtronic Diabetes. https://www.medtronicdiabetes.com/products/guardian-connect-continuous-glucose-monitoring-system

(accessed January 19, 2019).15. Eversense User Guide. Food and Drug Administration. https://www.accessdata.fda.gov/cdrh_docs/pdf16/P160048c.pdf (accessed February 6, 2019).16. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes

Care 2019;42:1593–1603 | https://doi.org/10.2337/dci19-0028

CGM References

1. Sorkness CA, Blake KV, Asthma. In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells, BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10 e New York, NY: McGraw Hill.

2. Fanta C. An overview of asthma management. UpToDate. Accessed 13 December 2019.

3. Global Initiative for Asthma. 2019 GINA Report, Global Strategy for Asthma Management and Prevention. https://ginasthma.org/gina-reports/ Accessed 13 December 2019.

4. Beasley R, et al. Controlled trial of budesonide‐formoterol as needed for mild ashtma. N Eng J Med 2019; 380(21): 2020‐30.

5. O’Byrne P, et al. Inhaled combined budesonide‐formoterol as needed in mild asthma. N Eng J Med 2018; 378(20):1865‐76.

6. COPD Foundation Education Videos https://www.youtube.com/user/COPDFoundation Accessed 13 December 2019.

Asthma References

133

134

135

leadership weekend 2020 presentation-use weekend 2020...criteria median follow up (years) primary...

Documents