NW Convention June 2016 HANDOUT Session 1 [Read-Only] · XX XXX Pharmacotherapy X XXX Bariatric Surgery XX *cutoff point for Asian American individuals X: treatment may be indicated

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Cacophony To Harmony: A Composition of Chronic Disease State Updates

Northwest Pharmacy ConventionCoeur d’Alene, Idaho

June 2016

Sonia Allen, PharmD, BCACPAndrea Corona, PharmD, BCACP, CDEDaniela Dandridge, PharmD, BCACP

Session Composition

Session 1

• Case Presentation

• Lipid Treatment

• Diabetes Update

• Venous Thromboembolism

• Case Review

Session 2

• Case Presentation

• Asthma and COPD

• Inhaler Round Table

• E-cigarettes and Vaporizers

• Heart Failure

• Case Review

Objectives – Session 1

1. Recommend appropriate statin therapy for a specific patient and identify patients who may benefit from PCSK9 inhibitors.

2. Identify place in therapy for new concentrated basal insulin products and SGLT2 inhibitors in diabetes treatment.

3. Summarize updated venous thromboembolism guidelines.

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Patient Case55 yo Caucasian female with type 2 DM who presents to clinic for evaluation of newly diagnosed PE secondary to proximal DVT. No provoking factors identified. The emergency room provider initiated LMWH anticoagulation therapy last evening and sends her to clinic for further anticoagulation therapy management.

Past medical history includes HTN, hyperlipidemia (TC 240, HDL 30, LDL 150, TG 175). She is a current smoker, 1 ppd. BP in clinic today is 130/78. Chem 7 reveals Scr 0.8 (estimated GFR > 60) and electrolytes WNL.

Current medications include Lisinopril, insulin glargine 80 units SQ nightly and metformin at target dose.

Recent A1c is 9.5% (Est Avg 220 mg/dL). She presents her BG log which reveals 3 episodes of nocturnal hypoglycemia in the last month however, the majority of her blood glucose readings are > 180 mg/dL.

Allergies include penicillin and a clearly documented intolerance to statins (she has tried multiple agents with equal intolerance)

Questions

1. How would you address therapy management of new VTE?

2. How would you address diabetes drug therapy management?

3. How would you address her CV risk? Would you consider additional therapy?

Lipid Treatment

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Similarities between ACC/AHA and NLA Guidelines

• Screen for primary prevention every 5 years

• Lifestyle therapy is first-line

• ASCVD risk reduction is goal of therapy

• Moderate- or high-intensity statin use

• Regular lipid follow-up to assess adherence to therapy

Stone NJ, et al. 2013 ACC/AHA Blood Cholesterol Guideline. Circulation. Published online November 12, 2013. Jacobson TA, et al. NLA Recommendations for Patient‐Centered Management of Dyslipidemia. Journal of Clinical Lipidology (2015) 9, 129‐169

Notable Differences

ACC/AHA

• Pooled cohort risk calculator

NLA

• Count number of risk factors


NLA Major Risk Factors

Jacobson TA, et al. NLA Recommendations for Patient‐Centered Management of Dyslipidemia. Journal of Clinical Lipidology (2015) 9, 129‐169

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Notable Differences

ACC/AHA


• No recommendation for or against lipid goals

NLA


• Maintenance of lipid goals with emphasis on non-HDL


NLA Lipid Goals

Jacobson TA, et al. NLA Recommendations for Patient‐Centered Management of Dyslipidemia. Journal of Clinical Lipidology (2015) 9, 129‐169

Notable Differences

ACC/AHA


• No recommendation for or against lipid goals

• Discourage non-statin therapy due to less favorable net benefit

NLA


• Maintenance of lipid goals with emphasis on non-HDL

• +/- non-statins if necessary to achieve lipid goals


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UPDATE: FDA pulled non-statin indications

• If patient is on a statin, no indication to add niacin or fenofibric acid for CV risk reduction– Despite HDL raising or TG lowering there is not evidence to

support risk reduction

http://www.empr.com/news/fda‐withdraws‐indications‐for‐two‐cholesterol‐medications/article/490515/?DCMP=EMC‐MPR_DailyDose_cp&cpn=fp_md,pcp_md,harvoni64297,pcp_all,respiclick70052,Arnuity71530&hmSubId=aLsnDgbTgIQ1&hmEmail=y9‐jV8Tk8w7I_kBkCqKHCWSfvDHhcXvDDl

"based on the collective evidence from several large cardiovascular outcome trials… the totality of the scientific evidence no longer supports the conclusion that a drug‐induced reduction in triglyceride levels and/or increase in HDL‐cholesterol levels in statin‐treated patients results in a reduction in the risk of cardiovascular events.”

Why are there differences?

• ACC/AHA

– RCT with ASCVD outcomes and meta-analyses

• NLA

– RCT with ASCVD outcomes and meta-analyses

– Post-hoc analyses of RCT

– Genetic, metabolic and mechanistic studies


AHA/ACC Algorithm

Progression of questions for eligibility for statin use. Algorithm‐ Adapted from Figure 2.

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Algorithm- Adapted from Figure 2.

Stone NJ, et al. 2013 ACC/AHA Blood Cholesterol Guideline. Circulation. Published online November 12, 2013.

Reminder of Definition of ASCVD*

• Acute coronary syndromes

• Myocardial Infarction

• Stable or unstable angina

• Revascularization

• TIA/CVA

• Peripheral artery diseaseStone NJ, et al. 2013 ACC/AHA Blood Cholesterol Guideline. Circulation. Published online November 12, 2013.



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% LDL Reduction of Statin Dose^

Generic Brand 10 mg 20 mg 40 mg 80 mg

Rosuvastatin Crestor 51% 57% 63%

Atorvastatin Lipitor 35‐39% 43% 50% 55‐60%

Simvastatin Zocor 28% 35% 41% 46%

Pravastatin Pravachol 22% 32% 34% 37%

Lovastatin Mevacor 21% 24‐27% 30‐31% 40‐42%

Fluvastatin Lescol 20% 25% 35%

1 mg 2 mg 4 mg

Pitavastatin Livalo 31‐32% 36‐39% 41‐45%



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Calculate a life-time risk

• Motivational tool for lifestyle modification

• http://tools.acc.org/ASCVD-Risk-Estimator/

32yo, White, Male, TC 190, HDL 32, SBP 120, No treatment for hypertension, not diabetic but smokes

If he stops smoking life‐time risk reduces to 36%

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45yo, White, female, TC 210, HDL 36, SBP 135, Treatment for hypertension, diabetic and does not smoke

Same patient as a smoker



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Same patient as a smoker but without diabetes


1. Secondary Prevention?2. LDL > 190 mg/dL?3. > 40 years old?4. Diabetes diagnosis?5. Primary prevention?

New Lipid Agents

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PCSK9 Inhibitor MOA

Evolucumab (Amgen): OSLER-1, OSLER-2 Trials

– 140 mg SQ Q2 weeks OR 420 mg SQ Q 4 weeks

Alirocumab (Sanofi): ODYSSEY FH I & II, Long-Term, and combo trials

– 150 mg SQ Q 2 weeks

PCSK9: Proprotein Convertase Subtilisin Kexin 9Hepatic enzyme that breaks down hepatocyte LDL receptors—inhibiting this enzyme will lead to higher concentrations of LDL receptors on the surface of the hepatocyte and lower serum

LDL levels as LDL is taken from blood into hepatocyte

Who is a candidate for PCSK9 Inhibitors?

1. Secondary Prevention (i.e. post-MI)

2. Patients with CV disease intolerant to statin therapy

3. Hypertriglyceridemia

4. All of the above

PCSK9 Inhibitor Place in Therapy

• High risk CV patients who are intolerant to statin therapy

• As add-on therapy to maximal statin therapy to get additional LDL lowering in patients with CV disease

• Familial Hypercholesterolemia

– Alirocumab—Heterozygous FH FDA indication only

– Evolucumab—Heterozygous FH + Homozygous FDA indications

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PCSK9 Inhibitor Trial Data

ALIROCUMAB (Praluent)

ODDYSEY LONG-TERM Trial

n = 2341; 78 weeks

Treatment Groups• Alirocumab + statin• Placebo + statin

PRIMARY: % change in LDL at week 24

SAFETY: safety & incidence of ADR;

POST-HOC SAFETY: CV events

EVOLUCUMAB (Repatha)

OSLER 1 & 2

n = 4465; 12 months

Treatment Groups• Evolucumab + statin • Statin alone

PRIMARY: safety & incidence of ADR

SECONDARY: % change in LDL @ week 12

PRESPECIFIED EXPLORATORY: CV events

PCSK9 Inhibitor % LDL Reduction



PRIMARY ENDPOINT:

% LDL reduction at week 24

62% reduction with alirocumab vs 0.8% with placebo (p<0.001)


OSLER 1 & 2

SECONDARY ENDPOINT:

% change in LDL @ week 12

61% further LDL reduction in Evolucumabgroup (p<0.001)

PCSK9 Inhibitor Safety



SAFETY ENDPOINTS:

No significant difference in ADR between Treatment and Placebo groups except Myalgias (5.4% Treatment vs 2.9% Placebo, p <0.05)

37.1% pts in Treatment Group had LDL levels fall < 25 mg/dL


OSLER 1 & 2

PRIMARY ENDPOINT:

No significant difference between Evolucumab and Standard-Therapy groups but neurocognitive ADR more frequent with Evolucumab Group

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PCSK9 Inhibitor CV Events and Limitations



POST-HOC SAFETY: CV event rates

Alirocumab group (1.7%) vs. placebo group (3.3%) (HR 0.52, 95% CI, 0.31-0.90; p=0.02)

Study Limitations• Lack of formal neurological testing as

part of study design• Low CV event rates


OSLER 1 & 2

PRESPECIFIED EXPLORATORY: CV event rates

Evolucumab group (0.95%) vs. statin-only group (2.8%) (p=0.003)

Study Limitations• Open-label design• Low CV event rates

PCSK9 Inhibitor Cost

~ $14,000 to $15,000 per year

Results currently inconclusive- require outcomes trial data

• FOURIER

• ODYSSEY OUTCOME

PCSK9 Inhibitor Safety


ODYSSEY OUTCOMES Trial

18,000 patients enrolled

Evaluating Alirocumab in patients with ACS for the reduction of primary endpoint of CHD death, nonfatal MI, fatal & non-fatal ischemic stroke and USA requiring hospitalization

Results expected in 2018


FOURIER Study

27,500 patients enrolled

Evaluating Evolucumab in patients with known CV disease for the reduction of primary composite endpoint of CV death, MI, USA requiring hospitalization, stroke or coronary revascularization.

Results expected in 2016

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PCSK9 Inhibitor Payor Coverage

Express Scripts:

October 2015 statement released

– Cover both PCSK9 Inhibitors

– Must have evidence of failed statin therapy or LDL lowering

still required while on max dose of statin

CVS:

November 2015,

– Included evolucumab (Repatha) as only PCSK9 inhibitor

on formulary

Diabetes Update

Standards of Medical Care in Diabetes--2016

General Changes– No longer use the word “diabetic” when referring to individuals with diabetes– “Diabetic” is used as an adjective for complications related to diabetes

(e.g. diabetic retinopathy)

Section 2: Classification and Diagnosis of Diabetes*– No one test is preferred over another test for diagnosis – ADA revised screening recommendations:

• Test all adults ≥ 45 regardless of weight• Test symptomatic adults of any age who are overweight/obese

AND ≥ 1 additional risk factors for diabetes

Section 4: Glycemic Targets– People who use continuous glucose monitoring and insulin pumps should

have continued access after they turn 65 years of age

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Section 6: Obesity Management for the Treatment of Type 2 Diabetes*

Adapted from: http://care.diabetesjournals.org/site/misc/2016‐Standards‐of‐Care.pdf

BMI category (kg/m2)

23* or

25‐26.927‐29.9 30‐34.9 35‐39.9 ≥ 40

Diet, physical activity

& behavioral therapyX X X X X

Pharmacotherapy X X X X

Bariatric Surgery X X

*cutoff point for Asian American individuals

X: treatment may be indicated for selected motivated patients

At what age would you recommend aspirin for primary prevention in a diabetic patient?

1. ≥ 40 years

2. ≥ 50 years

3. ≥ 60 years

4. ≥ 65 years

Section 8: Cardiovascular Disease and Risk Management*

Aspirin

– men and women aged ≥ 50 years with diabetes AND

• 10 year ASCVD risk > 10%

• one or more major risk factors: – smoking– hypertension– dyslipidemia– family history of premature ASCVD– albuminuria

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Aspirin (continued)

– Not recommended if low risk of ASCVD:

• Men & women < 50 years old

• No other major ASCVD risk factor

• 10-year ASCVD risk < 5%

– Clinical judgment should be used if intermediate risk of ASCVD

• Younger patients with one or more risk factors

• Older patients with no risk factors

• Those with 10-year ASCVD risk of 5-10%


Ezetimibe

– IMPROVE-IT Trial (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial)

– Adding ezetimibe to moderate-intensity statin provides additional cardiovascular benefits for select individuals with diabetes and should be considered

Section 11: Children and Adolescents

– Obtain a fasting lipid profile in children starting at age 10 years (changed from starting at 2 years)

Section 12: Management of Diabetes in Pregnancy*

– New recommendation to highlight the importance of discussing family planning and effective contraception with women with pre-existing diabetes

– A1C recommendations for pregnant women with diabetes changed:

• Target of 6-6.5% (from target < 6%)

• Glyburide in gestational diabetes was deemphasized

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New Concentrated Insulins

What are the characteristics of an ideal basal insulin?

1. Peak-less basal coverage

2. 24 hour duration of action

3. Low volume/concentrated

4. Low risk for hypoglycemia

5. All of the above

Comparison of Basal Insulins

NPHInsulin Detemir

Levemir®

Insulin Glargine

Lantus®

Regular Insulin

U‐500

Concentration 100units/ml 100units/ml 100units/ml 500units/ml

Onset (hrs) 1‐2 1‐2 1 0.5

Peak (hrs) 4‐12 ‐‐ ‐‐ 1‐3

Duration (hrs) 16‐24 7‐24 11‐24 6‐10

Cost ($/unit)0.11 (vial)

0.23 (pen)

0.25 (vial)

0.25 (pen)

0.25 (vial)

0.25 (pen)

0.05 (vial)

0.2 (pen)

Adapted from Pharmacist Letter. < http://pharmacistsletter.therapeuticresearch.com>.

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Comparison of Basal Insulins

NPH

Insulin

Detemir

Levemir®

Insulin

Glargine

Lantus®

Regular

Insulin

U‐500

Insulin

Glargine

Toujeo®

Insulin

Degludec

Tresiba®

Concentration100units/ml 100units/ml 100units/ml 500units/ml 300units/ml

100units/ml

200units/ml

Onset (hrs) 1‐2 1‐2 1 0.5 6 0.5‐1.5

Peak (hrs) 4‐12 ‐‐ ‐‐ 1‐3 ‐‐ ‐‐

Duration (hrs) 16‐24 7‐24 11‐24 6‐10 >24 42

Cost ($/unit) 0.11 (vial)

0.23 (pen)

0.25 (vial)

0.25 (pen)

0.25 (vial)

0.25 (pen)

0.05 (vial)

0.2 (pen)0.25 (pen) 0.30 (pen)

Adapted from Pharmacist Letter. < http://pharmacistsletter.therapeuticresearch.com>.

Insulin Glargine U-300 (Toujeo®)

• Same molecule as Lantus® only concentrated

• Decreased surface area:

– Slows absorption

– Prolongs duration

– Lowers peak effectLantus 20 units

Toujeo 20 units

Switching Insulin Products

Switching TO Toujeo Dose Adjustments Comments

From NPH Once daily: unit‐per‐unitTwice daily: ↓ dose 20%

•May take ≥ 5 days to see max effect•Do not increase more than every 3‐4 days•Give doses once daily

*for patients controlled on Lantus, expect that a 10‐18% higher daily dose will be needed to maintain control

From insulin glargine(Lantus)

Once daily: unit‐per‐unitTwice daily: unit‐per‐unit (or ↓ by 10% or less)*

From insulin detemir(Levemir)

Once daily: unit‐per‐unitTwice daily: ↓ dose 20%

Adapted from Pharmacist’s Letter 6/2014, www.PharmacistsLetter.com

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Switching Insulin ProductsSwitching FROM Toujeo Dose Adjustments Comments

To NPH No specific informationConsider↓ 20% to be conservative

Divide dose & give twice daily

To insulin glargine (Lantus) ↓ dose 20% to be conservative

To insulin detemir (Levemir) No specific information↓ dose 20% to be conservative


Study: EDITION 1Toujeo® v Lantus®

• Multicentre, multinational, randomized, open-label, two-arm, parallel-group, phase 3a study

• 1:1 ratio– Insulin glargine U-100 (Lantus®) daily– Insulin glargine U-300 (Toujeo®) daily– Plus insulin aspart for meals

• Inclusion:– Adult patients with T2DM receiving basal/bolus insulin therapy– BMI ≤ 45 kg/m2– HbA1c between 7 and 10%

Diabetes Obes Metab 2015; 17: 835‐42.


Primary endpoint: A1C Lowering Effect


0.17% more A1C lowering[‐0.17 (95% CI: ‐0.3 to ‐0.05)]

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Secondary Endpoint: Nocturnal hypoglycemia

Not Significantly Different[0.90 (95% CI: 0.70‐1.16)]



Secondary Endpoint: Overall hypoglycemia

Not Significantly Different[1.06 (95% CI: 0.89‐1.27)]


Study: EDITION 1Toujeo® v Lantus® Secondary Endpoint: Basal insulin dose


Insulin Dose1.03 u/kg Toujeo ®

0.9 u/kg Lantus ®

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Summary - Insulin glargine U-300 (Toujeo®)

• Nocturnal hypoglycemia

– Less during titration period

– Possibly less overall

• Basal insulin dose

– Need 11-14% more insulin for same A1C lowering as Lantus

• Possibly less weight gain


Insulin Degludec (Tresiba)

http://mediacenter.novomedlink.com/v/tresiba‐mechanism‐of‐protraction

Insulin Degludec

• Ultra Long-Acting Insulin

• Human insulin analog (rDNA origin)

• Duration 42 hours

• Dose given once daily, any time of day

• Formulation:

– 100 units/ml

– 200 units/ml

• Stable 56 hours at room temp

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Switching Insulin ProductsSwitching TO Insulin Degludec

Dose Adjustment Comments

NPH Convert total daily dose unit‐per‐unit & give once daily

•Consider 20% dose reduction if switching from twice daily schedule•Consider dose reduction if switching from once daily schedule•Do not increase dose more than every 3‐4 days

Insulin glargine (Lantus, Toujeo)

Insulin detemir (Levemir)

To insulin detemir Limited information: Consider converting unit‐per‐unit

•Give glargine and detemir once daily (divide dose if necessary for control)


Switching Insulin Products

Switching FROM Insulin Degludec

Dose Adjustment Comments

To NPH Limited information: Consider converting unit‐per‐unit

•Give NPH twice daily

To insulin glargine •Give glargine and detemironce daily (divide dose if necessary for control)

To insulin detemir


Study: BEGIN Basal-Bolus Type 2Tresiba® v Lantus®

• Randomized, treat-to-target, parallel-group, open-label, multinational, non-inferiority, phase 3 trial

• 3:1 ratio– Insulin degludec (Tresiba®) vs insulin glargine(Lantus®) daily– Both in combination with insulin aspart for meals

• Inclusion:– Adult patients with T2DMfor on insulin for at least 6 months– BMI ≤ 40 kg/m2– HbA1c between 7 and 10%

Lancet 2012; 379: 1498‐507

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Lancet 2012; 379: 1498‐507

Primary Endpoint: A1C Lowering effect


Non‐inferiority for A1C lowering

Lancet 2012; 379: 1498‐507

Secondary Endpoint: Nocturnal hypoglycemia


25% lower rate of nocturnal hypoglycemia[0.75 (0.58‐0.99); p=0.0399]

Lancet 2012; 379: 1498‐507

Secondary Endpoint: Overall hypoglycemia


18% lower rate of overall hypoglycemia[0.82 (0.69‐0.99); p=0.0359]

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Pharmacodynamic Variability between Lantus® and Tresiba®

Diabetes Obes Metab. 2012; 14: 859‐64.

4 fold decrease in variability seen in Tresiba

Summary - Insulin degludec (Tresiba®)

• Basal insulin dose – 11 to 14% LESS insulin needed

• U100 and U200 pens – max dose of 160units/injection

• Nocturnal hypoglycemia - Decreased rate by 25-40% compared

to Lantus

Diabetes Care. 2013; 36: 2536‐42.Lancet. 2012; 379: 1489‐97.Lancet 2012; 379: 1498‐507.

Final Thoughts

• Toujeo® use in patients:

– Concerned with weight gain

– Basal insulin wears off prior to redosing

• Tresiba® use in patients:

– Recurrent nocturnal hypoglycemia

– Requiring more than 80 units of basal insulin

– Basal insulin wears off prior to redosing

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SGLT-2 Inhibitors

SGLT-2 Inhibitors

• Sodium-Glucose Co-transporter Type 2 (SGLT2)

• Benefits:

– Decreases A1C by 0.5-1%

– Weight loss

– Lower blood pressure

Micromedex. Truven Health Analytics.

Brand Generic Initial Dose

Invokana® Canagliflozin 100 mg daily

Farxiga® Dapagliflozin 5 mg daily

Jardiance® Empagliflozin 10 mg daily

Empagliflozin

https://hcp.jardiance.com/clinical‐pharmacology.php#clinicalpharmacology

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Adverse Reactions

• Urinary Tract Infection (7.6-9.3%; 15% ≥ 75 years old)

• Hypoglycemia (0.4% monotherapy)

• Genital mycotic infections (5.4-6.4%)

• Dyslipidemia (2.9-3.9%)

• Precautions– Hypotension – renal impairment, elderly, concomitant diuretic– Impairment of renal function – dehydration, elderly– Ketoacidosis – post-market finding in majority of patients

EMPA-REG Outcome Trial

• Randomized, double-blind, placebo-controlled trial– 590 sites– 42 countries

• Patients– 7028 patients underwent randomization between 9/2010 and 4/2013– 7020 treated and included in primary analysis– 97% completed the study

• Median duration of treatment: 2.6 years• Median observation time: 3.1 years

N Engl J Med 2015; 373:2117‐2128

Inclusion Criteria

• Adult (≥ 18 years of age)

• BMI ≤ 45 kg/m2

• eGFR ≥ 30ml/min/1.73m2

• Established cardiovascular disease

• Standard blood glucose lowering treatment

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Study Procedure

• 2 week open-label, placebo run-in period during which background glucose lowering therapy was unchanged

• Patients then randomly assigned 1:1:1

– 10mg empagliflozin

– 25mg empagliflozin

– Placebo

Outcomes

Primary outcome:

• composite of death from cardiovascular causes, non-fatal MI (excluding silent MI), or non-fatal stroke

Key secondary outcome:

• composite of primary outcome + hospitalization for unstable angina

EMPA-REG OUTCOME TrialPrimary Outcome: Composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke

N Engl J Med 2015; 373: 2117‐28.

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EMPA-REG OUTCOME Trial

N Engl J Med 2015; 373: 2117‐28.

Secondary Outcome: Hemoglobin A1C Reduction

Mean A1C reduction: ‐0.24 % (95% CI, ‐0.4 to ‐0.08)

Mean A1C reduction: ‐0.54 % (95% CI, ‐0.58 to ‐0.49)

SafetyConfirmed hypoglycemia

• Blood glucose ≤ 70mg/dL• Event requiring assistance

Adverse effects reflecting:• UTI• Genital infection• Volume depletion• Acute renal failure• Bone fracture • Diabetic ketoacidosis• Thromboembolic events

Safety Analysis

• Genital infections reported in a significantly (p < 0.001) higher percentage of patients in the pooled empagliflozin group (6.4% vs. 1% placebo)– 5% empagliflozin group vs. 1.5% in men– 10% empagliflozin group vs 2.6% in women

• No imbalance in overall rates of UTI, complicated UTI, or pyelonephritis

• Rates of hypoglycemia similar (about 28%)

• Similar drop out rates

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Discussion

• Dosing of empagliflozin: 10m vs. 25mg

• Effect on HgA1C

• What caused the benefit in survival?

• Who might benefit from empagliflozin?

• Are there patients that should not use this drug?

• Is this a class effect?

Venous Thromboemoblism

VTE Treatment Decision Making

American College of Chest Physicians (ACCP) evidence-based antithrombotic therapy practice guideline

– 9th ACCP (AT9) released in 2012

– 10th ACCP (AT10) released in 2016

AT10 clarifies role of New Oral Anticoagulants (NOACs) based on trial data:– DABIGATRAN: RELY (NVAF); RECOVER (VTE)

– RIVAROXABAN: ROCKET-AF (NVAF); EINSTEIN PE/EINSTEIN DVT (VTE)

– APIXABAN: ARISTOTLE (NVAF); AMPLIFY (VTE); AMPLIFY-EXTENDED (VTE)

– EDOXABAN: ENGAGE-AF TIMI (NVAF); HOKUSAI VTE (VTE)

AT10 better identifies those patients at high risk of VTE recurrence who should be considered for extended therapy (i.e. no stop date)

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Review of Cascade & Target MOAs

Changing landscape of Oral Anticoagulants (OAC)

Warfarin– Benefits: highly effective when managed appropriately; affordable– Drawbacks: difficult to maintain in therapeutic range, which

increases risk of adverse outcomes; burden of INR monitoring; many interactions

NOAC Approval– Dabigatran: 2010 NVAF; 2014 prevention & Tx DVT/PE– Rivaroxaban: 2011 prevention & Tx DVT/PE, NVAF – Apixaban: 2012 NVAF; 2014 prevention & Tx DVT/PE– Edoxaban: 2015 NVAF & prevention/treatment DVT/PE

NVAF = nonvalvular atrial fibrillation Tx DVT/PE = treatment of deep vein thrombosis and pulmonary embolism

AT10: Duration of Therapy

Provoked DVT/PE : – 3 months DOT recommended over shorter period or over a longer period

Unprovoked DVT/PE (1st or 2nd event): Decision based on bleed risk– Low & Moderate bleed risk : extended therapy (no stop date) preferred– Very High bleed risk: 3 month DOT preferred with new role for ASA

therapy in this population.

DVT/PE in the setting of active cancer: – Extended therapy for all (no stop date) despite bleed risk

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AT10—NOAC Role More Clearly Defined

• NOACs take role of first line agents over warfarin for initial and long-term treatment of VTE in patients WITHOUT cancer

• NOACs and VKA have equal efficacy for recurrent VTE risk reduction

• NOACs considered safer as bleed risk, particularly intracranial bleeding

• VTE in setting of active cancer: LMWH remains preferred agent

Making The Choice Between Anticoagulants

History of GI Bleed:

– Apixaban may be preferred agent

Elderly (> 75 years age):

– Apixaban, Edoxaban or Rivaroxaban preferred

Extremes of body weight (< 60 kg or > 120 kg):

– Warfarin preferred agent

When is LMWH preferred?

1. Liver Disease

2. Active Cancer

3. Pregnancy

4. All of the above

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Clinical Scenarios where LMWH is Agent of Choice

• Liver Disease– NOACs contraindicated in severe liver disease– Warfarin remains an option, but INR is difficult to control

• Active Cancer– Ongoing trials are seeking to validate NOACs in setting of cancer

• Pregnancy– Warfarin is teratogenic – NOACs have potential to cross placenta

When is warfarin preferred?

1. Variable INR

2. Alcohol abuse

3. Breastfeeding

4. Non-adherence

5. All of the above

Clinical Scenarios Where Warfarin Preferred

Warfarin has advantage of using INR to estimate &

titrate anticoagulation response

Specific patient factors are present that lend concern about whether intensity of anticoagulation is appropriate

– Alcohol abuse

– Drug Interactions

– Medication adherence concerns

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AT10: New Role for Aspirin Therapy

Aspirin in extended treatment of VTE based on RCT data– Extended therapy reduces risk of VTE recurrence by one-third

– Benefits outweigh the increased risk of bleeding

– Consider ASA as an alternative for patient who does not want or unable to continue anticoagulation therapy

Unprovoked DVT/PE : if patient discontinues anticoagulation therapy and does not have contraindication to ASA:

– AT10 suggests aspirin over no aspirin to help prevent recurrent VTE

– ASA less effective at preventing VTE recurrence than anticoagulation therapy

– ASA provides some degree of protection for VTE recurrence

– Other potential ASA benefits:

• Stroke risk reduction

• Colon cancer risk reduction

AT10: VTE Occurrence while on AnticoagulationRecurrent VTE while on oral anticoagulant

– Evaluate if patient has been compliant with anticoagulation therapy– Consider the presence of underlying risk factor for hyper-coagulable

state– Stop oral anticoagulant and switch to LMWH for at least 1 month

Recurrent VTE while on LMWH therapy– Confirm compliance with LMWH– If compliance confirmed, increase dose of LMWH by ¼ to 1/3 – If patient was on a once-daily LMWH regimen, switch to BID

regimen to enhance efficacy

AT10: Additional Updates• Prevention of Post-Thrombotic syndrome

– AT10 no longer recommends use of compression stockings routinely to prevent Post-Thrombotic Syndrome

• Subsegmental PE Treatment Guidance Clarified

• Acute PE—Outpatient Treatment Prefered for Low-Risk PE

• Additional Management Guidance Per AT10: – Thrombolytic Therapy for PE– Catheter-Based Thrombus Removal– Pulmonary Thromboendarterectomy– Thrombolytic Therapy for Upper Extremity DVT

5/30/2016

35

Patient Case55 yo Caucasian female with type 2 DM who presents to clinic for evaluation of newly diagnosed PE secondary to proximal DVT. No provoking factors identified. The emergency room provider initiated LMWH anticoagulation therapy last evening and sends her to clinic for further anticoagulation therapy management.

Past medical history includes HTN, hyperlipidemia (TC 240, HDL 30, LDL 150, TG 175). She is a current smoker, 1 ppd. BP in clinic today is 130/78. Chem 7 reveals Scr 0.8 (estimated GFR > 60) and electrolytes WNL.

Current medications include Lisinopril, insulin glargine 80 units SQ nightly and metformin at target dose.

Recent A1c is 9.5% (Est Avg 220 mg/dL). She presents her BG log which reveals 3 episodes of nocturnal hypoglycemia in the last month however, the majority of her blood glucose readings are > 180 mg/dL.

Allergies include penicillin and a clearly documented intolerance to statins (she has tried multiple agents with equal intolerance)

Questions

1. How would you address therapy management of new VTE?

2. How would you address diabetes drug therapy management?

3. How would you address her CV risk? Would you consider additional therapy?

Cacophony To Harmony: A Composition of Chronic Disease State Updates

Northwest Pharmacy ConventionCoeur d’Alene, Idaho

June 2016

Sonia Allen, PharmD, BCACPAndrea Corona, PharmD, BCACP, CDEDaniela Dandridge, PharmD, BCACP

Documents

NW Convention June 2016 HANDOUT Session 1 [Read-Only] · XX XXX Pharmacotherapy X XXX Bariatric Surgery XX *cutoff point for Asian American individuals X: treatment may be indicated