I am also proud to present to you our newest committee chairs:

Parleen Shahi - New Practi-

tioner Committee Chair

Michelle Ito - Community

Outreach Committee Co-chair

Bianca Khishaveh - Member-

ship Committee Chair

Heeral Bhatt - Continuing

Education Chair Our immediate past president Jennifer Pham has been working hard as the chair of our Nomina-tions committee. We are calling for volunteers and candidates for our 2019 QCSHP board mem-bers and officers. Whether you are a student, a resident, a sea-soned pharmacist or a director, if you want to get involved, please join us at our October board meeting and I would like to meet you in person. You can also con-tact me directly by email if you have any questions or sugges-tions: qcshp@cshp.org.

I cannot believe that three quarters have already passed and I am glad to report that Quatra’s board has continued to do great work for our local community and our pharmacy profession. Thank you once again to all the Quatra board members, committee chairs and team members who volun-teered their time and efforts in making all of the Quatra events possible and in supporting the CSHP mission. Members have asked us to host more educational events which provide continuing edu-cation units and we have paid attention to your comments and interests. A big shout out to Vincent and Connie who have put together 8 CE and 12 educational events in the past 9 months. Your participation in these educational events is important and the great turnout always make our committee chairs feel that their hard work is paying off. On August 25th, the Quatra delegates for CSHP attended

the Regional Delegates Con-ference (RDC) at John Muir Hospital in Walnut Creek. Before the RDC, our delegates had spent hours reviewing the House of Delegates (HOD) proposals of several policy changes. They participated in a teleconference in the eve-ning after a long day of work to discuss and share recommen-dations in ensuring that we had a good understanding of the proposals before the RDC. Quatra delegates are exercis-ing diligence in their represen-tation for the upcoming HOD meeting at CSHP Seminar in October. I encourage you to participate in the open forum and town hall meeting to voice your opinions at the Seminar Conference if you did not have a chance to speak to our dele-gates at our own Quatra town hall meeting on September 26th. In this newsletter, you will discover the winner of our 2nd annual QCSHP Pharmacy Student Scholarship Award.

President’s Corner: Betty Lee, Pharm.D.

I N S I D E

T H I S I S S U E :

Sepsis in the

News 2

A Review of

Landmark

Diabetes

Trials

2

Weekend

Breakfast CE 2

Member

Spotlight 3

Call for

Nominations 3

Membership

Update 3

SB 1254

Passed! 4

QCSHP Student Scholarship Opportunity

Q C S H P P U B L I C A T I O N

S E P T E M B E R 3 0 , 2 0 1 8V O L U M E 3 , I S S U E 3

S P E C I A L

P O I N T S O F

I N T E R E S T :

Sepsis in the

News

A Review of

Landmark

Diabetes

Trials

Member

Spotlight:

Sandy Bardas

Call for

Nominations

Membership

Update

SB 1254

Passed!

- Heeral Bhatt (Public Relations Chair) heeral.bhatt@tu.edu

The Scholarship Committee is pleased to present the 2nd Annual Quatra CSHP Pharmacy Student Schol-arship Award to Viet Nguyen, Pharm.D. Candidate 2020 at California Northstate University College of Pharmacy. Viet was the Co-President of both his P1 and P2 Class, 2016 and 2017, respec-tively. He is also the student liaison to CSHP Sacramento Valley Chapter. In addition, he was a part of the CAP-SLEAD team at California Northstate University. Their team focused on the Drug Take-Back Program in Sacra-

mento. Despite being an extremely busy student with various leadership roles at school and in his community, Viet is also a part of the United States Navy. The Scholarship Committee felt Viet’s strong leadership skills and desire to serve his community and country made him a strong candidate for this scholarship. We are excited for the role Viet will play in patient care and advocacy as a future phar-macist.

P A G E 2

Seven day treatment

with IV

hydrocortisone and

oral fludrocortisone

resulted in lower

mortality than

placebo among

adults with septic

shock.

A Review of Landmark Diabetes Trials

Weekend Breakfast CE Series

Hydrocortisone plus Fludrocortisone for Sepsis

specific bariatric surgery

procedures, design a new

medication post-operative

patient plan post bariatric

surgery and demonstrate

the role of the pharmacist in

pre-operative and post-

operative medication plan-

ning for bariatric surgery.

On August 11th, a Joint

Quatra-CSHP, NCCCP and

PPA Breakfast CE was

hosted at Kaiser Perma-

nente - Santa Clara. Dr. Kim

Kelly, Pharm.D., BCPS,

FCCP, CDTC, CPCP, CEC

On July 7th, QCSHP

hosted a Breakfast CE with

Dr. Elaine Law, Pharm.D.,

BCPS, FCSHP (Assistant

Clinical Professor, Phar-

macy Practice, UOP). Dr.

Law presented a 1-hr CE on

“Medication Absorption

Considerations and Nutrient

Deficiencies Post Bariatric

Surgery.” Members learned

to evaluate patients for nu-

trient deficiencies and how

to manage complications,

describe changes to medi-

cation absorption based on

anatomical changes from

(President, Kelly Diabetes Asso-

ciates, LLC) presented a 1-hr

CE on “The Gut Microbiome and

Diabetes: What We Know, and

What We Don’t.” Members

learned the 3 major roles that

the gut microbiome has in

health, to write a brief descrip-

tion of the ‘hygiene hypothesis’

and the ‘diet hypothesis’ of im-

mune system dysregulation and

type 1 diabetes, to write a brief

description of the role of probiot-

ics in diabetes and obesity de-

velopment, and to describe the

effects of at least three medica-

tions on the gut microbiome.

revealed that a more intense

glycemic control had little to

no impact on the reduction of

macrovascular and microvas-

cular complications. One ap-

proach to intensive glucose

control is a stricter HbA1C

target. ACCORD (2018) ex-

plored a target HbA1C < 6%

and found increased mortality

compared to placebo. Con-

versely, ADVANCE (2009)

employed a target HbA1C <

6.5% and results signified a

reduction in microvascular compli-

cations. As novel drugs are being

developed, safety and efficacy

trials remain a critical require-

ment.

With the growing prevalence of

diabetes, it is vital for pharmacists

to be reminded of these landmark

trials that have undoubtedly de-

fined the medication and glucose

management of diabetes today.

See attached handout for a sum-

mary of these trials.

Approximately 1.5 million

Americans are newly diag-

nosed with diabetes every

year and it remains the 7th

leading cause of death in

the United States.

One of the leading clini-

cal concerns regarding dia-

betic patients is the extent

of glucose control and the

prevention of long-term vas-

cular complications. UKPDS

(1998) and VADT (2009)

- Connie Ha (Weekend Breakfast CE Chair) connieha@gmail.com

- Runa Akahoshi, Pharm.D. Candidate 2020 runa.akahoshi@tu.edu

- Tiffany Chui, Pharm.D. Candidate 2019 tiffany.chui@tu.edu

septic shock >24 hours were excluded. The authors concluded that 7 day treatment with IV hydrocortisone and oral flud-rocortisone resulted in lower mortality than placebo among adults with septic shock. For more details, refer to the attachment authored by Runa Akaho-shi, Pharm.D. Candidate.

Septic shock is a life-threatening complication of an infection, characterized by dysregulation of the host re-sponse. While glucocorticoids have been considered as adjunct therapy under the Surviving Sepsis Campaign guidelines, mortality benefits are still unclear and debated. A recent multicenter, dou-ble-blind, randomized trial evaluated the efficacy of hy-

drocortisone plus fludrocorti-sone therapy for the treatment of septic shock. The study in-cluded patients age 18 and older with septic shock, de-fined as presence of docu-mented infection, SOFA score of 3 or higher for > 6 hours, and receipt of vasopressor therapy for > 6 hours. Patients with underlying condition af-fecting survival, previous treat-ment of corticosteroids, and

Member Spotlight: Sandy Bardas, RPh P A G E 3 V O L U M E 3 , I S S U E 3

Consultant Pharmacist for Ambulatory Surgery Centers

Sandy received her pharma-

cist’s degree from Massachu-

setts College of Pharmacy and

completed an ASHP residency

at Massachusetts General Hos-

pital. Sandy is currently a con-

sultant pharmacist for Ambula-

tory Surgery Centers. She spent

the vast majority of her career at

Stanford Healthcare where she

has been a Satellite Pharmacist,

Ambulatory Care Pharmacist,

OR Pharmacist, Night Pharma-

cist, Investigational Drug Phar-

macist and Emergency Medicine

Pharmacist. Sandy has pub-

lished journal articles and con-

tributed to textbooks in a wide

range of these areas.

What piece of advice would

you like to provide to our new

practitioners?

For the new practitioners out

there, I would like to tell them to

be more outgoing and to not let

opportunities to learn pass you

by. Say YES more often and

give everything a try. Many of

the new graduates can be very

shy and reserved.

Call for Nominations!

“Be more outgo-

ing. Do not let

opportunities to

learn pass you

by.”

- Interviewed by Tiffany Chui, Pharm.D. Candidate 2019 tiffany.chui@tu.edu

In the last year, I’ve enjoyed

watching Quatra grow stronger

guided by the leadership of

President Betty Lee and the

dedicated board. The key to

cementing our achievements as

an organization is to ensure it

continues to be led by those

who care. If you are reading

this, it means you care.

Please consider running or nominating

someone for the Secretary position, contact:

Carol.Lee@hhs.sccgov.org for questions).

SECRETARY (one-year commitment):

- Keep minutes of all QCSHP Board meetings - Assist in the planning and scheduling of meetings - Provide communication to membership - Conduct correspondences on behalf of QCSHP - Attend Board meetings

Further, Public Affairs

(contact: heeral.bhatt@tu.edu)

and Legislative Affairs

(diana.devore@tu.edu) commit-

tees need a liaison. These posi-

tions are unelected so please

step forward if you’d like to start

off with a non-elected position to

be more active in the organiza-

tion.

- Jennifer Pham, Pharm.D., BCPS (Nominations Chair) jenniferthupham@gmail.com

provided to prospective members. Any

new or renewing member who joined

Quatra in July and August was auto-

matically entered into our raffle where

one of those lucky members would be

randomly selected and given the op-

portunity to have their CSHP Seminar

Conference registration fee waived by

During the months of July and Au-

gust, CSHP Quatra County has con-

ducted a raffle in effort to not only pro-

mote membership but also to provide a

unique opportunity for our members to

stay involved within the field of phar-

macy. During this summer, 98 mem-

bers with expiring memberships were

contacted and membership flyers were

Quatra (sponsored by CSHP up to $470

value). Our lucky winner will be contacted

in the upcoming week. We are excited to

help advocate pharmacist involvement in

professional organiza-

tions and conferences!

Membership Update - Bianca Khishaveh, Pharm.D. Candidate (Membership Chair)

(2) The accurate medication profile or

list may be acquired by the pharmacist

during the hospital pharmacy’s hours of

operation.

(b) Notwithstanding any other law, a phar-

macy technician or an intern pharmacist

may perform the task of obtaining an ac-

curate medication profile or list for a high-

risk patient if both of the following condi-

tions are satisfied:

(1) The hospital pharmacy has a qual-

ity assurance program to monitor compe-

tency.

(2) The hospital has established poli-

cies and procedures for training and proc-

toring pharmacy technicians or intern

pharmacists by the hospital pharmacy

department and the pharmacy technician

or intern pharmacist has completed that

On September 22, California lawmak-

ers passed Senate Bill 1254 requiring

hospital pharmacy staff to obtain an accu-

rate medication profile for each high risk

patient upon admission under specified

circumstances.

Medication errors are reduced by 80%

when pharmacists or trained technicians

obtain medication lists for high risk pa-

tients.

Section 4118.5 is added to the Busi-

ness and Professions Code, to read:

(a) A pharmacist at a hospital pharmacy

shall obtain an accurate medication profile

or list for each high-risk patient upon ad-

mission of the high-risk patient under the

following conditions:

(1) The hospital has more than 100

beds.

training and proctoring.

(c) The hospital shall establish criteria

regarding who is a high-risk patient for

purposes of this section, and shall deter-

mine the timeframe for completion of the

medication profile or list, based on the

patient populations served by the hospi-

tal.

(d) The board may adopt rules and regu-

lations to carry out the purposes and

objectives of this section.

(e) This section shall not apply to the

State Department of State Hospitals.

(f) Nothing in this section shall be con-

strued to prohibit a healing arts licensee

licensed pursuant to this division from

obtaining an accurate medication profile

or list.

Editor-in-Chief

Jackie Ho, Pharm.D., MPH, BCPS

San Leandro Hospital

Clinical Pharmacy Coordinator

Phone: 510-667-4552

Board Officers Chapter President: Betty Lee President-Elect: Yunchen Ding Immediate Past-President: Jennifer Pham Secretary: Carol Lee Treasurer: Fred Nishioka Delegates to CSHP: Vincent Cheng, Connie Ha, Jennifer Pham, Jessica Song Alternate Delegates: Jenny Hong, Lawrence Troxell

Board Liaisons CSHP Board Liaisons: Helen Park, Jeannette Hanni Clinical Director of Pharmacies Liaison: Jeannie Sohn Pharmacy Residency Liaison: Lawrence Troxell

Committee Chairs Legislative Affairs Chair: Vacant Organizational Affairs Co-Chairs: Jenny Hong, Helen Park Continuing Education Chair: Vincent Cheng Weekend CE Chair: Connie Ha Financial Review Co-Chairs: Doris Kao, Nikki Uyehara Investment Chair: Betty Jue Nominations Chair: Jennifer Pham Membership Chair: Bianca Khishaveh New Practitioners Chair: Anna Zhou (incoming Chair-Parleen Shahi) Public Relations Chair: Heeral Bhatt Community Outreach Co-Chairs: Crystal Diep, Winnie Trieu Social Activities Chair: Sandy Bardas Webmaster/Communications Chair: Colleen DeLizza Newsletter Editor-in-Chief: Jackie Ho

QCSHP Publication

Pharmacists

Legislative Update - Senate Bill 1254 Passed!

Quatra Vision: Leading Pharmacy Practice in

patient safety and medication therapy

management.

http://www.cshp.org/group/QuatraCounty

QCSHP@CSHP.org

- Jackie Ho, Pharm.D., MPH , BCPS (Newsletter Editor-In-Chief) jackie.ho@tu.edu

Runa Akahoshi, PharmD Candidate, 2020

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock The New England Journal of Medicine

March 1, 2018

BACKGROUND

INTRODUCTION Septic shock is a potentially life-threatening complications of an infection, characterized by dysregulation of the host response. Currently, the SSC guidelines recommend hemodynamic and respiratory resuscitation along with appropriate anti infectives for the treatment of septic shock.1 The use of glucocorticoids is still controversial. However, this recent trial found that 90-day all-cause mortality was lower among patients who received hydrocortisone-plus-fludrocortisone in addition to standard therapy. 2

STUDY OBJECTIVES The objective of this study was to evaluate the effect of hydrocortisone plus-fludrocortisone therapy for the treatment of septic shock, compared to the placebo. FUNDING SOURCES Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health

METHODS

STUDY DESIGN & METHODOLOGY The study was a multicenter, double-blind, randomized trial with a 2-by-2 factorial design. PATIENT SELECTION & ENROLLMENT

Inclusion Criteria: Exclusion Criteria:

Indisputable or probable septic shock < 24 hrs

Septic shock was defined as the following: ● Presence of clinically or microbiologically documented infection ● Sequential Organ Failure Assessment (SOFA) score of 3 or 4 for at

least two organs for > 6 hrs ● Receipt of vasopressor therapy for > 6 hrs to maintain SBP > 90

mmHg or mean BP > 65 mmHg

● Septic shock > 24 hrs ● High risk of bleeding ● Pregnancy or lactation ● Underlying conditions that could affect short-term survival ● Known hypersensitivity ● Previous treatment with corticosteroids

INTERVENTION 1. Hydrocortisone 50 mg IV bolus q6 hrs plus Fludrocortisone 50 ug tablet via nasogastric tube once daily 2. Placebo

ENDPOINTS ● Primary Outcomes: 90-day all-cause mortality ● Secondary Outcomes:

○ All-cause mortality at intensive care unit (ICU) discharge, hospital discharge, day 28 and day 180 ○ Number of days alive and free of vasopressors, mechanical ventilation or organ failure ○ Safety outcomes (ex: superinfection, GI bleeding, hyperglycemia episodes)

STATISTICAL ANALYSIS This was a intention-to-treat analysis. The intervention was assigned at 1:1 ratio with P < 0.05 being considered statistically significant.

RESULTS

PARTICIPANT BASELINE CHARACTERISTICS A total of 1241 patients were enrolled in the study from 34 participating centers. ● 614 patients were assigned to the Hydrocortisone plus Fludrocortisone group ● 627 patients were assigned to the Placebo group

Most patients had community acquired infections, commonly in the lungs. The initial antimicrobial treatment was evaluated by the steering committee (ex: site of infection and sensitivity) and concluded to be adequate in both groups (96.2% vs 96.9%).

Runa Akahoshi, PharmD Candidate, 2020

SUMMARY OF OUTCOMES ● Primary Outcomes: 90-day all-cause mortality

Hydrocortisone + Fludrocortisone Placebo

90-Day All-Cause Mortality (%) 43.0% (95% CI, 39.0 to 47.0) 49.1% (95% CI, 45.1 to 53.1)

Relative Risk of Death 0.88 (95% CI, 0.78 to 0.99)

(P = 0.03) ● Secondary Outcomes

All-Cause Mortality Hydrocortisone + Fludrocortisone Placebo P Value

At ICU Discharge 35.4% 41.0% 0.04

At Hospital Discharge 39.0% 45.3% 0.02

At Day 180 46.6% 52.5% 0.04

○ Patients in the hydrocortisone-plus-fludrocortisone group had a significantly shorter time than those in the placebo group to:

● Wean from mechanical ventilation (P = 0.006) ● Wean from vasopressor therapy (P < 0.001) ● Reach SOFA score < 6 (P < 0.001)

○ Patients in the hydrocortisone-plus-fludrocortisone group had more vasopressor-free days & organ-failure-free days to day

28 (P < 0.001 & P = 0.003, respectively). ○ Safety Outcomes: There was no statistical difference in the number of serious adverse events by day 180 (P=0.08).

Relative Risk P Value Significant?

Gastroduodenal Bleeding 0.88 (95% CI, 0.58 - 1.34) 0.56 No

Superinfection 1.09 (95% CI, 0.92 - 1.30) 0.30 No

Hyperglycemia 1.07 (95% CI, 1.03 to 1.12) 0.002 Yes

DISCUSSION

Study Limitations ● The study did not meet the total number of patients needed in each group to detect the absolute difference of 10% in 90 days

mortality (power of 95%). ● There were some imbalances in the distribution of pathogens between the two groups.

CONCLUSION

Authors’ Conclusion In conclusion, 7 day treatment with a 50 mg intravenous bolus of hydrocortisone every 6 hours and daily dose of 50 microgram of oral fludrocortisone resulted in lower mortality than placebo among adults with septic shock. Clinical Implication The evidence from this trial suggested that the addition of hydrocortisone-plus-fludrocortisone had survival benefit in adults with sepsis shock and persistent vasopressor dependency and organ failure. Further studies should be warranted to identify additional risks and benefits of this adjunct therapy, and to determine its place in sepsis shock treatment for potential SSC guideline update.

REFERENCES

1. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 2. Annane, D, et al. “Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.” The New England Journal of Medicine, vol. 378, no. 9, pp. 809–818.,

doi:10.1056/NEJMoa1705716.

Member Spotlight:

Sandy Bardas, RPh

Consultant Pharmacist for Ambulatory Surgery Centers

Sandy received her pharmacist’s degree from Massachusetts College of Pharmacy and completed an ASHP residency at Massachusetts General Hospital. Sandy is currently a consultant pharmacist for Ambulatory Surgery Centers. She spent the vast majority of her career at Stanford Healthcare where she has been a Satellite Pharmacist, Ambulatory Care Pharmacist, OR Pharmacist, Night Pharmacist, Investigational Drug Pharmacist and Emergency Medicine Pharmacist. Sandy has published journal articles and contributed to textbooks in a wide range of these areas. Why pharmacy? How did you choose your current career?

When I graduated from college, I started working in research and development. One day, the vice president called me into her office and asked if I wanted to go back to school and learn chemistry and math. Once I was in pharmacy school, I enjoyed it. When I graduated, I completed a residency with ASHP.

I appreciated working with research instruments but I wanted to do something more personable that required more interactions with people.

What advice would you like to provide to our new practitioners, residents and student pharmacists?

For the new practitioners out there, I would like to tell them to be more outgoing and to not let opportunities to learn pass you by. I strongly encourage them to say YES more often and give everything a try. Many of the new graduates can be very shy and reserved.

For example, I once attended a seminar in Atlanta and one of the classes there was learning how to set up a specific type of ventilator. I was very surprised that I actually knew the most about the process as a pharmacist. I knew so much about it because it doesn’t matter if it is directly related to pharmacy or not, I will always say yes if there is someone willing to teach me.

Throughout your educational and professional career, what would you say was your biggest accomplishment?

My biggest accomplishment would have to be when I worked with Vicky Ferraresi (the past president of CSHP) on designing a new operating room for Stanford Hospital. At first, we were viewed as intruders, going into a space that pharmacists have never gone into before and it took a long time to overcome these barriers and challenges; but now, OR pharmacists have become a standard of care. It took a very long time to plan everything but the experience and outcome were extremely rewarding.

What is the driving force or inspiration that motivates you every day to perform the demands of the job?

My driving force that motivates me every day in my career is to know that I might have helped someone lead a better life. The smile of gratitude that they give you in return and their sincere appreciation that you took the time to listen to them is what really inspires me to do my best job every day. I think that this holds true in all the different types of pharmacy settings I have worked in.

What are the biggest opportunities (and challenges) you see in the near future for pharmacy?

The biggest challenge in the future of pharmacy is to be able to gain provider status and we can achieve this by not being shy. Without some sort of provider status, we will just be administrators and doing the technical work of pharmacy (i.e., look for missing doses, doing inventory, compounding, etc.).

What critical skills do you wish you had developed earlier to help you throuhgout your career?

I wish I could have learned how to be more hands on, such as physical exams, and learning how to use all the different types of equiments, especially IV pumps. We need to be able to show that we are essential and in order to achieve that, we need to step up to that role.

What do you like to do for fun on your time off?

In addition to consulting for ambulatory surgery centers, I am also a certified aquatic fitness instructor. I got into it because I have always been a master swimmer and I very much enjoy swimming by the ocean where I grew up. However, I have come to realize that resiliency and wellness of healthcare professionals is extremely important because if we don’t take care of ourselves, the career can burn you out very quickly.

Tiffany Chui, Pharm.D. Candidate 2019 Touro University, California

Study Methods Results Conclusion UGDP (1970)1

823 patients were randomized: Tolbutamide (sulfonylurea) Insulin standard Insulin variable Placebo group Phenormin added 18 months after initiation

The tolbutamide group was terminated due to an excess of cardiovascular deaths. The 2 insulin groups compared to placebo: Not more effective in prolonging life or delaying

onset of vascular complications

Tolbutamide and phenformin were associated with higher mortality. Neither insulin nor the oral hypoglycemic agents provided greater protection against vascular complications than diet alone.

UKPDS (1998)2,3

5,102 newly diagnosed T2DM were followed for 10 years. Determine the effect of intensive glycemic control on the incidence of vascular complications and compare the advantages

25% risk reduction in microvascular endpoints in the treatment-intensive group versus the conventional-treatment group

Intensive glycemic control in T2DM was associated with a reduction in microvascular complications. No statistically significant effect on macrovascular disease or mortality.

PROactive (2005)4

5,238 T2DM patients with evidence of macrovascular disease Pioglitazone + their hypoglycemic medications Placebo + their hypoglycemic medications

Pioglitazone compared to placebo: Not statistically significant for reducing

macrovascular events (all-cause mortality, nonfatal MI, stroke, acute coronary syndrome)

Slightly more hospitalized for heart failure

In high-risk T2DM patients, pioglitazone didn’t reduce the risk of the primary macrovascular endpoint.

ADVANCE (2008)5

More than 11,000 T2DM with a median 5 year follow-up Intensive-control group: target HbA1C < 6.5%

In the treatment-intense group, there was a statistically significant 10% reduction in a composite of macrovascular and microvascular events

Intensive glycemic control targeting HbA1C < 6.5% improved microvascular outcomes but had no impact on macrovascular outcomes.

ACCORD (2008)6

10,251 men and women were randomly assigned Intensive therapy group: target HbA1C < 6% Standard therapy group: target HbA1C 7-7.9%

Intensive therapy group: 6.4% (median) Standard therapy group: 7.5% (median) After a median follow-up of 3.7 years, the trial was stopped early due to increased all-cause and CV mortality.

A more intensive glycemic target (HbA1C < 6.0%) increased mortality versus standard control (7%, 7.9%)

VADT (2009, 2011)7,8

1,791 patients were randomized Intensive glucose control Standard glucose control

Median 5.6 years follow-up Intensive therapy group 6.9% Standard therapy group 8.4% No significant differences found in time to first CV event

Intensive glycemic control has minimal impact on both macrovascular and microvascular endpoints in T2DM.

EMPA-REG OUTCOMES (2015)9

7,020 patients randomized Daily oral empagliflozin 10mg Daily oral empagliflozin 25mg Placebo

Empagliflozin compared to placebo: Significantly lower risk of death from CV causes,

death from any cause, and HF hospitalization Small reductions in weight, waist circumference,

and SBP/DBP

Empagliflozin reduced the rate of CV events among T2DM patients with a high CV risk.

LEADER (2016)10

More than 9,000 adults Liraglutide Placebo

Liraglutide compared to placebo: Statistically lower risk of death from CV causes,

nonfatal MI, or nonfatal stroke Lower risk of death from any cause and

microvascular events

T2DM patients treated with liraglutide had significant reductions in CV events versus placebo.

Tiffany Chui, Pharm.D. Candidate 2019 Touro University, California

Landmark Diabetes Trials Every Pharmacist Should Know

According to the American Diabetes Association (ADA), approximately 1.5 million Americans are newly diagnosed with diabetes every year and it remains the 7th leading cause of death in the United States.

One of the leading clinical concerns regarding diabetic patients is the extent of glucose control and the prevention of long-term vascular complications. UKPDS (1998) and VADT (2009) revealed that a more intense glycemic control had little to no impact on the reduction of macrovascular and microvascular complications. One approach to intensive glucose control is a stricter HbA1C target. ACCORD (2018) explored a target HbA1C < 6% and found increased mortality compared to placebo. Conversely, ADVANCE (2009) employed a target HbA1C < 6.5% and results signified a reduction in microvascular complications.

As novel drugs are being developed, safety and efficacy trials remain a critical requirement. Drug-specific trials, such as UGDP (1970), PROactive (2005), EMPA-REG OUTCOMES (2015), and LEADER (2016), have sought to assess the efficacy of reducing mortality and macrovascular events along with the possibly fatal cardiovascular risks. With the growing prevalence of diabetes, it is vital for pharmacists to be reminded of these landmark trials that have undoubtedly defined the medication and glucose management of diabetes today. References

1. Meinert CL, Knatterud GL, Prout TE, Klimt CR. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. Diabetes. 1970;19(suppl):789-830.

2. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet. 1998;352:837-853.

3. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):703-713.

4. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005. 366(9493):1279-1289.

5. ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24): 2560– 2572.

6. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008. 358(24):2545-2559.

7. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129-139.

8. Duckworth WC, Abraira C, Moritz TE, Davis SN, Emanuele N, et al. The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA Diabetes Trial. J Diabetes Complications 2011;25(6):355-361.

9. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, et al. Empagliflozin, CV outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015. 373(22):2117-2128.

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