empagliflozin use and reduction of cardiovascular events and

EMPAGLIFLOZIN USE AND REDUCTION OF CARDIOVASCULAR EVENTS AND MORTALITY IN TYPE 2 DIABETICSLAUREN BYRNESPHARMACY INTERNALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES

PRESENTATION OVERVIEW

Brief Overview Pillarisetti article Zinman B, Wanner C, Lachin J, Fitchett D, Bluhmki E, Hantel S et al.

article Conclusions Questions

BRIEF OVERVIEW

Approximately 65% of patients living with Type 2 Diabetes Mellitus (T2DM) will die from cardiovascular disease (CVD) T2DM is a known risk equivalent for CVD due to the micro and macrovascular damage done by the

disease. T2DM patients often present with other known risk factors for CVD such as obesity,

hypertension (HTN), dyslipidemia and insulin resistance. HbA1c levels are also strongly associated with CVD Tight control of fasting plasma glucose (FPG) and dyslipidemia have not shown compelling

data for CVD protection

Pillarisetti S. Potential Drug Combinations to Reduce Cardiovascular Disease Burden in Diabetes. Trends in Pharmacological Sciences. 2016;37(3):207-219.

POTENTIAL DRUG COMBINATIONS TO REDUCE CARDIOVASCULAR DISEASE BURDEN IN DIABETESSIVARAM PILLARISETTITRENDS IN PHARMACOLOGICAL SCIENCES

REVIEW OF CURRENT LITERATURE

Postprandial glucose (PPG) levels are strongly connected with a reduction in CVD events. This can been seen in the Chicago Peoples Gas Company study, Diabetes Intervention Study (DIS)

and the DECODE study PPG can be especially hard to control in T2DM due to insulin resistance. Elevated PPG can lead to elevated levels of glucagon in the blood which, in turn, can lead

to postprandial lipemia (PPL) Trying to eliminate excess glucose and lipids from the vasculature increases stress and can

lead to an increase in atherosclerosis


APPROACHES TO REDUCE PPG AND PPL


EMPAGLIFLOZIN, CARDIOVASCULAR OUTCOMES AND MORTALITY IN T2DMZINMAN B, WANNER C, LACHIN J, FITCHETT D, BLUHMKI E, HANTEL S ET AL. NEW ENGLAND JOURNAL OF MEDICINE

STUDY METHODS

Design Randomized control trial Double-blind Placebo controlled 590 sites in 42 countries

Inclusion Criteria > 18 years old BMI < 45 Newly diagnosed untreated T2DM: HgA1c 7.0-9.0% Treated T2DM: HgA1c 7.0-10.0% Estimated glomerular filtration rate >30 ml/min/1.73m2 BSA

Zinman B, Wanner C, Lachin J, Fitchett D, Bluhmki E, Hantel S et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine.

STUDY METHODS

Procedure 1:1:1 ratio

10 mg empagliflozin 25 mg empagliflozin Placebo

Background glucose lowering measures remained unchanged Outcomes

Primary outcomes Death from CVD, nonfatal myocardial infarction (MI) or nonfatal stroke

Excluded silent MI Secondary outcomes

Composite of primary outcomes and included hospitalization from unstable angina


STUDY METHODS

Statistical Analysis Noninferiority of empagliflozin vs placebo

Both primary and secondary outcomes 1.3 margin for hazard ratio

Study population (n = 7020) 71.5% male 72.3% White 68.6% A1c <8.5% 48.4 % BMI < 30


OUTCOMES

PRIMARY OUTCOMES


Primary outcomes overall 14% relative risk reduction Included death from CVD, nonfatal MI, or nonfatal stroke

Death from Cardiovascular Causes 38% relative risk reduction

Death from Any Cause 32% relative risk reduction

Hospitalization for Heart Failure 35% relative risk reduction

These differences were significant for not only noninferiority but demonstrated the superiority of empagliflozin to placebo

SECONDARY OUTCOMES


Secondary Outcomes 11% relative risk reduction Included hospitalization for unstable angina as the key secondary outcome in addition to all primary

outcomes These results demonstrated noninferiority to the placebo but failed to show superiority

Patients did not see a reduction in hospitaliztions from unstable angina

ADVERSE EVENTS


Jardiance did not cause more adverse events than placebo Placebo—91.7% Jardiance 10 mg—90.1% Jardiance 25 mg—90.4% Empagliflozin pooled—90.2%

Patients did not withdraw at an increased rate in the Jardiance group than from placebo Placebo—19.4% Jardiance 10 mg—17.7% Jardiance 25 mg—17.0% Empagliflozin pooled—17.3%

DISCUSSION

DISCUSSION

Primary outcomes Significant reductions in all primary outcomes between empagliflozin groups and placebo

CVD related death, nonfatal MI, nonfatal stroke No significant difference between empagliflozin groups

Secondary outcomes No significant difference between any groups

Hospitalization for unstable angina

CONCLUSIONS

Data is evident to support long-term use of empagliflozin Dose should be based a individual patient health and metabolic outcomes

Patients with T2DM at high risk for CVD receiving empagliflozin were at significantly lower risk for developing primary cardiovascular outcomes and death than placebo when added to standard of care No difference between dosing

QUESTIONS?

REFERENCES

1. Pillarisetti S. Potential Drug Combinations to Reduce Cardiovascular Disease Burden in Diabetes. Trends in Pharmacological Sciences. 2016;37(3):207-219.

2. Zinman B, Wanner C, Lachin J, Fitchett D, Bluhmki E, Hantel S et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine. 2015;373(22):2117-2128.

empagliflozin use and reduction of cardiovascular events and

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