Skriv ut
Kategori: Nyheter

ABSTRACT

Introduction:

Were the participants of the

EMPA-REG OUTCOME trial representative of

patients receiving empagliflozin in clinical

practice?

The aim of the present study was to

examine the prevalence of cardiovascular disease

(CVD) in type 2 diabetes patients starting

empagliflozin treatment in routine clinical

practice in Sweden.

Methods:

We used nationwide data from the

Swedish National Diabetes Register (NDR), the

Swedish Prescribed Drug Register, and the

Swedish National Patient Register to provide

clinical characteristics and ongoing treatments.

Results:

The total study cohort included

460,558 patients, of whom 130,508 (28.3%) had

a history of CVD. The number of patients

starting empagliflozin during the study period

was 16,985. Among these, 1952 (11.5%) had a

history of CVD. The patients starting empagliflozin

were younger than the total cohort and

were more likely to have retinopathy despite

having a similar duration of diabetes to the

overall cohort. They also exhibited higher BMI,

HbA1c, and eGFR, and were more likely to be

treated with insulin and lipid-lowering and

blood-pressure-lowering medications. The

patients with CVD who were starting empagliflozin

were slightly older and had been diabetic

for slightly longer than the patients without

CVD who were starting empagliflozin, but they

also had lower eGFR. Among the patients with

CVD who were starting empagliflozin, 87% had

coronary heart disease, 8% had suffered a

stroke, 13% had peripheral artery disease, 16%

had atrial fibrillation, and 20% had congestive

heart failure.

Conclusion:

The prevalence of CVD in patients

with type 2 diabetes in clinical practice in

Sweden was 28.3% during the study period, and

it was 11.5% in the patients starting empagliflozin

treatment. Patients of the latter cohort

were, however, younger, more obese, and more

likely to have unsatisfactory glycemic control,

requiring additional treatment. Overall, a large

proportion of type 2 diabetes patients should be

considered at high cardiovascular risk.

 

Björn Eliasson . Jan Ekelund . Rikard Amberntsson .

Mervete Miftaraj . Ann-Marie Svensson

 

From the article

INTRODUCTION

Persons with type 2 diabetes mellitus (T2DM)

are at elevated risk for premature death or

developing cardiovascular complications.

Although recent observational data show considerable

improvements in cardiovascular incidence

and mortality rates in persons with T2DM

between 1998 and 2013, these risks are still

clearly higher than in the general population

[1]. Cardiovascular disease (CVD) prevention

and management are thus essential parts of

diabetes care [2].

The EMPA-REG OUTCOME trial examined

the effects of empagliflozin, a sodium glucose

cotransporter-2 (SGLT-2) inhibitor, on cardiovascular

morbidity and mortality in patients

with type 2 diabetes at high risk for cardiovascular

events. The results showed reductions in

cardiovascular death, hospitalization from heart

failure, and all-cause mortality with empagliflozin

treatment on top of standard care (i.e.,

other treatments that lower glucose, blood

pressure, and blood lipids) as compared with

placebo [3].

Only patients with established cardiovascular

disease participated in the EMPA-REG OUTCOME

trial. Are these participants

representative of patients receiving empagliflozin

in clinical practice, and are the results

generalizable? Recently, a Swedish survey suggested

that the proportion of patients with type

2 diabetes (defined as being treated with any

glucose-lowering medication) in clinical practice

who had cardiovascular disease (coronary

heart disease, stroke, peripheral artery disease,

congestive heart failure, and atrial fibrillation)

was 34.2% in 2013, implying a clearly elevated

risk [4]. That study, however, lacked information

on clinical characteristics and risk factors.

The aim of the present study was to examine

the prevalence of CVD in patients with type 2

diabetes in routine clinical practice in Sweden—

applying a similar definition to that used in the

EMPA-REG OUTCOME trial—as well as the

prevalence of established CVD in patients who

were starting empagliflozin treatment. We used

nationwide data from the Swedish National

Diabetes Register (NDR) as well as the Swedish

Prescribed Drug Register and the Swedish

National Patient Register (National Board of

Health and Welfare) to probe clinical characteristics

and ongoing treatments.

 

DISCUSSION

This nationwide survey showed that patients

starting empagliflozin treatment were relatively

young compared with the overall cohort of

T2DM patients, and were generally more obese

and more likely to have unsatisfactory HbA1c

levels. In addition, retinopathy, micro- and

macroalbuminuria, and smoking were quite

common in the T2DM patients starting empagliflozin

treatment, in agreement with their

long mean duration of diabetes ([ 10 years).

Thus, a large proportion of the patients in this

nationwide cohort—even those with no history

of cardiovascular disease—would qualify as

high-risk individuals in recent major cardiovascular

outcome trials using SGLT-2 inhibitors

or GLP1-1 receptor agonists [8, 9].

In the multinational EMPA-REG OUTCOME

trial, 71% of the participants randomized to

empagliflozin treatment were male, and this

cohort presented the following mean values:

 age 63.1 years, BMI 30.6 kg/m2 , HbA1c

65 mmol/mol, blood pressure 135.3/

76.6 mmHg, LDL cholesterol 2.2 mmol/l, and

eGFR 74.2 ml/min/1.73 m2  (MDRD) [3 ]. 48.0%

of the patients in the pooled empagliflozin

group were on insulin treatment, 94.9% were

on blood pressure-lowering treatment, and

81.5% were on blood lipid-lowering therapy.

Almost all of the patients in the empagliflozin

group had cardiovascular disease (99.4%),

75.6% had coronary heart disease, 23.1% had a

history of stroke, 21.0% had peripheral artery

disease, and 9.9% had congestive heart failure.

The Swedish patients with CVD who were

starting empagliflozin were quite similar to the

participants in the EMPA-REG OUTCOME trial.

The patients with no history of CVD were

younger, slightly more obese, and had higher

HbA1c, whereas the patients with a history of

CVD showed higher levels of coronary heart

disease and congestive heart failure but lower

levels of stroke and peripheral artery disease

than the participants in EMPA-REG OUTCOME.

A recent systematic review and meta-analysis

based on the results of the EMPA-REG OUTCOME

and DECLARE–TIMI 58 trials as well as

the CANVAS program recently concluded that

SGLT-2 inhibition should be considered in

patients with type 2 diabetes regardless of the

presence of atherosclerotic cardiovascular disease

or a history of heart failure, due to its

positive effects on glycemic control and the

risks of heart failure and renal disease progression

[9 ]. Cardiovascular benefits seem to be

more pronounced in patients with established

atherosclerotic cardiovascular disease, as most

clearly demonstrated by the EMPA-REG OUTCOME

trial [3 ]. The CANVAS program and the

DECLARE–TIMI 58 trial, which tested the safety

of canagliflozin and dapagliflozin, respectively,

had larger proportions of patients at elevated

cardiovascular risk, similar to the Swedish

cohort, but they did not have established CVD

[10 , 11 ]. This difference may have contributed

to the outcome differences between the three

trials.

The major strength of the present survey was

its nationwide scope and the high validity of

the data obtained, but one limitation of the

study is that we did not address other

comorbidities at baseline. We also used a crosssectional

design and did not follow the patients

longitudinally in this study. However, in a

recent observational cohort study of side effects

that used nationwide registers from Sweden and

Denmark, we found a numerically low but

increased risk of lower limb amputation and

diabetic ketoacidosis in patients using SGLT-2

inhibitors compared with those on GLP1

receptor agonists, but there were no other serious

adverse events of concern [12 ].

Other recent studies in general or high-risk

populations in clinical practice have also

investigated patients offered treatment with

empagliflozin or other SGLT-2 inhibitors and

the results of such treatment [13 –16 ]. In

essence, those studies have highlighted the

positive effects as well as the safety aspects of

this class of glucose-lowering medications.

These effects have been attributed to several

mechanisms, such as diuresis, natriuresis, and

their glucose-lowering, metabolic, and renal

effects [17 –19 ].

 

CONCLUSION

 The prevalence of CVD in patients with type 2

diabetes in clinical practice in Sweden was

28.3% during the study period, and it was

11.5% in patients starting empagliflozin treatment.

Patients in the latter cohort were, however,

younger and more obese and had

unsatisfactory glycemic control, requiring

additional treatment. Overall, a large proportion

of T2DM patients should be considered at

high cardiovascular risk.

 

Nyhetsinfo

www red DiabetologNytt

Träffar: 1224