The DDG clinical practice guidelines are updated regularly during the second half
of the calendar year. Please ensure that you read and cite the respective
current version.
UPDATES TO CONTENT COMPARED TO THE PREVIOUS YEAR’S VERSION
Change 1: Recently, another large cardiovascular outcome study, DELIVER, with the
SGLT2 inhibitor dapagliflozin, showed that treatment with dapagliflozin significantly
reduced the combined endpoint of hospitalization due to heart failure or CV death
compared to placebo in patients with an ejection fraction greater than 40%.
Predetermined subgroup analyses showed no significant difference between patients
with
and without DM.
Reason: Relevant new marketing authorisation for the treatment of heart failure
with an ejection fraction>40%
Supporting reference:
[20]
Change 2: Two studies (FIGARO-DKD and FIDELIO-DKD) investigated the effect of the
new non-steroidal mineralocorticoid receptor antagonist finerenone in patients with
diabetes, CKD and albuminuria. In both studies, finerenone reduced the risk of kidney
failure and cardiovascular events compared to placebo. A prespecified analysis of
both
studies together (FIDELITY) showed in 13171 patients that finerenone, in combination
with optimized RAS blockade, reduced the risk of the composite cardiovascular endpoint
consisting of time to cardiovascular death, non-fatal myocardial infarction, non-fatal
stroke or hospitalization due to heart failure by 14%. This effect was mainly
due to a reduction in hospitalization due to heart failure, although patients with
symptomatic heart failure with reduced pumping function were excluded from these
studies. Whether finerenone can reduce heart failure outcomes in patients with HFpEF
is
currently being investigated in a large cardiovascular endpoint study (FINARTS-HF;
NCT04435626).
Reason: New treatment options for patients with diabetes and CKD with a positive
effect on hospitalization due to heart failure
Supporting reference:
[21]
[23]
Cardiovascular risk
Patients with diabetes mellitus have a significantly increased risk of developing
cardiovascular diseases with their sequelae of acute myocardial infarction, stroke
and cardiovascular death. For example, even today a 60-year-old male patient with
diabetes has 6 years less life expectancy compared to a metabolically healthy male
of the same age, and a 60-year-old patient with diabetes and a previous history of
a
heart attack has 12 years less [2]. These data
highlight the need for targeted risk stratification of patients with diabetes and
the consistent treatment of diabetes, associated risk factors and cardiovascular
disease.
Patients with diabetes mellitus should be categorized according to their
cardiovascular risk into those with very high cardiovascular risk, high
cardiovascular risk and moderate cardiovascular risk [3].
Very high cardiovascular risk
Diabetes mellitus and existing cardiovascular disease, or end organ damage,
or≥3 risk factors or diabetes duration>20 years.
High cardiovascular risk
Diabetes mellitus with a diabetes duration>10 years without end organ
damage, but with an additional risk factor.
Moderate cardiovascular risk
Young patients (type 1 diabetes<35 years; type 2 diabetes<50
years) with a diabetes duration<10 years without other risk factors.
Further risk stratification
In addition to diagnostics for the above-mentioned risk stratification, patients
with diabetes and hypertension or clinical suspicion of cardiovascular disease
should receive a resting ECG. At present, no convincing data exist to use
additional imaging techniques such as echocardiography, stress echocardiography,
scintigraphy or MRI in asymptomatic patients with diabetes mellitus. As part of
clinical routines, no determination of circulating biomarkers should be carried
out as part of risk stratification.
Cardiovascular risk reduction
Cardiovascular risk reduction
For the recommendations on the reduction of cardiovascular risk in diabetes
treatment, refer to the DDG practice recommendations on the therapy of type 2
diabetes (see p. 65–92) and on the treatment of lipid metabolic disorders
(see p. 160–165). Therefore, only the basic statements are listed here:
-
Patients with diabetes should receive structured advice on how to stop
smoking. For patients with diabetes, a Mediterranean diet enriched with
polyunsaturated and monounsaturated fatty acids is recommended. Patients
with diabetes should perform moderate to strenuous physical activity for at
least 150 min/week.
-
In patients with type 2 diabetes and very high cardiovascular risk, a target
value for low-density lipoprotein (LDL) cholesterol of<55
mg/dL and a minimum of 50%reduction in cholesterol is
recommended. For patients with a high cardiovascular risk, a target value of
70 mg/dL and a minimum of 50%reduction in cholesterol is
recommended. For patients with a moderate risk, a reduction in LDL
cholesterol to<100 mg/dL is recommended.
-
The administration of aspirin (100 mg/day) is recommended for
secondary prevention in patients with diabetes mellitus. In the context of
primary prevention, patients with diabetes should not receive antiplatelet
therapy. Platelet aggregation inhibition after acute coronary syndrome
and/or coronary intervention (duration of dual antiplatelet therapy,
etc.) should be coordinated with the treating cardiologist.
-
In accordance with the new guideline of the European Society of Cardiology,
patients with diabetes mellitus should have a target systolic blood pressure
of 130 mmHg. If possible, systolic values<130 mmHg should be
targeted. The diastolic blood pressure target is<80 mmHg. A blood
pressure setting<120/70 mmHg should be avoided.
-
When adjusting blood glucose levels, patients without a cardiovascular
pre-existing condition should be treated according to the recommendations
for type 2 diabetes; in patients with a pre-existing cardiovascular
condition, hypoglycaemia should be avoided and proven therapy strategies in
reducing cardiovascular risk should be used. Therefore, GLP-1 receptor
agonists and/or SGLT-2 inhibitors with proven event reduction should
be used for reducing cardiovascular events and mortality based on the
results of large cardiovascular endpoint studies in cases of type 2 diabetes
and cardiovascular diseases or a high/very high cardiovascular
risk.
Diabetes and coronary heart disease
Diabetes and coronary heart disease
All patients with coronary heart disease should be examined for the presence of
diabetes mellitus (see Diagnostics and Classification of Diabetes Mellitus, see
P9–17). For prognostic factors, patients with diabetes mellitus and coronary
heart disease should receive platelet aggregation inhibitors, ACE inhibitor therapy
and lipid-lowering therapy with statins. The first year after myocardial infarction
the administration of a beta-blocker leads to an improvement of the prognosis,
whereby this effect decreases over the course of time. With respect to antidiabetic
therapy, for patients with type 2 diabetes at high cardiovascular risk, a
significant reduction in the 3-point Major Adverse Cardiac Event (MACE) was shown
with empagliflozin [4] or canagliflozin [5] versus placebo. In addition, empagliflozin
significantly reduced all-cause mortality [3]. In
DECLARE, there was no significant effect for dapagliflozin vs. placebo [6]. However, it seems that the individual substance
is less important for the different results in the studies than the patient
population. Similarly, in LEADER with liraglutide [7], in SUSTAIN-6 semaglutide [8], in
HARMONY with albiglutide [9], in REWIND with
dulaglutide [10], and in PIONEER-6 [11] with oral semaglutide vs. placebo showed a
significant reduction in the 3-point MACE endpoint. In addition, liraglutide and
oral semaglutide vs. placebo reduced all-cause mortality in the LEADER trial and
PIONEER 6 trial, respectively. Administration of semaglutide resulted in significant
reduction of cardiovascular events [12]. Against
the background of these data, therapy with one of these substances should be an
integral part of blood glucose-lowering therapy in patients with diabetes and
cardiovascular disease.
In the presence of coronary artery disease requiring intervention or surgery, the
therapy of coronary revascularization in patients with diabetes does not differ from
the therapy in patients without diabetes. In complex coronary findings with
multi-vascular disease and low perioperative mortality, bypass surgery appears to
be
superior to coronary intervention. The decision on the revascularization procedure
to be performed (coronary intervention or bypass surgery) should always be made by
the interdisciplinary cardiac team in the case of complex coronary heart
disease.
Diabetes and heart failure
Diabetes and heart failure
Epidemiological and clinical data of recent years have shown that patients with
diabetes mellitus have a significantly increased risk of developing heart failure
and that the prognosis of patients with diabetes and heart failure is significantly
worse than that of patients with heart failure without diabetes [13]
[14].
According to the recommendation of the European Cardiology Guideline, a distinction
is made between heart failure with reduced ejection fraction (HFrEF), heart failure
with preserved ejection fraction (HFpEF) and heart failure with mildly reduced
ejection fraction (HFmrEF) ([Tab. 1]) [15]. In principle, it can be said that half of
patients with heart failure and diabetes have impaired left ventricular function.
In
patients with HFrEF, the treatment of heart failure does not differ between patients
with and without diabetes. This applies to both drug and device therapy (implantable
cardioverter defibrillator [ICD], cardiac resynchronization therapy [CRT]). In terms
of medication, HFrEF is treated as standard with a quadruple therapy consisting of
angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor
neprilysin inhibitor (ARNI), β-blocker, mineralocorticoid receptor
antagonist (MRA) and SGLT-2 (sodium-dependent glucose co-transporter 2) inhibitor.
The addition of SGLT2 inhibitors to initial heart failure therapy is based on data
from the DAPA-HF and EMPEROR-Reduced trials, both of which were conducted in
patients with HFrEF with and without diabetes. Administration of dapagliflozin or
empagliflozin significantly reduced worsening heart failure, cardiovascular death,
or all-cause mortality regardless of the presence of diabetes mellitus in patients
with HfrEF [16]
[17]
[18]. On the basis of these data,
both substances are approved for the treatment of HFrEF.
Tab. 1 Definition of heart failure with preserved (HFpEF),
mildly reduced (HFmrEF) and reduced ejection fraction
(HFrEF).
|
HF type
|
HFrEF
|
HFmrEF
|
HFpEF
|
|
Criteria
|
1
|
Symptoms±signsa
|
Symptoms±signsa
|
Symptoms±signsa
|
|
2
|
LVEF≤40%
|
LVEF 41–49%b
|
LVEF≥50%
|
|
3
|
–
|
–
|
Objective evidence of structural and/or functional
cardiac abnormalities suggestive of diastolic LV
dysfunction/increased LV filling pressures, including
elevated natriuretic peptidesc
|
a In the early stages of HF (especially HFpEF) and in optimally
treated patients, signs of heart failure may be absent. b The
presence of other examination findings of structural heart disease
(e. g., enlarged left atrium, LV hypertrophy, or echocardiographic
evidence of impaired LV filling) makes the diagnosis of HFmrEF more likely.
c The following applies to the diagnosis of HFpEF: The more
abnormalities there are, the higher the likelihood of HFpEF. LVEF: Left
ventricular ejection fraction.
For patients with HFpEF and HFmrEF (left ventricular ejection fraction
[LVEF]>40%), there were no data for a long time that reliably
demonstrated an improvement in the prognosis of patients. Recently, 2 large
cardiovascular outcome trials, EMPEROR-preserved [1] and DELIVER [20] with the SGLT2
inhibitors empagliflozin and dapagliflozin, respectively, have shown that treatment
with SGLT2 inhibitors significantly reduced the combined endpoint of hospitalization
due to heart failure or cardiovascular death compared to placebo in patients with
an
ejection fraction greater than 40%. Predetermined subgroup analyses showed
no significant difference between patients with and without diabetes mellitus [1]. On the basis of these data, empagliflozin and
dapagliflozin are now approved for the treatment of heart failure regardless of the
ejection fraction. In addition to the administration of the SGLT2 inhibitor,
patients should continue to receive symptomatic therapy, e. g., diuretics,
and therapy for comorbidities, e. g., cessation of arterial hypertension. In
addition, in patients with diabetes and heart failure, it should be noted that
glitazones and the dipeptidyl peptidase-4 (DPP4) inhibitor saxagliptin are
contraindicated in patients with heart failure due to the increased risk of
hospitalization for heart failure.
Two studies (FIGARO-DKD [21] and FIDELIO-DKD [22]) investigated the effect of the new
non-steroidal mineralocorticoid receptor antagonist finerenone in patients with
diabetes, chronic kidney disease (CKD) and albuminuria. In both studies, finerenone
reduced the risk of kidney failure and cardiovascular events compared to placebo.
A
prespecified analysis of both studies together (FIDELITY) showed in 13171 patients
that finerenone, in combination with optimized renin–angiotensin system
(RAS) blockade, reduced the risk of the composite cardiovascular endpoint consisting
of time to cardiovascular death, non-fatal myocardial infarction, non-fatal stroke
or hospitalization due to heart failure by 14%. The effect was mainly due to
a reduction in hospitalization due to heart failure, although patients with
symptomatic heart failure with reduced pumping function were excluded from these
studies [23]. Whether finerenone can reduce heart
failure outcomes in patients with HFpEF is currently being investigated in a large
cardiovascular endpoint study (FINARTS-HF; NCT04435626).
Diabetes and atrial fibrillation
Diabetes and atrial fibrillation
The presence of diabetes mellitus is a separate risk factor for thromboembolic events
in patients with atrial fibrillation. All patients with atrial fibrillation should
be risk stratified for their risk of thromboembolism using the CHADS-VASC score
([Tab. 2]) and accordingly receive
anticoagulation with vitamin K antagonists or new oral anticoagulants (NOACs) [19]. At this stage, no data exists that show a
prognostic advantage of a rhythm restoration (cardioversion in the sinus rhythm) or
frequency control in atrial fibrillation. In this respect, the procedure is
comparable for patients with and without diabetes.
Tab. 2 Approach based on risk factors, expressed as point
system with the acronym CHA2DS2 -VASc
score.
|
Risk factor
|
Score
|
|
Chronic heart failure or left ventricular dysfunction
|
1
|
|
Hypertension
|
1
|
|
Age≥75 years old
|
2
|
|
Diabetes mellitus
|
1
|
|
Stroke/TIA/thromboembolism
|
2
|
|
Vascular disease history1
|
1
|
|
Age 65–74 years
|
1
|
|
Female
|
1
|
|
Maximum score
|
9
|
Note: As the age can be evaluated with 0, 1 or 2 points, the maximum score is
9. 1 Condition after myocardial infarction, peripheral arterial
occlusive disease, or plaque in the aorta.
