In line with the clinical practice guideline policy of the Spanish Society of Cardiology (SEC),1 the current article presents the novel, relevant, and conflicting aspects of the 2019 joint update of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) on the management of cardiovascular disease in patients with diabetes mellitus (DM) and prediabetes.2

These, the third guidelines jointly drafted by the ESC and EASD, are justified by recent advances, most of which are related to treatment. Although common to all guidelines, we would nonetheless like to stress that the aim of the recommendations is to support health care professionals, because these are the people ultimately responsible for clinical decision-making for each patient receiving treatment.

The guidelines are designed to be more practical and clear and include new sections, such as recommendation tables, that summarize the fundamental and novel aspects with respect to previous editions, ordered according to the level of supporting evidence. The guidelines use the well-known levels of evidence (A, B, and C) and classes of recommendations (I, IIa, IIb, and III).

At the suggestion of the SEC Guidelines Committee and the coordinators assigned to these guidelines, a group of expert cardiologists and endocrinologists was selected to review the document. The objective was to comment on the nature and timeliness of the guidelines, analyze the methodology, and highlight the novelties (Table 1) and the positive, questionable, or omitted aspects. With these evaluations, a joint document has been prepared and reviewed by cardiologists appointed by the Clinical Cardiology, Cardiovascular Risk and Cardiac Rehabilitation, Ischemic Heart Disease, Catheterization, and Heart Failure sections of the SEC, as well as by the Spanish Society of Endocrinology and Nutrition (SEEN).

This aspect is relevant because no changes have been made to the consensus, with the baseline blood glucose or glycated hemoglobin (HbA1c) level still recommended for DM diagnosis and the oral glucose tolerance test only for doubtful cases and for the diagnosis of impaired glucose tolerance (IGT). The guidelines recognize that there are certain barriers to the correct evaluation of HbA1c. For its correct interpretation, it may be useful to consider other causes besides those listed2 (hemoglobinopathies and hemolytic or iron deficiency anemias) because people can be iron deficient without having anemia, Graves disease, or severe hepatic and kidney disease.3 It should also be remembered that HbA1c might not be affected by these clinical conditions in people with DM.

The guidelines stress the need to repeat the test to confirm the diagnosis. Notably, the American Diabetes Association guidelines4 indicate that the confirmatory diagnosis of DM, in the absence of unequivocal hyperglycemia, requires 2 different methods in the same sample or a repeated test in different samples.

One of the main novelties of these guidelines is the reclassification of cardiovascular risk in DM (Table 7 of the guidelines2). The document introduces the major feature of sex differences (higher relative risk and earlier major cardiovascular events in women with DM). That is, women are no longer are considered to be protected against premature cardiovascular disease (CVD). There is a final recommendation Table2 for the use of laboratory, electrocardiographic, and diagnostic imaging tests to evaluate cardiovascular risk in asymptomatic patients with DM; this table is highly detailed and useful for evidence grading.

Noteworthy controversial aspects include the amalgamation of type 1 DM (T1DM) and type 2 DM (T2DM), which is particularly counterproductive in this section and may lead to misunderstandings. The concept of prediabetes is exclusively applicable to T2DM.

The degree of cardiovascular risk given to each entity differs; in addition, each entity has a different clinical manifestation. Although the baseline blood glucose level is very useful for DM/pre-DM screening, the HbA1c level should also be considered. In addition to differences in sex and time of onset, DM also affects the risk of distinct cardiovascular events differently5; thus, it would have been interesting to consider it. In contrast to other recent guidelines, the epidemiological evidence, and the stated objective of the guidelines themselves, the document states that prediabetes is not associated with increased cardiovascular risk. The clearest screening-related recommendation (I C) is possibly the performance of resting ECG in DM patients diagnosed with hypertension or suspected of having CVD. Such a general recommendation in this highly prevalent population should be supported by clear evidence, which is not provided in the guidelines.

Finally, the guidelines do not recommend systematic screening for CVD in asymptomatic patients with DM. However, positive results have been achieved with different imaging techniques. This may support the current discretional use of screening tests for silent ischemia without cost-effectiveness criteria.

This section covers aspects related to the medical therapy of diabetic patients with established CVD or with high or very high CVD risk, as well as aspects related to coronary revascularization.

This section is probably the one with the most changes from the 2013 guidelines.6 The results of SGLT2 inhibitor studies has redirected the recommendations for the prevention and management of heart failure (HF) in patients with DM.9

Regarding the epidemiological characteristics, compared with the 2013 guidelines,6 emphasis is still placed on the close relationship between HF and DM, as well as the negative effects of the combination of these 2 entities on hospitalizations, cardiovascular mortality, and all-cause mortality. The prevalence of HF in patients with DM is estimated to exceed 30%, assuming that underdiagnosis persists, which demonstrates the lack of understanding of the cause and pathophysiology of diabetic cardiomyopathy.

A new classification of HF is introduced based on the ejection fraction: preserved (HFpEF), intermediate, and reduced (HFrEF). In addition, effort is now being expended to indicate the secondary pathophysiological implications of the different HF phenotypes on DM. The current data give proportions of 25% to HFrEF and 75% to HFpEF.

In terms of HF treatment in patients with DM, the only change is the incorporation of angiotensin receptor-neprilysin inhibitors as therapies that improve prognosis in patients with HFrEF and DM, as in patients with HFrEF without DM; in addition, angiotensin receptor-neprilysin inhibitors improve glycemic control and delay the need for insulinization.

As already mentioned, the most important change has been the introduction of SGLT2 inhibitors as first-line therapy for patients with DM and HF, with level of evidence I A due to HF hospitalization reductions with empagliflozin, canagliflozin, and dapagliflozin and cardiovascular and all-cause mortality reductions with empagliflozin. Benefits have recently been reported with dapagliflozin (after publication of the guidelines). Metformin remains second-line treatment (IIa C), and GLP1-RAs are newly awarded a IIb A recommendation due to the neutral effect in HF of liraglutide, dulaglutide, and semaglutide, as well as their ability to reduce cardiovascular risk. Glitazones are contraindicated because they can increase fluid retention. Regarding the dipeptidyl peptidase-4 (DPP4) inhibitors, saxagliptin has a class III recommendation due to increased HF hospitalizations in the SAVOR study, and the other drugs in this group appear to have a neutral effect on HF.

Notably, the recommendations of these guidelines are in line with the position of the SEC,6 published months before, with SGLT2 inhibitors deemed the first-line drugs for patients with DM and CVD and particularly for those with HF.

The guidelines describe DM as an independent risk factor for atrial fibrillation, particularly in young patients. This association increases the risks of death, HF, and stroke. Accordingly, atrial fibrillation screening should be performed using pulse palpation, ECG, or Holter monitoring. Patients with a CHA2DS2-VASc embolic risk score ≥ 2 should be anticoagulated (I A) and direct oral anticoagulants are preferred to vitamin K antagonists, with doses adjusted to renal function.

The diagnosis and management of ventricular arrhythmias (extrasystole and sustained and nonsustained ventricular tachycardias) do not differ from those in patients without DM. However, both DM and prediabetes increase the risk of sudden cardiac death. After an acute myocardial infarction, the need must be evaluated for an implantable cardioverter-defibrillator and, in patients with HF, the possibility of resynchronization therapy, with or without defibrillator, once the medical therapy has been optimized using beta-blockers, inhibitors of the renin-angiotensin-aldosterone axis (including sacubitril/valsartan), and mineralocorticoid receptor antagonists. The impact of the new antidiabetic drugs on sudden cardiac death remains unknown.

In the new document, cerebrovascular disease is not included as a section, although carotid atherosclerotic disease is mentioned and recommendations are made, as in the previous guidelines. The recommendations for aneurysm screening are the same as those in patients without DM.

An annual clinical assessment is recommended to screen for lower extremity peripheral artery disease. However, a new recommendation is that of measurement of the ankle-brachial index alone at diagnosis and every 10 years if normal. The guidelines repeatedly refer to the specific and recently published SEC guidelines on peripheral artery disease,10 without delving as deeply as the 2013 guidelines; we consider it an attempt to not duplicate content. In addition, the document includes the evaluation of amputation risk using the WIFI (Wound, Ischemia, and Foot Infection) classification, which enables appropriate risk stratification.

Regarding treatment, the guidelines once again show the lack of specific evidence in patients with DM supporting the various revascularization treatment strategies, as well as the importance of a multidisciplinary team approach. The treatment targets for patients with this complication reflect the guidelines’ view that these patients are at very high risk. In addition, antiplatelet therapy is recommended for patients with lower extremity peripheral artery disease who do not have a contraindication. Indeed, for chronic symptomatic lower extremity artery disease, low-dose rivaroxaban (known as the vascular dose) and aspirin should be combined if the bleeding risk is not high.

Finally, it is important to note that carotid ultrasound screening is not recommended to detect the risk of future cerebrovascular disease. However, regarding this vascular imaging technique, the authors do specify that measurement of the intimal-medial thickness is not recommended; instead, the detection of carotid and femoral plaque is noted to contribute to risk stratification in patients with DM and moderate and high risk.

Notably, whereas the previous guidelines included retinopathy as a microvascular complication, this edition specifically includes chronic kidney disease alone. Accordingly, there are no specific treatment recommendations for diabetic retinopathy; however, due to recent data on the possible nephroprotective properties of the new antidiabetic agents (SGLT2 inhibitors and GLP1-RAs), chronic kidney disease receives greater attention in the current guidelines.

Chronic kidney disease, defined as an estimated glomerular filtration rate <60mL/min/1.73 m2 or albuminuria that lasts 90 days or more, shows elevated prevalence in diabetic patients and is associated with high cardiovascular risk. The annual screening and evaluation of renal function requires determination of both the estimated glomerular filtration rate and the creatinine:albumin ratio.

The blood pressure targets for chronic kidney disease have been changed: a systolic blood pressure of a maximum of 130mmHg is recommended, but not <120mmHg, and always individualized. For patients older than 65 years, the recommended values are 130 to 139mmHg. For its treatment, the most strongly recommended drugs continue to be ACEIs/ARBs, particularly in patients with proteinuria, albuminuria, or left ventricular hypertrophy.

Optimization of glycemic control reduces nephropathy progression. However, a fall in the glomerular filtration rate increases the risk of adverse effects from oral antidiabetic agents and limits their use. Recent clinical trials have obtained promising data on the neuroprotective properties of GLP1-RAs (liraglutide and semaglutide) and SGLT2 inhibitors (empagliflozin, canagliflozin, and dapagliflozin), although these clinical trials have some limitations, such as the exclusion of advanced chronic kidney disease or a primary outcome that did not consider nephroprotection. The CREDENCE study11 was stopped prematurely due to a 30% reduction in the relative risk of the primary outcome variable (composite outcome of end-stage renal disease, serum creatinine concentration, and cardiovascular or renal death) in patients assigned to the canagliflozin group vs the placebo group in a high-risk population. Accordingly, although there is some evidence of nephroprotection with both pharmacological drugs, there are still gaps in the evidence, such as the effect of drug class, which will probably be resolved with new clinical trials.

DM is a chronic disease that requires solid health behaviors, oriented toward specific understanding of the disease and its treatment. The benefits of DM and cardiovascular risk factor control are well defined and reported in these guidelines. However, patients still struggle to achieve and maintain lifestyle changes.12

Numerous studies have shown the effectiveness of training and support programs for self-management in patients with DM.13 Even in patients with prediabetes, structured lifestyle-focused empowerment and education interventions have proven benefits on DM progression and cardiovascular risk factor control. However, more studies are required to determine the effects of these programs on CVD progression.

The guidelines stress a multifactorial approach to diabetic patients, beyond simple glycemic control. Patients should acquire understanding of healthy habits, self-care, and effective management of their therapeutic regimen. Nursing care should be focused on promoting self-care and healthcare education. The objective is to achieve better control of the disease that avoids delayed complications and improves the quality of life of patients and their family members.

Healthcare education programs are mainly implemented in primary care. However, we must not forget that DM is a chronic disease that is accompanied by comorbidities that require the use of hospital services. Diabetic patients can have various hospitalization events over time. In the hospital context, particularly at discharge, education of the patient/family is thus also a hospital nursing competence.

The recommendations of the guidelines concerning healthcare education have already been mentioned in other sections, but the empowerment aspects for the control of cardiovascular risk factors in diabetic patients are particularly interesting. Thus, the guidelines recommend the scheduling of individual and group training sessions, both coordinated and complementary, to improve DM understanding, glycemic control, and disease management. Self-management of the blood glucose concentration should be individualized according to the patient's DM type, treatment, and self-management capabilities for better T2DM control and to avoid hypoglycemia. The guidelines indicate that the role of the new glucose self-monitoring technologies remains to be defined. Patients and their relatives should be informed and educated to achieve self-care and prevent foot injuries. Annual assessment is recommended of the amputation risk through evaluation of the presence of wounds, ischemia, and infection. From the point of view of nursing, the treatment algorithms included in the guidelines that use the WIFI classification are useful and enable appropriate patient stratification.

None declared.