The European Society of Cardiology (ESC) in partnership with the European Association for the Study of Diabetes (EASD) has recently updated their guidelines for the management and prevention of cardiovascular disease in patients with diabetes or pre-diabetes. The new guidelines, which update the 2013 guidelines, address a range of topics including the diagnosis of diabetes and pre-diabetes, cardiovascular risk assessment, management of arrhythmia and heart failure in diabetes as well as the management of chronic kidney disease in diabetes. This article will focus on a few new recommendations in the 2019 guidelines that differ from the 2013 guidelines in terms of blood pressure targets, lipid targets, antiplatelet therapy and glucose lowering.

         The previous blood pressure target was defined as less than 140/85 mmHg for all patients. The 2019 guidelines recommend individualized targets¹. A systolic blood pressure (SBP) of less than 130 mmHg, but not less than 120 mmHg, is recommended. For older individuals (age > than 65 years), a SBP blood range of 130-139 mmHg is the target. The range for diastolic blood pressure is aimed between 70 to 80 mmHg for patients of all ages. Meta-analysis of 13 randomized controlled trials in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes, found that patients in the intensive blood pressure control group with SBP of less than 135 mmHg, there was a ten percent reduction in all-cause mortality (odds ratio, 0.90; 95% confidence interval, 0.83 to 0.98) and a seventeen percent reduction in stroke. Outcomes for macrovascular and microvascular complications were similar, however there was a twenty percent increase in adverse events in the intensive BP control group². Intensive SBP control resulting in a level of 130 mmHg was associated with a greater reduction in stroke, hence a lower target may be beneficial for those at high risk of cerebrovascular accident³.

         The current guidelines also include cardiovascular risk categories in patients with diabetes based on the 2016 European guidelines on cardiovascular disease (CVD) prevention in clinical practice⁴. Patients with T2DM and CVD or with target organ damage, such as proteinuria or kidney failure, are considered at very high risk (10 year risk of CVD death >10%). This category also includes patients with T2DM with three or more risk factors such as age (> 40 years), hypertension, dyslipidemia, smoking or obesity. Patients with type 1 diabetes mellitus (T1DM) with a long duration of disease (> 20 years) were also in this very high-risk category. This is followed by the high-risk group (10-year risk of CVD death 5-10%), seen in patients with diabetes for more than ten years without target organ damage or other additional risk factors. The moderate risk group (10-year risk of CVD death <5%) includes younger patients with diabetes (T1DM aged < 35 years old, T2DM < 50 years old) with less than ten years of diabetes duration without additional risk factors.

         Based on these risk categories, the 2019 guidelines include new recommendations for glucose-lowering agents as well as lipid targets. The guidelines have also incorporated the findings from recent cardiovascular outcome trials involving the glucagon-like peptide-1 receptor agonists (GLP-1 RA) and the sodium-glucose cotransporter-2 (SGLT-2) inhibitors. In drug-naïve T2DM patients with atherosclerotic cardiovascular disease or patients in the very high or high-risk group, for the first time in diabetes guidelines GLP-1 RA or SGLT-2 inhibitors monotherapy have been favored over metformin monotherapy. In patients already on metformin, the two classes of medication are also recommended. Further medications should be added if glycemic targets are not achieved.

         In the 2019 ESC guidelines lipid targets were more stringent, following the recommendations from the recent 2019 ESC/EAS Guidelines for the management of dyslipidaemias. In those at very high cardiovascular risk, a low-density lipoprotein cholesterol (LDL-C) target of less than 55mg/dl (<1.4mmol/L) and LDL-C of at least fifty percent reduction was recommended. A secondary goal of non-high density lipoprotein cholesterol of less than 85 mg/dl (<2.2mmol/L) was also identified for this high-risk group. Statins are effective lipid lowering agents and meta-analysis has found that statin-induced reduction of LDL-C by 40 mg/dL (1.0mmol/L) had a nine percent reduction in all-cause mortality and a twenty-one percent reduction in the incidence of major cardiovascular events⁵. In patients who are intolerant to statins, the use of ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor can be used for LDL-C reduction.

         The role of antiplatelet therapy in primary prevention of CVD for diabetic patients has not been as straightforward as the role of this therapy in secondary prevention. Various international guidelines have made recommendations based on patient age and cardiovascular risk⁶. The recent trial, A Study of Cardiovascular Events In Diabetes (ASCEND), which involved a large group of patients with diabetes without evident CVD, found a twelve percent reduction in serious vascular events; however, there was an increased risk of major gastrointestinal bleed of up to twenty nine percent. This was consistent with previous meta-analysis which included patients with and without diabetes⁷. Hence in the ESC 2019 guideline, aspirin for primary prevention was not recommended in patients who were at moderate cardiovascular risk. Aspirin should be considered for those at very high and high risk, who do not have any contraindication.

         The landscape of diabetes is continuously changing based on findings from various clinical trials; the latest ESC guidelines reflect that evolution. Newer diabetes guidelines not only focus on achieving glycemic targets but also take into consideration a patient’s cardiovascular risk factors⁸. With the selection of more appropriate pharmacotherapy for patients in different risk categories, we ultimately aim to improve patient outcomes.

References:

1. Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). Eur Heart J. 2019:ehz486.
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3. Mancia G, Grassi G. Blood pressure targets in type 2 diabetes. Evidence against or in favour of an aggressive approach. Diabetologia. 2018;61:517–525.
4. Hobbs FD, Piepoli MF, Hoes AW, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-2381.
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6. Raber, I, McCarthy CP, Vaduganathan M, et al. The rise and fall of aspirin in the primary prevention of cardiovascular disease. Lancet. 2019; 393(10186):2155–2167.
7. Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–1860.
8. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2019. Diabetes Care. 2019;42:S90–S102.

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