Use a Combined Cardio–Renal–Metabolic Approach to Treat Cardiovascular Disease in Patients With Kidney Disease or Diabetes

The CaReMe UK Partnership Has Developed Best Practice Guidance for Cardiovascular Disease, Kidney Disease, and Diabetes; Professor Stephen Wheatcroft Explains How Cardiologists Can Optimise This Guideline to Manage Cardiovascular Risk and Prevent Disease Progression

Cardiovascular disease, chronic kidney disease, and diabetes frequently cluster together in the same individuals.¹ Collectively, these conditions represent the largest cause of mortality globally.² Shared risk factors and common pathological mechanisms mean that the presence of one of these conditions leads to a substantially increased risk of developing the others.³ In people with atherosclerotic cardiovascular disease or heart failure, the presence of chronic kidney disease, diabetes, or both substantially increases the risk of major adverse cardiovascular events, hospitalisation, and mortality.^4,5

The proportion of patients encountered in clinical practice with multiple chronic disorders is on the rise.⁶ Although this poses challenges to clinical management, it also generates opportunities in patients with cardiovascular disease, kidney disease, and diabetes because many options for preventing disease progression are common to all three disorders. Weight management, regular physical activity, blood pressure control, and lipid modification are of critical importance in people with any or all of these conditions.^7–9 The need for cohesive management of cardiovascular disease, kidney disease, and diabetes is further exemplified by the recent expansion of clinical indications for the sodium–glucose co-transporter-2 inhibitors (SGLT-2is) class of medications,¹⁰ some of which now have marketing authorisations for heart failure^11,12 and/or chronic kidney disease,¹¹ as well as for diabetes.

CaReMe UK Guidance

Condition-specific clinical guidelines to support healthcare providers managing cardiovascular disease, chronic kidney disease, and diabetes are readily available;^7–9,13 however, clinicians in these specialties need to work more closely together. The Cardio—Renal—Metabolic (CaReMeUK) Partnership¹⁴ is a collaboration between UK national societies representing cardiovascular disease, kidney disease, and diabetes across primary and secondary care (the British Cardiovascular Society, the Renal Association, the Association of British Clinical Diabetologists, the Primary Care Cardiovascular Society, and the Primary Care Diabetes Society). Established in 2019, CaReMe UK focuses on education, guidance, and support for healthcare practitioners to provide them with the skills and knowledge necessary to optimise management of people with cardiovascular disease, chronic kidney disease, or diabetes.

To date, CaReMe UK has published two ‘best-practice’ guidelines covering cardiovascular risk optimisation in people with type 2 diabetes¹⁵ and optimal management of chronic heart failure.¹⁶ The guidelines are intended to provide practical advice to healthcare practitioners who see patients with cardio–renal–metabolic disease, regardless of their clinical background. The guidelines are not intended to replace more detailed condition-specific guidance, but to facilitate opportunistic optimisation of management of individuals with cardiovascular disease, kidney disease, or diabetes, irrespective of clinical setting.

CaReMe UK guidance is published online, which supports a responsive approach to new evidence and enables CaReMe UK to provide contemporary recommendations for clinicians in the period between updates to NICE guidance.

Cardiovascular Risk Optimisation in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease

CaReMe UK guidance on cardiovascular risk optimisation¹⁵ provides a pragmatic, single-page, best-practice guide to allow healthcare practitioners to manage cardiovascular risk in people with type 2 diabetes and cardiovascular disease. The guide is intended for use by practitioners without specialist knowledge of diabetes, who see patients with cardiovascular disease in their day-to-day clinical practice—for example, general practitioners, cardiologists, pharmacists, cardiac nurses, and practice nurses. It is designed to be used opportunistically at any relevant clinical contact, which may include outpatient appointments in secondary care or long-term condition reviews in primary care.

The guidance is focused on appropriate treatment selection in patients with cardiovascular disease to maximise the opportunity for cardiovascular risk reduction. In patients with type 2 diabetes and atherosclerotic cardiovascular disease, SGLT-2 is or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with evidence of cardiovascular benefit are recommended in addition to metformin, irrespective of glycaemic control (HbA_1c).¹⁵

Selection of either an SGLT-2i or a GLP-1 RA is dependent upon consideration of individual patient factors and the characteristics of the medications.¹⁵ For example, in patients with left ventricular systolic dysfunction or kidney disease, SGLT-2is are expected to provide benefit in reducing heart failure events and slowing renal decline.¹⁵ In contrast, GLP-1 RAs are preferred when weight loss and reduction in risk of myocardial infarction and stroke are desirable.¹⁵ It is recognised that, for many people, combined treatment with an SGLT-2i and GLP-1 RA provides the optimum strategy to achieve glycaemic control and maximise cardiovascular and renal benefit.¹⁷

CaReMe UK guidance was published before NICE Guideline 28 (NG28) Type 2 diabetes in adults: management was updated in February 2022. This included new recommendations on drug treatment for adults with type 2 diabetes to reflect the findings of cardiovascular outcomes trials in people with cardiovascular disease or at high cardiovascular risk.⁷ The updated NICE guidance recommends routine prescribing of an SGLT-2i with cardiovascular benefit in people with type 2 diabetes and cardiovascular disease, and consideration of an SGLT-2i in people at high cardiovascular risk (defined as QRISK2 >10% in adults aged 40 years and over).⁷ NICE decided not to recommend GLP-1 RAs as first-line treatment as they were not considered to be cost effective for people with a high risk of developing cardiovascular disease or those with established cardiovascular disease. A further update to NG28, which will take into account the entirety of clinical evidence for GLP-1 RAs, including their effects on weight loss, is expected.¹⁸

Heart Failure

CaReMe UK guidance on the management of heart failure¹⁶ is a modified version of the visual summary of the recommendations for managing chronic heart failure that was published by NICE alongside its guideline on chronic heart failure.¹³ The CaReMe UK heart failure guidance recommends diuretic therapy for initial management of fluid overload, with subsequent treatment guided by the presence or absence of reduced left ventricular ejection fraction.¹⁶

In patients with heart failure with reduced ejection fraction (HFrEF), CaReMe UK recommends foundation therapy with:

• an angiotensin converting enzyme inhibitor (ACEi) (or an angiotensin receptor blocker if intolerant of ACEi) or sacubitril/valsartan if ejection fraction (EF) is less than 35%, and
• beta-blocker, and
• mineralocorticoid receptor antagonist.

The guidance recommends that dapagliflozin or empagliflozin is offered in addition to foundation therapy if the patient is still symptomatic.¹⁶ This recommendation was added because of studies that observed the benefits of dapagliflozin (DAPA-HF)¹⁹ and empagliflozin (EMPEROR-REDUCED)²⁰ in patients with HFrEF after NG106 was published in 2018.¹³

In patients with heart failure with preserved ejection fraction (HFpEF), CaReMe UK guidance recommends management of comorbidities (such as hypertension, atrial fibrillation, ischaemic heart disease, and diabetes), and highlights that empagliflozin is licenced for the treatment of symptomatic chronic heart failure, irrespective of ejection fraction. This refers to the clinical benefit from empagliflozin observed in the EMPEROR-PRESERVED study.²¹ Similar changes for the prescribing of dapagliflozin are anticipated following publication of the DELIVER trial, which demonstrated that dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction.²²

The guideline also provides practical prescribing advice, including when it may be necessary to adjust other glucose-lowering medications in people with diabetes, and the importance of counselling patients about sick day rules.

Enabling an Interdisciplinary Approach to Cardio–Renal–Metabolic Disease

The prevalence of diabetes in the UK has doubled over the past 15 years, and is predicted to continue to rise.²³ Most people with type 2 diabetes are not under regular review by secondary care diabetes services; therefore, opportunities to modify the risk of developing progressive cardiovascular or renal disease will often fall to primary care or occur during clinical contacts with other secondary care teams. Patients with diabetes and atherosclerotic cardiovascular disease are at particularly high risk of mortality. Cardiology teams are closely involved with management of these patients when they present with acute coronary syndromes or require revascularisation. Lipid modification and blood pressure control are embedded in cardiology practice. However, cardiology teams may not feel empowered to initiate glucose-lowering medication to optimise the management of cardiovascular or renal disease risk.²⁴

The Association of British Clinical Diabetologists (ABCD) and Diabetes UK has recently published a joint position statement and recommendations on the use of SGLT-2is in people with type 2 diabetes.²⁵ The guidance is for practitioners without specific expertise in diabetes and provides practical advice on initiation of SGLT-2is to reduce the risk of cardiovascular events and declining kidney function.

Interdisciplinary approaches are critical to optimising cardio–renal–metabolic disease management.^26,27 Dedicated cardio–renal clinics are operational in several centres in the UK²⁸ and, in other regions, secondary care cardiometabolic clinics have been established to bring cardiology and diabetes expertise together in the management of high-risk individuals.^29,30 Local multidisciplinary CaReMe UK advisory groups are emerging within the new integrated care systems to bring together stakeholders from primary and secondary care. Expansion of the clinical pharmacist workforce within primary care networks³¹ has allowed pharmacists to participate in cardio–renal–metabolic risk optimisation through structured medication reviews, in addition to their participation in community heart failure and diabetes services.

Conclusion

Despite the interconnectivity between and common clustering of diabetes, cardiovascular disease, and kidney disease, much of the current guidance and clinical management addresses each of these diseases separately.  

Originally launched as a treatment for type 2 diabetes, SGLT-2is are now increasingly being used as part of a holistic management strategy for their cardiac and renal benefits alongside diabetes care. In the future, GLP-1 RAs may also play a similar role as a treatment that provides additional renal and cardiac benefits to patients with type 2 diabetes. Therefore, it is important to raise awareness of these treatments and unite clinicians working in these specialties to enable cohesive management of cardiovascular disease, kidney disease, and diabetes.

CaReMe UK will continue to update and publish new guidance for healthcare providers to support the provision of optimal care to patients with combinations of cardiovascular disease, kidney disease, and diabetes, regardless of the clinical setting.