Unmet Role of Cardiologists: Use of Cardiometabolic Drugs that Lower Cardiovascular Risk
Cardiovascular disease (CVD) is the leading cause of death and disability among patients with type 2 diabetes (T2D).1 CVD patients with T2D face an especially heightened risk of adverse cardiovascular events, contributing to an estimated 12-year reduction in life expectancy.2 Despite their elevated cardiovascular hazards, most patients with T2D still do not meet treatment goals for cardiovascular risk factors, and intensive glucose control alone does not appear to improve macrovascular outcomes.3-5 Consequently, disparities in CVD-associated mortality between patients with and without T2D have remained persistent and relatively unchanged over the past two decades.6 Clearly, there remains an urgent unmet need to provide cardiovascular protection for patients with T2D, especially in the face of an escalating global epidemic of diabetes.
A recent wave of clinical trials has revealed a novel therapeutic strategy to mitigate the elevated cardiovascular risks within this vulnerable population. In 2008, in response to concerns about the cardiovascular safety of glucose-lowering drugs, The Food and Drug Administration (FDA) issued new guidance requiring the rigorous evaluation of cardiovascular outcomes for new antihyperglycemic therapies.7 Since this change was instituted, numerous resulting cardiovascular outcomes trials (CVOTs) have demonstrated that many SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA), drugs which were initially approved for glucose control, also independently provide cardiovascular protection to patients with T2D and CVD.8
To reflect these ground-breaking results, the FDA has expanded the labels for many of these drugs, and the American College of Cardiology (ACC), the American Diabetes Association (ADA), the European Society of Cardiology (ESC), and the European Association for the Study of Diabetes (EASD) have all released new consensus guidelines on their use.9-11 These recommendations endorse broader prescription of these drugs among patients with T2D and clinical CVD while also encouraging cardiologists to embrace a more active role in identifying and treating eligible patients. Importantly, the ACC has identified three areas in which cardiologists can play a key role in the management of diabetes: (1) routinely screening for T2D in their patients, (2) treating cardiovascular risks, and (3) incorporating the recent outcomes data for SGLT2i and GLP-1 RA into clinical practice.9
Are cardiologists suited to lead in diabetes management?
In addition to these widespread calls by medical associations for cardiologists to become more involved in diabetes care, multiple systemic factors suggest that cardiologists may be well-positioned to lead in diabetes management. In the US, cardiologists outnumber endocrinologists and nephrologists 3:1 and 2:1, respectively. In a given year, a patient with T2D is three times more likely to encounter a cardiologist than an endocrinologist and five times more likely if the patient also has coexisting CVD.12 At the same time, incidence of T2D is outstripping access to endocrinologists and nephrologists in many states.13 Although screening for T2D and initiating diabetes therapy have not been historically viewed as the role of cardiologists, their relatively high physician density and their access to the high-risk patients with T2D and CVD who are most likely to benefit from new cardioprotective drugs make them well suited to this responsibility.
Are cardiologists currently engaged in diabetes diagnosis and management?
Early evidence suggests that cardiologists' use of cardioprotective SGLT2i or GLP-1 RA for the patients who could most benefit remains disappointingly low, despite updated guidelines and an accompanying plethora of CVOTs.14,15 In a cross-sectional analysis of 183,000 outpatients with T2D in US clinics from the Diabetes Collaborative Registry, of the patients meeting eligibility criteria to benefit from SGLT2i or GLP-1 RA, only 5% and 6% were prescribed the appropriate drug, respectively.14 Surprisingly, while T2D patients who are predominantly seen by their cardiologist (as opposed to an endocrinologist or primary care physician) were more likely to meet eligibility criteria for the drugs, they were actually less likely to be prescribed these drug classes. Recent studies have mirrored these data, suggesting a severe underutilization of cardioprotective SGLT2i and GLP-1 RA for T2D patients with CVD.15-17
Even when these drugs are prescribed to the appropriate patients, it seems cardiologists are unlikely to be the ones initiating their use. Two studies from the Partners HealthCare system in Boston, MA show that cardiologists account for a startlingly low proportion of the newly initiated prescriptions for SGLT2i (5%) and GLP-1 RA (5%).18,19 Instead, endocrinologists are taking the leading role in prescribing these drugs, followed by primary care physicians. These patterns have not changed appreciably over time, even after the publication of landmark CVOTs and the broadening of drug labelling by the FDA. However, these data do not capture any potential inflection points that may have followed updates to clinical guidelines since 2018.
Screening for T2D
The Centers for Disease Control and Prevention (CDC) estimates that approximately a quarter of Americans with T2D remain undiagnosed.20 These undiagnosed individuals likely represent a sizeable portion of the patients routinely seen by cardiologists. The proportion of patients with previously undiagnosed diabetes was 11% among heart failure patients from the RESOLVD trial, 19% among patients with coronary artery disease in the EUROASPIRE IV trial, and 22% among similar patients in the Euro Heart Survey on Diabetes.21-23 Given the insidious connection between T2D and cardiovascular risk, combined with the fact that patients with T2D can now benefit from an arsenal of targeted antihyperglycemic drugs that mitigate cardiovascular outcomes, identifying these patients is of the utmost importance. Despite this fact, screening for diabetes by cardiologists is far from universal. Data from the National Cardiovascular Data Registry's PINNACLE program suggest that only 13% of coronary artery disease outpatients were screened by their cardiologists for diabetes, and a survey of 103 United Kingdom (UK) cardiologists reported that only 30% measured HbA1c in all of their patients with acute coronary syndrome.24,25 Thus, while cardiologists are well-poised to act as key points of care in the identification and management of diabetes, there are enormous opportunities to expand their role in clinical practice.
What could account for the lackluster engagement of cardiologists in diabetes care?
Traditional perceptions of specialist roles
One prominent hypothesis for why cardiologists have thus far been reluctant to engage in T2D screening and treatment is that physicians are wary of overstepping traditional interdisciplinary boundaries.9,13,19 Amidst the prior lack of cardiovascular therapies targeted specifically to patients with T2D and evidence that aggressive glucose management alone does not prevent cardiovascular mortality, cardiologists have justifiably focused on blood pressure management, lipid modulation, and anti-coagulation therapy as the primary means of mitigating cardiovascular risks in their T2D patients.25 Because T2D has historically been viewed as a disease of high blood glucose and SGLT2i/GLP-1 RA were initially approved as agents for glucose control, many cardiologists may still regard the responsibility of screening for diabetes and initiating these evidence-based treatments as the domain of endocrinologists or primary care physicians.9
Lack of expertise
Another hypothesis is that cardiologists remain unfamiliar with the benefits and risks of these new agents, as well their appropriate use and monitoring.26 They may not be fully acquainted with the avalanche of CVOTs and guidelines recently published regarding these drugs or the myriad anti-diabetic agents available, along with their complex treatment algorithms. Further, many cardiologists may be reluctant to initiate medications if they are inexperienced with HbA1c targets or fear triggering hyperglycemia/hypoglycemia in patients with T2D (even though SGLT2i and GLP-1 RA agents rarely cause hypoglycemia and have generally favorable safety profiles).10,26 Although many of these legitimate concerns have been addressed in clinical guidelines and treatment pathways, the literature suggests that there is normally a lag of about 17 years between the publication of primary research, the development of clinical guidelines, and the eventual application into routine practice.27 Even in cases where cardiologists themselves are familiar with these novel drugs, they may be concerned that others in their team, including nurses and physician assistants, remain unfamiliar or poorly situated to manage new side effects. Without crucial support from the entire team, an increasing burden may be placed directly onto physicians.
Lastly, another reason behind the slow uptake of cardioprotective diabetes drugs among cardiologists may be systemic factors discouraging their use. These include the many fold higher costs for these novel therapies over older antihyperglycemic agents, patients' concerns about the need for injections for certain GLP-1 RA (semaglutide is now available in oral formulations), electronic medical record (EMR) systems that are not yet updated with the latest care pathways for use of newer therapies, and the inconvenience of added clinical time to counsel patients about diabetes.
Survey of cardiologists' perceptions
Despite widespread discussion in the literature about possible barriers to cardiologists becoming more involved in the management of diabetes, quantitative analyses or systematic ethnographies to determine physician attitudes remain limited. A 2019 survey in the UK of 103 consultant cardiologists across seven sub-specialties provides some key insight in this area.25 Researchers found that half of the surveyed cardiologists admitted they would not initiate clinically indicated diabetes medication for patients hospitalized with acute coronary syndrome (ACS), but the majority said they do routinely (36%) or occasionally (38%) uptitrate existing medications. When presented with a hypothetical ACS patient with sub-optimal glycemic control on metformin alone and asked to select which drug they would prescribe from a menu of options, less than 10% chose an SGLT2i or GLP-1 RA, as is clinically indicated. Instead, the overwhelming majority preferred to refer the patient to the diabetes team. These data seem sensible given that only a minority of the respondents felt they were very familiar with the outcomes data for SGLT2i (30%) or GLP-1 RA (20%). Instead, about a quarter of the physicians admitted to being unfamiliar with these CVOTs. Thankfully, the vast majority of cardiologists agreed that diabetes management is a high priority in ACS patients, but most (88%) felt this care was best delivered by specialist diabetes teams. Only 11% of cardiologists believed that they were best suited to deliver diabetes treatment to these patients. Taken together, these results suggest that among this cohort of cardiologists, most do not feel comfortable prescribing cardioprotective diabetes medications, lack adequate familiarity with trial outcomes for these drugs, and perceive that management of glucose-lowering therapies is beyond their purview or expertise. Additional surveys of cardiologists' knowledge of and attitudes towards diabetes management are necessary to better diagnose the persistent barriers to progress in this area.
How can we empower cardiologists to improve diabetes management?
Literature regarding the dissemination of research findings to influence clinical practice has consistently shown that passive forms of dissemination, such as the publication of clinical guidelines in journals or mass mailing of educational materials, produce only modest changes in behavior when used alone.27 Rather, they must be supplemented with more intensive interventions, such as the use of computerized decision support systems, educational outreach experiences, or audit and feedback mechanisms.28 In this context, it is worth exploring some proposed strategies by which cardiologists and other physicians can be empowered to apply the lessons of recent CVOTs and updated guidelines into their clinics and to engage more actively in appropriate care for patients with T2D.
The ACC has highlighted educational initiatives as an important avenue to improve physician awareness of new CVOT data, touting its multi-stakeholder CardioMetabolic Health Alliance and the Succeed in Managing Cardiovascular Risk in Diabetes initiative.29 This initiative provides, among other resources, curated news on its cardiometabolic webpage, case challenges, expert roundtables, and clinical guidance tools. Similarly, the Know Diabetes by Heart joint venture between the AHA and ADA provides educational resources to patients as well as providers, including podcasts, webinars, and the A1CVD Pro mobile app to support physicians treating T2D patients.30 While educational interventions can be highly effective mechanisms of influencing clinical practice, traditional didactic meetings such as lectures are shown to be relatively low yield interventions.28 Educational experiences aimed at healthcare providers should strive to be interactive, involving workshops that include discussion of practice, and should incorporate local opinion leaders and consensus processes. In addition, educational initiatives are most likely to be effective when complemented with ongoing training and implemented within organizations that exhibit a culture of valuing research-informed practices.28
In addition to educational campaigns, many physicians have emphasized the importance of cross-disciplinary coordination to improve diabetes care.9,31 More intimate collaboration between various medical specialties and professions involved in the management of T2D may prevent medication errors and redundant testing, improve coordination in managing the myriad chronic conditions often characteristic of patients with T2D, and support patients in efforts to modify behaviors outside of the clinic.31 Proposed models for improved coordination include the "consultative" approach, the "medical neighborhood" plus "primary care home" system, or care within cardiometabolic centers of excellence.9,13,31 In addition, the consolidation of care into a new cardiometabolic subspecialty, incorporating relevant areas of cardiology, endocrinology, and internal medicine, could streamline treatment in the future to optimize early assessment and targeted interventions.32 Coordinated models of care may alleviate some of the concerns that cardiologists have expressed about "stepping on the toes" of referring clinicians, but will require difficult re-evaluation of the traditional boundaries between medical specialties.
- Baena-Diez JM, Penafiel J, Subirana I, et al. Risk of cause-specific death in individuals with diabetes: a competing risks analysis. Diabetes Care 2016;39:1987-95.
- Collaboration TERF. Association of cardiometabolic multimorbidity with mortality. JAMA 2015;314:52-60.
- Andary R, Fan W, Wong ND. Control of cardiovascular risk factors among US adults with type 2 diabetes with and without cardiovascular disease. Am J Cardiol 2019;124:522-7.
- Fan W, Song Y, Inzucchi SE, et al. Composite cardiovascular risk factor target achievement and its predictors in US adults with diabetes: The Diabetes Collaborative Registry. Diabetes Obes Metab 2019;21:1121-7.
- Gerstein HC, Miller ME, Genuth S, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011;364:818-28.
- Rawshani A, Rawshani A, Franzén S, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med 2017;376:1407-18.
- Food and Drug Administration, US Department of Health and Human Services. Guidance for industry: diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. 2008. Available at: https://www.federalregister.gov/documents/2008/12/19/E8-30086/guidance-for-industry-on-diabetes-mellitus-evaluating-cardiovascular-risk-in-new-antidiabetic. Accessed 04/30/2020.
- Cosentino F, Ceriello A, Baeres FMM, et al. Addressing cardiovascular risk in type 2 diabetes mellitus: a report from the European Society of Cardiology Cardiovascular Roundtable. Eur Heart J 2018;40:2907-19.
- Das SR, Everett BM, Birtcher KK, et al. 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2018;72:3200-23.
- 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;41:255-323.
- American Diabetes Association. 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2020. Diabetes Care 2020;43:S111-s134.
- Gunawan F, Partridge C, Kosiborod M, Inzucchi S. SUN-149 Cardiologist vs. endocrinologist encounters in patients with T2D and CVD: potential implications for glucose-lowering therapy use and education. J Endocr Soc 2019;3:Suppl 1.
- Patel RB, Al Rifai M, McEvoy JW, Vaduganathan M. Implications of specialist density for diabetes care in the United States. JAMA Cardiol 2019;4:1174-5.
- Arnold SV, Inzucchi SE, Tang F, et al. Real-world use and modeled impact of glucose-lowering therapies evaluated in recent cardiovascular outcomes trials: an NCDR® Research to Practice project. Eur J Prev Cardiol 2017;24:1637-45.
- McGovern A, Feher M, Munro N, de Lusignan S. Sodium-glucose co-transporter 2 (SGLT2) inhibitor: comparing trial data and real-world use. Diabetes Ther 2017;8:365-76.
- Arnold SV, de Lemos JA, Rosenson RS, et al. Use of guideline-recommended risk reduction strategies among patients with diabetes and atherosclerotic cardiovascular disease. Circulation 2019;140:618-20.
- Pantalone KM, Misra-Hebert AD, Hobbs TM, et al. Antidiabetic treatment patterns and specialty care utilization among patients with type 2 diabetes and cardiovascular disease. Cardiovasc Diabetol 2018;17:54.
- Vaduganathan M, Sathiyakumar V, Singh A, et al. Prescriber patterns of SGLT2i after expansions of U.S. Food and Drug Administration labeling. J Am Coll Cardiol 2018;72:3370-72.
- Vaduganathan M, Patel RB, Singh A, et al. Prescription of glucagon-like peptide-1 receptor agonists by cardiologists. J Am Coll Cardiol 2019;73:1596-8.
- Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020 (CDC website). 2020. Available at: https://www.cdc.gov/diabetes/library/features/diabetes-stat-report.html Accessed 04/30/2020.
- Suskin N, McKelvie RS, Burns RJ, et al. Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J 2000;21:1368-75.
- Kotseva K, Wood D, De Bacquer D, et al. EUROASPIRE IV: a European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol 2016;23:636-48.
- Bartnik M, Rydén L, Ferrari R, et al. The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe: The Euro Heart Survey on diabetes and the heart. Eur Heart J 2004;25:1880-90.
- Chan PS, Oetgen WJ, Buchanan D, et al. Cardiac performance measure compliance in outpatients: the American College of Cardiology and National Cardiovascular Data Registry's PINNACLE (Practice Innovation And Clinical Excellence) Program. J Am Coll Cardiol 2010;56:8-14.
- Slater TA, Drozd M, Palin V, et al. Prescribing diabetes medication for cardiovascular risk reduction in patients admitted with acute coronary syndromes: a survey of cardiologists' attitudes and practice. Eur Heart J Cardiovasc Pharmacother 2020;6:194-6.
- O'Keefe JH, Nassif ME, Magwire ML, O'Keefe EL, Lavie CJ. The elephant in the room: why cardiologists should stop ignoring type 2 diabetes. Prog Cardiovasc Dis 2019;62:364-9.
- Brownson RC, Kreuter MW, Arrington BA, True WR. Translating scientific discoveries into public health action: how can schools of public health move us forward? Public Health Rep 2006;121:97-103.
- Bero LA, Grilli R, Grimshaw JM, Harvey E, Oxman AD, Thomson MA. Closing the gap between research and practice: an overview of systematic reviews of interventions to promote the implementation of research findings. BMJ 1998;317:465-8.
- American College of Cardiology. Succeed in managing cardiovascular risk in diabetes initiative (ACC website). 2020. Available at: https://www.acc.org/tools-and-practice-support/quality-programs/cardiovascular-risk-in-diabetes-initiative. Accessed 04/30/2020.
- Sanchez EJ, Cefalu WT. Know diabetes by heart. Circulation 2019;140:526-8.
- Pignone M. Optimizing the physician workforce for care of patients with type 2 diabetes. JAMA Cardiol 2019;4:1175-7.
- Eckel RH, Blaha MJ. Cardiometabolic medicine: a call for a new subspeciality training track in internal medicine. Am J Med 2019;132:788-90.
Keywords: Metabolic Syndrome X, Coronary Artery Disease, Glucagon-Like Peptide 1, Cardiovascular Diseases, Physicians, Primary Care, Blood Glucose, Hemoglobin A, United States Food and Drug Administration, Incidence, Drug Labeling, Cross-Sectional Studies, Hypoglycemic Agents, Metformin, Electronic Health Records, Glucose, Mobile Applications, Consensus, Insurance Pools, Consultants, Diabetes Mellitus, Type 2, Diabetes Mellitus
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