- Guidelines strongly recommend the use of an SGLT2 inhibitor or GLP-1 receptor agonist in patients with type 2 diabetes and symptoms of CVD or at high risk of CVD. However, the use of these cardioprotective drugs in 2020 remains low (<3% in a recent article).
- Cardiologists represent a small percentage (<5%) of those who prescribe these drugs, although their main benefit is the reduction of cardiovascular risk.
- Surveys of cardiologists suggest that the two main barriers to their use include a lack of knowledge about these drugs and a belief that diabetes care is not the responsibility of cardiologists.
Cardiovascular diseases (CVD) are the main cause of mortality and morbidity in patients with type 2 diabetes (T2D).1,2Adults with T2DM are twice as likely to die from heart disease or stroke as those without diabetes.3Although diabetes itself is an important risk factor for cardiovascular mortality, the risk is doubled for T2DM patients who are also diagnosed with CVD.3Despite this increased risk, most T2DM patients fail to meet treatment goals for traditional CV risk factors, and intensive glucose therapy alone does not seem to improve the effects of macroangiopathy.4,5As the global prevalence of diabetes continues to rise, and is estimated to reach 700 million by 2045, specific strategies are urgently needed to better manage cardiovascular health in this vulnerable population.6
The wave of cardiovascular outcome studies (CVOT) over the past five years for two classes of drugs, sodium glucose cotransporter-2 (SGLT2i) inhibitors and glucagon-like peptide-1 receptor (GLP-1RA) agonists, has changed. the overall management of CV risk in diabetic patients.7These drugs were originally approved as antihyperglycemic agents, but have since become even more useful for their cardiovascular benefits. CVOT meta-analyses suggest that in patients with RA T2DM, GLP-1 reduces patients' risk of serious cardiovascular adverse events by 12%, while SGLT2i reduces the risk of cardiovascular death and hospitalization for heart failure by 23%.8,9In fact, two recent clinical trials show that SGLT2i is effective not only in the primary prevention of heart failure in T2DM patients, but also in the secondary prevention of heart failure, regardless of whether the patient is diabetic or not.10,11Thus, AR SGLT2i and GLP-1 have become powerful tools in physicians' arsenal to combat CVD in T2DM patients. Updated guidelines from the American College of Cardiology (ACC), American Diabetes Association (ADA), European Society of Cardiology (ESC), and European Association for the Study of Diabetes (EASD) strongly recommend the use of SGLT2i or GLP-1 RA in patients with DM2 who already have CVD or are at high risk.7,12,13
A recent study by Hamid et al. - Project
Recently, Hamid et al. studied SGLT2i and GLP-1 RA prescribing patterns at the University of Mississippi Medical Center between January 2013 and June 2019.14Data from electronic health records were retrospectively analyzed for T2DM patients (n=66,368) as well as a subset of high-risk patients (n=21,173) who had T2DM and clinical manifestations of CVD, defined as any case. of chronic ischemic heart disease coronary artery disease, stroke, myocardial infarction, unstable angina or peripheral vascular disease. The authors characterized the demographics of patients receiving SGLT2i or GLP-1 RA therapy, including insurance status, and examined trends in prescribing volumes over time, prescribing other antihyperglycemic medications, and prescribing specialties. in AR with SGLT2i/GLP-1.
Are patients receiving RA with SGLT2i/GLP-1?
The researchers found that among patients with DM2 and CVD, only 1.4% received SGLT2i and 1.6% received RA with GLP-1. These fractions were significantly lower than the proportion of patients prescribed insulin (60%), biguanides (20%), sulfonylureas (10%) or dipeptidyl peptidase-4 inhibitors (7%). The most common RAs of SGLT2i and GLP-1 were empagliflozin (52%) and liraglutide (66%), respectively. For these two drugs, the authors observed an increase in new prescriptions as the US Food and Drug Administration (FDA) expanded their drug labels to include an indication of cardiovascular risk reduction. Prescriptions for all other SGLT2i and GLP-1 RA agents did not increase significantly during the study period (January 2013 - June 2019). Interestingly, the same proportion of T2DM patients with CVD were prescribed RA with SGLT2i or GLP-1 compared to all T2DM patients. Most guidelines explicitly recommend these drugs for patients in the first high-risk subgroup, but provide less clear recommendations for use in the broader T2D population. Together, these results suggest that the vast majority of patients with T2DM and CVD do not receive optimal treatment to reduce the high risk of adverse CV outcomes.
As this study was limited to patients from a single institution, its findings may be of limited generalizability. For example, contrary to country demographics, the majority of patients in this registry were black (56%) and very few were Hispanic (0.2%) or Asian (0.4%). Of T2DM patients, 28% in this cohort were uninsured, compared to an estimated 10% nationally.15However, the overall results of this study are consistent with many previous studies, suggesting that less than 15% of patients in the US with T2DM and CVD receive RA with SGLT2i or GLP-1.16-18
Do cardiologists prescribe these cardioprotective therapies?
CVOTs showing unexpected CV benefits from using SGLT2i and GLP-1 RA have generated considerable buzz in the CV community, and cardiologists have finally been equipped with targeted tools to specifically improve CV outcomes in patients with T2DM and disease-prone CVD. At the same time, many prominent publications and most professional guidelines strongly encourage cardiologists to take a more active role in screening for T2DM and initiating evidence-based treatment.7,13,19However, the data suggest that cardiologists have so far played only a minor role in implementing RA therapies with SGLT2i and GLP-1. For example, a survey of cardiologists at Duke University found that over 80% had never prescribed any type of medication.20Vaduganathan et al. observed that in the Partners Healthcare system in Boston, cardiologists dispensed only 5% of RA prescriptions with SGLT2i and GLP-1.21,22Similarly, Hamid et al. found that cardiologists prescribed only 6% of the total dose of SGLT2i and 1% of GLP-1 AR in their academic hospitals.14In contrast, the highest proportion of prescriptions were written by primary care providers (45% for GLP-1 RA and 53% for SGLT2i), followed by endocrinologists (45% for GLP-1 RA and 30% for SGLT2i). Although cardiologists represent only a small proportion of prescribers, estimates suggest that a patient with T2DM and CVD is four times less likely to see an endocrinologist, and the risk of seeing a primary care physician is the same as that of a cardiologist in a given year .23Nationally, endocrinologists provide less than 15% of diabetes care.24These data suggest that cardiologists are well positioned to improve access to these cardioprotectors.
What are the main barriers to wider acceptance?
Most of the discussion in the literature about the reasons for slow RA use with SGLT2i and GLP-1, especially among cardiologists, is largely speculative. Some of the hypothetical barriers to drug acceptance include drug cost, lack of medical knowledge about drug classes, GLP-1 RA injection phobia, concern about crossing traditional specialty boundaries, and "clinical inertia" which delays the adoption of new therapies for chronic diseases. illness. Hamid et al. noted that because comparable priced DPP4i drugs were prescribed four times more often than GLP-1 or SGLT2i RA prescriptions, and because a quarter of SGLT2i and GLP-1 RA drug prescriptions were filled at uninsured patients, cost may not be the most important barrier to access. However, there are few rigorous quantitative analyzes or systematic ethnographies to identify key barriers.
Two recent surveys of how cardiologists approach these new therapies provide some insight. A 2019 UK survey of 103 consulting cardiologists found that only a minority of respondents felt familiar with outcome data for SGLT2i (30%) or GLP-1 RA (20%).25Only 11% felt they were better suited to treat diabetes in a hypothetical T2DM patient hospitalized with acute coronary syndrome, and only 5% would initiate guideline-recommended RA with SGLT2i or GLP-1 in this patient. Instead, most chose to see a diabetes specialist. The results of another survey of small suppliers support these conclusions. Yumin et al. interviewed 41 primary care providers, 17 endocrinologists, and 32 cardiologists at the Duke University Health System in North Carolina.20They found that while endocrinologists and primary care physicians cite cost and unapproved prior authorization as the main barriers to prescribing these drugs, cardiologists reported that the main barriers were lack of knowledge about the drugs, fear of confusing the diabetes treatment plan and feeling that prescribing "diabetes drugs" is not the cardiologist's responsibility. Taken together, these studies suggest that among cardiologists, the main obstacles to wider use of these therapies are lack of familiarity with these therapies and the perception that managing diabetes is beyond their capabilities.
Although recently well-designed CVOTs revealing the cardioprotective benefits of RA with SGLT2i and GLP-1 have provided a much-needed strategy to reduce the excessive risk of adverse cardiovascular events in T2DM patients, many studies, including the recently published results of Hamidet et al. al. who could benefit the most was slow.14,16,17It is disappointing that although the main benefit of these drugs is cardiovascular risk management, cardiologists still play a minor role in initiating drug prescriptions.14,21,22Among the many possible obstacles to wider use of these therapies by cardiologists, the main obstacles may be a lack of knowledge about these therapies and a belief that diabetes care is best left to other specialists.20,25Therefore, initiatives that directly address these factors can more effectively change clinical practice. These include newly published treatment pathways to simplify prescribing, physician and patient education programs such as the ACC program"Successful Management of Cardiovascular Risk in Diabetes" (SIM-CVRiD)and interdisciplinary and coordinated care models to reassess traditional boundaries between medical specialties.7,12,13,26Furthermore, the medical community would benefit from adapting language standards to refer to SGLT2i/GLP-1 AR not only as an antidiabetic drug, but as a cardiometabolic drug, particularly useful in reducing the risk of cardiovascular disease. Recent data demonstrating a dramatic reduction in the risk of heart failure as a result of SGLT2i, even among non-diabetic patients, further underscores the need to stop treating these medications simply as a treatment for diabetes. To better diagnose the remaining barriers to progress in this field, nationally representative studies characterizing SGLT2i/GLP-1 RA prescribing patterns, as well as broader studies of cardiologists' knowledge and attitudes toward these, are also needed. cardiometabolic drugs.
- Rawshani A, Rawshani A, Franzén S et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes.N Engl J Med2017;376:1407-18.
- Gregg EW, Li Y, Wang J et al. Changes in diabetes complications in the United States, 1990–2010.N Engl J Med2014;370:1514-23.
- Di Angelantonio E, Kaptoge S, Wormser D et al. Relationship between cardiometabolic multimorbidity and mortality.JAMA2015;314:52-60.
- Andary R, Fan W, Wong N.D. Control of cardiovascular risk factors in US adults with type 2 diabetes with and without cardiovascular disease.I am J.Cardiol2019;124:522-27.
- Gerstein HC, Miller ME, Genuth S et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes.N Engl J Med2011;364:818-28.
- Saeedi P, Petersohn I, Salpea P et al. Global and regional estimates and projections of diabetes prevalence from 2019 to 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.Diabetes Resurrection Clinic2019;157:107843.
- Das SR, Everett BM, Birtcher KK et al. 2020 expert consensus decision path on new therapies to reduce cardiovascular risk in patients with type 2 diabetes.J Am Coll Cardiol2020;76:1117-45.
- Kristensen SL, Rørth R, Jhund PS et al. Cardiovascular, mortality, and renal effects of GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of studies on cardiovascular outcomes.Lancet Diabetes Endocrinol2019;7:776-85.
- Zelniker TA, Wiviott SD, Raz I et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal complications in type 2 diabetes: a systematic review and meta-analysis of studies on cardiovascular outcomes.Lanceta2019;393:31-39.
- McMurray JJV, Solomon SD, Inzucchi SE et al. Dapagliflozin in patients with heart failure and reduced ejection fraction.N Engl J Med2019;381:1995-2008.
- Packer M, Anker SD, Butler J et al. Cardiovascular and renal effects associated with empagliflozin in heart failure.N Engl J Med2020;383:1413-24.
- American Diabetes Association. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2020.diabetes care2020;43:S111-s134.
- Cosentino F, Grant PJ, Aboyans V et al. ESC 2019 Guidelines on Diabetes, Pre-Diabetes and Cardiovascular Disease developed in partnership with EASD.Euro Heart J2020;41:255-323.
- Hamid A, Vaduganathan M, Oshunbade AA et al. Antihyperglycemic therapies with US Food and Drug Administration indication extension to reduce cardiovascular events: drug prescribing patterns at an academic medical center.J Cardiovasc Pharmacol2020;76:313-20.
- Stark Casagrande S, Cowie CC. Health insurance coverage among people with and without diabetes in the US adult population.diabetes care2012;35:2243-49.
- Arnold SV, Inzucchi SE, Tang F et al. Real-world application and modeled effects of hypoglycemic therapies evaluated in a recent cardiovascular outcomes study: NCDR® Research to Practice project.Eur J Prev Cardiol2017;24:1637-45.
- Arnold SV, de Lemos JA, Rosenson RS et al. Use guideline-recommended risk-reduction strategies for patients with diabetes and atherosclerotic cardiovascular disease.Circulation2019;140:618-20.
- Pantalone KM, Misra-Hebert AD, HobbsTM et al. Diabetes treatment regimens and use of skilled care among patients with type 2 diabetes and cardiovascular disease.Cardiovasc Diabetol2018;17:54.
- Nassif ME, Kosiborod M. Are we ready to call the cat? A plea to cardiologists to use hypoglycemic therapies that have been shown to improve cardiovascular outcomes.Circulation2018;138:4-6.
- Gao Y, Peterson E, Pagidipati N. Barriers to prescribing hypoglycemic therapies with cardiometabolic benefits.I am the heart of J2020;224:47-53.
- Vaduganathan M, Patel RB, Singh A et al. Prescribing glucagon-like peptide 1 receptor agonists by cardiologists.J Am Coll Cardiol2019;73:1596-98.
- Vaduganathan M, Sathiyakumar V, Singh A et al. SGLT2i prescriber standards following US Food and Drug Administration label extension.J Am Coll Cardiol2018;72:3370-72.
- Gunawan F, Nassif ME, Partridge C, Ahmad T, Kosiborod M, Inzucchi SE. Relative frequency of cardiology visits versus endocrine visits in patients with type 2 diabetes and cardiovascular disease in the US: implications for implementing evidence-based hypoglycemic drug use.Cardiovasc Endocrinol Metab2020;9:56-59.
- Vigersky RA, Fish L, Hogan P et al. Clinical endocrinology workers: current status and future projections of supply and demand.J Clin Endocrinol Metab2014;99:3112-21.
- Slater TA, Drozd M, Palin V et al. Prescription of antidiabetic drugs to reduce cardiovascular risk in hospitalized patients with acute coronary syndromes: a study of cardiologists' attitudes and practices.Farmakolog Eur Heart J Cardiovasc2020;6:194-96.
- Success in managing cardiovascular risk in the diabetes initiative (ACC.org). 2020. Available at:https://www.acc.org/CVRiD. Accessed on: 11/01/2020.
Clinical Topics: acute coronary syndromes,Cardiac Care Team,diabetes and cardiometabolic diseases,Heart failure and cardiomyopathies,Prevention,vascular Medicine,atherosclerotic disease (CAD/PAD),Acute heart failure
Key words: Diabetes,metabolic syndrome,Dipeptidyl peptidase IV inhibitors,cardiotonic agents,Type 2 diabetes,hypoglycemic agents,Glucagon-like peptide 1,Cardiovascular disease,Insulin,secondary prevention,biguanidia,do not have medical insurance,Doctors, primary health care,acute coronary syndrome,acute coronary syndrome,retrospective studies,pharmaceutical preparations,vulnerable populations,prior authorization,Glucose,Electronic Health Records,hospitalized patients,African-American,United States Food and Drug Administration,cardiac insufficiency,provision of health care,myocardial infarction,Risk factors,primary prevention,angina, unstable,Hospitalization,AVC,records,Risk mitigation behaviorperipheral vascular diseases,Hispanic-Americans,Insurance coverage,hospitals,Chronic disease,Chronic disease,Risk management,Risk management,revenues,Anthropology, Culture,phobic disorders,basic health care
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