Towards optimising therapy in high-risk type 2 diabetes with the COORDINATE-Diabetes trial
Optimal medical therapy, as recommended in clinical guidelines, is underused in high-risk patients with type 2 diabetes and cardiovascular disease, heart failure and chronic kidney disease. The COORDINATE-Diabetes trial, which aims to close this prescription gap, was discussed by an expert panel at the recent American Diabetes Association’s 83rd Scientific Sessions. Dr Susan Aldridge reports.
COORDINATE-Diabetes is a randomised trial aiming to improve the care of people with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) who are attending cardiology clinics. Jennifer Green, Professor of Medicine at Duke Clinical Research Institute (the coordinating centre for the trial), set the scene. She noted that rates of many serious diabetes complications fell between 1990 and 2010, thanks to better control of blood pressure, glucose and lipids. However, the number of events has not decreased because there are so many more people with diabetes. “Even if we treat everyone to target, there remains a residual risk because diabetes, cardiovascular disease and kidney disease frequently coexist, and the presence of more than one substantially increases the risk of adverse outcomes,” she said. “This is not fully addressed by traditional risk-reduction strategies.”
The most recent ADA/EASD guidelines recommend the use of GLP-1 receptor agonists and/or SGLT-2 inhibitors with known cardiovascular benefit for people with type 2 diabetes with ASCVD, heart failure or chronic kidney disease (CKD). The COORDINATE-Diabetes team carried out some background work on 150,000 patients to see how far these guidelines were already being followed and how patients were being cared for in the community.
They found that 24.7% were on a high-intensity statin, 53.1% on an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and 9.9% were on an SGLT-2 inhibitor or GLP-1 receptor agonist. Only 2.7% were on all three classes of recommended medication, while 37.4% were on none of them. “These medications are substantially underused in clinical practice,” said Professor Green. “These patients had insurance and the statins, ACE inhibitors and ARBs are not new or expensive, and all of these medications have been shown to improve outcomes.”
She continued that the usual response is to say that there is a problem of access, but she does not believe this is the whole story. Data from Veterans Affairs centres shows that SGLT-2 inhibitors have been widely available there since shortly after the EMPA-REG trial results in 2015. If they can do this, then why is it not happening in the community and how can this be changed to improve outcomes for people with type 2 diabetes and ASCVD? These are the questions that COORDINATE-Diabetes set out to explore.
Setting up COORDINATE-Diabetes
The objective of COORDINATE-Diabetes was to test the impact of a clinic-level, multifaceted intervention on the prescription of the three key groups of evidence-based therapies (statins, ACE inhibitors/ARBs and SGLT-2 inhibitors/GLP-1 receptor agonists) in people with type 2 diabetes and ASCVD Unlike a conventional clinical trial, the focus was not upon efficacy, but on improving the quality of care that these patients received.
Dr Neha Pagidipati, Director of Duke Cardiometabolic Prevention Clinic, took to the stage to talk about the design and conduct of the trial. “An important part was the multidisciplinary and extremely engaged steering committee, which included diabetologists, primary care physicians, diabetes specialist nurses, pharmacists and cardiologists,” she said. “That was the key component and why the trial has worked so well.”
Forty-three cardiology clinics took part, all working with a local diabetes specialist, with 20 randomised to the intervention and 23 to usual care, following guidelines. The participants had type 2 diabetes and ASCVD, peripheral arterial disease and/or cerebrovascular disease. The primary outcome was prescription of all three key groups of medication during six to 12 months of follow-up. Secondary outcomes were prescription of agents in each medication group and clinical outcomes such as blood pressure, HbA1c and hospitalisation.
There were three components of the intervention. First, a team consisting of a nurse, cardiologist and endocrinologist visited each site to assess local practices and barriers to prescription of the key medications. Second, various strategies were put in place to encourage an increase in take-up of the medication, including patient and clinician education and development of pathways. And, finally, there was audit and feedback.
A successful outcome
Dr Christopher Granger of the Duke Clinical Research Institute presented the results of COORDINATE-Diabetes. “There is nothing more important in the health of our patients than to implement what we know is effective,” he said. The barriers to implementation uncovered by the trial were many: patient, provider and system factors, cost, inertia, lack of education, fragmented care and lack of ownership. Exploring these led to opportunities for alignment, leadership and engagement, while behaviour-change strategies included feedback, incentives, education and simple tools such as reminders.
The proportion receiving all three of the key medications actually improved in both groups to 37.9% in the intervention group and 14.5% in the usual care group. This represents a 23.4% absolute improvement when the researchers were aiming for 10%, said Dr Granger, so it’s a better-than-expected outcome.
There were also increases in statin, ACE/ARB and SGLT-2/GLP-1 prescriptions in both groups, with greater increases in the intervention group. The biggest shift was in the SGLT-2 inhibitors, with use increasing from 10.9% to 34.8% in the intervention group. There were no significant improvements in blood pressure, lipids or HbA1c, but that was not the intention of the study. “More importantly, we did see a tendency for improvement in clinical outcomes, including all-cause mortality or hospitalisation for myocardial infarction, stroke, decompensated heart failure or urgent revascularisation,” said Dr Granger. “This was a 21% risk reduction, which was non-significant but nonetheless in the range of what we’d expect, given the change in medication.”
He added that while the trial was not resource-intensive, it did need a ‘champion’ to ensure its success. The next step is to scale it up. He concluded: “As Bill Gates has said, ‘Humanity’s greatest advances lie not in its discoveries, but in how those discoveries are applied’ and we think that this project has provided some meaningful information on how we might be able to do that.”
The endocrinologist’s point of view
Ildiko Lingvay, Professor of Medicine and Endocrinology at the University of Texas Southwestern Medical Center, noted that the prescription gap is also very high for patients seen in endocrinology and primary care. She carried out a study of 11,000 people with type 2 diabetes and ASCVD, heart failure or CKD and looked at the proportion receiving prescriptions for SGLT-2 inhibitors or GLP-1 receptor agonists. For primary care, endocrinology, cardiology and nephrology, the figures were 20.1%, 24.8%, 20.3% and 18.3%, respectively. “So there is a 75% gap in how we, as endocrinologists, should be treating our patients,” she said.
However, the COORDINATE intervention can be applied to any specialty, particularly with the three-pronged approach targeting the patient, provider and system, where everyone involved is responsible for ensuring that best-care practices are followed. She strongly recommends team-based care where, if another specialist initiates the treatment, other specialties should help with titration, side-effects and encouraging others to initiate them. “The results of COORDINATE-Diabetes are absolutely fantastic, but we have a long way to go,” she said. “Our role is to make sure the uptake goes to 100%. Why care about COORDINATE-Diabetes? Because we all want our patients to get the right treatment for the best outcomes.”
Spreading the word
COORDINATE-Diabetes shines a light on the goals of care in cardiometabolic disease – prolong life, keep the patient out of hospital and improve their quality of life. “Absolutely, we have the tools to achieve this and we have never had more tools,” said Dr Mikhail Kosiborod, Executive Director of the Cardiometabolic Center Alliance (CMCA) at St Luke’s Mid America Heart Institute, who was chairing the panel. “Do the guidelines tell us what we should be doing? Yes. Every major professional society, including the ADA, has undergone substantial revisions and have all given the highest level of recommendations to these treatments.” Yet, at least according to a study of 5000 patients in the US from 2016 to 2018, less than 7% are actually receiving optimal medical therapy.
Cost and access are issues, of course, but studies show that making medicines cheap or even free only leads to a modest increase in adherence. There are numerous other barriers, including a lack of effective clinical care models with poor communications, inadequate patient support, lack of accountability, education gaps and misaligned incentives. “We now have proof of concept on what happens if you address these issues,” said Dr Kosiborod. “Addressing systemic barriers can improve prescription rates and address clinical inertia.”
COORDINATE-Diabetes was a good start but not a ‘silver bullet’ – 62% in the intervention group were still not on optimal therapy. However, there are many other initiatives underway on team-based comprehensive care. For instance, the CMCA has some new data on a type 2 diabetes/ASCVD ‘bundle’, consisting of optimal, guideline-directed medical therapy, which shows an increase in the proportion of patients receiving it from 28.2% to 67.1% in a six-month period. Similar data apply to patients with type 2 diabetes and CKD.
“The questions that remain are: is this sustainable, is it scalable to more and more centres around the country and will it have a lasting impact on care transformation?” said Dr Kosiborod. To address these questions needs changes in the system and among stakeholders, such as the pharmaceutical industry, patient and professional organisations.
He took inspiration from one example where rapid care transformation was actually achieved in the US. The D2B (door-to-balloon) Alliance dramatically reduced the waiting time for interventional radiology after myocardial infarction in five years.
So, in conclusion, cardiometabolic disease is a huge public health threat. Many tools exist to treat it and there has been a fundamental shift in management when it comes to optimising medical therapy. However, these disease-modifying therapies are underused in high-risk patients. A shift in focus to comprehensive risk reduction is needed, as set out in clinical guidelines, but implementation has been slow. “COORDINATE-Diabetes and the CMCA signal the start of care transformation,” said Dr Kosiborod, “and I certainly hope that we will see transformation in my lifetime like the one we have seen for myocardial infarction.”
For more information, go to coordinatediabetes.org.
To learn more, enrol on the EASD e-Learning course ‘GLP-1 receptor agonists’.
Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.