Heart In Diabetes 2019:

Choosing Treatments: Optimizing Care in Patients with Diabetes and CVD

with Reddy Pallavy, MD, John J. Reusch, MD, and Gina Slobogin, DNP, APRN

With so much content packed into this three-day continuing medical education program, EndocrineWeb sought out three attendees who were willing to offer their "ah ha" moment, when prompted to share key clinical key takeaway messages gleaned from the sessions.

Need to Treat Renal Disease More Aggressively in Patients with Diabetes  

Until the FREEDOM trial,1 patients with chronic kidney disease were not included in diabetes-related research studies, Mandeep S. Sidhu, MD, MBA, FACC, FAHA, said in a presenting data on the influence of chronic kidney disease (CKD) on outcomes in patients with diabetes and coronary artery disease who require revascularization.

However, the incidence of three-year cumulative end stage renal disease is greater than death from cardiovascular disease,3 said Dr. Sidhu. 

Pallavy Reddy, MD, a clinical endocrinologist practicing in Dublin, Ohio.Dr. Reddy same away from the Heart in Diabetes meeting prepared to treat patients with diabetes more aggressively for chronic kidney disease. Photo: JR Godfrey

“So far, the data presented on high risk CKD patients was very compelling,” said Pallavy G. Reddy, MD, FACE, a clinical endocrinologist in private practice in Dublin, Ohio, in sharing her insights with EndocrineWeb, regarding a key clinical treatment strategy she is taking away from the sessions at the 3rd annual Heart in Diabetes conference in Philadelphia, Pennsylvania.

“Our patients don’t see chronic kidney disease coming, and we don’t adequately convey the urgency of their condition when it progresses—dialysis or death. Given the dire implications of this disease complication, I will change how I approach these patients in my practice going forward, relying on polypharmacy to treat them.”

“In fact, I will plan to stratify my patients at higher risk to more aggressively treat individuals with chronic kidney disease among those with diabetes and cardiovascular disease,” she said, “and I will tell them: ‘Your different.’ While they may be stable as far as their diabetes, they need to know they remain at much higher risk for both CVD events and kidney disease progression.”

What to recommend to patients? “These individuals live in a precarious position between type 2 diabetes, cardiovascular disease, and renal disease, and their care falls between the cardiologist and the nephrologist who do not typically speak to the patient’s endocrinologist or primary care physician,,” said Dr. Sidhu.

The recommendation to give patients on dialysis a moderate statin still holds, but it is important to recognize that as the patient's estimated glomerular filtration rate (eGFR) decreases, the efficacy of the statin will decline,2 he said.

Even with the results of four trials,4-7 we don’t have a definitive answer on continuing or withdrawing statin therapy because the protocol for each trial was slightly different.

Yet, a bigger randomized trial may not provide any clearer an answer, said Dr. Sidhu. One option for these patients may be a PCSK9 inhibitor,8 said Robert S. Rosenson, MD, professor of medicine (cardiology) and director of cardiometabolic Disorders at the Icahn School of Medicine at Mount Sinai in New York City, during the panel discussion.

Treatment to Yield Better Outcomes in Patients with Diabetes & CVD

“I’m attending this conference to gain a better sense of how to use the newer agents in the growing number of my patients who have diabetes,” John J. Reusch, MD, a cardiologist at Colorado Permanente Medical Group in Denver, Colorado tells EndocrineWeb.

Dr. Reusch finds the issue of treating high triglycerides of great interest in light of the findings from the JELIS and REDUCE-IT trials,9,10 which identified high triglycerides as a “red flag” for elevated residual risk even among individuals on statin therapy with an normalized LDL (< 70 mg/dL). In fact, TGs appear proinflammatory with prooxidative and prothrombotic activity due to production of remnants.11,12

While giving fibrates or niacin to a patient who is already on a strong statin has failed to demonstrate a reduction in cardiovascular events, the combination of a strong stain and a pure EPA (icosapent ethyl) or a PCSK9 inhibitor (ie, ezetimibe) both appear to result in fewer cardiovascular events 13 according to compelling evidence shared by Eliot A. Brinton, MD, president of the Utah Lipid Center in Salt Lake City.

With an estimated 26 million adults having borderline high triglycerides and another 30 million with triglycerides in the high range (200-499 mg/dL),14 “we’ve been very LDL-centric in our management approach, not even considering the effects of obesity, which has been fostered by a lack of data, so we have had no clinical impulse to treat beyond LDL," said Dr. Briton.

However, appreciating the independence of LDL-cholesterol and elevated triglycerides, both contributing to a predisposion of plaque, mounting evidence suggests the timing is right to shift our treatment paradigm,” he said.

While Dr. Reusch considers the data compelling enough to prescribe EPA product for secondary prevention in patients with elevated tricylcerides, and would like to consider giving a PSK9 inhibitor to appropriate patients who present with an LDL > 135 mg/dL, he said, “I am concerned about the cost since health insurers are not yet regularly or readily reimbursing for these therapeutic agents.”

“The other interesting new drug approach is the use sodium-glucose co-transporter-2 inhibitors (SGLT2i) instead of diuretics for patients with heart failure,” said Dr. Reusch.  

Could Troponin Be Used to Distinguish MI from Hypoglycemia in Type 2 Diabetes?

For Gina Slobogin, DNP, APRN, FNPL-BC, a nurse practitioner with Family Practice Associates in Wilmington, Delaware, the tracking of elevated troponin as a marker of hypoglycemia in patients with diabetes and coronary artery disease proved reaffirming.

“I come from a background as an ER nurse where we always checked troponin for myocardial infarction but we don’t have historical [trends] data so if a patient normally has a troponin of 13 mg/dL because of hypoglyemic episodes, knowing that in advance that this is normal for them rather than they are having a cardiac event, we won’t need to worry about keeping that patient for any kind of monitoring,” she told EndocrineWeb.

“Troponin is a marker of cardiac injury that is mostly used to detect an acute MI in emergency room patients. As troponin as said get more sensitive, we have been studying them as potential prognostic markers in patients with chronic, stable coronary artery disease, and some or maybe many studies have found that patients (not during an acute MI) with higher troponin have worse prognosis,” said Paulo Cury Rezende, MD, PhD, of the Heart Institute at the University of Sao Paulo Medical School in Sao Paulo, Brazil,15 in commenting to EndocrineWeb following his presentation at Heart in Diabetes 2019.

“In this clinical (outpatient) setting, in patients with chronic, stable coronary artery disease, we studied the association of hypoglycemia and troponin,” said Dr. Rezende since people who are taking insulin to manage their diabetes are at heightened risk for severe hypoglycemic events.15

“As such, finding an elevated troponin level in individuals with diabetes and coronary artery disease may act as a subclinical biomarker for hypoglycemia—a point reinforced by the premature halting of the ACCORD trial,” he said. The ACCORD trial was stopped because of higher cardiovascular event rates in patients treated more intensively (target HbA1c < 6.0%).16

Many researchers including me believe that hypoglycemia may be one of the most important reasons for this finding as the intensively treated subgroup had triple the hypoglycemic events as compared to the standard therapy group,” said Dr. Rezende. “However, the role of troponin levels in chronic coronary artery disease (CAD) patients as a therapeutic goal is not yet determined, and the variation/evolution of troponin during follow-up in this setting also has not be defined.”

“Although one can argue that patients with troponin higher than 14 would have higher CV risk, there are no known effective therapeutics that could be given to patients to result in lower levels,” he told EndocrineWeb.

Thus, troponin may act as a marker of subclinical myocardial damage, that in our work was also related to hypoglycemic events, but it remains to determine whether lowering it (if possible) would result in better cardiovascular outcomes.

Dr. Renzende offered two other takeaway messages:15

“The three indicators of cardiac damage are based on changes noted from electrocardiograms. In many diseases that cause cardiac damage, we may see imaging changes as well as elevated troponin levels that offer signs of myocardial infarction. The sum of these observations adds reliability to detect myocardial injury.”

“Lastly, the take home message for clinical practitioners is that avoiding hypoglycemia should be a goal for treating diabetic patients, especially if they have coronary artery disease, because these episodes might be associated with subclinical myocardial damage, represented by higher levels of troponin.”

Next Summary:
Need to Amplify Peripheral Artery Disease as a Risk of CVD in Diabetes
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