Managing CV Disease Risk in Diabetes
ACC Heart House Roundtable: June 20th, 2017
Laura Ross, PA-C - APAC Board of Directors
The American College of Cardiology invited APAC to participate in this roundtable to join experts from cardiology, endocrinology, and prevention to discuss recent trials with exciting results. We now have several new medications that significantly decrease cardiovascular risk with drugs traditionally used just to treat diabetes.
Historically, lowering the glucose with diabetic medications has not been enough to decrease cardiovascular risk, and certainly not as much as lipid and blood pressure management. We have seen that although drugs such as insulin are effective for glucose lowering, the results of the ORIGIN trial failed to demonstrate any CV benefit 2. In fact, many diabetic medications increase the risk of adverse cardiac events such as heart failure (Saxagliptin and rosiglitazone). Metformin has been the only medication until recently that showed evidence of CV benefit seen in the UKPDS study 3, which showed there was a 30% lower risk for macrovascular disease. We discussed recent studies and new FDA indications that show that there are new opportunities to add medications that not only treat diabetes and are safe for our cardiology patients, but they also have been shown to significantly decrease adverse cardiovascular events. 1
Sodium-Glucose Cotransporter 2 Inhibitor - Inhibiting SGLT2, which is responsible for 90% of glucose reabsorption, leads to glycosuria and sodium loss. This promotes diuresis, blood pressure lowering, and weight loss.
EMPA-REG OUTCOME -7,020 patients with diabetes II (HbA1C 7%-10%) and CV disease treated with Empagliflozin (Jardiance) for 3.1 years. Endpoints included CV mortality, nonfatal MI, and nonfatal stroke. Minor difference in HgbA1C, -0.4% with treatement. 4
- Empagliflozin produced a 38% risk reduction in cardiovascular mortality, 35% decrease in CHF hospitalization, and a 32% risk reduction in all-cause mortality compared with placebo, all of whom were already being treated with statins, angiotensin-converting inhibitors, and aspirin. Survival curves separated by 3 months and persisted over 3 years. It was investigator reported heart failure.
- The FDA granted an indication in 2016 for Empagliflozin to reduce the risk for CV death for patients with DM II and CV disease.
- Other benefits – Improved renal perfusion, reduction in worsening nephropathy, and increased hemoglobin
- Possible side effects –Absolute 4.6% increase in genital infections, more often in women. These resolved with a course of antifungal agents, and once treated did not typically come back. No increase in hypoglycemia or ketoacidosis for patients with type II diabetes. Low risk of hypoglycemia as the effect is proportional to glucose levels, except if using Insulin or Sulfonylureas.
- Use in primary prevention is currently in trials.
GLP-1 (glucagon-like peptide-1) receptor agonists glucose-dependent increase in insulin secretion and inhibition of glucagon secretion. Reduced CV death and/or major adverse CV events, lowers blood pressure and weight, but did not decrease heart failure risks.
- This class may have atherothrombotic effects seen 12-18 months later vs. hemodynamic effects seen after a few months with empagliflozin
- Side effects: Most common is transient nausea. Low risk of hypoglycemia unless combined with insulin or sulfonylureas. Excess of retinopathy events, although small number of events.
LEADER (2) –Liraglutide is a once-daily injectable medication. 9,340 patients with HbA1C of >7.0% (>50 yo with CV disease, or >60 yo with 1 or more CV risk factor) enrolled for 3.8 years. The primary endpoint of major adverse cardiac events (MACE)was reduced by 13%. There was a greater benefit for secondary prevention. There was a reduction in new-onset macroalbuminuria, but not on other renal endpoints or CHF. HbgA1C decreased 0.4%.5
SUSTAIN (3) - Semaglutide is a once-weekly injectable medication. 3,297 patients with HbA1C >7% followed for 2.1 years. Treatment reduced the primary endpoint of MACE by 2.3% over 2 years. CV mortality was not affected, but nonfatal stroke was improved. 6
How does this affect my practice as a cardiology PA?
- Cardiology clinicians should consider measuring the hemoglobinA1C in all patients with cardiovascular disease, similar to how our colleagues in endocrinology have checked lipids and blood pressure.
- Consider prescribing Empagliflozin to patients with cardiovascular disease and type 2 diabetes who are not on Insulin or sulfonylureas. Safe to add to Metformin. Could also consider sending recommendations to primary care. Monitor for side effects such as genital infections.
- Be aware of the diabetes drugs that have been associated with adverse CV outcomes. Sulfonylureas (such as glipizide and increased CV mortality), Thiazolidinediones (such as Rosiglitazone and increased CHF), DPP-4 inhibitors (higher risk for CHF with saxagliptin and alogliptin)1.
- Raise awareness for our patients and colleagues! Tthere are new indications for starting medications for diabetes that lower CV risk, and also happen to mildly lower the hemoglobinA1C for patients with type 2 diabetes and established cardiovascular disease.
- Sattar, N, Petrie M, Zinman B, et al. Novel Diabetes Drugs and the cardiovascular specialist. J Am Coll Cardiol 2017;69:2646-56.
- ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J med 2012;367:319-28
- UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes. Lancet 1998;352:854-65
- Zinman B, Wanner C, Lachin JM, et al., EMPA-REG OUTCOME Investigators. N Engl J Med 2015;373:2117-28.
- Marso SP, Daniels GH, Brown-Franden K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311-22.
- Marso SP, Bain SC, Consoli A, et al.,SUSTAIN-6. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375:1834-44.