Two new drugs

Two new drugs have arrived to challenge our prescription pad or electronic record, depending on which you use. Empagliflozin (Jardiance), a drug used to modify glucose metabolism in type 2 diabetes in patients with preexisting cardiovascular disease, demonstrated a decrease in cardiovascular mortality. The other drug, Entresto, appears to provide an added benefit in heart failure therapy and was compared with a standard ACE inhibitor.

The results of EMPA-REG OUTCOME, reported at the European Association for the Study of Diabetes meeting in Stockholm, showed empagliflozin to be the first drug to decrease the mortality and morbidity of cardiovascular disease in diabetes. It is one of a group of new sodium-glucose cotransporter 2 (SGLT-2) blockers being tested in type 2 diabetes with established cardiovascular disease. Patients were randomized to placebo or empagliflozin while receiving standard medical and cardiovascular medications. After 3 years of follow-up, patients receiving the drug experienced a lower cardiovascular mortality rate, compared with placebo patients (3.7% vs. 5.9%, a 38% reduction) in addition to a decrease in hospitalization for heart failure and death from any cause. No effect was observed on the incidence of myocardial infarction or stroke. In addition, the drug also lowered blood glucose and blood pressure and led to some significant weight loss. The drug also was shown to decrease vascular resistance and albuminuria (N Engl J Med. 2015. 373:2117-2).

Dr. Sidney Goldstein

Furthermore, an analysis of EMPA-REG OUTCOME presented in November at the American Society of Nephrology meeting in San Diego, showed a profound benefit on the new onset and progression of chronic renal disease in diabetes patients. The importance of these results needs emphasis. Up until recently, the Food and Drug Administration has given a pass to diabetes drugs in regard to cardiovascular endpoints; approval has been based on their primary effect on lowering blood glucose. Some drugs in the past, such as rosiglitazone, actually have shown an increase in mortality in some diabetes patients. At long last, FDA approval for diabetes drugs hinges on acceptable outcomes in cardiovascular endpoints. The addition of a drug that can actually affect cardiovascular mortality and morbidity, the major risk factor of diabetes, provides an important addition to therapy.

The other drug that provides a choice of drugs for the treatment of heart failure is Entresto, a combination of sacubitril, a neprilysin inhibitor, and the angiotensin receptor inhibitor valsartan, approved in July 2015. In PARADIGM-HF, the compound was compared to enalapril in the treatment of patients with class II, III, and IV heart failure who were also receiving beta-blockers. Entresto-treated patients reported a 21.8% incidence of the primary outcome measure, cardiovascular death and hospitalization for heart failure, compared with the enalapril alone incidence of 26.5% (P less than .001) (N Engl J Med. 2014;371:993-1004). Investigators initially excluded 11.4% of the recruited patients from the study who could not tolerate Entresto or enalapril therapy. The drugs were well tolerated without any adverse reactions during therapy. Entresto was more effective than enalapril in regards to the occurrence of heart failure and death from any cause over a 27-month average follow-up.

The observations in this study emphasize how much the mortality of heart failure has decreased over the last decade. Cardiovascular deaths have decreased to roughly 7% per year and rehospitalization occurs in about 8% in the first year. Both drugs provide an important incremental benefit in heart failure patients.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.