Top News in Heart Failure: 2018
ARNIs for acute decompensated HF, MitraClip trials, an amyloidosis drug, and studies investigating diabetes meds and the heart made this year’s list.
Heart failure (HF) therapies had a banner year in 2018, with trials both positive and negative that kept this growing population of patients top-of-mind for cardiologists across the field.
According to José Ramón González-Juanatey, MD, PhD (Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain), two topics dominated the heart failure space in 2018. On the pharmaceutical side there was PIONEER-HF showing that treating acute decompensated heart failure patients with an angiotensin receptor/neprilysin inhibitor (ARNI) combining sacubitril and valsartan (Entresto; Novartis) significantly reduced N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and serious clinical events, driven by a 44% reduction in HF rehospitalizations.
“In the current guideline recommendations, you can start with sacubitril/valsartan in the chronic stable phase in patients already treated with an ACE inhibitor or an ARB, but the PIONEER-HF trial demonstrated the safety of using sacubitril/valsartan for hospital discharge,” González-Juanatey told TCTMD. “I think this new information may be useful for improving the optimal treatment of patients with patients with HF and reduced ejection fraction,” he continued. “This is, for me, one of the major news this year in the drug treatment of heart failure.”
Clyde Yancy, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), who spoke with TCTMD for an upcoming episode of On Record agreed, noting that while the primary endpoint in PIONEER-HF was a biomarker change, the “harder” secondary endpoints “were statistically significant in a surprising strong way.” The results suggest that the use of an ARNI during hospitalization for acute decompensated heart failure could be “critically important,” Yancy said, potentially changing the natural history of this disease, “changing the readmission experience, and changing the progression to a more advanced disease.”
Yancy and González-Juanatey also highlighted the MitraClip (Abbott) trials: MITRA-FR and COAPT. “Earlier this year was presented the French clinical trial with the MitraClip in patients with mitral regurgitation (MR) with heart failure, and in this trial the clip failed to achieve any clinical improvement in the prognosis of patients,” González-Juanatey summarized. “But later in the year, COAPT, an American trial, was presented and published that demonstrated an impressive improvement in the survival and complications for patients with HF and severe MR.” Experts considering a patient for a MitraClip need to carefully consider the differences in patient mix between these two trials, he continued, since the different outcomes can likely be explained by the disease characteristics of the two study populations.
“I'd like to see another trial—another positive trial—for helping us with more accurate selection of the patient population that improves with MitraClip,” González-Juanatey said. “This is a critical issue: who is the patient who would benefit most from this costly and risky procedure?”
Other HF Trials Make a Splash
Yancy highlighted a number of other important drug trials, among them TRED-HF and ATTR-ACT. The TRED-HF trial showed that, in patients with dilated cardiomyopathy (DCM) who have had their symptoms and heart function resolve on medication, withdrawal of their heart failure meds is likely to lead to a return of their disease. ATTR-ACT looked at a tafamidis (Vyndaqel; Pfizer) in patients with transthyretin amyloid cardiomyopathy and found that the agent significantly reduced the risk of all-cause mortality compared with placebo. The drug is still investigational, not yet available for clinical use but available under compassionate use, and is moving through the regulatory hurdles, Yancy noted. “This is great news—it’s new science for an important disease that is probably is more important than we appreciate.”
Others who spoke with TCTMD for our Year in Review agreed. “This is a really big deal, Mintu Turakhia, MD (Stanford University and VA Palo Alto Health Care System), observed. “This is actually one of the biggest studies of 2018, period, for the heart.”
Both Yancy and González-Juanatey pointed beyond heart failure treatments to highlight the diabetes drug trials presented or published over the last few months that have cemented a role for certain meds in reducing the risk of developing heart failure and cardiovascular disease in patients with diabetes. These include CV outcomes studies for the sodium-glucose co-transporter 2 (SGLT2) inhibitors—DECLARE, CANVAS, and EMPA-HEART—as well as the glucagon-like peptide 1 (GLP-1) receptor agonists, with 2018 results for HARMONY-OUTCOMES and PIONEER-6,
“I think this year is the year of diabetes in cardiology,” González-Juanatey told TCTMD. “The most important message for the cardiology community is that we need to think more about our diabetic patients. . . . These new clinical trials definitively demonstrate that two classes of drugs, the SGLT2 inhibitors and the GLP-1 receptor agonists improve—a lot—the prognosis of patients with diabetes and ischemic heart disease.”
Click here for more from TCTMD’s 2018 Year in Review.