Log in to MyACC
Journal Wrap
The hottest research from various peer-reviewed journals – handpicked weekly by the ACC.org Editorial Board led by Kim Eagle, MD, MACC.
Greater NT-proBNP With Sacubitril-Valsartan Vs. Enalapril in HFrEF Patients
In patients with heart failure with reduced ejection fraction (HFrEF) hospitalized for acute decompensated HF, sacubitril-valsartan therapy led to a greater reduction in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration than enalapril therapy, according to research presented at AHA 2018 and simultaneously published in the New England Journal of Medicine.
HFrEF patients hospitalized for acute decompensated HF at 129 sites in the U.S. were enrolled and randomly assigned to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the NT-proBNP concentration from baseline. Read More >>>
A total of 881 patients were included with 400 randomly assigned to receive sacubitril-valsartan and 441 randomly assigned to receive enalapril. At randomization, the median systolic blood pressure was 118 mm Hg (interquartile range, 110 to 132), and 23.4 percent of patients had a systolic blood pressure <110 mm Hg. At screening, the median NT-proBNP concentration was 4,812 pg/mL (interquartile range, 3,050 to 8,745) and the median BNP concentration was 1,063 pg/mL (interquartile range, 718 to 1,743).
With the exclusion of discontinuation owing to death, the trial drug was discontinued prematurely in 87 patients (19.6 percent) in the sacubitril-valsartan group and in 90 patients (20.3 percent) in the enalapril group. By the week eight visit, 243 patients (55.2 percent) in the sacubitril-valsartan group and 268 (60.8 percent) in the enalapril group were receiving the target dose of the assigned trial drug.
The NT-proBNP concentration decreased in both treatment groups. The time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group. The greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as week one of the trial. The rates of worsening renal function, hyperkalemia and symptomatic hypotension did not differ significantly between the sacubitril-valsartan group and the enalapril group.
According to the authors, these results expand the evidence base regarding the use of sacubitril-valsartan to populations for which there had been limited or no data, including patients hospitalized for acute decompensated HF, patients with new HF, patients not exposed to high doses of guideline-directed medications for HF, and patients not receiving conventional renin-angiotensin system inhibitors.
Velazquez EJ, Morrow DA, DeVore AD, et al. N Engl J Med 2018;Nov 11:[Epub ahead of print].
REGROUP: Open vs. Endoscopic Vein-Graft Harvesting?
While no significant difference in overall risk of major adverse cardiac events (MACE) was observed in patients undergoing CABG with either open or endoscopic vein-graft harvesting, a trend towards lower rates of individual cardiac events using endoscopic-harvesting was observed in REGROUP. The study findings were presented at AHA 2018 and simultaneously published in the New England Journal of Medicine.
A total of 1,150 patients undergoing CABG at 16 Veterans Affairs cardiac surgery centers were randomized to either open or endoscopic vein-graft harvesting performed by operators with documented experience. Groups were balanced in terms of age, sex, smoking status, race or ethnicity, body mass index and coexisting conditions. Of note, 95.5 percent of total patients were male. The primary outcome was a composite of MACE. Researchers led by Marco A. Zenati, MD, also evaluated leg-wound complications. Median follow-up was 2.78 years. Read More >>>
Overall, the primary outcome occurred in 89 patients (15.5 percent) in the open-harvest group compared with 80 patients (13.9 percent) in the endoscopic-harvest group. Broken down by event, however, researchers noted a trend toward lower rates of MACE in the endoscopic-harvest group.
Specifically, a total of 46 patients (8.0 percent) in the open-harvest group and 37 patients (6.4 percent) in the endoscopic-harvest group died. Other events in the open-harvest and endoscopic-harvest groups, respectively, were: myocardial infarction in 34 patients (5.9 percent) and 27 patients (4.7 percent); revascularization in 35 patients (6.1 percent) and 31 patients (5.4 percent). Leg wound infections were higher in the open-harvest group (18 patients/3.1 percent) compared with the endoscopic-harvest group (8 patients/1.4 percent).
Zenati and colleagues noted that better harvest-site healing was observed in the endoscopic-harvesting group compared with the open-harvest group – a finding consistent with previous studies. They also suggest that longer-term follow-up will be necessary to explore whether observed trends are persistent. Additionally, they highlight the need for further studies "to establish standards for harvester expertise to ensure the safety of patients and effectiveness of the procedure."
Zenati MA, Bhatt DL, Bakaeen FG, et al. N Engl J Med 2018;Nov 11:[Epub ahead of print].
ODYSSEY OUTCOMES: Growing Evidence Suggests Benefit of PCSK9 in Highest-Risk Patients
The risk of recurrent ischemic cardiovascular events was lower in patients on high-intensity statin therapy who received alirocumab following an acute coronary syndrome than those who received placebo, based on findings from ODYSSEY OUTCOMES published Nov. 7 in the New England Journal of Medicine.
The large multicenter trial involved 18,924 patients who had experienced an acute coronary syndrome within the previous one to 12 months; had an LDL-C level >70 mg/dL; non-HDL-C level ≥100 mg/dL; and were on high-intensity statin therapy. Researchers randomly assigned patients to receive alirocumab (70 mg) subcutaneously or matching placebo every two weeks. Alirocumab dosing was adjusted under blinded conditions to target an LDL-C level of 25-50 mg/dL. Median follow-up was 2.8 years. The primary endpoint was a composite of death from coronary heart disease, nonfatal myocardial infarction (MI), ischemic stroke or unstable angina requiring hospitalization. Read More >>>
Results found the primary endpoint occurred in 9.5 percent (n=903) of the alirocumab group compared with 11.1 percent (n=1,052) of the placebo group. Researchers noted that 3.5 percent of patients in the alirocumab group died compared with 4.1 percent in the placebo group.
They also observed that patients with a baseline LDL-C level of ≥100 mg/dL had the greatest benefits from alirocumab with respect to the primary endpoint.
In terms of safety, the incidence of adverse events and of laboratory abnormalities was similar across both groups, with the exception of local injection-site reactions, which occurred more frequently in the alirocumab group (3.8 vs. 2.1 percent in placebo group).
ODYSSEY OUTCOMES joins FOURIER and SPIRE in adding to the growing body of research evaluating PCSK9 inhibitors in reducing vascular events. Compared with the other two trials, ODYSSEY OUTCOMES had a longer duration of follow-up that allowed for assessment of efficacy and safety.
It also addressed high-risk patients who had a previous acute coronary syndrome. ODYSSEY OUTCOMES researchers said the infrequent use of ezetimibe was a limitation of all three trials and that additional research is warranted.
Schwartz GG, Steg PG, Szarek M, et al. N Engl J Med 2018;Nov 7:[Epub ahead of print].
Moderate Benefit on MACE Seen With SGLT-2 Inhibitors
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have moderate benefits on atherosclerotic major adverse cardiovascular events (MACE) that seem confined to patients with established atherosclerotic cardiovascular disease (ASCVD), according to a study presented at AHA 2018 and simultaneously published in the Lancet. However, they have robust benefits on reducing hospitalization for heart failure and progression of renal disease regardless of existing ASCVD or a history of heart failure.
Researchers performed a systematic review and meta-analysis of randomized, placebo-controlled, cardiovascular outcome trials of SGLT-2i in patients with type 2 diabetes. Efficacy outcomes included MACE (myocardial infarction, stroke or cardiovascular death), the composite of cardiovascular death or hospitalization for heart failure, and progression of renal disease. Read More >>>
A total of three trials and six secondary analyses from the same trials were included, with data from a total of 34,322 patients. A total of 20,650 (60.2 percent) patients were known to have ASCVD and 13,672 (39.8 percent) had multiple risk factors but without known ASCVD. MACE occurred in 3,342 (9.7 percent) patients, of which most occurred in the group with established ASCVD (2,588 patients/77.4 percent).
Overall, SGLT-2i reduced the risk of MACE by 11 percent, but this was restricted to a 14 percent reduction in patients with ASCVD. No treatment effect was found in patients with multiple risk factors. Overall, SGLT-2i significantly reduced the risk for the composite of cardiovascular death or hospitalization for heart failure by 23 percent and hospitalization for heart failure by 31 percent. SGLT-2i significantly reduced the risk for all-cause death by 15 percent overall. SGLT-2i were also renoprotective and reduced the composite of worsening of renal function, end-stage renal disease or renal death by 45 percent.
"These data suggest that SGLT-2i should be considered in patients with type 2 diabetes regardless of presence of atherosclerotic cardiovascular disease or history of heart failure, given that they safely reduce HbA1c and reduce the risk of hospitalization for heart failure and progression of renal disease broadly across the spectrum of these patients," the authors write.
Zelniker TA, Wiviott SD, Raz I, et al. Lancet 2018;Nov 10:[Epub ahead of print].
DTU Pilot Study First to Assess Safety, Feasibility of Delayed Reperfusion After LV Unloading
Does delaying reperfusion by 30 minutes following left ventricular (LV) unloading impact safety and feasibility compared with LV unloading followed by immediate reperfusion? Findings from the Door-to-Unload (DTU) pilot study presented at AHA 2018 and published in Circulation suggest the answer may be no on both counts.
Navin A. Kapur, MD, FACC, et al., randomized 50 patients to either LV unloading plus immediate reperfusion (U-IR) or LV unloading plus a 30-minute delay before reperfusion (U-DR). The primary safety outcome was no difference in the composite of major adverse cardiovascular and cerebrovascular events including cardiovascular mortality, reinfarction, stroke and major vascular events at 30 days between groups. Additionally, researchers also looked at differences in infarct size normalized as a percent of total LV mass at 30 days between the two groups.
Overall results found no increase in the primary safety outcome between the two groups. Additionally, LV unloading first then delaying reperfusion for 30 minutes did not increase infarct size, researchers said. They also noted that "among patients with sum STE >6 mm, infarct size normalized to the area at risk was significantly lower with 30 minutes of LV unloading before reperfusion" compared with U-IR.
Based on the pilot findings, Kapur and colleagues said there are no "prohibitive safety signals" that would preclude moving forward with a larger study of LV U-DR.
Kapur NK, Alkhouli M, DeMartini T, et al. Circulation 2018;Nov 11:[Epub ahead of print].
Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Cardiovascular Care Team, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, ACS and Cardiac Biomarkers, Anticoagulation Management and ACS, Nonstatins, Novel Agents, Statins, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Smoking
Keywords: ACC Publications, Cardiology Magazine, Acute Coronary Syndrome, Aminobutyrates, Angina, Unstable, Antibodies, Monoclonal, Blood Pressure, Body Mass Index, Brain Ischemia, Coronary Disease, Diabetes Mellitus, Type 2, Enalapril, Follow-Up Studies, Heart Failure, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperkalemia, Hypotension, Incidence, Myocardial Infarction, Natriuretic Peptide, Brain, Peptide Fragments, Pilot Projects, Random Allocation, Renin-Angiotensin System, Risk Factors, Smoking, Stroke, Stroke Volume, Tetrazoles, Veterans, Wound Infection
< Back to Listings
