Hot Line 8: RED-CVD, NITRATE-CIN, DICTATE-AHF and PUSH-AF
28 Aug 2023
With trials on proactive screening, prevention of contrast-induced nephropathy (CIN) and new approaches to diuresis in acute heart failure (HF), Hot Line 8 provided plenty of clinical ‘food for thought’.
Doctor Amy Groenewegen (University Medical Center Utrecht - Utrecht, The Netherlands) kicked off the session with results from RED-CVD, a cluster randomised, pragmatic trial examining the ability of a stepwise diagnostic strategy to identify coronary artery disease (CAD), atrial fibrillation (AF) and HF in 1,216 patients with type 2 diabetes (T2DM) or chronic obstructive pulmonary disease (COPD). Conducted in The Netherlands, 25 primary care practices were randomised to the intervention or a usual-care control arm. The intervention involved a questionnaire on risk factors and symptoms prior to a routine visit, then if needed, a nurse-led physical examination focused on signs of HF, 12-lead ECG and NT-proBNP measurements, and a cardiologist referral or echocardiography if deemed necessary by the GP. In total, 8.0% of patients in the intervention group and 3.2% in the control group were newly diagnosed with at least one of HF, AF or CAD (adjusted odds ratio [OR] 2.83; 95% CI 1.62 to 4.95), most commonly HF (4.5% versus 1.5%), followed by CAD (2.6% versus 1.4%) and AF (2.1% versus 1.0%). Dr. Groenewegen concludes, “Because there are so many adults in the community with COPD or T2DM, this approach could translate into tens of thousands of new diagnoses when applied at large.”
Next, Doctor Dan Jones (Barts Health NHS Trust - London, UK) described the NITRATE-CIN trial, which investigated once-daily inorganic (potassium) nitrate versus placebo (potassium chloride) for the prevention of CIN in 640 patients with non-ST elevation acute coronary syndrome referred for invasive coronary angiography and at risk of CIN. The primary endpoint – CIN using Kidney Disease Improving Global Outcomes (KDIGO) criteria – was significantly reduced with inorganic nitrate treatment (9.1% versus 30.5%; p<0.001). Secondary outcomes were also improved, with lower rates of procedural myocardial infarction (2.7% versus 12.5%; p=0.003), improved 3-month renal function (between-group change in eGFR 5.17; IQR 3.94–7.39) and reduced 1-year major adverse cardiac events (9.1% versus 18.1%; p=0.001) versus placebo. Dr. Jones comments, “These findings could have important implications for health systems by reducing the burden of CIN and the associated prolonged admissions, dialysis and significant costs. Further studies powered for adverse cardiac events are needed to confirm these findings.”
As discussed by Professor Zachary Cox (Lipscomb University College of Pharmacy - Nashville, USA), the DICTATE-AHF trial examined the efficacy and safety of dapagliflozin initiated within 24 hours of hospital presentation in 240 patients with hypervolaemic acute decompensated HF. The primary outcome was diuretic efficiency expressed as the cumulative change in weight per cumulative loop diuretic dose (IV and oral) to day 5 or discharge, if sooner. After adjusting for baseline weight, the OR for diuretic efficiency with dapagliflozin versus structured usual care was 0.65 (95% CI 0.41 to 1.01; p=0.06). The secondary endpoints of in-hospital worsening HF and 30-day readmission for HF or diabetes-related reasons did not differ between the groups, and there was no difference in the incidence of adverse events. For exploratory endpoints, dapagliflozin significantly increased both 24-hour natriuresis (p=0.025) and 24-hour urine output (p=0.005) and decreased both time to completing IV diuretic therapy (p=0.006) and time to hospital discharge (p=0.007). “Although our study did not show statistical significance for its primary endpoint,” explains Prof. Cox, “the totality of data supports the early initiation of dapagliflozin to facilitate decongestion while rapidly and safely optimising guideline-directed medical therapy.”
The last presentation was by Doctor Jozine ter Maaten (University Medical Centre Groningen - Groningen, The Netherlands). She notes, “The PUSH-AHF trial provides the first randomised evidence supporting the natriuresis-guided treatment approach advised in the ESC HF guidelines.” In total, 310 patients presenting with acute HF requiring IV loop diuretics were randomised to natriuresis-guided diuretic therapy or standard care using electronic health records. In the natriuresis-guided group, spot urinary sodium was determined at various intervals after starting IV loop diuretics and was intensified using a prespecified stepwise approach if spot urinary sodium was <70 mmol and/or diuresis <150 mL/hour. Natriuresis during the first 24 hours was significantly higher in the natriuresis-guided versus standard-care group (p=0.0061). However, the combined endpoint of all-cause mortality or first HF rehospitalisation at 180 days occurred in a similar proportion (31%) in both groups (p=0.6980). Dr. ter Maaten concludes, “Although 180-day clinical outcome was not affected in this relatively small sample size, the strategy was safe and did not result in significant renal or electrolyte perturbations compared with standard of care. Clinicians should consider natriuresis-guided diuretic therapy as a first step to a personalised treatment approach in patients with acute HF to improve decongestion.”