DyeVert Systems for reducing the risk of acute kidney injury in coronary and peripheral angiography

4.1 There is consistent evidence that DyeVert Systems can reduce contrast volume received by the patient by up to 40%. Clinical experts said that using DyeVert Systems can maintain the pressure of the injection needed to preserve image quality, while reducing the overall amount of contrast given. The committee acknowledged national and international guidance that says that increasing volume of contrast agent is a risk factor for acute kidney injury (AKI), including NICE's guideline on acute kidney injury. Clinical experts said that contrast volume is a modifiable parameter that could help to reduce AKI risk. They said that accepted practice is to minimise the amount of contrast given, especially for patients with an estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73 m² who need complex procedures that are likely to need larger volumes of contrast. However, clinical experts also explained that the cause of AKI is multifactorial and complex. Although contrast media is 1 risk factor for AKI, it can be difficult to identify its direct cause (or causes), given other confounding factors such as comorbidities (which are often significant in people having angiography) and procedural complexities. As a result, it was uncertain whether reducing the contrast dye received using DyeVert Systems would directly lead to reduced incidence of AKI. The committee felt that the strength of evidence on AKI incidence reduction after using DyeVert Systems was not convincing enough to address these concerns, and it could not be confident in the results of the meta-analyses (for more about the meta-analyses results, see section 4.4).

4.2 The evidence presented on peripheral angiography included 9 people in 2 studies. Clinical experts explained that it was unlikely that the evidence for coronary angiography was transferable to peripheral angiography procedures. Types of peripheral angiography procedure vary. Different volumes of contrast dye and different injection pressures are needed, making comparisons with coronary angiography difficult. Clinical experts also explained that peripheral angiography can be done without using contrast media, for example when used for diagnosis.

4.3 The evidence presented on the Power XT version of the DyeVert System included 2 studies on 35 people and was based on an older model of the system. The company said that the PLUS EZ and Power XT versions work in a similar way, with both devices responding to pressure going through the valve. Clinical experts thought that the power injector was more likely to be used in peripheral angiographies, especially when large volumes of contrast dye are needed to be given quickly. The committee was uncertain if the evidence on the PLUS EZ device was generalisable to the Power XT device. It felt that more evidence was needed before the devices could be considered comparable.

4.4 The company submitted meta-analyses for several parameters, which the EAC said were statistically valid. However, some of the analyses, such as a reduced risk of AKI because of DyeVert Systems use, mainly used data from abstracts and posters. The committee was concerned that it was difficult to assess the methodological quality of some studies, making it difficult to quantify the size and direction of bias in the meta-analysis. This made the reliability of the outcome measures uncertain.

4.5 Most of the clinical evidence was limited by only having data during the procedure. If AKI incidence was reported, not all may have been identified because the studies were retrospective. Clinical experts said that most AKI events happen 4 to 5 days after the contrast exposure, and sometimes as late as 7 to 10 days afterwards. Incidence of AKI may be difficult to track because serum creatinine measurements may not be done routinely and there may not be consistent post-procedure renal monitoring. Overall, the committee felt that more long-term evidence on AKI incidence was needed.

4.6 Because the clinical evidence was limited by the follow-up evidence, the committee thought that further data collection was needed to capture secondary end points. This includes the need for temporary or end-stage dialysis and hospital stay.

4.7 The clinical experts said that people with chronic kidney disease (CKD) stage 4 and over (eGFR less than 30 ml/min/1.73 m²) would most benefit from DyeVert Systems and are likely to be the target population in clinical practice. The committee acknowledged that there are several factors that could increase the risk of developing AKI after procedures that use iodine-based contrast media. Evidence presented on DyeVert Systems was in people with CKD stages 2 and 3 (eGFR 30 ml/min/1.73 m² to 89 ml/min/1.73 m²), so the evidence on people with CKD stage 4 and over was limited. The company said that the population included in the studies had additional comorbidities, making them at greater risk of developing AKI after a contrast procedure.

4.8 Clinical experts said that procedures that are expected to use larger contrast volumes could lead to a higher risk for AKI. Larger volumes of contrast would likely be given during more complex procedures such as percutaneous coronary intervention, rather than diagnostic angiography. The clinical experts felt that procedure type should be considered when deciding whether to use DyeVert Systems.

4.9 The cost model for DyeVert Systems used a well-constructed decision tree and Markov model, with appropriate outcomes based on NICE clinical guidelines, and an appropriate time horizon. The clinical experts thought that the EAC's revised assumption of a relative risk of AKI of 8.72% was reasonable.

4.10 The committee considered that the most robust evidence for DyeVert Systems was on surrogate markers, such as contrast volume reduction, rather than AKI incidence. Clinical experts explained that the direct causal relationship between contrast agent and AKI is not certain (for more about AKI incidence and the relationship with contrast agents, see section 4.1). The results of the cost analysis were sensitive to the reduction in relative risk of AKI from using DyeVert Systems. Three of the 4 studies that reported that DyeVert Systems reduced the relative risk of AKI were abstracts or posters. These were included in the meta-analysis that provided the values used in the economic model. Including these studies led the committee to question the robustness of and risk of bias in the meta-analysis. The reduction in relative risk of AKI for DyeVert was reported as 42% in the 1 full text published study and 41% in the meta-analysis. The EAC's sensitivity analysis found the break-even reduction in relative risk to be 38.5%. Because the economic model was very sensitive to this parameter, there was uncertainty around whether using DyeVert Systems would lead to a cost saving.

4.11 The committee concluded that further research is needed to address uncertainties in the clinical effectiveness of DyeVert Systems compared with standard care. It concluded that, although there is clear evidence that DyeVert Systems can reduce contrast volume received while maintaining image quality, the evidence around AKI incidence was weaker. The committee concluded that a randomised controlled trial was needed. It should collect data on AKI incidence, renal replacement therapy, hospital stay, and biochemical markers of kidney injury, and should follow up for enough time to capture these outcomes. The population must include people having an elective coronary or peripheral angiography procedure who have an eGFR less than 30 ml/min/1.73 m². Further evidence should be collected to resolve the uncertainties around the generalisability between the 2 DyeVert devices. The committee noted that collecting evidence for DyeVert in peripheral angiography will be more difficult because of the different ways the procedure is done. It concluded that for peripheral angiography, it may be appropriate to trial the system in procedures that use a consistent volume of contrast, such as endovascular aneurysm repair.

4.12 The committee thought that confounding factors make interpreting real-world evidence challenging. Comorbidities and procedural factors affect the risk of developing AKI after a contrast procedure, and these may not be clearly reported. There may also be inconsistencies in routine post-procedure renal monitoring, including timing and frequency of serum creatinine measurements.