Discussion
We observed strong inverse linear associations between worsening eGFR category and the receipt of invasive management following both NSTE-ACS and STEMI, on a relative and absolute scale. For example, following NSTE-ACS, people with an eGFR <30 mL compared with ≥90 mL/min/1.73 m2 were half as likely to receive angiography (OR 0.50, 95% CI 0.40, 0.64), resulting in 15 per 100 fewer procedures. Clinically significant reductions in rates of invasive management were not limited to those with the worst kidney function but there was in general a dose-response pattern across the range of function from eGFR <60 mL/min/1.73 m2. The disparities we identified did not appear to be driven by the increased prevalence of frailty among those with reduced kidney function.
Reduced kidney function has been associated with less use of invasive management in previous research.1 4 Our work adds to and extends these observations by testing for the possible mediating role of frailty status. This is, to our knowledge, a variable that has not been considered previously and could theoretically mediate the association between eGFR and invasive management. The inability of frailty to explain the observed associations suggests that kidney function per se, rather than associated demographics or health state, affects receipt of invasive management after ACS. Potential explanations include the fear of causing contrast nephropathy,19 vascular access difficulties and uncertainty regarding the mortality benefits of invasive management in people with low eGFR, whose risks may be compounded by coexistent anaemia or reduced left ventricular function.20 ,21 ,5 Attempts to lower the risk of contrast nephropathy by administering intravenous fluids or awaiting resolution of AKI may explain the reduced timeliness of angiography in people with low eGFR after NSTE-ACS. These findings are harder to explain in STEMI, where the urgency of intervention would be expected to supersede concerns about eGFR.
When we restricted our analysis to individuals who had received angiography, reduced eGFR continued to be associated with lower odds of revascularisation following NSTE-ACS, but not STEMI. For people with STEMI, the key decision regarding invasive management appears to be angiography, as this is almost always followed by immediate PCI. For those with NSTE-ACS, further decision-making occurs regarding revascularisation. Compared with those with normal kidney function, people with NSTE-ACS and reduced eGFR may be more likely to develop troponin elevation either without angiographically detected disease or with extensive disease not amenable to revascularisation.
We also observed strong linear associations between eGFR category and mortality after ACS; an increased risk of death before and after 30 days from ACS was seen in people with an eGFR <90 mL/min/1.73 m2. Again, variation in rates of frailty appeared to explain little of these associations. Inverse associations between kidney function and mortality have been described previously.1 2 4 People with low eGFR (especially with proteinuria) have higher baseline rates of all-cause and cardiovascular mortality, than those with normal eGFR.22 Those with ACS experience accelerated progression to end-stage kidney failure,23 and a greater risk of heart failure and recurrent ACS.24 ,25
Strengths and limitations
Our study had many strengths, including a sample size of over 10 000 people, and the identification of kidney impairment via biochemistry, which is preferable to the use of diagnostic codes.14 We used cost-effective real-world, routinely collected data and performed numerous sensitivity analyses. However, we recognise limitations associated with our data. First, the use of routine healthcare records prevented us from (1) assessing for potential confounding and mediation by socioeconomic position, left ventricular ejection fraction, severity of comorbidities, pharmacotherapy and/or individual healthcare preferences26 ; (2) being able to differentiate between acute and chronic kidney disease (CKD); (3) identifying type two MI27 and (4) Using a performance-based frailty measure (eg, grip strength). Although the mFI has not been validated in UK data, we chose this score as it is applicable in younger people than others calculable from NIHR HIC codes: Frailty is common in people with CKD as young as 65 years.8 Neither objective measures nor calculated frailty scores may reflect physicians’ subjective frailty assessments.
Second, due to low numbers, we decided to (1) include people receiving dialysis with those with eGFR <30 mL/min/1.73 m2, and kidney transplant recipients with their respective eGFR categories3; (2) categorise people in ethnic groups other than white as a single group while acknowledging this is a heterogeneous population and (3) we were not powered to fully exclude interactions between frailty and eGFR category.
Third, our methodology may have introduced limitations, such as (1) potential exaggeration of the association between eGFR and angiography following STEMI, as repeating the analysis using a PS attenuated this association. The qualitative message was, however, unchanged. (2) We excluded people with missing ethnicity data from multivariable models, however, no meaningful change was demonstrated when ethnicity was estimated using multiple imputation. (3) We assumed the pattern of missingness was missing at random and multiple imputation may have been biased if this was incorrect.
Further research is needed to explain what drives treatment disparities between people with and without reduced eGFR, to determine if there is inequity in care. Analysis of a more granular quantitative dataset would show whether receipt of other aspects of ACS care (further investigations, pharmacotherapy, outpatient follow-up) is also associated with kidney function, as well as the relationship between angiography findings and revascularisation in people with and without reduced eGFR. Qualitative research with patients and clinicians would contribute to our understanding of why differences exist, via the investigation of (a) treatment decision-making, (b) how risks and benefits of invasive management are deliberated and (c) the involvement and wishes of patients regarding treatment decisions.