Our comprehensive analysis of over 450,000 individuals admitted with NSTEMI, with follow-up of up to 10 years, reveals important disparities in care and long-term outcomes between those with diabetes and those without diabetes. First, those with diabetes were less likely to undergo invasive investigation with ICA or revascularisation but were more likely to receive guideline-directed medical therapy including statins, β-blockers and ACE inhibitors. Reassuringly, the quality of care received overall as measured by the OBQI score was better for those with diabetes than for those without diabetes. Second, the risk of mortality at 30 days, 1 year and up to 10 years of follow-up was significantly higher for the diabetes population, but, importantly, receipt of higher quality guideline-recommended care was associated with better long-term mortality risk across all groups of individuals with diabetes.

Previous studies have reported disparities in AMI care for people with diabetes [16, 20]; however, these studies mostly investigated ACS, broadly including both individuals with STEMI and those with NSTEMI [21]. Management of individuals with STEMI is more protocolised and typically managed within specialist centres, whereas the management of NSTEMI shows greater heterogeneity [22]. It is therefore difficult to generalise ACS results to NSTEMI cohorts. Additionally, many previous analyses were limited by including smaller cohorts and shorter periods of follow-up and did not consider diabetes groups based on their treatment regimen. Our study included a large cohort of individuals with diabetes, with up to 10 years’ follow-up for a proportion of the study participants, which far exceeds that of comparable studies.

We observed that participants with diabetes were more likely to present acutely unwell with NSTEMI, with a higher Killip class and a higher proportion of moderate to severe LVSD. Similar, to Killip class, left ventricular dysfunction is an independent risk factor for worse outcomes following PCI [23]. Those with diabetes were also more likely to have prevalent comorbidities such as chronic kidney disease (CKD). CKD increases bleeding risk from invasive therapy [24] and may require caution from operators providing invasive procedures in which nephrotoxic contrast media is used [25]. Furthermore, individuals with CKD and diabetes are more likely to present with diffuse multivessel coronary artery disease that is not amenable to PCI [26]. These factors may explain why people with diabetes do not receive timely revascularisation, but it must be highlighted that this is in direct contrast to the 2018 ESC/European Association for Cardio-Thoracic Surgery (EACTS) guidelines on ACS revascularisation, which recommend early revascularisation in people with diabetes [27]. The clinical implications of this delay remain controversial, with some studies suggesting that an early invasive strategy leads to improved long-term mortality risks in people with NSTEMI [28]. However, other contemporary trials suggest that there is no mortality benefit of early intervention in those with NSTEMI, although these studies reported lower rates of angina and shorter hospitalisations [29]. Of interest, despite our diabetes cohort presenting as more unwell and with additional comorbidities, the overall rate of cardiogenic shock within the whole cohort was low at 1%, this is lower than the estimated rates of cardiogenic shock post NSTEMI of 2.5% [30]. This difference may be explained by advancements in therapies or a lack of identification or clear documentation from treating clinicians.

Canto et al showed in a cohort of 434,877 individuals with myocardial infarction that diabetes was more common in those presenting with atypical chest pain (32.6% vs 25.4%) [31]. This may also directly contribute to invasive therapy delays. Our observed lower rate of invasive management could also represent a known selection bias that occurs whereby lower risk individuals are more likely to receive guideline-directed invasive therapy than individuals at higher risk over concerns of complications during procedures, a so-called risk–treatment paradox [32]. In contrast to this, individuals with diabetes in this study were more likely to be prescribed guideline-directed medical therapy such as β-blockers, ACE inhibitors and statins.

Considering the effect of quality of care further, participants with diabetes were less likely to be admitted to a specialist cardiology ward. Being cared for on a specialist cardiology ward leads to increased delivery of guideline-directed medical therapy [33]. Individuals are also more likely to receive specialist investigations such as echocardiograms and cardiac MRI, which allow rapid diagnosis and treatment of post-infarct complications and prompt more aggressive titration of heart failure therapy [34]. Additionally, specialists are more likely to understand and use local referral pathways on discharge for cardiac rehabilitation. Previous studies have shown the importance of cardiac rehabilitation in post-AMI care [35] and that non-cardiac specialists are less likely to refer eligible patients for these services [36].

Outcomes for people with diabetes have consistently been shown to be worse post AMI than for those without diabetes. Donahoe et al showed in a multinational cohort of 62,036 individuals with ACS from 1997 to 2006 that the mortality risk was significantly higher at 30 days and 1 year of follow-up in those with diabetes than in those without diabetes [37]. Similarly, Fojt et al showed in a Polish-based cohort of 58,394 individuals with AMI from 2009 to 2012 that the presence of diabetes was associated with a higher risk of mortality up to 3 years of follow-up [38]. Our study builds on this previous evidence in key areas, with up to 10 years of follow-up for mortality events. We demonstrate that in UK individuals with NSTEMI, those with diabetes have a higher risk of mortality, which is 16% greater at 5 years and 11% greater at 10 years of follow-up than in individuals without diabetes. It is interesting that, over this long follow-up duration, the disparity in mortality between those with diabetes and those without remains, suggesting that the impact of diabetes on NSTEMI outcomes persists long after the index cardiac event.

Furthermore, our study is also the first to compare quality of NSTEMI care and show how this is related to long-term mortality risks. Many factors that contribute to higher mortality risk in people with diabetes, such as common cardiovascular risk factors, exist at the point of index NSTEMI presentation and are non-modifiable by the hospital specialist caring for them. However, the quality of care that clinicians deliver is a modifiable aspect of care and this study demonstrates the positive association between higher quality inpatient care and long-term mortality risks in UK NSTEMI patients. Our study highlights the importance of clinicians delivering guideline-led, high-quality inpatient care to all those with diabetes.

Our study was able to stratify a large cohort of individuals by diabetes treatment modality and follow these individuals over a long time period. We show that, over time, mortality trends in our population with diabetes improved and that individuals managed with insulin had significantly higher mortality over all time periods. This may have occurred for several reasons. First, medications used by those with diabetes, such as metformin, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors, all have strong cardioprotective qualities [39,40,41], although the MINAP registry does not yet collect data on these medications. It is also possible that once people are diagnosed with diabetes they begin to address other comorbid factors such as body weight, diet, exercise and smoking. It is also possible that improved recognition and prompt medical management of diabetes increases the amount of contact that these individuals have with medical professionals, increasing the opportunity for preventative intervention. When considering why insulin-treated individuals have the poorest outcomes, it is important to highlight that our insulin-treated cohort was made of two distinct groups, those with type 1 diabetes and those with type 2 diabetes of longer duration who have failed to establish optimal glycaemic management with other therapies. This group will have the highest rate of intrinsic insulin resistance. Studies have shown that insulin resistance advances the atherosclerotic process [42], with individuals with diabetes being more likely to present with multivessel involvement [43] and having a propensity for in-stent restenosis [44]. This in turn could partly explain their higher short- and long-term mortality risk [45] and our finding that individuals with diabetes more often had a history of previous AMI.

To our knowledge, this is the first study to investigate the relationship between inpatient quality of care and long-term mortality risks in individuals with diabetes and NSTEMI in a large, national healthcare setting. We suggest that further studies should focus on identifying and addressing the disparities in access to guideline-directed medical therapy, cardiac rehabilitation referral and prompt invasive investigations and therapies in the highest risk individuals with diabetes post AMI to enable major improvements to be made in the long-term survival rates of this growing population.

There are several other major strengths to this study. The MINAP registry collects robust data, with many variables recorded from all those presenting to hospital with NSTEMI in the UK. This allows for regional differences within the UK to be balanced out and thus our results are more likely to be representative of other publicly funded healthcare models globally. Our post-discharge mortality data from the ONS, with a long mean duration of follow-up of 1900 days, enabled us to assess mortality risks. Furthermore, our study has the additional benefit of studying patients within the UK where healthcare is free at the point of use. Compared with private healthcare systems, where up to a quarter of patients avoid hospital because of the high associated costs, our study is likely to have captured a more complete spectrum of diabetes/NSTEMI presentations [46]. Overall, this study reports on a large, contemporary cohort with a far greater follow-up duration than in previous studies in this patient group.

There are also several important limitations to consider in this study. The MINAP database is limited in similar ways to other national databases. First, there is no external validation of data inputs. Second, although the MINAP database collects many variables of interest, it does not collect data on frailty, rationale for treatment options or an exhaustive list of comorbidities. Additionally, the MINAP database has strict definitions for recorded comorbidities. For example, CKD was defined in this study as a creatinine level of >200 µmol/l. Therefore, CKD defined by MINAP encompasses those with moderate CKD to those established on dialysis. This limited our ability to subclassify participants depending on their degree of kidney disease. Similarly, MINAP defines hypercholesterolaemia as an ‘elevation of serum cholesterol requiring dietary or drug treatment’ and does not provide guidance on severity. Additionally, although the MINAP dataset should only include type 1 myocardial infarctions, there will undoubtedly be some misclassification with some type 2 myocardial infarctions also included. This distinction affects the use of invasive therapies as well as clinical outcomes.

It is important to recognise that diabetes recording in the MINAP registry occurs at the point of NSTEMI diagnosis. This database does not record when individuals were diagnosed with diabetes and therefore our cohort will contain those who were diagnosed prior to admission and those who, when admitted, had an index diagnostic HbA1c level recorded. These newly diagnosed individuals are often recorded as ‘diet-controlled’; however, they will have had no prior diabetes intervention or advice. This group will be heterogeneous and this may explain the difference in mortality between the diet- and tablet-treated groups. Equally, this database collects generic information around insulin use in individuals with diabetes. It does not capture whether insulin-treated individuals have type 1 or type 2 diabetes. There is likely to be a subgroup of individuals with type 2 diabetes in our insulin-treated group who are also taking a range of oral agents. We are therefore unable to assess if a combination of methods to control plasma glucose or the specific aetiology of diabetes makes a difference to outcomes in NSTEMI. With regard to our assessment of mortality risk, we have no data on longer term participant adherence to medications, nor were we able to delineate sub-cohorts of individuals who transition through different diabetes treatments over time. Additionally, there was a possible selection bias in our quality-of-care groups because, to receive a referral to cardiac rehabilitation, patients need to be fit enough to attend and have sufficient renal function for ACE inhibitor initiation, and their prognosis needs to be good enough to start on statins.

Although we present prospective data and our modelling adjusted for many important confounding variables, these observational data have the potential for residual confounding and therefore caution is needed when making causal inferences. We stratified our participants by treatment modality but were not able to identify individuals treated with SGLT2i or GLP-1 receptor agonists. Future research should aim to assess the potential benefits of these agents in the setting of NSTEMI.

Our nationwide analysis of the long-term outcomes of over 450,000 UK individuals presenting with NSTEMI shows that there are stark disparities in NSTEMI management between those with and those without diabetes. Those with diabetes had an elevated risk of mortality at all study time points up to 10 years compared with those without diabetes. In the group with diabetes, insulin-treated individuals had the highest risk of long-term mortality. In addition, in those with diabetes, higher quality of inpatient care was associated with lower risks of mortality; thus, this study highlights the importance of high-quality inpatient care in all individuals with diabetes.