Diabetes and Atrial Fibrillation

Tell us about the ADVANCE study. How many patients were included? What was the purpose of this study? ADVANCE is the largest clinical trial conducted to date in patients with Type 2 diabetes. The objective was to determine the effects of routine blood pressure lowering (regardless of initial BP level) and of intensive blood glucose control on vascular outcomes in these patients. The study included 11,140 patients from 20 countries, who were followed for an average of 4.3 years (for the BP lowering arm) and 5 years (for the blood glucose arm). The main findings of the trial were that routine blood pressure lowering significantly reduced the risks of vascular events and cardiovascular death. Intensive glucose control reduced the risks of microvascular events (particularly nephropathy), but did not significantly reduce the risks of macrovascular events (MI, stroke or cardiovascular death). Is it common for diabetic patients to experience atrial fibrillation? How many are at risk for developing atrial fibrillation? Atrial fibrillation does appear to be more common in people with diabetes, compared to people without this condition (about twice as common). In our study, just under 8% of patients (all of whom had diabetes, but were also all over the age of 55 years and had at least one additional risk factor for vascular disease) had atrial fibrillation at baseline. People with diabetes are more likely to have other co-morbidities that may increase their risk of atrial fibrillation (e.g., high blood pressure, heart failure). Explain the study findings. What percentage of diabetics with atrial fibrillation were at an increased risk of or experienced cardiovascular problems and/or death? How did this compare to diabetic patients without atrial fibrillation? We already know from many other studies that people with diabetes have about twice the risk of cardiovascular complications (including cardiovascular death) compared with non-diabetics. However, from the ADVANCE study, we can now show that if you are diabetic and also have atrial fibrillation, these risks are even higher. We usually only think about atrial fibrillation being a risk factor for embolic stroke and other embolic events. What we have shown here is that atrial fibrillation is a marker for a broader range of adverse cardiovascular outcomes and overall mortality. We are not concluding that atrial fibrillation causes these poor outcomes directly, but that atrial fibrillation is a risk marker for poor outcomes. This means that if someone has diabetes and atrial fibrillation, they are at a particularly high risk and should be especially targeted for intensive overall cardiovascular risk-reducing strategies. Why did the risk for atrial fibrillation in diabetic patients increase dramatically? There is a clear and well-established mechanism by which atrial fibrillation is causally linked with some outcomes (e.g., embolic stroke), but for other outcomes, the increased risk in patients with atrial fibrillation may simply be related to the fact that patients with atrial fibrillation tend to be older, have higher blood pressure, etc. However, we found that atrial fibrillation was associated with higher risks even after we adjusted for these other known predictors of poor outcome. This suggests that, independent of other factors that we are know are risk factors for cardiovascular events and mortality in patients with diabetes, atrial fibrillation is also a marker. What course of medical treatment was used in these patients with atrial fibrillation? How did this compare to treatment for patients without atrial fibrillation? How much did treatment decrease the risk of cardiovascular events and mortality in atrial fibrillation patients? Overall in ADVANCE, we showed that routine blood pressure lowering (using a fixed combination of perindopril and indapamide) reduced combined vascular events (by about 10%), cardiovascular death (by 18%) and all-cause mortality (by 14%). In these new analyses, we showed that there was no difference in relative treatment effect whether or not patients also had atrial fibrillation. However, because patients with atrial fibrillation were at higher risk to begin with, this means they would benefit more from treatment in absolute terms (i.e., the number needed to treat to avoid events is lower in people with atrial fibrillation, compared to people without atrial fibrillation). Discuss the role of gender in this population of patients with atrial fibrillation. What were the differences in outcomes between male and female diabetics with atrial fibrillation? Diabetic women with atrial fibrillation appear to be at even higher risk, compared to diabetic men with atrial fibrillation. However, we were only able to demonstrate that this difference was statistically different for one outcome (cardiovascular death), so we have to be a little cautious with this finding. In light of this study, what special considerations do you think are needed for diabetic patients? How often should they be monitored for atrial fibrillation? Clinicians should be aware if their diabetic patients also have atrial fibrillation, they are at particularly high risk. The presence or absence of atrial fibrillation should be actively determined in patients with diabetes through clinical examination and possibly ECG screening, although our study was not designed to assess this. What is unique about this study? This is the largest cohort in which the association between atrial fibrillation and a broad range of adverse cardiovascular outcomes has been evaluated, and to the best of our knowledge, this is the first to have particularly looked at people with diabetes. Will further research be done? What will be the focus of ongoing research? There may be future research done to incorporate atrial fibrillation in risk prediction tools, as well as clinical trials that may look at global cardiovascular risk-reducing therapies in patients with atrial fibrillation.