LVH is a determinant of left atrial size and remodelling, and it would be expected that aggressive blood pressure control should prevent AF occurring in patients with diabetes. Angiotensin converting enzyme inhibitors (ACE inhibitors) do seem to prevent AF in hypertension supporting this hypothesis. A large cohort study, L’Allier et al. (2004), of eight million people on a database showed a reduced incidence of AF in patients on ACE inhibitors with hypertension . By contrast the GISSI-AF study found that the angiotensin receptor blocker (ARB’s) valsartan did not reduce the incidence of AF in patients who before recruitment had two or more documented episodes of AF . The important point here is that GISSI-AF recruited patients who had already had episodes of AF whereas in the L’Allier et al. (2004) study, the use of ACE inhibitors was restricted to patients with no previous history of AF. Interestingly in GISSI-AF, there was a reduced incidence of AF in the patients with diabetes subgroup but this was not significant (p = 0.11).
It is more conclusive that angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blocker (ARB’s) reduce the incidence of new onset AF in heart failure. Heart failure is linked to diabetes due to the reasons discussed previously. There are three main meta-analysis published in this area [47-49] . A metaanalysis by Kalus et al. (2006) of four clinical trials reports resulting effect of renin angiotensin system blockade in reducing new onset AF . All four studies included patients with left ventricular dysfunction and showed a reduction in new onset AF in patients treated with ACE inhibitors or ARB’s. Anand et al. (2006) analysed nine randomised control trials and found that the use of ACE inhibitors and ARB’s across the trials showed a 18% risk reduction in the onset of new AF, but most importantly there was a 43% risk reduction in the subset of patients with heart failure . Jibrini et al. (2008) included 11 randomised trials and included patients with heart failure, myocardial infarction and hypertension . They found that treatment with ACE inhibitors or ARB’s reduced the relative risk for the development of new onset AF by 23% in hypertension, 11% in post myocardial infarction patients and by 32% in heart failure patients. These three meta-analyses of the major trials are the most compelling evidence for the use of ACE inhibitors and ARB’s to prevent new onset AF in patients with impaired left ventricular function. None of these trials published sub-group analysis of patients with diabetes.
A final discussion point is the use of thiazolidinediones. A case report from Greece has described two patients with type 2 diabetes who had an improvement in paroxysmal AF with rosiglitazone . There is some evidence that thiazolidinediones reduce C reactive protein levels and inhibit oxidative stress [51,52] . It could be that thiazolidinediones with their pleitropic properties affect atrial remodelling . However, thiazolidinediones are controversial in their links to heart failure and ischaemic heart disease, which may limit their potential use to prevent AF.
AF is one of the most common cardiac arrhythmias, and seems to be more common amongst people with diabetes. AF has a significant impact on morbidity and mortality, and in particular increases the long term risk of stroke. The reasons for AF being more common in patients with diabetes remain unclear. The specific combination of AF and diabetes is an under researched area that needs further research. Thiazolidinediones may prevent AF but at this stage the evidence for this is limited to theory and case reports. ACE inhibitors and ARB’s have shown promise in preventing new onset AF especially in patients with heart failure. Although the evidence for ACE inhibitors and ARBs preventing AF in diabetes is sparse, it is reasonable to presume they do so, although many patients with diabetes will have alternative indications for them anyway e.g. hypertension or microalbuminuria. Our review article highlights the need for more research into AF prevention and treatment in diabetes.
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AF Atrial fibrillation;
ACCORD Action to Control Cardiovascular Risk in Diabetes trial;
ACE Angiotensin converting enzyme;
ARB Angiotensin receptor blocker;
TIA Transient ischaemic attack;
HOT Hypertension Optimal Treatment trial;
GISSI-AF Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico-Atrial Fibrillation trial.
*Declaration of competing interests: nothing to declare.