Archief Roodbont

Discussion

The primary finding of this study is the high prevalence of AF among patients with atherothrombosis, ranging from 11.5% in patients with PAD to 13.7% in patients with CVD. Indeed, the prevalence of AF in patients with symptomatic atherothrombotic disease (CAD, CVD, or PAD) was 11.7%. Even among RFO patients, the prevalence of AF (6.2%) is substantially higher than the estimated prevalence in the general population aged 40 years and older (2.3%) and also in the population aged 65 years and older (5.9%).^[4] This higher than expected prevalence of AF among patients with atherothrombosis has clinical implications because atherothrombotic patients usually require chronic antiplatelet therapy and frequently protracted periods of dual antiplatelet therapy after acute coronary syndromes or percutaneous coronary intervention.^[17-20] As such, the fact that 12.5% of patients with chronic CAD have AF highlights the magnitude of this problem. Yet, prospective trials have not addressed the optimal management of this subgroup of patients with respect to the combined use of oral anticoagulants and antiplatelet agents. The Atrial Fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE-W) trial, however, showed that antiplatelet therapy alone did not provide adequate protection against the risk of stroke in AF patients, compared with warfarin.^[21]

Secondly, the study found that AF was associated with a major increase in CV mortality and morbidity, even after adjustment for age, gender, and risk factors. Although the increase in mortality, risk of stroke, and TIA were anticipated,^[1,22-24] it is also striking that unstable angina was more frequent among patients with AF, particularly for patients who were enrolled in REACH because of prior CVD or PAD.

Finally, this study shows the higher incidence of chronic heart failure (requiring hospital admission) and severe bleeding in patients with AF at baseline. Importantly, there were notable differences in the baseline characteristics and risk factor profile of patients with AF compared with non-AF patients, with an older age, a higher prevalence of hypertension, and a larger waist circumference. These differences may contribute to worse CV outcomes for patients with AF.

There is a consensus that the presence of AF is a major risk factor for ischemic stroke.^[25] However, marked heterogeneity was reported for the risk of ischemic stroke in AF patients, ranging from <2%>10%, depending on the associated risk factors.^[26] The CHADS₂ score is a simple and practical method for the risk stratification of future stroke in patients with AF.^[15] However, the validity of CHADS₂ score in predicting future CV events has not been tested in AF patients with or at high risk of atherothrombosis. Our study demonstrates that the CHADS₂ score classification was useful in predicting not only stroke but also CV death in stable outpatients with established or at high risk of atherothrombosis. However, it was not as useful in the prediction of nonfatal MI.

Although there is a consensus that oral anticoagulants offer better protection than antiplatelets against ischemic stroke in patients with AF,^[21,25-30] the use of oral anticoagulants in these patients in our study was low even with patients at high risk of stroke--an observation consistent with the findings of previous studies, for example, the US Medicare Cohort Study.^[31] The low use of oral anticoagulants in the REACH population is coupled with a markedly high background use of antiplatelet agents in patients with, or at high risk of, atherothrombosis. The increased risk of bleeding associated with using combined therapy,^[32] in particular aspirin and clopidogrel,^[33] could account for the low use of oral anticoagulants observed. Increased risk of bleeding was also associated with aspirin in combination with oral anticoagulant in AF patients with CAD.^[34] Clinicians may favor long-term oral antiplatelet therapy over oral anticoagulant or combined therapy: however, unlike previously published smaller studies,^[35] ACTIVE-W^[21] have established that oral anticoagulants provide superior protection against stroke compared with antiplatelet therapy, even if the latter combines aspirin and clopidogrel.

There are several limitations to this analysis. Approximately 5% of patients were lost to follow-up and an additional 1,388 patients did not have their AF history documented at baseline; however, there were no significant differences in baseline characteristics between these patient subsets and the rest of the cohort.^[13] Data on the classification of AF (paroxysmal, persistent, or chronic), duration of AF, or use of antiarrhythmic agents were not available (although a previous study^[36] and a meta-analysis demonstrate that this does not influence the risk of thromboembolic events^[37]). The presence of AF in the REACH Registry population was determined by participating physicians and not independently adjudicated. Given the large size of the population studied, some of the differences observed in the baseline characteristics of AF and non-AF patients, for example, blood pressure, may be statistically significant but of little clinical relevance. The REACH Registry is an observational registry, which makes it difficult to clarify the causality link between AF and the increased risk of CV events, as this may be in part be confounded by differences in measured or unmeasured baseline characteristics. However, regardless of whether AF is an independent predictor or simply a correlate of higher baseline risk, the presence of AF in patients with atherothrombosis remains a major marker of increased risk of subsequent serious CV events, including CV mortality. We should also emphasize that our data and observations pertain to AF patients with atherothrombosis and should not be generalized to the universal AF patient population.

In conclusion, in this large, global, and contemporary registry, there is a high prevalence of AF among patients with, or at high risk of, atherothrombosis. These patients have a relatively low frequency of use of oral anticoagulants, although they are at high risk of ischemic stroke, probably due to the widespread use of antiplatelet agents for the treatment of atherothrombosis. The presence of AF at baseline was associated with serious and multiple CV events including a higher rate of all-cause and CV mortality, nonfatal stroke, and a modest increase in the risk of acute coronary events including non-fatal MI and unstable angina. Clearly, atherothrombosis patients with AF are a group at particularly high risk of major adverse cardiac events. Efforts should be devoted to improving the care of these patients, particularly to ensure the appropriate use of oral anticoagulants. There is a need for the optimal antithrombotic therapy among AF patients to be clarified to balance the increased risk of thrombotic events and the increased risk of bleeding associated with combined anticoagulant and antiplatelet therapy.