ABC | Volume 114, Nº4, April 2020

Viewpoint Ferreira et al. Anticoagulant Search Trends and Stroke Arq Bras Cardiol. 2020; 114(4):726-729 exist. This association has been shown with statins and several non-cardiovascular drugs. 9,10 A previous study by Lippi et al. 6 also found an increase in worldwide online search volume for DOACs, which has been consistent with the escalation in clinical use. Internet search trends for oral anticoagulants and stroke Despite a progressive increase in the number of publications in this area, an association between specific patterns of treatment search and subsequent variations in populational clinical events has yet to be clearly demonstrated. If a relationship really exists, search data would have the potential to function as a surrogate for large-scale effects of a given drug or intervention regarding specific clinical outcomes. The influence of oral anticoagulants in the epidemiology of stroke-related deaths serves as an adequate example in this scenario, considering that most ischemic cerebrovascular events are cardioembolic and effectively prevented by oral anticoagulants. Hernandez et al. 11 have previously correlated geographic variation in the use of anticoagulation with stroke rates among Medicare beneficiaries, demonstrating an inverse relationship between the two variables. 11 According to the Department of Information Technology of the Brazilian Unified Health System (DATASUS), the total number of stroke-related deaths in Brazil declined between 2006 and 2015, although the most significant reduction was after 2011. 12 In addition, ischemic strokes and those not classified as a specific type (ICD-10 codes I63 and I64) comprised most of the cerebrovascular events (70,2%), and presented a similar pattern of decline since 2011 (mean of 49,406.4 ± 451 vs. 46,447.2 ± 1633 deaths per year before and after 2011, respectively). Conversely, hemorrhagic stroke deaths (ICD-10 codes I60, I61 and I62) increased in the same period, albeit at a much lower proportion (mean of 19,740.4 ± 278 vs 20,933.8 ± 446 deaths per year before and after 2011, respectively). 13 During the same period, when warfarin, dabigatran and rivaroxaban were used as search topics (“drug”) and Brazil was defined as the only search region, there was a clear tendency for a decline in warfarin’s Google Trends search scores after 2011. In 2015 the popularity value reached approximately the same level as 2009. Conversely, rivaroxaban’s score increased considerably after 2011, and surpassedwarfarin’s popularity after 2013. Dabigatran’s search score remained consistently below the other two anticoagulants throughout the analyzed time interval. It should be noted that when a topic (i.e. “drug”) is used as the search option, terms that are associated with the corresponding drug, including commercial names, are also contemplated. When stroke-related deaths and search scores are appreciated in combination there appears to be an inverse correlation with ischemic strokes and a positive association with hemorrhagic events. Between 2011 and 2015, total and ischemic stroke deaths decreased (Figure 1) and hemorrhagic events increased (Figure 2) concurrently to an escalation in DOAC Google Trends’ search scores. Most importantly, this relationship seemed to be primarily driven by a rise in rivaroxaban’s popularity. Since there has been a progressive increase in the prescription of oral anticoagulants in clinical practice, and also a rise in the internet popularity of DOAC worldwide, changes in the incidence of both ischemic and hemorrhagic cerebrovascular events may be anticipated. 1,6 In Brazil, such an impact would also be expected, since in 2015 rivaroxaban was already the drug with the third highest sales revenue in the national market, only four years after it became available to the public. 14 In only two years, rivaroxaban surpassed warfarin in Internet search volume in most of the country. This finding is probably related to an increase in the use of DOACs, rather than a transition between anticoagulant categories. DOACs have become attractive options when stroke prevention is considered in AF, mainly because of their predictable pharmacokinetics, probably safer profile and non-inferior effectiveness when compared to vitamin K antagonists. Contrary to what was found with ischemic strokes, hemorrhagic stroke-related deaths apparently increased since 2011. Although such an escalation occurred at a lower rate, the trend also appeared to be related to rivaroxaban´s search patterns. Perhaps this tendency was also a result of a greater number of previously untreated patients that progressively received anticoagulants, since DOACs tend to reduce intracranial bleeding when compared to warfarin. The greater adoption of the CHA 2 DS 2 -Vasc Score could also have contributed in expanding the number of patients on anticoagulant therapy during the study period. 1 Furthermore, considering that total stroke deaths decreased significantly, the epidemiological pattern is comparable to the net benefit of DOACs that has been found in multiple trials. 4 The possibility that other factors, such as public health policies, greater cardiovascular risk factor control and improvements in socioeconomic conditions, may have influenced the annual number of deaths cannot be entirely excluded. However, a reduction in hemorrhagic stroke-related deaths would be expected solely from these interventions. Until 2017, a persistent decline in ischemic deaths was still observed, whereas hemorrhagic events continued to increase. 12 Although search scores may provide an estimate of prescription patterns, they are not a direct reflection of regional drug utilization or sales. Internet access in 2014 was available in approximately 50% of all households in Brazil and the illiteracy rate in individuals over 65 years of age was still high (26.4%). 15 As such, these patterns must be interpreted considering all of the potential biases, especially because the specific algorithms that were employed by Google Trends were not disclosed. Nevertheless, as Internet access expands throughout theWorld and new policies are developed to reduce illiteracy rates, search trends will become increasingly more correlated to daily behavioral patterns. Conclusion The progressive worldwide populational growth has demanded the development of new mechanisms to monitor epidemiological changes in both treatment tendencies and disease patterns. In this context, the Internet has become a valuable tool for gathering information to aid in daily decision making, particularly in health care, where the critical 727