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Observational Study
. 2018 Mar 10;7(6):e008034.
doi: 10.1161/JAHA.117.008034.

Safety and Effectiveness of Direct Oral Anticoagulants Versus Vitamin K Antagonists: Pilot Implementation of a Near-Real-Time Monitoring Program in Italy

Flavia Mayer  1 , Ursula Kirchmayer  2 , Paola Coletta  3 , Nera Agabiti  1 , Valeria Belleudi  1 , Giovanna Cappai  1 , Mirko Di Martino  1 , Sebastian Schneeweiss  4 , Marina Davoli  1 , Elisabetta Patorno  4
Affiliations
Observational Study

Safety and Effectiveness of Direct Oral Anticoagulants Versus Vitamin K Antagonists: Pilot Implementation of a Near-Real-Time Monitoring Program in Italy

Flavia Mayer et al. J Am Heart Assoc. .

Abstract

Background: Real-time monitoring is used to the ends of postmarketing observational research on newly marketed drugs. We implemented a pilot near-real-time monitoring program on the test case of oral anticoagulants. Specifically, we evaluated the safety and effectiveness of direct oral anticoagulants compared to vitamin K antagonists in nonvalvular atrial fibrillation secondary prevention during 2013-2015 in the Lazio Region, Italy.

Methods and results: A cohort study was conducted using a sequential propensity-score-matched new user parallel-cohort design. Sequential analyses were performed using Cox models. Overall, 10 742 patients contributed to the analyses. Compared with vitamin K antagonists, direct oral anticoagulant use was associated with a reduction of all-cause mortality (0.81; 95% confidence interval [CI] 0.66-0.99), cardiovascular mortality (0.71; 95% CI 0.54-0.93), myocardial infarction (0.67; 95% CI 0.43-1.04), ischemic stroke (0.87; 95% CI 0.52-1.45), hemorrhagic stroke (0.25; 95% CI 0.07-0.88), and with a nonsignificant increase of gastrointestinal bleeding (1.26; 95% CI 0.69-2.30).

Conclusions: The present pilot study is a cornerstone to develop real-time monitoring for new drugs in our region.

Keywords: anticoagulant; comparative effectiveness; drug therapy; monitoring; pharmacoepidemiology; pilot; real‐world; surveillance.

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Figures

Figure 1
Figure 1
Cohort selection. AF indicates atrial fibrillation; DOAC, direct oral anticoagulants; ICD‐9‐CM, the International Classification of Diseases, 9th Revision, Clinical Modification; PS, propensity score; VKA, vitamin K antagonists.
Figure 2
Figure 2
Mortality—sequential analysis of new users of DOACs vs VKAs—HR and 95% CI. CI indicates confidence interval; DOAC, direct oral anticoagulants; HR, hazard ratio; PS, propensity score; VKA, vitamin K antagonists.
Figure 3
Figure 3
Cardiovascular mortality—sequential analysis of new users of DOACs vs VKAs—HR and 95% CI. CI indicates confidence interval; DOAC, direct oral anticoagulants; HR, hazard ratio; PS, propensity score; VKA, vitamin K antagonists.
Figure 4
Figure 4
Acute myocardial infarction—sequential analysis of new users of DOACs vs VKAs—HR and 95% CI. CI indicates confidence interval; DOAC, direct oral anticoagulants; HR, hazard ratio; PS, propensity score; VKA, vitamin K antagonists.
Figure 5
Figure 5
Ischemic stroke—sequential analysis of new users of DOACs vs VKAs—HR and 95% CI. CI indicates confidence interval; DOAC, direct oral anticoagulants; HR, hazard ratio; PS, propensity score; VKA, vitamin K antagonists.
Figure 6
Figure 6
Hemorrhagic stroke—sequential analysis of new users of DOACs vs VKAs—HR and 95% CI. CI indicates confidence interval; DOAC, direct oral anticoagulants; HR, hazard ratio; PS, propensity score; VKA, vitamin K antagonists.
Figure 7
Figure 7
Gastrointestinal bleeding—sequential analysis of new users of DOACs vs VKAs—HR and 95% CI. CI indicates confidence interval; DOAC, direct oral anticoagulants; HR, hazard ratio; PS, propensity score; VKA, vitamin K antagonists.
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