Study selection and data extraction
The subsequent review and selection process were divided into two rounds. In the first round, articles were screened by their titles and abstracts independently by two reviewers (AEE and AOS), and discrepancies were solved via consensus. Studies were eligible for initial inclusion if they reported original data evaluating a possible drug-drug interaction associated with concomitant use of VKA and statins, as judged via the abstract. Further, we excluded conference proceedings. Lastly, if no abstract was available, the title should indicate that the study concerned concomitant use of VKA and statins.
In the second round, we required studies to meet the same inclusion criteria as mentioned above, as judged by full text read. Furthermore, we required that i) the studies presented data from humans, ii) the statin treatment should be initiated during stable VKA treatment; and iii) the studies should report an outcome related to degree of coagulation, including changes in INR, PTT, VKA dose adjustments, or the clinical outcomes bleeding or thrombosis. Case reports, reviews and publications concerning healthy volunteers were excluded.
Lastly, we cross-reference-searched all included original publications for additional original publications meeting the abovementioned inclusion criteria.
Data were extracted from the included publications, by the two reviewers (AEE and AOS) based on a pre-defined data collection form and interpreted and analyzed by the entire author group.