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.