Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years

Haaland, Gry; Falk, Ragnhild Sørum; Straume, Oddbjørn; Lorens, James B.

doi:10.1001/jamainternmed.2017.5512

Cited by 66 publications

(84 citation statements)

References 36 publications

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“…We screened 2,389 titles and abstracts and selected 29 studies for full–text screening (Appendix B, Supporting Information). Of these, 6 studies were included . We excluded 18 studies that did not report original data, e.g.…”

Section: Resultsmentioning

confidence: 99%

“…prostate cancer survival, and 1 study that reported a composite outcome of urogenital malignancies but not prostate cancer specifically . We identified 2 eligible studies from cross–referencing resulting in a total of 8 included studies; 7 observational studies and 1 secondary analysis of data from a randomized controlled trial . In the secondary analysis of the randomized trial, patients were assigned to either 6 weeks (n = 419) or 6 months (n = 435) of VKA therapy after first occurrence of venous thromboembolic disease and followed for occurrence of cancer for a mean of 8.1 years from recruitment .…”

Section: Resultsmentioning

confidence: 99%

“…When stratifying by type of effect estimate, heterogeneity was smaller for studies reporting ORs or RRs (I 2 : 64.2%) compared to studies reporting HRs or IRRs (I 2 : 93.0%). The post hoc sensitivity analysis that excluded a study with high risk of immortal time bias showed less heterogeneity for studies reporting rate ratios (I 2 : 66.8%) as well as less overall heterogeneity (I 2 : 58.4%) (Appendix B, Supporting Information). The pooled effect estimate of this analysis was 0.94 (95% CI, 0.83–1.07).…”

Section: Resultsmentioning

confidence: 99%

“…Because the present study partially included the same population as a previous study on VKA use and risk of selected cancers in Denmark, the previous study was omitted from the meta–analysis. Further, we carried out a post hoc sensitivity analysis excluding a study with high risk of immortal time bias …”

Section: Methodsmentioning

confidence: 99%

“…The authors reported a lower incidence of urogenital cancers in patients treated with VKAs for 6 months compared to patients treated for 6 weeks . This finding was followed by observational studies reporting 20–30% reductions in prostate cancer risk with VKA use as well as studies reporting neutral associations . In laboratory studies, VKAs have been demonstrated to inhibit Axl–receptor signaling involved in cell growth regulation and to reduce transcriptional activity of the androgen receptor in prostate cancer cells …”

Section: Introductionmentioning

confidence: 94%

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Use of vitamin K antagonists and risk of prostate cancer: Meta–analysis and nationwide case–control study

Kristensen

Jensen

Skriver

et al. 2018

Intl Journal of Cancer

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Use of vitamin K antagonists (VKAs) has been suggested to reduce the risk of prostate cancer. We conducted a nested case–control study using Danish demographic and health data registries and summarized existing evidence in a meta‐analysis. The case–control study included all Danish men aged 40–85 years with incident histologically verified prostate adenocarcinoma between 2005 and 2015 (cases). For each case, we selected 10 age–matched controls. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CI) for prostate cancer associated with long–term VKA use adjusted for concomitant drug use, medical history and socioeconomic status. Among 38,832 prostate cancer cases, 1,089 (2.8%) had used VKAs for 3 or more years compared to 10,803 (2.8%) controls yielding a crude OR of 1.01 (95% CI, 0.95–1.08). Multivariable adjustment for covariates had limited influence on the association (OR, 1.03; 95% CI, 0.97–1.10). We observed no dose–response relationship (e.g. OR for 5–10 years of use, 1.06 95% CI, 0.97–1.16). We included 8 studies in the meta–analysis reporting effect estimates from 0.51 (95% CI, 0.23–1.13) to 1.10 (95% CI, 0.94–1.40). Using random effect methods, a pooled effect estimate of 0.86 (95% CI, 0.70–1.05) was obtained; however, there was considerable across–study heterogeneity (I2: 93.9%). In conclusion, we did not observe a reduced risk of prostate cancer associated with VKA use in this nationwide study and, taken together with previous study findings, a major protective effect of VKAs against prostate cancer seems unlikely.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

See 3 more Smart Citations

Use of vitamin K antagonists and risk of prostate cancer: Meta–analysis and nationwide case–control study

Kristensen

Jensen

Skriver

et al. 2018

Intl Journal of Cancer

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Lower Cancer Incidence—Warfarin Effect or Immortal Time Bias?—Reply

2018

Self Cite

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Otulana, are of low quality, consisting primarily of case series, small uncontrolled single-arm studies, and several observational studies of health care utilization. 3 Dr Otulana asserts that revenue from Acthar, which exceeded $1.2 billion in 2016, 4 is funding research to "generate the evidence to fill in the gap." We identified 47 Actharrelated prospective studies funded by Mallinckrodt registered to clinicaltrials.gov, 21 of which had a single arm with no comparison group. Of the remaining "controlled" studies, the median enrollment was 40 patients. Given the preponderance of small and uncontrolled single-arm studies, we have serious doubts that these studies will provide scientific evidence sufficient to justify use of Acthar at its current price.We believe that drug prices need to be related in some way to value, which at a minimum, is derived from a solid foundation of clinical evidence. Regardless of the ultimate validity of Mallinckrodt's Acthar research program, we question an inverted business model that justifies an excessively inflated medication cost based on the need to generate evidence to support the high cost. Moreover, it does not seem likely that definitive evidence will be forthcoming.

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