New Norwegian study below.
Nordic studies are great, since the entire population is on the database.
"The cohort comprised all persons (N = 1 ,256, 725) born between January 1, 1924, and December 31, 1954, who were residing in Norway from January 1, 2006, through December 31, 2012. The cohort was divided into 2 groups-warfarin users and nonusers; persons taking warfarin for atrial fibrillation or atrial flutter were the subgroup."
"Warfarin use was defined as taking at least 6 months of a prescription and at least 2 years from first prescription to any cancer diagnosis."
"Of the 1, 256, 725 persons in the cohort, 607, 350 (48.3%) were male, 64,9 375 (51.7%) were female, 132, 687 (10.6%) had cancer, 92, 942 (7.4%) were classified as warfarin users, and 1, 163, 783 (92.6%) were classified as nonusers"
Users had 31% less risk of PCa. In contrast, the reduction in BCa risk was only 10%.
"In a subgroup analysis of patients with atrial fibrillation or atrial flutter", PCa risk was reduced by 40% (BCa by 28%).
...
My own concern is metastatic disease. I try to lower the risk of additional mets by inhibiting microclots. It has been suggested by a number of researchers that circulating tumor cells cannot survive in the absence of microclots. I use nattokinase to accelerate their removal. & so I would expect Warfarin to protect against mets, though not PCa itself.
The idea behind Warfarin is to increase clotting time. This does not address coagulation dysfunction, but it allows plasmin (the body's equivalent of nattokinase) to dissolve clots as fast as they are forming. Warfarin does not itself dissolve clots. Plasmin acts slowly - as it must when a clot is due to bleeding - so the strategy is to make clot formation even slower.
A complication of such studies is that a DVT might be the first sign of PCa or other cancer. This is presumably why the user group members had to start at least 2 years before a cancer diagnosis. Ideally, men presenting with a DVT should be screened for cancer. If that isn't done it might take more than 2 years before a PCa diagnosis occurs.
In the U.S., I understand that the usual protocol is to use Warfarin for 3 months unless there is another risk factor (such as cancer), in which case 6 months is used. If a clot recurs, the patient is condemned to lifetime use. In the study, 3-month users were excluded. Ideally, only lifers should have been studied. Temporary use might only delay cancer diagnosis.
In a 2016 Finnish study [2], Warfarin was not found to be protective. In fact there was increased risk for "short-term, low-dose use". "The increase in risk disappeared in long-term, high-dose use."
In a 2017 follow-up [3], Warfarin did not improve survival.
From a 2015 Docetaxel study [4]:
"In univariate analysis, anticoagulant use was associated with improved survival (hazard ratio [HR], 0.61 ...). Median survival was 20.9 months in the anticoagulation group versus 17.1 months in the control group ... In multivariable analysis, anticoagulant use remained a significant predictor of survival after adjusting for other baseline prognostic factors (HR, 0.49 ...). When each anticoagulant was considered separately in the multivariable model, LMWH remained significantly prognostic for survival (HR, 0.48 ...), whereas warfarin use did not."
Overall, the case for Warfarin is weak at best IMO. Why would Norwegian data look so good?
"Norway tops the statistics of prostate cancer related deaths in the western world, and is in third place overall. This means that a larger percentage of Norwegian men diagnosed with prostate cancer are likely to die from the disease than when compared to other countries. This is despite the fact that Norway is one of the countries in the world with the highest health care expenditure per capita."
"Approximately 5,000 new cases are diagnosed annually. Around 1100 Norwegian men die of prostate cancer each year."
(The Norwegian Prostate Cancer Foundation [5])
Does this suggest that Norway has a greater propotion of metastatic disease at diagnosis? That would be a situation where Warfarin might make a difference by greatly reducing microclots.
Poor mortality stats suggests that there is poor PSA screening in Norway, but it leads in PCa incidence rate at 130 cases per 100,000 males compared to 98 in the U.S. & 73 in the U.K. [6]
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/291...
JAMA Intern Med. 2017 Nov 6. doi: 10.1001/jamainternmed.2017.5512. [Epub ahead of print]
Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years.
Haaland GS1,2, Falk RS3, Straume O2,4,5, Lorens JB1,2.
Author information
Abstract
IMPORTANCE:
In cancer models, warfarin inhibits AXL receptor tyrosine kinase-dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and cancer incidence in a large, unselected population-based cohort.
OBJECTIVE:
To examine the association between warfarin use and cancer incidence.
DESIGN, SETTING, AND PARTICIPANTS:
This population-based cohort study with subgroup analysis used the Norwegian National Registry coupled with the Norwegian Prescription Database and the Cancer Registry of Norway. The cohort comprised all persons (N = 1 256 725) born between January 1, 1924, and December 31, 1954, who were residing in Norway from January 1, 2006, through December 31, 2012. The cohort was divided into 2 groups-warfarin users and nonusers; persons taking warfarin for atrial fibrillation or atrial flutter were the subgroup. Data were collected from January 1, 2004, to December 31, 2012. Data analysis was conducted from October 15, 2016, to January 31, 2017.
EXPOSURES:
Warfarin use was defined as taking at least 6 months of a prescription and at least 2 years from first prescription to any cancer diagnosis. If warfarin treatment started after January 1, 2006, each person contributed person-time in the nonuser group until the warfarin user criteria were fulfilled.
MAIN OUTCOMES AND MEASURES:
Cancer diagnosis of any type during the 7-year observation period (January 1, 2006, through December 31, 2012).
RESULTS:
Of the 1 256 725 persons in the cohort, 607 350 (48.3%) were male, 649 375 (51.7%) were female, 132 687 (10.6%) had cancer, 92 942 (7.4%) were classified as warfarin users, and 1 163 783 (92.6%) were classified as nonusers. Warfarin users were older, with a mean (SD) age of 70.2 (8.2) years, and were predominantly men (57 370 [61.7%]) as compared with nonusers, who had a mean (SD) age of 63.9 (8.6) years and were mostly women (613 803 [52.7%]). Among warfarin users and compared with nonusers, there was a significantly lower age- and sex-adjusted incidence rate ratio (IRR) in all cancer sites (IRR, 0.84; 95% CI, 0.82-0.86) and in prevalent organ-specific sites (lung, 0.80 [95% CI, 0.75-0.86]; prostate, 0.69 [95% CI, 0.65-0.72]; and breast, 0.90 [95% CI, 0.82-1.00]). There was no observed significant effect in colon cancer (IRR, 0.99; 95% CI, 0.93-1.06). In a subgroup analysis of patients with atrial fibrillation or atrial flutter, the IRR was lower in all cancer sites (IRR, 0.62; 95% CI, 0.59-0.65) and in prevalent sites (lung, 0.39 [95% CI, 0.33-0.46]; prostate, 0.60 [95% CI, 0.55-0.66]; breast, 0.72 [95% CI, 0.59-0.87]; and colon, 0.71 [95% CI, 0.63-0.81]).
CONCLUSIONS AND RELEVANCE:
Warfarin use may have broad anticancer potential in a large, population-based cohort of persons older than 50 years. This finding could have important implications for the selection of medications for patients needing anticoagulation.
PMID: 29114736 DOI: 10.1001/jamainternmed.2017.5512
[2] ncbi.nlm.nih.gov/pubmed/276...
[3] ncbi.nlm.nih.gov/pubmed/288...
[4] ncbi.nlm.nih.gov/pubmed/249...
[5] prostatakreftstiftelsen.no/...
[6] oecd-ilibrary.org/sites/hea...
JAMA Intern Med. 2017 Nov 6. doi: 10.1001/jamainternmed.2017.5512. [Epub ahead of print]
Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years.
Haaland GS1,2, Falk RS3, Straume O2,4,5, Lorens JB1,2.
Author information
1
Department of Biomedicine, University of Bergen, Bergen, Norway.
2
Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway.
3
Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
4
Clinical Institute 1, University of Bergen, Bergen, Norway.
5
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Abstract
IMPORTANCE:
In cancer models, warfarin inhibits AXL receptor tyrosine kinase-dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and cancer incidence in a large, unselected population-based cohort.
OBJECTIVE:
To examine the association between warfarin use and cancer incidence.
DESIGN, SETTING, AND PARTICIPANTS:
This population-based cohort study with subgroup analysis used the Norwegian National Registry coupled with the Norwegian Prescription Database and the Cancer Registry of Norway. The cohort comprised all persons (N = 1 256 725) born between January 1, 1924, and December 31, 1954, who were residing in Norway from January 1, 2006, through December 31, 2012. The cohort was divided into 2 groups-warfarin users and nonusers; persons taking warfarin for atrial fibrillation or atrial flutter were the subgroup. Data were collected from January 1, 2004, to December 31, 2012. Data analysis was conducted from October 15, 2016, to January 31, 2017.
EXPOSURES:
Warfarin use was defined as taking at least 6 months of a prescription and at least 2 years from first prescription to any cancer diagnosis. If warfarin treatment started after January 1, 2006, each person contributed person-time in the nonuser group until the warfarin user criteria were fulfilled.
MAIN OUTCOMES AND MEASURES:
Cancer diagnosis of any type during the 7-year observation period (January 1, 2006, through December 31, 2012).
RESULTS:
Of the 1 256 725 persons in the cohort, 607 350 (48.3%) were male, 649 375 (51.7%) were female, 132 687 (10.6%) had cancer, 92 942 (7.4%) were classified as warfarin users, and 1 163 783 (92.6%) were classified as nonusers. Warfarin users were older, with a mean (SD) age of 70.2 (8.2) years, and were predominantly men (57 370 [61.7%]) as compared with nonusers, who had a mean (SD) age of 63.9 (8.6) years and were mostly women (613 803 [52.7%]). Among warfarin users and compared with nonusers, there was a significantly lower age- and sex-adjusted incidence rate ratio (IRR) in all cancer sites (IRR, 0.84; 95% CI, 0.82-0.86) and in prevalent organ-specific sites (lung, 0.80 [95% CI, 0.75-0.86]; prostate, 0.69 [95% CI, 0.65-0.72]; and breast, 0.90 [95% CI, 0.82-1.00]). There was no observed significant effect in colon cancer (IRR, 0.99; 95% CI, 0.93-1.06). In a subgroup analysis of patients with atrial fibrillation or atrial flutter, the IRR was lower in all cancer sites (IRR, 0.62; 95% CI, 0.59-0.65) and in prevalent sites (lung, 0.39 [95% CI, 0.33-0.46]; prostate, 0.60 [95% CI, 0.55-0.66]; breast, 0.72 [95% CI, 0.59-0.87]; and colon, 0.71 [95% CI, 0.63-0.81]).
CONCLUSIONS AND RELEVANCE:
Warfarin use may have broad anticancer potential in a large, population-based cohort of persons older than 50 years. This finding could have important implications for the selection of medications for patients needing anticoagulation.
PMID: 29114736 DOI: 10.1001/jamainternmed.2017.5512
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