Monday October 10 2011
The study found associations but they are still unclear
Beta-blocker drugs could be a “skin cancer ‘lifesaver’,” the Daily Mail has today reported. The newspaper said that the inexpensive heart pills “could save the lives of thousands of patients with the deadliest form of skin cancer”.
This news is based on research examining how the risk of death among patients with malignant melanoma skin cancer related to their use of beta-blocker drugs, which are often used to treat heart problems and high blood pressure. Using Danish medical records on over 4,000 patients, researchers identified those who used beta-blockers before their cancer diagnosis and compared their survival with patients who had never used them.
Contrary to what news reports might have suggested, they found the use of beta-blockers was not linked to the risk of dying from melanoma, although it was associated with a reduced risk of death from other causes.
The design of this study and the fact that it did not record certain types of vital information (such as specific cause of death) means it can only suggest a relationship between beta-blockers and death risk but not expand upon the reasons why.
While it is possible that these commonly used drugs genuinely did prevent deaths in this study, more data will be needed confirm that this is the case. In addition to this, why this occurred and why the drugs did not reduce deaths from melanoma in any meaningful way also needs to be established.
Where did the story come from?
The study was carried out by researchers from Ohio State University in the US and Aarhus University Hospital in Denmark. The research was funded by the US National Institutes of Health, and the Gilbert and Kathryn Mitchell Endowment.
The study was published in the peer-reviewed journal Cancer, Epidemiology, Biomarkers & Prevention.
The reporting on this research had a number of flaws and the Daily Mail’s headline describing beta-blockers as a ‘skin cancer lifesaver’ that keeps tumours from growing is inaccurate. The study did not directly assess the impact of previous beta-blocker use on tumour growth.
The newspaper also quoted figures suggesting a reduced risk of death from melanoma among patients who had taken beta-blockers within 90 days of diagnosis, but these figures were not statistically significant.
What kind of research was this?
This cohort study aimed to determine whether the use of beta-blocker drugs prior to patients’ melanoma diagnosis related to their subsequent risk of dying, either directly due to the cancer or from any cause.
The researchers say that evidence is increasingly pointing to the role of stress hormones in the progression of certain types of cancer, including melanomas. They hypothesised that the use of beta-blockers, which are commonly prescribed for the treatment of heart conditions, could be effective in preventing the growth of melanoma tumours through their ability to inhibit stress hormones known as catecholamines.
A cohort study is an appropriate design to assess the association between two factors (in this case previous medication use and death), although the observational nature of this study makes it an inappropriate method by which to determine causality.
What did the research involve?
The researchers identified all cases of malignant melanoma by examining data from three registries: the Danish Cancer Registry, the Causes of Death Registry and the Danish National Registry of Patients. They then used registry databases to collect information for all identified melanoma patients on:
- the exposure of interest, use of beta-blockers and other drugs
- the outcomes of interest, death due to melanoma or any cause
- the presence of possible confounding factors, such as age and the diagnosis of other illnesses and cancer stage at time of diagnosis
The researchers divided the melanoma patient cohort into subgroups based on the use of beta-blockers. The patients were split into three groups of those who had been prescribed beta-blockers in the 90 days before cancer diagnosis, those who had been prescribed beta-blockers more than 90 days before cancer diagnosis, and those who had never been prescribed beta-blockers.
The researchers then conducted two separate analyses. The first examined the risk of dying from melanoma in each group and the second looked at the risk of dying from any cause in each group.
What were the basic results?
The researchers identified a total study population of 4,279 melanoma patients in northern Denmark. The found that 660 (15.8%) of these patients had been prescribed beta-blockers before their cancer diagnosis. Of these:
- 372 (8.9%) patients had been prescribed beta-blockers within the 90 days prior to their cancer diagnosis. They had used the drug for an average of eight years.
- 288 (6.9%) patients had been prescribed beta-blockers more than 90 days prior to their cancer diagnosis and used the drug for an average of 27 years.
The remaining 3,619 participants had never used beta-blockers prior to their diagnosis. Among these participants:
- 314 (8.9% of the total study population) were prescribed the drug after their cancer diagnosis and used the drug for an average of 2.5 years.
- The remaining 3,305 patients did not use the drug before or after diagnosis. This group was considered to be ‘unexposed’ to beta-blockers.
The researchers found that those who had been prescribed beta-blockers at any time prior to cancer diagnosis tended to be older (in their 60s) and to take more cardiovascular drugs than the group with no exposure to the drug (who were in there 50s).
The researchers then analysed the risk of death within a given time period due to melanoma, controlling for the influence of age and the presence of other illnesses. They found that:
- There was no significant difference in risk of death in patients who had been prescribed beta-blockers in the 90 days before cancer diagnosis compared to those who had never taken beta-blockers. (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.64-1.20, p=0.408).
- Patients who had been prescribed beta-blockers more than 90 days before diagnosis had a 64% reduced risk of dying from melanoma compared to patients who had never used the drugs (HR 0.36, 95% CI 0.20-0.66, p=0.001). Only 11 of these long-term users had died by the time of the analysis.
When the researchers analysed the risk of death due to any cause within a given time period (all-cause mortality), adjusting for age and the presence of other illnesses, they found that:
- Patients who had been prescribed beta-blockers in the 90 days before diagnosis had a 19% reduced risk of dying from any cause compared to those who had never used beta-blockers (HR 0.81, 95% CI 0.67-0.97, p=0.02).
- There was no significant difference in risk of death from any cause in patients who had been prescribed beta-blockers more than 90 days before diagnosis compared to the unexposed patients (HR 0.78, 95% CI 0.60-1.00, p=0.052).
How did the researchers interpret the results?
The researchers conclude that their study uncovered an “association of beta-blocker use with reduced risk of death in patients diagnosed with malignant melanoma, the most deadly form of skin cancer”. They say that this observed increase in survival time ‘suggests that this class of drugs may hold promise (as a) treatment strategy for these patients’.
This study suggests that there is an association between beta-blocker use and risk of death from any cause in patients diagnosed with malignant melanoma. The research has the advantage of being a large, population-based study that used data from several regularly updated databases. This aids in ensuring that the sample of patients studied was representative of the wider population, and that the information on drug use and cause of death was accurate.
However, the study has several limitations that should be considered when interpreting the results. For example, the study was not controlled, and while the researchers attempted to adjust for likely or known confounding factors, there may be other unknown patient characteristics that account for the relationship. For example, heart failure is a common reason for prescribing beta-blockers but the researchers do not record the reasons why people were taking beta-blockers or how many died from heart failure.
The dataset used to perform the analyses was also incomplete. Across the whole study population, 18.4% of the patients had missing information on how advanced their melanoma was at time of diagnosis, and in the group who were taking long-term beta-blockers, 50% of patients did not have this data noted. This amount of missing information could result in bias.
Additionally, this study did not report the results of the association between beta-blocker prescription after diagnosis and risk of death. In order to understand whether beta-blockers could be prescribed as a treatment for patients with malignant melanoma these results would be valuable.
While the study does examine the association between beta-blocker use before diagnosis and reduced risk of all-cause mortality, this may be of limited clinical usefulness as it is unlikely that beta-blockers would be suitable as a long-term preventative measure given before the onset of any disease.
The researchers hypothesise that beta-blockers could be an effective means of inhibiting tumour growth, by preventing the formation of new blood vessels. However, this study did not test this hypothesis because it did not examine the formation of new blood vessels in the patients.
The researchers also say that previously published studies have indicated that beta-blockers may provide an effective treatment for melanoma patients. While this study may prove useful in terms of justifying further research, it does not in itself provide sufficient evidence for the use of beta-blockers in the treatment or prevention of melanoma.