“Millions of healthy people with no obvious sign of illness could be put on cholesterol-lowering drugs” says The Daily Telegraph. The front-page story discusses the possibility that these cholesterol-reducing statin drugs might be more widely prescribed as a measure to cut the risk of health problems like heart attacks. The newspaper also highlights new research that it says shows statins are even more effective than was previously thought for people who appear healthy.
For several years the study followed the use of statins by 230,000 people with and without cardiovascular disease. It was designed to test what happens in practice when people discontinue statins, rather than to compare people who took statins to those who did not. It found that those who took over 90% of their medication reduced their risk of death by 45% compared with people who only took 10% of their medication.
Raised cholesterol has long been recognised as one of the risk factors for heart attacks, and statins are a valuable daily protective medication for people at risk of a cardiovascular event such as a heart attack. However, statins can have harmful effects and are not required for everyone.
Each person who is considered for statin medication should continue to have their individual coronary (heart-related) risk assessed according to their blood cholesterol level, age, sex and the presence of other risk factors such as diabetes, high blood pressure and smoking.
Where did the story come from?
This research was conducted by Dr Varda Shalev and colleagues of the Medical Division, Maccabi Healthcare Services (MHS), and Sackler Faculty of Medicine, Tel Aviv University, Israel. No sources of funding were reported. The study was published in Archives of Internal Medicine, a peer-reviewed medical journal.
What kind of scientific study was this?
This was a cohort study investigating the effect that statin drugs have on death from any cause in people with and without a history of cardiovascular disease. The researchers also looked at mortality in people who already have established cardiovascular disease, although evidence in this area is already more clearly established.
The researchers examined medical records from MHS, the principal health organisation in Israel. They identified all new users of statins between January 1998 and December 2006, with statin use being defined as having at least one prescription filled within this period. The date of first prescription was used to define an index date for subjects. This gave a total of 229,918 eligible people.
The researchers divided the cohort into two: those with any diagnosis of cardiovascular disease prior to the prescription (hence taking statins as secondary prevention against another cardiac event), and those without any identifiable cardiovascular disease diagnosis prior to prescription (taking a statin for primary prevention). All information on medical diagnoses was identified through the MHS and medical records, laboratory reports, hospital notes and so on.
From the index date, the researchers looked at the period of time statins were first taken until either time of death, leaving the MHS or the end of the study period (December 2006), whichever came first. Statin medications were classed into three groups (low, moderate and high efficacy) according to the drug used and dose taken.
They also collected information on socioeconomic data, disability, other hospital admissions and outpatient visits, and other prescription drugs. Information on mortality was obtained through the Israel National Population Registry and the National Insurance Institute.
What were the results of the study?
A total of 93,866 individuals in the secondary prevention group (those with established cardiovascular disease) and 136,052 individuals in the primary prevention group (those without) were identified as being newly treated with statin drugs during the study period.
The total study population was reported to be representative and was 21.6% of the entire MHS adult population. There were equal proportions of men and women in the cohort and average age was 57.6 years, with slightly older people in the secondary prevention group.
During the study period, 13,165 individuals (5.7%) died and 3,745 (1.6%) left the MHS. Within the primary prevention group (those with cardiovascular disease) the average follow-up was 4.0 years. The group featured 4,259 deaths (7.8 per 1,000 person years). Within the secondary prevention group the average follow-up time was 5.0 years, and there were 8,906 deaths (19.0 per 1,000 person years). Several medical comorbidities were associated with increased risk of death, for example diabetes, cancer and high blood pressure.
Continuity of statin use was defined in terms of “proportion of days covered” (PDC). In both groups, a PDC of 90% was associated with at least a 45% reduction in risk of death from any cause compared with those with a PDC of less than 10%. Also, in both groups, reduction in mortality risk was greatest by a significant degree for those who were treated initially with a high-efficacy statin.
What interpretations did the researchers draw from these results?
The researchers conclude that improved continuity of statin treatment provides an ongoing reduction in deaths from any cause among people with and without a known history of cardiovascular disease.
They also say the observed benefits from statins were greater than shown by previous randomised controlled trials.
What does the NHS Knowledge Service make of this study?
This study has demonstrated a link between improved overall survival and use of statins in people with and without known cardiovascular disease. The study is strengthened by being of very large size, having a relatively long duration of follow-up and including a large proportion of adults enrolled in the Israel health system who were taking statins.
There are points to note when interpreting this research:
- The study featured several statistical comparisons to look for different associations between statin use, other factors and risk of death from any cause. This may have increased the risk of inaccuracy in the risk estimates.
- Although the study has used reliable sources of data, there is still the possibility of missed or inaccurate information on the duration or frequency of statin use or misclassification of medical diagnoses. Continuity of statin use was estimated based on dispensing information, but whether or not statins were dispensed cannot prove that they were actually taken.
- One limitation to the conclusions of this study is that, though there is mention of the reduction in risk of mortality being greater than previously demonstrated in clinical trials, all people in this study were using statins, and so investigation of whether statin use reduced risk compared to no use of statins was not tested. Randomisation to statin use or not would still be the best way to assess whether statin use reduced overall risk of death.
- All people in this study were using statins, and so investigation of whether statin use reduced risk compared to no use of statins was not tested. Despite adjustments made in the study design it is possible that people who stop taking statins are different in some way, for example having poorer health behaviour in general, than those who continue taking the drugs. This might have affected the increased risk of death.
Statins can have adverse effects and are not needed by everyone. Each person who is being considered for a statin medication should continue to have their individual coronary risk assessed according to their blood cholesterol level, age, sex and presence of other risk factors such as diabetes, high blood pressure and smoking.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Telegraph, 9 February 2009
Links to the science
Arch Intern Med. 2009;169(3):216.