People older than 65 years are at increased risk for cardiovascular disease (CVD). Such disease accounts for more than 80 percent of deaths in this population. Age itself appears independently associated with risk, and risk factors such as high blood pressure, lipid disorders and diabetes are common among the elderly. An important question facing the medical community is whether statin drugs can reduce risk among elderly people without established CVD. Limited clinical research is available addressing statin treatment among healthy individuals above 65 years old.
Recently a meta-analysis was published by Savarese and coworkers in the Journal of the American College of Cardiology (JACC) addressing the effects of statins in elderly subjects without established cardiovascular disease. Eight trials were included in the final analysis. The results made the headlines and the message was quite clear. The authors concluded that their “meta-analysis provided the first-time evidence that the benefits of statins on major cardiovascular events extended to people above 65 years old”. Such a message is certainly something for authors of clinical guidelines to chew on.
In an accompanying editorial in JACC, David D. Waters, MD, wrote: “Older people differ more among themselves than younger people do in many ways, and the decision to treat or not treat an older individual with a statin often requires clinical discernment. The clear results of this meta-analysis will hopefully lead to more older individuals receiving treatment that vill reduce their cardiovascular risk”.
Savarese and coworkers conclude from their meta-analysis that 24 patients need to be treated with statins for a year to prevent one heart attack (myocardial infarction) and 42 patents need to be treated for a year to prevent one stroke. However, I suspect they may have miscalculated their data. My calculation, based on data presented in the paper, indicates that the number needed to treat (NNT) is approximately ten times higher. If this is true the effect of statin therapy is seriously exaggerated in the paper.
The Number Needed to Treat.
The meta-analysis by Savarese and coworkers did not show a significant effect of statin treatment on mortality compared to placebo. Myocardial infarction occurred in 2.7% of subjects allocated to statins compared with 3.9% of those on placebo during a mean-follow up of 3.5 years. The annual rate of myocardial infarction was 1.1% on placebo and 0.8 percent on statins. The absolute risk reduction is about 0.3 percent. Although the risk reduction is statistically significant, it is obvious that the number of patients needed to be treated for a year to prevent one event can not be 24.
The NNT is the inverse of the absolute risk reduction (ARR): NNT = 1/ARR.
- If ARR is 1 percent, the NNT will be 100 (1/0.01).
- If ARR is 10 percent, the NNT will be 10 (1/0.1).
- If ARR is 0.1 percent, the NNT will be 1.000 (1/0.001).
Accordingly, if the absolute risk reduction that is less than 1 percent, the NNT will always be above 100.
My calculation based on data from Table 2 in the paper indicates that about 234 patients need to be treated for one year to prevent one myocardial infarction, and that about 389 patients need to be treated for one year to prevent one stroke. I hope someone corrects me if I’m wrong. If I’m right, I may have a hard time understanding how such miscalculation can survive a peer-reviewed process in a respected medical journal. NNT is an important number to look at when deciding whether to give a certain treatment or not.
Studies of statins in primary and secondary prevention suggest these drugs increase the risk of diabetes. For comparison, it is estimated that 250 patients need to be treated with a statin for one case of diabetes to be caused. So by looking at the data we can assume that by treating 250 elderly people with statins for a year, we may actually exchange one myocardial infarction for one case of diabetes .
The Emperor's New Clothes
One of the authors of the above mentioned meta-analysis, Dr. Antonio Gotto JR said in an interview following the publication of the paper: “Taking statins may not prolong life in older adults, but it may certainly improve the quality of life for people who might otherwise become disabled by heart attacks and strokes”.
Savarese and coworkers point out that statins reduce the risk of myocardial infarction by 39.4 percent and the risk of stroke by 23.8 percent compared with placebo. These are the numbers they get when calculating relative risk reduction. The results are statistically significant, certainly suggesting a positive effect of statin therapy.
However, let’s look closer at the magnitude of treatment effect. An individual not given statin therapy has a 98.9 percent chance of not having a heart attack, and a 99.2 percent chance of not having a stroke in a year. If given statins, the chance of not having a heart attack will be increased to 99.2 percent and the chance of not having a stroke will be increased to 99.4 percent. Not very impressive if we look at it this way.
Keep in mind when looking at these numbers that we don’t have access to data on the side effects of statins from these trials. Furthermore, it is possible that older people are more vulnerable to side effects than young people. There is evidence of harm linked to statins when given to elderly individuals, including muscle pain, liver disorders, impaired memory, increased risk of diabetes and gastrointestinal stress.
In my opinion, the meta-analysis by Savarese and coworkers does not provide strong support for statin treatment of elderly people with elevated cardiovascular risk. More data is needed until such marching orders are given to practicing clinicians.