May 2nd, 2014
A New Tool to Discuss Primary Prevention with a Statin with Patients: Life Expectancy Gain
A new Circulation study explores the spectrum of individual medication disutility for primary prevention of cardiovascular disease (CVD) in a sample of the general population, and juxtaposes it against the spectrum of expected longevity gain from initiation of statin therapy. Authors Darrel Francis, Professor of Cardiology at the National Heart and Lung Institute, Imperial College London, and Judith Finegold, Clinical PhD trainee in Cardiology, put the study’s findings into perspective for CardioExchange.
When we advise a patient on primary prevention of CVD we face a paradox. Current primary prevention practice recommends starting therapy largely based on cardiovascular risk. As age increases, annual risk goes up, which guideline convention interprets as increasing reason to initiate cardiovascular prevention (e.g., with statins). Taking this reasoning to its logical conclusion, however, initiation of statins would become mandatory in all of the very elderly. Practicing clinicians may feel uncomfortable with that concept.
There are two possibly unhelpful features of our current formal processes for deciding whether to recommend treatment with (for example) statins:
1. We judge the utility of initiating statin therapy, for life, based on artificially short time windows (e.g., 10 years), rather than examining lifetime benefit in terms of lifespan gain.
2. We assume that patients will universally consider prevention to be so desirable that it would always offset the inconvenience of having to take daily medication for life.
In our recently published study we present a new way of thinking about the pros and cons of cardiovascular primary prevention, and we propose two changes:
1. Estimate the benefit (utility) in terms of increase in life expectancy.
In our study we calculate not cardiovascular risk but life expectancy (i.e., lifespan) gain from a primary prevention intervention such as a statin (Figure 1). The pattern of life expectancy gain seems at first familiar, with increasing blood pressure and cholesterol associated with higher values (redder colors), but it has one crucial difference: Cardiovascular risk increases with increasing age, but life expectancy gain from statin initiation reduces with age of initiation. Initiating a lifetime of statins adds more to life expectancy if it is done earlier than later.
Figure 1. Distinction between cardiovascular risk and life expectancy gain. Both increase with increasing cholesterol and increasing blood pressure; but while risk (left panel) increases with age, the life expectancy gain from initiating a lifetime of preventative therapy (right panel) decreases with age. (The right panel is a simplified version of a chart in our paper, Fontana et al, Circulation 2014.)
2. Assess the patient’s willingness to take even an idealized medication to increase life expectancy: you might be surprised.
Population health policies have been based on the assumption that most people do not mind taking medication to increase their life expectancy, and, if patients do mind, this displeasure (called “disutility”) is so small as to be negligible compared to the financial cost of statins. However, with patent expiry, the financial cost of statins has fallen to near zero, so cost-effectiveness analyses can no longer afford to assume that disutility is zero or near-zero in everyone.
There are many reasons for not wanting to be on medication. We wanted to determine the lower limit on disutility in each subject, i.e., the disutility in an idealized situation where these main reasons are artificially removed. Real-world disutility is likely to be higher than that (but cannot be lower). We asked respondents to imagine a tablet treatment that had (a) no side effects, (b) no significant cost to them, (c) no requirement to visit a doctor, and (d) no consequences (apart from corresponding partial loss of benefit) of missing doses or stopping and restarting treatment at will.
Our study surveyed the general public. It found that, while there are many people who would be happy to take such an idealized medication for a small increase in life expectancy, there are also many who would do so only if the life expectancy increase was large. In fact, there is a substantial group who would not take daily medication even if it gave them 10 extra years of lifespan.
Figure 2. Juxtaposition of distribution of disutility (dislike of taking regular medication, upper panel) against distribution of utility (life expectancy gain from taking a statin, lower panel) in the general population. For patients with low disutility (green), regardless of their level of risk factors (and therefore utility) it appears rational to take preventative medication. For patients with high disutility (red), regardless of their level of risk factors, disutility seems to exceed utility. For the patients in between (the grey zone), the net effect of utility and disutility depends on their individual level of risk factors. Expressing both utility and disutility on a common scale, of extra life expectancy obtained or demanded, permits them to be juxtaposed easily and discussed openly. Redrawn from data in our paper, Fontana et al, Circulation 2014.
Our study indicates that there may be many patients whose dislike of daily medication may exceed the benefit delivered by statins. This becomes easy to see when both are expressed in common units such as lifespan gain.
It should be remembered that we have assessed only a lower limit on real-world disutility. We specifically asked respondents to assume there were no side effects. We did this to set aside the public controversy on whether statins do frequently cause side effects. A recent study from our group has examined the randomized blinded trial evidence on symptoms reported on statins versus on placebo, where both groups are given the same background information and same level of inquiry regarding symptoms. It found that under these blinded conditions there is very little difference between groups (i.e., very little incremental effect of statins). This information may at first seem difficult to believe when symptoms (such as muscle ache) are so common in daily primary prevention practice. However, the key message is not that the symptoms do not occur with statins, but rather that they occur equally on placebo when patients undergo the same level of questioning with neither the patient nor doctor knowing whether they are taking the real statin.
This calculation is not universally accepted because not everyone agrees that randomized, blinded, placebo-controlled data are the most reliable way to detect genuine mechanistic causation from other phenomena, as we have seen in the recent commotion over renal denervation . The powerful risk of bias from prior belief arising from our unblinded daily experience is all the more reason to seek out blinded data.
A new way to support primary prevention consultations?
Taken together, both our current and recent studies offer options for better-informed and more individualized consultations:
1. Doctors can now show patients charts that convey benefit of statin intervention in a readily understood language: that of life expectancy gain.
2. Doctors and patients now have reliable information on side effects, coming from 80,000 patients in blinded randomized controlled trials of statin versus placebo.
3. Patients can express their individual level of dislike of taking lifelong medication using the same metric (lifespan gain) as used to express benefit.
Ultimately, patients must make their own decisions and we must support them with the best quality information we can obtain.
Do you think the tools described here may be useful towards making primary prevention choices truly personalized?