October 14th, 2013
The Benefits of Switching From Hydrochlorothiazide to Chlorthalidone: What’s Stopping Us?
As a medical student, I’m currently on a nephrology service and hypertension, cardiovascular (CV) events, and diuretics have been on my mind a lot, particularly the issue of chlorthalidone (CTDN). Released at about the same time as hydrochlorothiazide (HCTZ) — 1959 and 1960, respectively — there is great evidence of CTDN’s non-inferiority, and with the exception of a study published a few months ago in the Annals of Internal Medicine that garnered some strong critiques of its validity, CTDN has consistently shown to be superior to HCTZ for the prevention of CV events in every analysis short of a head-to-head randomized, controlled trial. Additionally, the medication benefit cannot entirely be explained by the difference in systolic office blood pressure, which points to some other beneficial mechanisms.
Researchers at St. Vincent’s Medical Center in Bridgeport, CT, have published a nice analysis using data collected on over 50,000 patients from various trials that shows the calculated percentage risk reduction of CV events in patients with congestive heart failure who were prescribed CTDN vs. HCTZ was 23% (95% CI, 2-39; P=0.032), and in all CV events was 21% (95% CI, 12–28; P<0.0001). Relative to HCTZ, the number needed to treat with CTDN to prevent one CV event over five years was 27.
What other medication class could have a drug that is 23% more effective than standard practice with an equivalent side effect profile and the result not be considered a major breakthrough? If there are over 134 million prescriptions of HCTZ (48 million as the sole blood pressure medication), that’s 4.96 million fewer CV events in five years. This benefit could be gained simply by switching from one monetarily equivalent, generic, pharmacologically similar medication to another.
The part that bothers me is that this is something the more academically inclined clinicians are aware of and occasionally write about, lamenting how this is an unfortunate issue. It wasn’t hard to find articles on the data and information I listed above. If our ultimate goals are to be patient advocates and promoters of health, isn’t this something we should be actively trying to change? When I ask doctors about why they don’t prescribe it, I usually get:
1. I haven’t heard of that medication.
2. I didn’t know there was anything better.
3. It is only offered in combination with three other blood pressure meds.
4. It only comes in a dose that’s twice the actual recommended starting amount.
The first two reasons are a failure of dissemination and implementation of ideas, which to me are issues that should be soon resolved now that we live in a connected world that is transitioning care to EMR-based systems. It would be easy to have a clinical decision tool to search every patient on HCTZ and ask if you’d like to switch them to CTDN. To think that the flow of ideas still operates in Balas and Boren’s “17 years, 13% translation” is frustrating, and I think the CDC or the AHA could do more to promote these changes. Is a campaign to prevent almost 5 million CV events in five years unappealing? Can some monetary incentive (reward or punishment) be incorporated as part of the new focus on pay-for-performance?
The second two reasons are flaws in U.S. health policy. The fact that the only way drug regulatory changes occur is when a company stands to benefit monetarily is fully exposed in this setting. If Medicare is one of the major purchasers of these medications, as well as the sufferer of poor outcomes that can occur with CV events, the federal government would benefit monetarily from this change, as well. Is there a reason why it could not act like a commercial entity to apply to the FDA to allow for CTDN to be combined with the same medications as HCTZ? Or that it should be able to be dispensed at 12.5 mg a tablet rather than 25 mg?
Irrespective of the benefit the government would receive, how is it that this profession and organizations like the Patient-Centered Outcomes Research Institute don’t put forth a more concerted effort to tackle such an issue? No new incredible drugs need to be made. No fantastic leaps in science or efficiency. What stands in the way is simply a bureaucratic issue that’s non-ideological, and the overwhelming majority agree that these changes will lead to better health outcomes. What are the actual steps that would be necessary for regulatory approval for combination medications for something that has been reliably used with other hypertension medications for close to half a century?
It frustrates me because of how frequently physicians claim that the problems with healthcare in the U.S. are beyond our control. In recent surveys we place more blame on insurance companies, hospital management, etc., than we do ourselves. But when we have the opportunity to truly be an advocate for something that could have a tangible and meaningful impact far beyond an HCAHPS survey or proton accelerators for prostate therapy, we don’t go beyond decrying the reality of what is, and proceed to do nothing to change the problem.