I am Dr Henry Black, adjunct professor of medicine at the Langone New York University School of Medicine.
Of late, we are beginning to look at old drugs that might have new uses. This has been the case with spironolactone, for example, a mineralocorticoid antagonist. It has turned out to be good in heart failure and resistant hypertension.
There are also some ideas that this might be the case with allopurinol, a xanthine oxidase inhibitor widely used in the 1960s, 1970s, and 1980s. A couple of small studies in obese adolescents and adolescent patients with hypertension showed reductions in blood pressure.[1,2]
Is allopurinol a good drug for lowering blood pressure? That is the question that has been posed [in this study by Beattie and colleagues].
It is interesting because there is a plausible mechanism to explain why a xanthine oxidase inhibitor might reduce blood pressure and cardiovascular events. This also is seen with uricosuric agents, so is it just lowering of the uric acid level or is there something special about what allopurinol and similar drugs do?
This is an example of "big data." Investigators looked at the United Kingdom Clinical Practice Research Datalink to see whether they could tease out which individuals had received allopurinol. They looked at people who were older than 65 years of age, because there were no issues about paying for prescription drugs in that group. The sought to determine how many people were in that group and how the drug influenced their pressure.
Only 3% of the people in that very large database who were over the age of 65 had taken allopurinol. The investigators compared [a subsection of] these people [who had blood pressure readings taken before and after being prescribed allopurinol] with people who had not taken allopurinol, using a propensity analysis that matched people as closely as possible.
The findings were interesting: There was a modest reduction of blood pressure that was not related to the primary uric acid level or to other drugs the patients were taking (80% were on a thiazide diuretic, which can raise uric acid levels), and they saw an issue of physician preference for drugs. They also looked at patients who received no treatment or no change in treatment, with the same results. There was a hint, at least, in certain groups that allopurinol lowered blood pressure.
They recommended giving a high dose (≥ 300 mg daily) of allopurinol. No patient received a higher dose than 300 mg daily. Adolescents received 200 mg twice daily. This is a large assumption—that we ought to be giving people large doses of allopurinol, which can cause Stevens-Johnson syndrome and other side effects.
Before we embark on a good clinical trial, we had better decide whether we are willing to take on the risks associated with this agent. It is very good for the prevention of gout, but should we start giving it to people who don't have gout and to those in whom it is not indicated?
We will see. This may be a look at big data, but it might also be an abuse of big data before we can make recommendations for clinical practice.
- Soletsky B, Feig DI. Uric acid reduction rectifies prehypertension in obese adolescents. Hypertension. 2012;60:1148-1156. Abstract
- Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008;300:924-930. Abstract
- Beattie CJ, Fulton RL, Higgins P, et al. Allopurinol initiation and change in blood pressure in older adults with hypertension. Hypertension. 2014;64:1102-1107. Abstract