Allopurinol Reduces Left Ventricular Mass in Ischemic Heart Disease

February 25, 2013

By Will Boggs, MD

NEW YORK (Reuters Health) Feb 25 - Allopurinol reduces left ventricular mass (LVM) and improves endothelial function in patients with ischemic heart disease, researchers from UK report.

"Left ventricular hypertrophy (LVH) is a well-known risk factor whose regression is known to reduce sudden deaths, heart failure, and strokes," said Dr. Allan D. Struthers from the University of Dundee, Ninewells Hospital and Medical School in Scotland.

"So far only reducing blood pressure is known to regress LVH, and yet LVH persists in many with a controlled blood pressure. Our main message is that allopurinol is the first ever nonantihypertensive drug shown to regress LVH," he told Reuters Health by email.

Dr. Struthers and colleagues investigated whether nine months of therapy with allopurinol, a xanthine oxidase inhibitor, could regress LVM in 66 patients on optimal, evidence-based therapy for ischemic heart disease.

All of the patients in this randomized, placebo-controlled trial had an office blood pressure below 150/90 mm Hg and had LVH on echocardiography, according to the March 5 Journal of the American College of Cardiology report.

Allopurinol treatment reduced LVM by 5.2 g, whereas LVM dropped by 1.3 g in the placebo group (p=0.007); the LVM index was also significantly reduced in the allopurinol group compared with placebo.

Moreover, the within-group changes in LVM and LVM index were significant only in the allopurinol group.

Allopurinol significantly reduced left ventricular end-systolic volume and was associated with nonsignificant reductions in left ventricular end-diastolic volume and median B-type natriuretic peptide (BNP), compared with placebo.

Treatment with allopurinol also brought significant improvements in endothelial function and arterial stiffness, as evidenced by increases in flow-mediated dilation and reductions in augmentation index, respectively.

Office blood pressure and 24-hour ambulatory blood pressure did not change significantly with allopurinol treatment.

"Overall this means that allopurinol could be used to regress LVH in those with controlled blood pressure where no other method is known to be able to regress LVH, especially if they have concurrent ischemic heart disease," Dr. Struthers said.

"Previously as long as we treated blood pressure then we were doing all we could to regress LVH and therefore there was no need to identify those with persisting LVH despite controlled blood pressure," he added. "Since we now have a new way to regress LVH, then there is a greater need to screen for such patients because we can offer them a new treatment, i.e., allopurinol."

The trial was supported by the Medical Research Council in the UK. Dr. Struthers and his university have applied for a patent on the use of xanthine oxidase inhibitors to treat angina pectoris, and the researcher has been a consultant to Pfizer, Merck and Roche.

"The importance of this small single-center study lies in the fact that it adds further support for the development of xanthine oxidase inhibitors in the treatment of heart failure," an editorial on the new findings concludes.

"This class of drugs could address a pathophysiologic pathway in heart failure that is currently unaddressed -- nitroso-redox imbalance. More research is warranted on optimizing the drugs and approaches," Dr. Joshua M. Hare from University of Miami Miller School of Medicine in Florida, who co-wrote the editorial, added in an email to Reuters Health.

"There are longstanding ongoing attempts to develop inhibitors of xanthine oxidase for the treatment of heart failure," Dr. Hare added. "We tested this in the OPT-CHF study published in JACC in 2009. Only patients with high uric acid levels benefited. There is an ongoing trial now being conducted by the NIH. So the jury is still out on the eventual use of this class of drugs."


J Am Coll Cardiol 2013;61:926-932,933-935.