Common BPH medications raise cardiac failure risk

The most common medications used in routine care to manage lower urinary tract symptoms due to benign prostate hyperplasia (BPH) are associated with an increased risk of cardiac failure, according to a recently published population-based study.¹

Investigators studied data on more than 175,200 men with BPH treated with 5-alpha reductase inhibitors, alpha blockers, or a combination. They found that men treated with either therapy or a combination had a statistically increased risk of cardiac failure compared with those who did not take the medications. The highest risk for cardiac failure was among BPH patients taking alpha blockers alone or in combination, according to the study published in The Journal of Urology.

There are 2 key points for urologists, said study author D. Robert Siemens, MD, professor and Chair of Urology at Queen’s University School of Medicine, Ontario, Canada.

“This adds to the evidence that there may be some degree of association between symptomatic BPH and cardiovascular health. When we looked at those men with a diagnosis of BPH, there was a stronger association with new cardiac failure for those who had filled a subsequent prescription for medical therapy compared to those who didn’t. Conceptually, those who are diagnosed with lower urinary tract symptoms bad enough to fill a script for medical therapy may share some risk factors for cardiovascular disease,” Siemens said. “Secondly, the alpha blockers (maybe specifically nonselective alpha blockers) have a higher association with new cardiac failure. The absolute increase is low but still independent after adjusting for other well-known heart disease risk factors.”

The issue of cardiac failure and alpha blockers arose almost 20 years ago in the ALLHAT trial (NCT00000542), among the first studies to highlight a possible link between alpha blockers and hypertension. The landmark trial created some splash in the urological community, according to Siemens, but was followed with relatively little investigation and mixed results from other nonrandomized studies, he said.

“Potential mechanisms for the associations between cardiac failure and [5-alpha reductase inhibitors] include the deleterious impact on metabolic disorders and cardiac function through their antiandrogen effect and blockage of serum testosterone conversion to dihydrotestosterone,” wrote the authors of the current study. “[Alpha blocker] association with cardiac failure, on the other hand, may be linked to their vasodilatory effects and blood pressure variability.”

The data set Siemens and colleagues studied included 8339 BPH patients exposed to 5-alpha reductase inhibitors, 55,383 exposed to alpha blockers, and 41,491 who had taken a combination. Cardiac failure risk was an average 22% higher among those exposed to alpha blockers alone; 16% higher on combination; and 9% higher among men exposed to 5-alpha reductase inhibitor therapy alone. Nonselective alpha blocker treatment had an 8% higher risk of cardiac failure than selective alpha blocker therapy, according to the paper.

“Although it hasn’t changed my practice that much—I still of course use alpha blockers—it has made me more diligent in assessing cardiovascular health,” Siemens said.

The evidence also makes Siemens discuss the choice of his primary care colleagues’ use of nonselective alpha blockers when they are being prescribed for lower urinary tract symptoms. Hopefully, he said, the study highlights for urologists and primary care physicians that having lower urinary tract symptoms due to BPH should indeed make them think about cardiovascular health and consider it when evaluating and managing symptoms.

“Perhaps it should add to the shared decision-making discussion around long-term medical management for BPH [adding to the list of already well described, albeit usually minor side effects]. And perhaps it should add to the discussion around earlier surgical management, especially increasing minimal invasive techniques. That said, the evidence level this provides does not allow one to advocate for any changes in routine, guideline-concurrent care,” he said.

Siemens said that he believes this is the largest observational, population-based study of all men diagnosed with BPH and managed in routine care.

In an accompanying editorial comment,² Omar Salim Akhtar of the Government Medical College in Kashmir, India, asked about the incidence of cardiac failure in patients younger than 65 who need to be treated for BPH, who were not part of this study. Conceptually, the mechanism of alpha blocker association with cardiac failure may been linked to vasodilatory effects and BP variability, as well as other risks in the aging male, according to Siemens. “So, one could only make conjecture that there would be less of a strong association with those younger men with lower urinary tract symptoms,” Siemens said.

References

1. Lusty A, Siemens DR, Tohidi M. Cardiac failure associated with medical therapy of benign prostatic hyperplasia: a population based study. J Urol. Published online February 22, 2021. doi:10.1097/JU.0000000000001561

2. Akhtar OS. Editorial comment. J Urol. Published online February 24, 2021. doi:10.1097/JU.0000000000001561.01