Years after ALLHAT, alpha-blocker use common, risky

The risk of cardiovascular and hypotension-related events is higher with alpha-blockers than with other hypertension drugs, but almost 20 years after the pivotal ALLHAT trial first raised safety concerns, they are still widely used, according to investigators.

ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) linked the alpha-blocker doxazosin (Cardura) to an increased risk of heart failure and stroke, which led to the early cessation of the doxazosin arm. Guidelines no longer include alpha-blockers among the primary options for hypertension.

However, there’s been some doubt about ALLHAT; doxazosin patients had diuretics withdrawn as part of the study, which might have contributed to the increased risks. “A lot of arguments have been made that perhaps alpha-blockers aren’t that bad and maybe should still be used, so we took a second look,” said lead investigator.

What he and his team found “confirmed and expanded on the findings of ALLHAT.” Apart from a few specific situations, “don’t prescribe alphablockers. If a patient is on an alpha-blocker, consider prescribing an alternative,” investigator said .

The drugs are still widely used, according to the team’s review of health data. From 1995 to 2015, nearly 81,000 patients were prescribed alpha-blockers for hypertension, sometimes as monotherapy, with no real downward trend in prescriptions over time.

There are some selected indications for alphablockers, including intolerance of other antihypertensives, pheochromocytoma management, and resistant hypertension. “So I thought maybe there would be 5,000 or 10,000. The fact that we found almost 81,000 was an eye-opener. I’m pretty sure 81,000 patients in Ontario don’t have resistant hypertension,” investigator said.

Patients with benign prostatic hypertrophy, another indication, were excluded from the study.

Before ALLHAT, alpha-blockers were considered first-line drugs, so maybe prescribers are just “sticking with something they know and are familiar with,” he said.

To assess the risks of continued use, the investigators used propensity scoring to match 69,092 patients prescribed alpha-blockers to 69,092 who were prescribed other antihypertensives, based on age, comorbidities, date of treatment, and a slew of other potential confounders. Patients were considered to be on an alpha-blocker only when they were filling prescriptions for the drugs. If they were not filling prescriptions they flipped into the unexposed arm.

The incident rates of ED visits and hospitalizations for hypotension and related complications – syncope, falls, and fractures – were markedly higher among alpha-blocker users. After adjusting for the total number of antihypertensives patients were on, those on alpha-blockers were 34% more likely to go to the ED or be hospitalized for hypotension, 49% more likely for syncope, 27% more likely for falls, and 41% more likely for fractures. First-dose effects don’t explain the findings; patients were often on alpha-blockers for years beforehand.

Alpha-blocker patients were also 26% more likely to have a major cardiovascular event, including heart failure and MI. The risks were greatest in those older than age 85 years. The results were all statistically significant.

About 9,000 alpha-blocker patients had a fracture versus 3,351 matched patients on other antihypertensives; “9,000 patients out of 70,000 is a huge number. These drugs are useful in some situations, but be careful.”

This is observational data, but it’s consistent with ALLHAT, and the outcomes are even worse. We didn’t in [subsequent] guidelines say that you should [never] use an alpha-blocker in hypertension. Maybe we should have.