Alpha blocker initiation tied to increased stroke risk in non-hypertensive men

By Anne Harding

NEW YORK (Reuters Health) - Men who start taking alpha blockers face an increased risk of ischemic stroke, especially if they are not taking other antihypertensive drugs, according to a new study.

"We suggest physicians who intend to prescribe alpha blockers for patients without hypertension to start with a lower dosage, with slow up-titration, and educate patients about self-monitoring of blood pressure after initiation of the drugs," Dr. Chao-Lun Lai of National Taiwan University Hospital Hsin-Chu Branch in Hsin-Chu, Taiwan, told Reuters Health by email.

Alpha blockers, most commonly used to treat benign prostatic hyperplasia, can cause acute hypotension when people begin taking them, Dr. Lai and colleagues write in their report, published online December 7 in CMAJ.

This "first-dose effect" has been linked with dizziness, falls and hip and femur fractures. Given that acute cerebral hypoperfusion may bring on ischemic stroke, the researchers sought to investigate whether patients starting alpha blockers would also be at increased ischemic stroke risk.

Using Taiwan's National Health Insurance claims database, the researchers identified 7,502 men 50 and older in 2007 who started using alpha blockers and were diagnosed with an ischemic stroke between 2007 and 2009. They designated the first day of a patient's alpha blocker prescription as the index date, and looked at the incidence rate ratio (IRR) of ischemic stroke before and after exposure.

Pre-exposure risk period 1 was 21 days or less before the index date and pre-exposure risk period 2 was 22-60 days before. Post-exposure risk periods 1 and 2 were less than 21 days after and 22 to 60 days after the index date, respectively.

The overall adjusted IRR for ischemic stroke was 1.40 during post-exposure risk period 1, while it was 2.11 for those who were not taking other antihypertensive medications - both significant increases.

When the investigators looked separately at patients with prescriptions for other blood-pressure-lowering drugs, the IRR for stroke was not significantly different from 1 in post-exposure risk period 1, but was significantly reduced in post exposure risk period 2 (IRR, 0.67).

"Because the risk of ischemic stroke was not observed amongst patients with concomitant prescriptions of other anti-hypertensive drugs, alpha blockers can still be prescribed liberally for patients with underlying hypertension," Dr. Lai said. "Only patients without pre-existing hypertension carry the risk of hypotension-associated adverse events."

Dr. Lai and his colleagues had previously shown that alpha blocker therapy initiation was associated with an increased risk of hip and femur fracture, but only among patients without hypertension.

"We observed similar results after the initiation of diuretics and calcium channel blockers," he added. "It might be a group effect of all hypertensive agents concerning the adverse effects of acute cerebral hypoperfusion and acute ischemic stroke. More pharmacoepidemiological studies are needed to clarify this issue."

The researcher concluded: "Careful titration of dosage during the initiation period of alpha blockers seems mandatory for patients without hypertension."

SOURCE: https://bit.ly/1YWfEd9

CMAJ 2015.