Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville
Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Another Look at Bleeding Risk from Aspirin

Source: De Berardis G, et al. JAMA 2012;307:2286-2294.

THE ROLE OF ASPIRIN (ASA) FOR PRIMARY prevention of cardiovascular (CV) events has been a beleaguered topic for more than a decade. Although the risk reduction from ASA for secondary prevention of CV events clearly outweighs the bleeding risk, the balance for primary prevention of CV events is much less weighted toward the benefits side of the equation. Indeed, recent consensus groups have relied on the additional ASA benefits for prevention of colon cancer to make a case that when added to marginal CV event reduction, total risk reduction is sufficiently powerful to give primary prevention the green light.

De Berardis performed an analysis of bleeding risk among adults in Puglia, Italy, during the 2003-2008 interval. To qualify as a bleeding event, the study subject had to be hospitalized for either a gastrointestinal or intracerebral bleeding episode. A direct comparison between adults who received new prescriptions for low-dose (≤ 300 mg/d) ASA (n = 186,425) and matched controls who had not been prescribed ASA (n = 186,425) was done. A second question was whether the effects of ASA were different in diabetics than in others.

In the population as a whole (on ASA and control), diabetics had a higher risk of bleeding than non-diabetics, independent of ASA. Given that two recent randomized, controlled trials of ASA in diabetics have failed to show a CV benefit, the apparently inherently increased risk for bleeding in diabetics is concerning.

Can Aspirin Prevent Recurrence of Thromboembolism?

Source: Becattini C, et al. N Engl J Med 2012;366:1959-1967.

CURRENT RECOMMENDATIONS FOR MANagement of proximal deep venous thrombosis or pulmonary embolus suggest a minimum of 6 months treatment with a vitamin K antagonist (warfarin). Although more prolonged use of warfarin does continue to reduce the risk of recurrent DVT, the cost, inconvenience, and bleeding risk of long-term warfarin is substantial. Since as many as 20% of persons with an unprovoked thromboembolic event will suffer a recurrence within 2 years of warfarin discontinuation, well-tolerated agents to reduce this risk would be very welcome.

Becattini et al randomized patients (n = 402) who had sustained unprovoked thromboembolism and completed a standard therapeutic course of warfarin (6-18 months) to either 100 mg/d ASA or placebo. Study participants were followed for 2 years, looking at the incidence of new thromboembolism (primary efficacy outcome) and major bleeding events (primary safety outcome).

Risk of thromboembolism was reduced by 42% in the ASA group compared to placebo (6.6% vs 11.2% new events/yr). Major bleeding was uncommon and not different between the groups (one event each group).

At the conclusion of an approved course of warfarin post-pulmonary embolus, clinicians and patients are presented with the difficult choice of whether to continue warfarin long-term. These results are encouraging that low-dose ASA has a meaningful potential role in long-term secondary prevention of thromboembolism, especially when warfarin continuation is not a desirable option.

A New Approach to Tinnitus

Source: Cima RFF, et al. Lancet 2012; 379:1951-1959.

I WAS SURPRISED TO LEARN THAT AS MANY as 21% of adults will develop tinnitus (TIN) during their lifetime, as stated by Cima et al in the introduction to this clinical trial. Persons who develop TIN can experience a major decrement in quality of life. Despite thorough investigation, it is uncommon to find a correctible cause for TIN, which often persists indefinitely. Sufferers are left with sound-based therapies (e.g., a “masking” sound or neutral sound that distracts from the annoyance of the TIN sound) or cognitive behavioral treatment. Clinical trials to support either of these modalities are thus far somewhat insufficient.

Cima et al randomized TIN patients in the Netherlands to usual care vs specialized care (intervention). Components of specialized care included 8 weeks of intensive audiological diagnostics, audiological rehabilitation sessions, and individual cognitive behavioral therapy, followed by 12 weeks of group cognitive behavioral therapy.

At 12 months, the intervention group enjoyed a significant improvement in quality of life compared to usual care. TIN can create TIN-related catastrophic thinking; this aspect of the disorder was also improved to a greater degree with the specialized care. The authors note that efficacy was not altered by TIN severity; hence, all TIN sufferers might benefit from consideration of this methodology.