Clinical Briefs-By Louis Kuritzky, MD

Long-acting Beta2-Agonist Monotherapy vs. Continued Therapy with Inhaled Corticosteroids in Persistent Asthma

Current consensus documents recommend that for patients suffering persistent asthma, anti-inflammatory controller medication be instituted as first-line therapy, usually inhaled corticosteroids (ICSs). Long-acting beta agonists (LABA) show favorable effects on peak flow rates (PEF), asthma symptom scores, quality of life (QOL), and need for rescue short-acting beta agonists (SABA) in persons with persistent asthma. This 28-week study evaluated the effect of substitution of salmeterol for ICSs in patients with well-controlled asthma (n = 164).

Outcomes measurement—including PEF, asthma symptom scores, need for rescue SABA, and QOL—was not significantly different between asthmatics who were maintained on ICS and those substituted with LABA. On the other hand, LABA patients were 4 times as likely to experience treatment failure, and almost 3 times as likely to have exacerbations.

Asthma is acknowledged to be an inflammatory disease, with potential for detrimental airway remodeling. Lazarus and colleagues measured a variety of markers of inflammation in asthma, including sputum eosinophils, eosinophil cationic protein, and tryptase, each of which was less favorably impacted by LABA than ICSs. Lazarus et al conclude that for patients who are well controlled on ICSs, a switch to LABA may result in loss of asthmatic control, as well as relative augmentation of inflammatory markers.

Lazarus SC, et al. JAMA. 2001;285: 2583-2593.

Relation of Impaired Fasting and Postload Glucose with Incident Type 2 Diabetes in a Dutch Population

The burgeoning population of type 2 diabetes (DM2) patients in the United States is a matter of great concern to clinicians. Prevention of DM2 at this time rests upon identification of at-risk individuals. To this end, impaired glucose tolerance (IGT) is a helpful predictor: 23-62% of IGT patients progress to DM2 over long- term follow-up. We have less information about the predictive value of impaired fasting glucose (IFG). Much of the epidemiologic information in reference to progression from IGT to DM2 comes from populations with a disproportionate incidence of DM2, such as Pima Indians in the United States.

The current study investigated a large Caucasian population (n = 2484) age 50-75 years in the Netherlands who underwent both fasting and 2-hour post glucose load (75 g oral glucose) measurement on 2 occasions, 4-7 years apart.

Over the study period, almost two-thirds of persons with both IFG and IGT progressed to DM2. Using only IFG or IGT alone, subsequent progression to DM2 was 35.5-40.8%, respectively. Both IFG and IGT are significant predictors of progression to DM2, but the combination is superior still.

de Vegt F, et al. JAMA. 2001;285: 2109-2113.

NSAIDs and Selective COX-2 Inhibitors: Competition Between Gastroprotection and Cardioprotection

The special promise of cox-2 specific agents (ie, celecoxib, rofecoxib) was the hope that since they did not, within the therapeutic range, impair COX-1, they might be free of gastrointestinal (GI) risk, specifically GI bleeding. Some data on the COX-2 agents support the premise that GI bleeding in association with these drugs is similar to that of placebo-not zero, since numerous other paths than COX inhibition may lead to GI bleeding (eg, alcohol, bleeding diathesis, helicobacter disease). An additional potential benefit of COX-2 agents is that platelet inhibition is a COX-1 event, so that COX-2 agents do not impair platelet function.

Boers points out that in 2 of the largest COX-2 trials reported there appear to be tradeoffs related to cardioprotection and gastroprotection. In the VIGOR trial (n = 8000, rofecoxib vs naproxen), despite a substantial 60% reduction in GI bleed, Boers points out an unanticipated 4-fold increase in myocardial infarction in the rofecoxib group (0.4% vs 0.1%); in the CLASS trial (n = 8000, celecoxib vs ibuprofen or diclofenac), though no increase in MI was seen, there was not a demonstration of risk reduction in GI toxicity between celecoxib and traditional NSAIDs that reached statistical significance. Boers suggests that the issues of competing risks will need to be weighed in the decision process of when and how to use COX-2 agents.

Boers M. Lancet. 2001;357:1222-1223.