Thiazolidinediones, Metformin, and Outcomes in Older Patients With Diabetes and Heart Failure: An Observational Study

talized with heart failure in the U.S. in 1998 –1999, were analyzed to evaluate differences in quality of care and patient outcomes between men and women. Multivariable hierarchical logistic regression models and chi-square analyses were used to examine gender differences in the documentation of left ventricular systolic function (LVSF), prescription of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for patients with LV dysfunction and mortality within 30 days and 1 year of admission in the study cohort (n⫽30,996). Results: Women had lower overall rates of LVSF assessment than did men (64.9% vs. 69.5%; p⬍0.001). Among patients classified as candidates for ACE inhibitor prescription, women had lower crude rates of ACE inhibitor prescription than did men (70.1% vs. 74.2%; p⫽0.015), but treatment rates were similar when evaluating the prescription of ACE inhibitors or ARBs (78.9% women vs. 81.3% men; p⫽0.11). Despite lower rates of treatment, women had lower mortality rates than did men at 30 days (9.2% vs. 11.4%; p⬍0.001) and 1 year (36.2% vs. 43.0%; p⬍0.001) after admission. Results were similar after multivariable adjustment. Conclusions: There were small gender differences in the quality of care provided to fee-for-service Medicare patients hospitalized with heart failure, although women had higher rates of survival than did men up to 1 year posthospitalization. Perspective: We cannot exclude the possibility that unmeasured factors are responsible for the small difference in quality of care between men and women. As the investigators noted, this difference pales in comparison to the gap between present and optimal levels for either group. Of note, the survival advantage for women persisted after consideration of etiology and LVEF, raising the question of whether true biological differences exist between men and women in the natural history of established heart failure. KA

betic drug prescriptions and outcomes was assessed in multivariable hierarchical Cox proportional hazard models, with adjustment for patient, physician and hospital variables and accounting for the clustering of patients within hospitals. The primary outcome of the study was time to death due to all causes. Secondary outcomes included time to readmission for all causes or for heart failure. Results: Crude 1-year mortality rates were lower among the 2226 patients treated with a thiazolidinedione (30.1%) or the 1861 treated with metformin (24.7%) compared with rates among the 12,069 treated with neither insulin-sensitizing drug (36.0%; p⬍0.0001 for both comparisons). In multivariable models, treatment with the thiazolidinediones (hazard ratio [HR] 0.87; 95% CI 0.80 – 0.94) or metformin (HR 0.87; 95% CI 0.78 – 0.97) was associated with significantly lower risks of death. There was no association with treatment with sulfonylureas (HR 0.99; 95% CI 0.91– 1.08) or insulin (HR 0.96; 95% CI 0.88 –1.05) and mortality. Admissions for all causes did not differ with either insulin sensitizer. There was a higher risk of readmission for heart failure with thiazolidinedione treatment (HR 1.06; 95% CI 1.00 –1.09) and a lower risk with metformin treatment (HR 0.92; 95% CI 0.92– 0.99). Conclusions: The researchers concluded that thiazolidinediones and metformin are not associated with increased mortality and may improve outcomes in older patients with diabetes and heart failure. Perspective: This observational study suggests that treatment with insulin-sensitizing agents of the thiazolidinedione class and metformin was not associated with an excess risk of mortality and may confer important benefits to older patients with diabetes who are hospitalized for heart failure. Although further investigation to corroborate the findings of the present study is warranted, these results suggest that current recommendations to avoid the use of these medications in this context may deprive patients of important benefits. Further clarification of the best clinical approach to the use of insulin-sensitizing drugs, optimally with randomized clinical trials, will be important in advancing treatment of the rapidly growing population who have both diabetes and heart failure. DM

Thiazolidinediones, Metformin, and Outcomes in Older Patients With Diabetes and Heart Failure: An Observational Study Masoudi FA, Inzucchi SE, Wang Y, et al. Circulation 2005;111:583–90.

N-Terminal Pro-B-Type Natriuretic Peptide and Long-Term Mortality in Stable Coronary Heart Disease

Study Question: Insulin-sensitizing drugs of the thiazolidinedione class and metformin are commonly prescribed to treat diabetes in patients with heart failure despite warnings from the FDA against this practice. This study was intended to provide information about the balance of risks and benefits relevant to recommendations for use of these agents. Methods: Investigators conducted a retrospective cohort study of 16, 417 Medicare beneficiaries with diabetes discharged after hospitalization with the principal discharge diagnosis of heart failure. The association between antidia-

Kragelund C, Grønning B, Køber L, et al. N Engl J Med 2005;352:666 –75. Study Question: What is the relationship between N-Terminal Pro-B-Type natriuretic peptide (NT-pro-BNP) and mortality in stable coronary heart disease (CHD)? Methods: The NT-pro-BNP was measured in baseline serum samples from 1034 patients referred for angiography because of symptoms or signs of CHD. The rate of death from

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