匹格列酮：增加心衰风险，不增加死亡率

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Increased Serious Heart Failure Incidence With Pioglitazone

NEW YORK (Reuters Health) Nov 26 - Pioglitazone use is associated with an increased incidence of serious heart failure, but still provides clinical benefits, with no evidence that it increases subsequent mortality and morbidity, according to a report in the November issue of Diabetes Care.

\"Although there is an increased risk of CHF with pioglitazone, our analysis of serious heart failure events in PROactive showed that when serious heart failure does develop in pioglitazone-treated patients with type 2 diabetes and existing macrovascular disease, it does not increase (and may even decrease) risk of mortality or morbidity,\" Dr. Erland Erdmann from Universitaet zu Koeln, Germany, told Reuters Health.

Dr. Erdmann and colleagues studied investigator-reported heart failure rates and the treatment effect on sequelae after serious heart failure in more than 5200 patients with type 2 diabetes and preexisting cardiovascular disease in the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive).

Serious heart failure was reported in 41% more patients in the pioglitazone group than in the placebo group, the investigators say.

Elevated creatinine level, diuretic use, LDL cholesterol above 3 mmol/L, previous myocardial infarction, and diabetes duration of at least 10 years were additional significant predictors of serious heart failure.

Serious heart failure occurred more frequently among patients treated with insulin, the authors report, but the use of pioglitazone did not further elevate the risk among insulin-treated patients.

Fatal heart failure events were no more common among pioglitazone patients than among placebo patients, the researchers note, and pioglitazone patients had lower rates of all-cause mortality, nonfatal myocardial infarction, and stroke than did placebo patients.

Pioglitazone-treated patients were also more likely to develop non-serious heart failure and edema than were placebo-treated patients.

\"Because the rates for the composite endpoint subsequent to a report of serious heart failure were similar between pioglitazone and placebo,\" the authors write, \"the cardiovascular benefits observed in PROactive with pioglitazone were not diminished by the increased incidence of heart failure.\"

\"The mechanisms of action behind the fluid retention with thiazolidinediones remain unclear,\" the investigators continue, \"although it has been suggested that peroxisome proliferator-activated receptor-gamma may regulate sodium reabsorption in the cortical collecting ducts via stimulation of epithelial sodium channel activity.\"

\"The long-term study of pioglitazone use and heart failure, funded by the American Diabetes Association, argues against the possibility that thiazolidinediones cause heart failure,\" the researchers add.

\"ROactive demonstrated the macrovascular ischemic safety profile of pioglitazone in patients with type 2 diabetes who are at high risk for cardiovascular events,\" Dr. Erdmann said.

\"As a cardiologist, I have no reservations in its use in this condition when correctly and appropriately prescribed....When considering the appropriate therapeutic strategy for patients, the potential benefits and risks should be fully considered based on the evidence for both efficacy and safety,\" he concluded.