Rosiglitazone heart failure with

A 78-year-old man became short of breath. He had been taking rosiglitazone 8 mg/day for 6 months. He had renal insufficiency, atrial fibrillation, hypertension, and congestive heart failure, with pitting edema and bilateral pleural effusions. He was refractory to intravenous furosemide and metolazone. Withdrawal of rosiglitazone and administration of bumetanide gave a net fluid output of 9.5 litres and the edema resolved. 

Avandia (rosiglitazone) as with other thiazolidinediones is used either as monotherapy or in combination with either metformin or a sulphonylurea. A disadvantage of rosiglitazone is the risk of heart failure as a side-effect. This risk is increased when rosiglitazone is used in patients with cardiovascular disease and when used in combination with insulin. Blood-glucose control may deteriorate temporarily when a thiazolidinedione is substituted for an oral antidiabetic agent. 

Rosiglitazone, a thiazolinedione used to treat diabetes mellitus, is contraindicated in patients with heart failure especially if taken in combination with insulin. 

Cardiac effects Thiazolidinediones can cause fluid retention, which may exacerbate or lead to heart failure. Discontinue therapy if any deterioration in cardiac status occurs. Rosiglitazone and pioglitazone are not recommended in patients with NYHA Class 3 and 4 cardiac status. 

Edema Use pioglitazone and rosiglitazone with caution in patients with edema. Because thiazolidinediones can cause fluid retention, which can exacerbate or lead to CHF, use with caution in patients at risk for heart failure and monitor patients at risk for heart failure for signs and symptoms of heart failure. 

In a retrospective cohort study of interventions for chronic heart failure before and after the use of rosiglitazone in 139 patients aged 66-75 years (mainly men), 20 had received treatment for heart failure before therapy with rosiglitazone and 50 needed it within 6 months of starting therapy (100). 

Page II RL, Gozansky WS, Ruscin JM. Possible heart failure exacerbation associated with rosiglitazone case report and literature review. Pharmacotherapy 2003 23 945-54. 

The manufacturers say that pioglitazone and rosiglitazone can cause fluid retention, which may exacerbate or precipitate heart failure, particularly in those with limited cardiac reserve. " Because NSAIDs can also cause fluid retention, the manufacturers issue a warning that concurrent use may possibly increase the risk of oedema." ... 

Pioglitazone and rosiglitazone may cause fluid retention and peripheral oedema, which can worsen or cause heart failure. There is evidence that the incidence of these effects is higher when combined with insulin. The incidence of hypoglycaemia may also be increased. 

Advisory committee votes are not binding on the FDA, which is therefore free to determine its own course of action. On this occasion the FDA s action was consistent with the members votes rosiglitazone was not removed from the market. On November 19, 2007, the FDA announced that the drug s sponsor had agreed to add new information to the existing boxed warning (the text of which concerned heart failure) about a potential increased risk for myocardial ischemic events. Part of the new text read as follows (FDA 2007) ... 

Out-patients ( = 39 736) aged 66 years or older who had used either pioglitazone or rosiglitazone were identified from the Ontario Public Drug Benefit Program prescription records [81 ]. Those who had taken pioglitazone had a lower risk of death or hospital admission for either acute myocardial infarction or heart failure compared with rosiglitazone, with an adjusted hazard ratio of 0.8. Further analysis showed that this was due to a reduction in death (adjusted hazard ratio = 0.86) and heart failure (0.77). There was no difference in the risk of acute myocardial infarction (0.95). 

The safety of rosiglitazone has continued to be examined. The 2010 FDA metaanalysis did not include large trials, but included data from 52 studies of 2 months to 2 years duration in a total of 12 069 patients, mean age 58 years, 59% men, with a mean BMI of 30 kg/m [98 ]. The odds ratio for myocardial infarction in those taking rosiglitazone was 1.8 and for congestive heart failure 1.93. These data support the continued concern about the use of rosiglitazone in type 2 diabetes. 

Graham, D.J., Ouellet-Hellstrom, R., MaCurdy, T.E., Ali, F., Sholley, C., Worrall, C., and Kel-man, J.A. 2010. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA The Journal of the American Medical Association, 304(4), 411-418. 

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