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Heart failure is very common shortly after a patient starts antidiabetictherapy, according to a study published recently in DiabetesCare.
"But it's not the traditional antidiabetic medicine that's causingit," says Ross J. Simpson, MD, PhD, director of the lipid and preventionclinic at University of North Carolina, Chapel Hill.
Data suggest that drug therapy itself doesn't raise the risk of heartfailure, but is an indicator of how long a patient has had diabetes.
Simpson and colleagues reported a study of more than 25,000 patients newlydiagnosed with diabetes who were cared for by primary care physicians in theU.K.1 Followed foran average of 2.5 years, patients who received drugs to control diabeteswithin the first year of diagnosis were 4.75 times more likely to suffer heartfailure than those who did not takedrugs.
No link to any particular antidiabetic drug was observed, according to theresearchers, who studied patients taking insulin, metformin, or sulfonylureadrugs. Glitazone drugs were not studied, since they were not available whenthe study began.
"Patients with more advanced diabetes were more likely to getmedicines," Simpson says. "It wasn't the type of medicine theygot, it is a timing issue. The longer a patient had diabetes, the more likelythey were to develop heart failure."
The rising risk of heart failure "happens at a rapid rate," butwas not observed beyond the first year after the diagnosis of diabetes, hesays. The observation may have been a result of a "backup" of theadverse cardiovascular effects of untreated diabetes, he notes.
"The incomplete control of blood pressure and diabetes will make thelikelihood of heart failure worse," Simpson says. "Diabetesdoesn't start just when it's diagnosed. It was almost like a catch-up thatwent on."
About 4.7 Americans suffer from heart failure, which is closely associatedwith major risk factors for coronary heart disease, including diabetes,abnormal blood glucose, obesity, high cholesterol, and hypertension. Patientswith diabetes have a two- to eightfold increase in the risk of heartfailure.
"Heart failure is probably the most common complication ofdiabetes," Simpson says. "It's certainly one of the most commonreasons for hospitalizations with diabetes."
FLUID RETENTION AND HEART FAILURE
A separate study finds rosiglitazone (Avandia, GlaxoSmith- Kline), a memberof the class of antidiabetic drugs called thiazolidinediones (TZDs), can causefluid retention that may push a patient into heart failure or make an existingcase more severe, according to Janelle A. Goins, PharmD, of the Edward HinesVeteran's Affairs Hospital in Hines, Ill.
"There are a lot of confounding factors because these patients are athigh cardiovascular risk," says Goins. "Research shows that fluidretention is even greater when glitazones are given in combination withinsulin."
Goins and colleagues reviewed records of 139 patients who received insulinfor the treatment of diabetes and had rosiglitazone added to theirregimen.2 Adiagnosis of chronic heart failure (CHF) was made in 35 patients (25%). Within6 months of beginning rosiglitazone therapy, the number of patients with adiagnosis of CHF rose to 42 (30%).
Even more striking was that the number of patients requiring a medicalintervention for CHF rose from 20 (14%) in the 6 months before rosiglitazonetherapy to 50 (36%) in the next 6 months.
Primary care providers should make sure that patients know the signs ofheart failure—such as swelling of the ankles or lower extremities andshortness of breath—particularly if they are taking insulin, Goins says.In many cases, lowering the dose or taking the patient off the glitazone drugwill improve the symptoms of heart failure.
This research supports previous findings that prompted the AmericanDiabetes Association (ADA) and American Heart Association to publish aconsensus statement on the use of TZDs, fluid retention, andCHF.3 The statementrecommends that before starting TZD treatment, physicians should determine ifthe patient has any underlying cardiac disease and note if the patient istaking drugs associated with fluid retention, such as vasodilators ornonsteroidal anti-inflammatory drugs, or with pedal edema, such as calciumchannel blockers.
Further recommendations include evaluating the pathogenesis of edema thatmight already be present, and if it is, monitoring it closely during TZDtreatment. Patients with shortness of breath also should be carefullymonitored, especially during the first 3 months of TZD treatment.
Where appropriate, physicians may examine a recent electrocardiogram forsigns of silent myocardial infarction or left ventricular hypertrophy, tworisk factors for CHF. Finally, before starting a patient on a TZD, doctorsshould instruct the patient to report any new signs or symptoms, such asweight gain, pedal edema, shortness of breath, or fatigue without any otherapparent cause, the ADA/AHA statement says.
Simpson says because heart failure is a serious, often underappreciatedproblem in people with diabetes, clinicians should keep close tabs on thesepatients. "Primary care doctors should be aware of heart failure nomatter what the patient is treated with," he says. 
Footnotes
Heart failure is an elusive condition that can quickly put a patientin jeopardy. Be alert for these important signs and symptoms:
References
2. Marceille JR, Goins JA, Soni R, et al.: Chronic heartfailure-related interventions after starting rosiglitazone in patientsreceiving insulin. Pharmacotherapy 24: 1317–1322, 2004.[Medline]
3. Nesto RW, Bell D, Bonow RO, et al.: Thiazolidinedione use, fluidretention, and congestive heart failure: A consensus statement from theAmerican Heart Association and American Diabetes Association.Diabetes Care 27:256–263, 2004.
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