Cardiac Failure and Other Cardiac Effects
ACTOS, like other thiazolidinediones, can cause fluid retention when used alone
or in combination with other antidiabetic agents, including insulin. Fluid retention
may lead to
or exacerbate heart failure. Patients should be observed for signs and symptoms
of heart failure (see Information for Patients). ACTOS should be discontinued
if any deterioration in cardiac status occurs. Patients with New York Heart
Association (NYHA)
Class III and IV cardiac status were not studied during clinical trials; therefore,
ACTOS
is not recommended in these patients (see PRECAUTIONS, Cardiovascular).
In one 16-week U.S. double-blind, placebo-controlled clinical trial involving
566 patients with type 2 diabetes, ACTOS at doses of 15 mg and 30 mg in combination
with
insulin was compared to insulin therapy alone. This trial included patients
with longstanding diabetes and a high prevalence of pre-existing medical conditions
as follows:
arterial hypertension (57.2%), peripheral neuropathy (22.6%), coronary heart
disease
(19.6%), retinopathy (13.1%), myocardial infarction (8.8%), vascular disease
(6.4%),
angina pectoris (4.4%), stroke and/or transient ischemic attack (4.1%), and
congestive
heart failure (2.3%).
In this study two of the 191 patients receiving 15 mg ACTOS plus insulin (1.1%)
and
two of the 188 patients receiving 30 mg ACTOS plus insulin (1.1%) developed
congestive heart failure compared with none of the 187 patients on insulin
therapy alone. All
four of these patients had previous histories of cardiovascular conditions
including coronary artery disease, previous CABG procedures, and myocardial
infarction. Analysis of data from this study did not identify specific factors
that predict
increased
risk of congestive heart failure on combination therapy with insulin.