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Impressive results for istaroxime in patients with HF

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Patients hospitalized with heart failure may benefit from istaroxime, a novel intravenous agent with inotropic and lusitropic properties, when added to standard therapy.

The HORIZON-HF investigators studied istaroxime to determine its hemodynamic, echocardiographic and neurohormonal effects in 120 patients hospitalized with HF. Each patient received a pulmonary artery catheter within two days of hospitalization. The investigators randomly assigned three sequential cohorts (3-to-1 istaroxime–placebo) to a continuous six-hour infusion — first cohort, 0.5 mcg/kg per minute; second cohort, 1 mcg/kg per minute; and third cohort, 1.5 mcg/kg per minute.

Patients in all three groups experienced a rapid improvement in pulmonary capillary wedge pressure compared with placebo (0.5 mcg/kg per minute, –3.2 mm Hg; 1 mcg/kg per minute, –3.3 mm Hg; 1.5 mcg/kg per minute, –4.7 mm Hg). Istaroxime increased systolic BP and decreased heart rate, unlike other available inotropes, according to the investigators (1 mcg/kg per minute, 8.3 mm Hg; 1.5 mcg/kg per minute, 15.6 mm Hg; placebo, 1.3 mm Hg). No changes in diastolic BP were reported.

Patients assigned to the 1.5 mcg/kg per minute dose experienced significantly reduced deceleration time and left ventricular end diastolic volume compared with placebo (–14.1 mL vs. 3.1 mL). Those assigned to 1 mcg/kg per minute istaroxime experienced reductions in left ventricular systolic volume (–15.8 mL vs. –2.1 mL).

Istaroxime had no effect on troponin I, neurohormones, blood urea nitrogen or creatinine. No deaths were reported during treatment with istaroxime. The most common adverse events were vomiting and pain at the injection site. – by Katie Kalvaitis

J Am Coll Cardiol. 2008;doi: 10.1016/j.jacc.2008.03.015.

I am now even more impressed with istaroxime: The fact that it is a new mechanism of action and has inotropic and lusitropic properties is exciting. Even more exciting, in my opinion, is that it did this with an increase in BP and a decrease in heart rate — truly different from other agents tried in the past or currently in use. I look forward to the larger clinical trials where we can see the drug's effects on a broader range of patients.

– Frank Smart, MD

Cardiology Today Editorial Board member