Next I'll show the results of some sub-analyses we did of special patient populations using data from the VMAC trial, a study that compared two of the most-commonly administered IV vasoactives in acute heart failure: nesiritide and nitroglycerin in addition to standard background therapy.
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The VMAC trial studied 489 patients hospitalized for acutely decompensated heart failure. Patients were stratified into two groups depending on whether they received a Swan-Ganz catheter or not. Patients were then randomized to receive either nesiritide with standard therapy, IV nitroglycerin with standard therapy, or placebo with standard therapy. Standard therapy was furosemide, ACE inhibitors, or any other therapies the physician wanted except nitroglycerin or nesiritide.
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Subjects were stratified in the VMAC trial based upon right heart catheterization. Two hundred forty-six subjects were catheterized and then randomized to one of four treatment groups for 3 hours and then followed for an additional 6 months with the placebo group receiving nesiritide during this 6-month period. In the non-catheterized group (n=243), subjects were randomized to one of three treatment groups and again followed for three hours and an additional 6 months.
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Nesiritide was administered in a fixed dose to 211 subjects with a 2 mcg/kg bolus followed by a 0.01 mcg/kg/min infusion. Nesiritide was administered in an adjustable dosage schedule to 62 subjects. During the first 3 hours, the dose was the same as the fixed-dose group. Following this, every 3 hours, the investigators could increase nesiritide up to 0.03 mcg/kg/min.
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In the adjustable-dose group, where clinicians were permitted to titrate the nesiritide dose after the first 3 hours, 56% of patients had no change in dosing. In contrast, patients on nitroglycerin frequently developed tolerance requiring higher doses. At 1 hour, the dose of nitroglycerin was approximately 35 mcg/kg/min, but by 24 hours it had increased to almost 60 mcg/kg/min.
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One of the first subsets of VMAC that we looked at was patients with an acute coronary syndrome. There were 61 patients in VMAC who had some indices which suggested they had an MI: either ECG changes, chest pain sufficient to be diagnosed as unstable angina, a PTCA, CABG, or death. As with all patients in VMAC, these patients either received IV nitroglycerin or nesiritide in addition to standard background therapy.
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Overall, there were no differences in demographics or other baseline characteristics, and no differences in mortality, wedge pressures, or hypotension. So it seemed that this study would really go nowhere; however, differences emerge when you look at the patients who were catheterized compared to those who weren't. Remember that patients receiving a Swan-Ganz catheter represent a sicker cohort, with less myocardial function to work with, as compared to those who did not need to be catheterized.
<ss="VMAC and ACS: Dyspnea">
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Here we see that in the non-catheterized group of patients who received nesiritide, 75% experienced marked-to-moderate improvement in their dyspnea score at 24 hours, compared to 55% of patients in the nitroglycerin group.
<ss="VMAC and ACS: Readmits">
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Here are rates of readmission at 30 days for ACS patients. While nesiritide clearly has lower rates than nitroglycerin, these are not statistically significant because we had so few readmissions as a whole in this group.
<ss="Nesiritide and Renal Failure">
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The next subgroup of VMAC patients we looked at are those with renal failure. These are not dialysis patients, but, rather, patients with a creatinine over 2 mg/dL. There were 104 patients in the VMAC trial who met this criteria: 35 of them in the nitroglycerin group, 43 in the nesiritide group, and 26 in the placebo group.
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The safety profiles were similar for both the nesiritide and nitroglycerin groups, with a low incidence of symptomatic hypotension in both groups and a higher incidence of headache in the nitroglycerin group.
<ss="Renal Failure and Nesiritide Effect on PCWP">
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The results on reducing wedge pressure are shown here. As we see, at both 15 minutes and 3 hours nesiritide significantly reduced the wedge pressure compared to standard therapy, while nitroglycerin was not statistically different than standard therapy alone.
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This may be one of the hidden assets of nesiritide. In the treatment of HF with congestion, ultimately, the kidney is the rate-limiting step. When creatinine rises, diuretics fail and there is little left that the clinician can use to fight fluid overload except vasodilators. There are three commonly used IV vasodilators, which include nitroprusside (which is dangerous in renal failure), nitroglycerin, and nesiritide. In this analysis, nesiritide had greater clinical effect than nitroglycerin.
<ss="VMAC: Insights From a ^"Real Life^" Study">
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Because the VMAC trial had an "all comers" enrollment strategy, it provided "real life" results, and consequently has been a rich field for subset analysis. It established the currently recommended dose of nesiritide [2 mcg/kg bolus, then a 0.01 mcg/kg/min drip], demonstrated the safety of nesiritide in HF complicated by an ACS, and showed that nesiritide is safe in renal insufficiency.
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Welcome to our program on Acute Heart Failure: The Emergency Department and the Economics of Care. This is a CME-accredited program that focuses on optimizing treatment strategies in the Emergency Department in order to improve outcomes and reduce overall costs to the hospital.
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When you think about the overall hospital costs of a 5-day admission for an acute condition that often requires ICU care and invasive procedures, you don't necessarily think about the Emergency Department. After all, the patient is usually only in the ED for a few short hours, compared to the several days they will spend as an inpatient. But when it comes to treating acute heart failure, we are beginning to learn that what occurs during those critical initial hours in the Emergency Department has a direct and significant impact on overall treatment outcomes, including the length of stay as an inpatient, the utilization of expensive resources, and the likelihood of readmission to the hospital within the near term.
