Thursday, March 6, 2014

Nicardipine for Acute Decompensated Heart Failure

In a post on this blog last week, the topic of the nitroglycerin shortage was discussed, with the alternative of nesiritide as offered as a potential option in the setting of this shortage for patients with acute decompensated heart failure, and the data surrounding the use of nesiritide for this indication was reviewed.

Interestingly enough, we received a comment on the post that alluded to the fact that nicardipine could potentially be utilized as an alternative as well.

Upon reading this, at first, this did not make a whole lot of sense to me. Yes, I have mentioned several times on this blog that nicardipine is one of my favorite drugs to utilize in patients in the emergency department. But for acute decompensated heart failure? No way. However, after a little digging (which included having to retrieve articles that were published in the 1980s and 1990s), I have a new perspective regarding this.

Calcium channel antagonists as a class in and of itself have been long-touted to have negative inotropic effects, which can potentially worsen the hemodynamic effects observed in acute decompensated heart failure. However, compared to the other calcium channel antagonists, I found that these effects in nicardipine are actually relatively minimal, as found to be the case in several animal models and in vitro studies (1, 2, 3).

And then I stumbled upon this study:

 

There were actually two trials conducted within this one study. Patients were enrolled in the trials if they met the following criteria:
  • Age betweeen 20 and 80 years
  • Systolic blood pressure (SBP) > 100 mmHg
  • Cardiac index < 2.5 mL/min/m2
  • Pulmonary diastolic or wedge pressure > 15 mmHg

The first trial evaluated fourteen patients who received nicardipine at a dose of 0.5 mcg/kg/min, with an increase in the dose to 1 mcg/kg/min over the course of a two-hour period to determine if any improvement was made in increasing the cardiac index and decreasing diastolic pulmonary arterial pressure (the latter associated with systemic vascular resistance). In the majority of patients, the effects were more pronounced at doses of 1 mcg/kg/min.

In the second trial, 53 patients were randomized to receive nicardipine at a dose of 1 mcg/kg/min, 2 mcg/kg/min, or 3 mcg/kg/min over two hours. Across all treatment groups, the same effects were observed as in the first trial: cardiac index increased by 41%, 32%, and 35% after two hours, respectively, and diastolic pulmonary arterial pressure decreased by 27%, 26%, and 31% with each respective dose, all of which were found to be statistically significant. One major difference that was observed was that a greater decrease in SBP occurred with doses of 3 mcg/kg/min of nicardipine compared to 1 mcg/kg/min (which is to be expected). The investigators concluded that 1 mcg/kg/min for nicardipine is the optimal dose for the patients evaluated for the purposes of acute decompensated heart failure.

Imagine my surprise with this. Not only do we have an agent, where contrary to popular belief of negative inotropic effects across the board with calcium channel blockers, the effects seen do not occur to the same extent necessarily, but we also have evidence to show that in patients with acute decompensated heart failure, cardiac output is improved and a decrease in left ventricular end diastolic pressure can be achieved.

Suffice it to say that nicardipine has just gone up in my book. It's off the pages now in terms of being THE favorite agent that I use in the emergency department.

References:
  1. Razetti R, Bongrani S, Schiantarelli P. In vitro effects of nicardipine on vascular and cardiac muscle preparations. Pharmacol Res Commun 1984; 16:795-808.
  2. Rousseau MF, Vincent MF, Cheron P, et al. Effects of nicardipine on coronary blood flow, left ventricular inotropic state, and myocardial metabolism in patients with angina pectoris. Br J Clin Pharmacol 1985; 20:147S-157S.
  3. Bongrani S, Razetti R, Schiantarelli P. Cardiovascular effects of nicardipine in anesthetized open-chest dogs in the absence and presence of beta-adrenergic blockade: a comparison with nifedipine and verapamil. J Cardiovasc Pharmacol 1985; 7:899-905.

5 comments:

  1. Great post. I was doing a little research on treatments for heart failure since that is how my aunt died last month and I didn't realize how many different types of heart failure that was. I have never even heard of acute decompensated heart failure before. Very interesting and informative post. Thanks for sharing.

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  2. Great articles! Nadia and Craig, one major topic that is up for discussion in our ED is the use of icatibant (Firazyr), ecallantide (Kalbitor), or C1 esterase inhibitor concentrate (Berinert) for treating ace inhibitor induced angioedema. Mostly case reports showing success keeping in mind obvious publication bias as many don't publish the several cases treatment didn't work. Kalbitor manufacturer discontinued a phase 2 trial in 2012. With the expensive price tag for those meds listed above compared to intubation, what are your thoughts or experiences with the above treatments compared to FFP (considering needing time to thaw), epi, antihistamines, corticosteriods? If your facilty got P&T approval for this off-label use, what was the evidence/rationale to support the formulary addition? Might be a good topic to tackle too. Thank you.

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    1. Thanks for the great comment! I agree that the data supporting icabitant or any C1 esterase inhibitor for angioedema is very limited, and in my experience there is limited role for it in the acute setting. It is certainly an interesting debate with these medications, since their pharmacology suggest they may have a significant impact and perhaps the cost of the drug may be outweighed by a ventilated ICU bed or trip to the OR for a surgical airway.
      This is also a great topic for a future post! Thanks again!

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  3. Do you mind sharing the citation for this article? The image will not display on my computer. Thanks!

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    1. Here is the full citation for the article:

      Hirota Y, Kawai C, Hori R, et al. Determining the optimum dose for the intravenous administration of nicardipine in the treatment of acute heart failure--a multicenter study. The Nicardipine Heart Failure Study Group. Jpn Circ J. 1997;61(5):367-74.

      It is available for free as a PDF via PubMed: http://www.ncbi.nlm.nih.gov/pubmed/9192235

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