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Absence of hemodynamic tolerance to nicorandil in patients with severe congestive heart failure
T Tsutamoto1, M Kinoshita, I Nakae
1First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
Insights
Patients with chronic heart failure (CHF) developed tolerance to nitroglycerin (GTN) within 12 hours, but not to nicorandil, which maintained hemodynamic effectiveness for 24 hours. Plasma ANP levels correlated with hemodynamic changes.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Nitrate therapy is common for chronic heart failure (CHF).
- Hemodynamic tolerance can limit the long-term efficacy of vasodilators.
- Nicorandil, a nitrate and potassium channel opener, may offer an alternative with potentially different tolerance profiles.
Purpose of the Study:
- To compare the development of hemodynamic tolerance to nicorandil versus nitroglycerin (GTN) in patients with CHF.
- To assess the sustained hemodynamic effects of continuous infusions of nicorandil and GTN over 24 hours.
Main Methods:
- 14 patients with CHF received nicorandil, and 11 received GTN.
- Drug doses were adjusted to achieve a ≥20% reduction in pulmonary capillary wedge pressure (PCWP) within 1 hour.
- Infusions were maintained for 24 hours, with hemodynamic parameters and plasma atrial natriuretic peptide (ANP) concentrations monitored.
Main Results:
- Both nicorandil and GTN produced similar initial reductions in PCWP.
- Hemodynamic tolerance to GTN developed within 12 hours, with PCWP returning to baseline levels.
- Nicorandil maintained a significant reduction in PCWP for the entire 24-hour infusion period.
- Changes in plasma ANP concentrations correlated with PCWP changes (r = 0.84, p < 0.001).
Conclusions:
- CHF patients develop significant hemodynamic tolerance to continuous GTN infusion within 12 hours.
- Nicorandil remains hemodynamically effective for 24 hours in CHF patients, suggesting no significant tolerance develops.
- Plasma ANP may serve as a useful noninvasive marker for assessing hemodynamic tolerance during vasodilator therapy in CHF.
Abstract:
To evaluate whether hemodynamic tolerance develops to nicorandil, a nitrate and potassium channel opener, 14 patients with chronic heart failure (CHF) were treated with nicorandil and 11 were treated with nitroglycerin (GTN). Doses of GTN or nicorandil were titrated to achieve a > or = 20% reduction in pulmonary capillary wedge pressure (PCWP) within 1 hour, and the infusion was maintained at a constant rate for 24 hours. Both groups of patients had comparable hemodynamic parameters before drug infusions were started. The fall in PCWP was identical after 1 hour infusion of either GTN or nicorandil. In the GTN group, PCWP was not significantly different from the baseline value at 12 hours; however, in the nicorandil group, PCWP remained significantly lower than the preinfusion value for 24 hours. During the study period changes in plasma atrial natriuretic peptide (ANP) concentrations paralleled and correlated with changes in PCWP (r = 0.84, p < 0.001). These findings indicate that CHF patients develop hemodynamic tolerance to GTN within 12 hours of continuous infusion, but not to nicorandil, which remained hemodynamically effective during the 24-hour period of infusion. Furthermore, plasma ANP concentration may be a useful noninvasive index of hemodynamic tolerance during GTN or nicorandil therapy in patients with CHF.