Characterization of the Dose—Concentration‐Dependent Hemodynamic Effects of Nifedipine in Heart Failure

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Abstract
The hemodynamic effects of increasing oral doses of nifedipine (10 to 30 mg) were studied in 12 patients who had low output heart failure. With each set of hemodynamics, serum concentrations of nifedipine were measured to determine the concentration/response relationships. Eleven of twelve patients responded acutely to nifedipine, defined as a reduction in systemic vascular resistance (SVR), and an augmentation in cardiac index (CI) and stroke volume index (SVI). The differential dose effects (X ± SD) for SVR and SVI for baseline (N = 11), 10 mg (N = 10), 20 mg (N = 3) and 30 mg (N = 4) were: 1913 ± 486, 1102 ± 221, 1128 ± 166, 803 ± 176 and 17.9 ± 4.8, 23.8 ± 4.5, 31 ± 0.42, 33 ± 3.5, respectively. All nifedipine doses reduced SVR and increased CI and SVI compared with baseline (P < .001). The increase in CI and SVI was significantly correlated to the mg/kg dose of nifedipine (r = 0.79; P < .001). Nifedipine administration resulted in no significant change in central venous pressure, pulmonary capillary wedge pressure, or pulmonary vascular resistance. No relationship could be demonstrated between serum concentrations of nifedipine and any hemodynamic effect. Conclusions drawn were: [1) the afterload reduction effects of nifedipine are acutely efficacious in a large portion of patients with heart failure and this activity supercedes the negative inotropic effects of the drug at doses between 10 and 30 mg; (2) the magnitude of the hemodynamic effects are dose dependent; (3) large decrements in systemic blood pressure (≥20% reduction in mean arterial pressure) can be produced with single 10‐mg doses of nifedipine in patients with heart failure, indicating that the use of this drug in this population be closely supervised; and (4) the lack of a direct concentration‐effect relationship may indicate that the pharmacodynamics of nifedipine in heart failure differ from those demonstrated for other physiologic states.