Role of CCBs in Pulmonary Arterial Hypertension

Table 1.

Clinical Characteristics, Baseline Hemodynamics, and Exercise Capacity of the Studied Patient Sample

Used with permission from: Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111:3105-3111.

Table 2.

	Acute NO/Epoprostenol Responders Group (n = 70)	Long-term CCB Responders Group (n = 38)	CCB Failure Group (n = 32)	P*
Drug tested (NO:epoprostenol) (n)	57:13	33:5	24:8	.2
Mean PAP reached during acute vasodilator testing (mm Hg)	38 ± 11 (18-65)	33 ± 8 (18-50)	46 ± 10 (18-65)	< .001
Fall in mean PAP during acute vasodilator testing (mm Hg)	19 ± 7 (10-36)	21 ± 7 (10 - 36)	16 ± 6 (10 - 33)	.006
Percent fall in mean PAP	33 ± 11 (20-59)	39 ± 11 (20 - 59)	26 ± 7 (20 - 49)	< .001
PVR reached during acute vasodilator testing (WU)	6.6 ± 3.4 (1.1 - 17.4)	5.2 ± 2.7 (1.1 - 13.1)	8.6 ± 3.3 (1.1 - 17.4)	< .001
Fall in PVR during acute vasodilator testing (WU)	5.6 ± 3.3 (1.6 - 16.7)	5.1 ± 3.1 (1.7 - 15.4)	6.2 ± 3.4 (1.6 -16.7)	.16
Percent fall in PVR	45 ± 15 (24-77)	50 ± 15 (24 - 77)	40 ± 13 (26 - 75)	.007

Hemodynamic Values Reached During Vasodilator Testing in Acute Responders

Values are mean ± SD (range).
*Comparison between long-term CCB responders and CCB failure groups (unpaired Student t or x ² test, as appropriate.
CCB = calcium channel blockers; CO = cardiac output; NO = nitric oxide; PAP = pulmonary arterial pressure; PVR = pulmonary vascular resistance; WU = Wood units
Used with permission from: Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111:3105-3111.

Table 2.

	Acute NO/Epoprostenol Responders Group (n = 70)	Long-term CCB Responders Group (n = 38)	CCB Failure Group (n = 32)	P*
Drug tested (NO:epoprostenol) (n)	57:13	33:5	24:8	.2
Mean PAP reached during acute vasodilator testing (mm Hg)	38 ± 11 (18-65)	33 ± 8 (18-50)	46 ± 10 (18-65)	< .001
Fall in mean PAP during acute vasodilator testing (mm Hg)	19 ± 7 (10-36)	21 ± 7 (10 - 36)	16 ± 6 (10 - 33)	.006
Percent fall in mean PAP	33 ± 11 (20-59)	39 ± 11 (20 - 59)	26 ± 7 (20 - 49)	< .001
PVR reached during acute vasodilator testing (WU)	6.6 ± 3.4 (1.1 - 17.4)	5.2 ± 2.7 (1.1 - 13.1)	8.6 ± 3.3 (1.1 - 17.4)	< .001
Fall in PVR during acute vasodilator testing (WU)	5.6 ± 3.3 (1.6 - 16.7)	5.1 ± 3.1 (1.7 - 15.4)	6.2 ± 3.4 (1.6 -16.7)	.16
Percent fall in PVR	45 ± 15 (24-77)	50 ± 15 (24 - 77)	40 ± 13 (26 - 75)	.007

Hemodynamic Values Reached During Vasodilator Testing in Acute Responders

Table 3.

Used with permission from: Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary pulmonary hypertension in children. Circulation. 1999;99:1197-1208.

Palevsky HI, Schloo BL, Pietra GG, et al. Primary pulmonary hypertension. Vascular structure, morphometry, and responsiveness to vasodilator agents. Circulation. 1989;80:1207-1221. Abstract
McMurtry IF, Davidson AB, Reeves JT, Grover RF. Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs. Circ Res. 1976;38:99-104.
Yuan JX, Aldinger AM, Juhaszova M, et al. Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Circulation. 1998;98:1400-1406. Abstract
Pollock DM, Keith TL, Highsmith RF. Endothelin receptors and calcium signaling. FASEB J. 1995;9:1196-1204. Abstract
Corbin JD. Mechanisms of action of PDE5 inhibition in erectile dysfunction. Int J Impot Res. 2004;16(Suppl 1):S4-7. Abstract
Camerini F, Alberti E, Klugmann S, et al. Primary pulmonary hypertension: effects of nifedipine. Br Heart J. 1980;44:352-356. Abstract
Rubin LJ, Nicod P, Hillis LD, et al. Treatment of primary pulmonary hypertension with nifedipine. A hemodynamic and scintigraphic evaluation. Ann Intern Med. 1983;99:433-438. Abstract
Rich S, Brundage BH, Levy PS. The effect of vasodilator therapy on the clinical outcome of patients with primary pulmonary hypertension. Circulation. 1985;71:1191-1196.
Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation. 1987;76:135-141. Abstract
Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary hypertension. N Engl J Med. 1992;327:76-81. Abstract
Schrader BJ, Inbar S, Kaufmann L, et al. Comparison of the effects of adenosine and nifedipine in pulmonary hypertension. J Am Coll Cardiol. 1992;19:1060-1064. Abstract
Sitbon O, Brenot F, Denjean A, et al. Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension. A dose-response study and comparison with prostacyclin. Am J Respir Crit Care Med. 1995;151:384-389. Abstract
Sitbon O, Humbert M, Jagot JL, et al. Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur Respir J. 1998;12:265-270. Abstract
Berkenboom G, Sobolski J, Stoupel E. Failure of nifedipine treatment in primary pulmonary hypertension. Br Heart J. 1982;47:511.
Packer M. Vasodilator therapy for primary pulmonary hypertension. Limitations and hazards. Ann Intern Med. 1985;103:258-270. Abstract
Prigogine T, Waterlot Y, Gottignies P, et al. Acute nonhemodynamic pulmonary edema with nifedipine in primary pulmonary hypertension. Chest. 1991;100:563-564. Abstract
Partanen J, Nieminen MS, Luomanmaki K, et al. Death in a patient with primary pulmonary hypertension after 20 mg of nifedipine. N Engl J Med. 1993;329:812.
Badesch DB, Abman SH, Ahearn GS, et al; American College of Chest Physicians. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126:35S-62S. Abstract
Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111:3105-3111. Abstract
Galie N, Torbicki A, Barst R, et al; Task Force. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J. 2004;25:2243-2278. Abstract
Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary pulmonary hypertension in children. Circulation. 1999;99:1197-1208. Abstract
Yung D, Widlitz AC, Rosenzweig EB, et al. Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation. 2004;110:660-665. Abstract
Nootens M, Kaufmann E, Rich S. Short-term effectiveness of nifedipine in secondary pulmonary hypertension. Am J Cardiol. 1993;71:1475-1476. Abstract
Alpert MA, Pressly TA, Mukerji V, et al. Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease. Am J Cardiol. 1991;68:1687-1691. Abstract
Woodmansey PA, O'Toole L, Channer KS, et al. Acute pulmonary vasodilatory properties of amlodipine in humans with pulmonary hypertension. Heart. 1996;75:171-173. Abstract
Packer M, O'Connor CM, Ghali JK, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group. N Engl J Med. 1996;335:1107-1114. Abstract

processing....

Introduction

Calcium channel blockers (CCBs) have been used in the treatment of pulmonary arterial hypertension (PAH) for over 25 years. Despite this, they have never been evaluated in a randomized trial in patients with PAH. In addition, although there are presently 5 drugs approved for the treatment of PAH, including 2 oral medications, many clinicians still are familiar only with CCBs as a therapeutic option for patients with PAH. Although some patients exhibit significant improvement after treatment with CCBs, these drugs only benefit a small minority of patients with PAH and have been studied almost exclusively in patients with idiopathic PAH (IPAH).

Page 1 of 9

Rationale for Use of CCBs in the Treatment of PAH

References

Table 1.

Table 2.

Table 2.

Table 3.

The Role of Calcium Channel Blockers in Pulmonary Arterial Hypertension

Introduction

Table of Contents

Table 1.

Table 2.

Table 2.

Table 3.

References

Faculty and Disclosures

The Role of Calcium Channel Blockers in Pulmonary Arterial Hypertension

Introduction

Table of Contents