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.

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Safer Agents for Acute Vasodilator Testing

In the early 1990s, investigators began to use other agents to assess for acute vasoreactivity; these included adenosine, prostacyclin, and nitric oxide (NO). They found that short-term response to these agents was similar to that obtained with acute testing with high-dose CCBs (see Figure 5).^[11-13] Despite a number of publications cautioning against the use of CCBs in patients with evidence of significant right heart failure, there were a number of reports of patients dying during acute testing with CCBs, even with the use of conventional doses.^[14-17] With the introduction of parenteral (adenosine and epoprostenol) and inhaled (NO) agents with short half-lives (seconds to minutes), testing for vasoreactivity and determination of appropriateness for long-term treatment with CCBs became much safer. With the widespread use of these short-acting vasodilators, use of CCBs for acute testing is now rarely performed at large referral centers, and guidelines from the American College of Chest Physicians (ACCP) recommend using them only in patients who first demonstrate a vasodilator response with adenosine, epoprostenol, or NO.^[18] Until recently, however, there were no generally accepted guidelines for what constituted a positive acute vasodilator response that would predict long-term safety and benefit with CCB therapy.

Figure 5.

Enlarge

Individual change in mean pulmonary artery pressure (Ppa) in (a) responders and (b) nonresponders. One patient did not respond to a high dose of diltiazem (360 mg) but did respond to nitric oxide (NO). The 2 apparent responders had no significant change in total pulmonary resistance. (CCB = calcium-channel blockers)
Used with permission from: 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.