Comparison of ambulatory blood pressure-lowering effects of higher doses of different calcium antagonists in uncontrolled hypertension: the Calcium Antagonist Controlled-Release High-Dose Therapy in Uncontrolled Refractory Hypertensive Patients (CARILLON) Study

Figures & data

Figure 1. Study design. Uncontrolled hypertensive patients who were treated with two or more antihypertensive drugs with the usual dose of a renin-angiotensin system inhibitor and a calcium channel blocker were registered in this study. Abbreviations: SBP, systolic blood pressure; ABPM, ambulatory blood pressure monitoring.

Figure 2. Flow of study participants.

Table 1. Baseline characteristics of Japanese uncontrolled hypertensive patients (n = 51) medicated by two or more antihypertensive drugs.

Characteristic	NCR group, n = 25	AML group, n = 26	p-value
Age, yrs	66.7 ± 11.5	69.0 ± 13.3	.51
Male, %	56.0	69.2	.33
Body mass index, kg/m^2	27.8 ± 4.9	26.4 ± 4.3	.31
Creatinine, mg/dL	0.87 ± 0.43	0.89 ± 0.38	.85
eGFR, mL/min/1.73m^2	68.3 ± 22.5	69.0 ± 25.8	.92
Diabetes, %	40.0	34.6	.69
History of myocardial infarction, %	0.0	8.3	.26
History of stroke, %	4.0	3.8	.75
History of peripheral arterial disease, %	0.0	0.0	–
Two antihypertensive drugs, n (%)	19 (76.0)	16 (61.5)	.27
More than three antihypertensive drugs, n(%)	6 (24.0)	10 (38.5)	.27
Calcium channel blocker, n (%)	25 (100)	26 (100)	–
Angiotensin receptor blocker, n (%)	25 (100)	26 (100)	–
Angiotensin converting enzyme inhibitor, n (%)	1 (4.0)	0 (0.0)	.30
Direct renin inhibitor, n (%)	1 (4.0)	0 (0.0)	.30
Mineralocorticoid receptor blocker, n (%)	1 (4.0)	1 (4.0)	.98
Diuretic, n (%)	2 (8.0)	5 (19.2)	.24
Beta-blocker, n (%)	2 (8.0)	4 (15.4)	.41
Alpha-blocker, n (%)	2 (8.0)	3 (11.5)	.67

Data are means ± SDs or percentages.

NCR indicates nifedipine CR (80 mg per day); AML: amlodipine (10 mg per day); eGFR: estimated glomerular filtration rate.

Figure 3. Mean 24-hr SBP before and after treatment. Each patient’s mean 24-hr SBP before and after ten weeks of treatment. The central bar on the vertical bars represents the mean ± SD. NCR: nifedipine controlled-release; AML: amlodipine; SBP: systolic blood pressure.

Figure 4. Scatter plot of the linear relationship between the baseline blood pressure (BP) level and the change in BP and the interaction between treatment drugs concerning the baseline BP level and the change in BP. NCR: nifedipine controlled-release group; AML: amlodipine group.

Table 2. Changes in blood pressure.

	NCR group, n = 25	AML group, n = 26	p-value
Clinic SBP, mm Hg
Baseline	152.7 ± 11.5	153.2 ± 14.3	.88
End of 2 weeks	145.4 ± 14.6	148.2 ± 9.5	.42
End of the study	130.8 ± 12.2	133.6 ± 14.1	.47
Change after 10 weeks	−21.8 ± 12.5**	−19.7 ± 18.0**	.62
Clinic DBP, mm Hg
Baseline	81.0 ± 7.5	79.9 ± 12.2	.72
End of 2 weeks	76.9 ± 6.8	78.0 ± 10.8	.66
End of the study	72.1 ± 9.6	71.4 ± 11.3	.82
Change after 10 weeks	−8.9 ± 10.1**	−8.5 ± 11.0*	.90
Home SBP, mm Hg
Baseline	153.0 ± 11.5	159.5 ± 17.3	.13
End of the study	131.0 ± 10.6	142.1 ± 16.8	<.01
Change after 10 weeks	−22.0 ± 10.5**	−17.3 ± 15.3**	.21
Home DBP, mm Hg
Baseline	80.7 ± 9.9	82.1 ± 10.8	.64
End of the study	71.9 ± 5.9	75.7 ± 10.8	.13
Change after 10 weeks	−8.7 ± 9.3**	−6.3 ± 8.2*	.34
24-hr SBP, mm Hg
Baseline	140.1 ± 12.4	144.3 ± 13.5	.25
End of the study	127.0 ± 11.6	130.9 ± 12.7	.25
Change after 10 weeks	−13.1 ± 11.3**	−13.4 ± 11.7**	.93
24-hr DBP, mm Hg
Baseline	78.2 ± 5.8	79.1 ± 8.4	.65
End of the study	73.3 ± 5.5	72.6 ± 7.7	.72
Change after 10 weeks	−4.9 ± 5.1**	−6.5 ± 6.1**	.32
Daytime SBP, mm Hg
Baseline	146.3 ± 13.5	147.9 ± 14.9	.68
End of the study	132.9 ± 11.6	135.8 ± 15.8	.46
Change after 10 weeks	−13.4 ± 12.7**	−12.2 ± 12.8**	.73
Daytime DBP, mm Hg
Baseline	81.3 ± 6.1	81.3 ± 9.0	.99
End of the study	76.5 ± 6.1	75.2 ± 8.6	.52
Change after 10 weeks	−4.8 ± 5.6**	−6.2 ± 7.2**	.44
Nighttime SBP, mmHg
Baseline	128.6 ± 13.7	137.0 ± 15.6	.04
End of the study	115.0 ± 14.0	120.7 ± 11.5	.12
Change after 10 weeks	−13.5 ± 13.6**	−16.3 ± 12.7**	.46
Nighttime DBP, mmHg
Baseline	72.3 ± 6.4	74.8 ± 8.8	.24
End of the study	66.6 ± 6.2	67.3 ± 7.5	.73
Change after 10 weeks	−5.7 ± 6.9**	−7.5 ± 6.4**	.32
Early-morning SBP, mmHg
Baseline	149.8 ± 11.8	155.1 ± 20.9	.27
End of the study	129.5 ± 15.2	139.3 ± 17.2	.04
Change after 10 weeks	−20.3 ± 19.2**	−15.8 ± 24.4*	.47
Early-morning DBP, mmHg
Baseline	84.9 ± 7.4	83.6 ± 11.1	.62
End of the study	76.3 ± 9.1	76.5 ± 9.4	.94
Change after 10 weeks	−8.6 ± 11.7*	−7.1 ± 11.9*	.64
Lowest nighttime SBP, mmHg
Baseline	111.8 ± 13.5	120.3 ± 14.8	.04
End of the study	99.6 ± 15.4	106.5 ± 13.5	.09
Change after 10 weeks	−12.3 ± 15.1**	−13.8 ± 14.4**	.72
Morning blood pressure surge, mmHg
Baseline	37.9 ± 12.1	34.8 ± 19.8	.50
End of the study	30.0 ± 17.7	32.8 ± 17.5	.57
Change after 10 weeks	−8.0 ± 21.8	−2.0 ± 24.2	.36

Data are mean ± SD.

* p < .05.

** p < .001 vs. baseline by paired t-test.

NCR indicates nifedipine CR (80 mg per day); AML: amlodipine (10 mg per day); SBP: systolic blood pressure; DBP: diastolic blood pressure.

Table 3. Biomarker results in the NCR and AML treatment groups.

Biomarker	NCR group, n = 25	AML group, n = 25	p-value
UACR, mg/g cre
Baseline	50.4 (24.0–106.1)	26.4 (13.7–51.0)	.19
End of the study	33.0 (15.6–69.8)	21.4 (11.9–38.4)	.35
Change, %	−18.4 (−35.2 to −1.7)*	−9.2 (−25.8 to 7.4)	.42
NTproBNP, pg/mL
Baseline	60.3 (38.7–93.9)	79.7 (49.9–127.4)	.38
End of the study	55.0 (34.5–87.7)	64.3 (40.4–102.2)	.63
Change, %	−4.0 (−13.2 to 5.2)	−9.3 (−17.2 to −1.5)*	.37
hsCRP, mg/L
Baseline	0.057 (0.037–0.088)	0.050 (0.029–0.084)	.66
End of the study	0.061 (0.040–0.093)	0.039 (0.022–0.067)	.18
Change, %	2.8 (−16.6 to 22.2)	−10.9 (−28.2 to 6.5)	.29
hsTnT, ng/mL
Baseline	0.008 (0.005–0.011)	0.009 (0.007–0.012)	.53
End of the study	0.008 (0.006–0.012)	0.009 (0.007–0.012)	.61
Change, %	3.9 (−1.2 to 8.9)	2.2 (−3.7 to 8.1)	.66

Data are geometric mean (95% CI).

* p < .05 vs. baseline by paired t-test.

NCR indicates nifedipine CR (80 mg per day); AML: amlodipine (10 mg per day); UACR: urinary albumin creatinine ratio; NTproBNP: N-terminal prohormone of brain natriuretic peptide; hsCRP: high-sensitivity C-reactive protein; hsTnT: high-sensitivity troponin T.