Reduction in cardiovascular risk using a proactive multifactorial intervention is consistent among patients residing in Pacific Asian and non-Pacific Asian regions: a CRUCIAL trial subanalysis

Figures & data

Figure 1 Flow of PA and non-PA patients through the CRUCIAL trial.

Notes: ^aTreated patients with baseline and one or more postbaseline efficacy measurements. For one PMI investigator from a non-PA region, four out of 18 patients received UC during the treatment period and were analyzed in the UC arm for the safety population and in the PMI arm for the full analysis set; ^bhypertension: untreated: SBP ≥160 mmHg and/or DBP ≥100 mmHg; treated: SBP ≥140 mmHg and/or DBP ≥90 mmHg or diabetes: SBP >130 mmHg and/or DBP >80 mmHg.
Abbreviations: AE, adverse event; CHD, coronary heart disease; CHF, congestive heart failure; CRUCIAL, Cluster Randomized Usual Care versus Caduet Investigation Assessing Long-term-risk; CV, cardiovascular; DBP, diastolic blood pressure; HbA_1c, glycated hemoglobin; PA, Pacific Asian; PMI, proactive multifactorial intervention; SBP, systolic blood pressure; TC, total cholesterol; TG, triglycerides; TIA, transient ischemic attack; UC, usual care.

Table 1 Baseline characteristics and demographics in PA and non-PA regions

	Overall (n=1,417)			PA (n=448a)			Non-PA (n=969a)
	PA (n=448a)	Non-PA (n=969a)	P-value for region comparison	PMI arm (n=247a)	UC arm (n=201a)	P-value	PMI arm (n=513a)	UC arm (n=456a)	P-value
Male, n (%)	284 (63.4)	454 (46.9)	<0.001	162 (65.6)	122 (60.7)	0.285	244 (47.6)	210 (46.1)	0.638
Age, years, mean ± SD	62.5±9.5	59.1±10.1	<0.001	61.5±9.8	63.6±8.9	0.019	59.2±10.0	58.9±10.3	0.606
Current smoker, n (%)	121 (27.3)	424 (43.8)	<0.001	74 (30.2)	47 (23.6)	0.121	233 (45.4)	191 (41.9)	0.268
BMI, kg/m^2, mean ± SD	25.9±3.8	30.1±5.0	<0.001	25.6±3.8	26.3±3.7	0.064	30.2±5.1	30.0±5.0	0.694
SBP, mmHg, mean ± SDb	147.6±17.2	147.5±13.9	0.976	151.0±17.4	143.3±15.9	<0.001	150.0±13.5	144.8±13.8	<0.001
DBP, mmHg, mean ± SDb	86.1±10.5	89.1±8.5	<0.001	87.9±11.1	84.1±9.2	<0.001	90.6±8.0	87.5±8.9	<0.001
Heart rate, bpm, mean ± SD	72.8±10.6	73.7±9.4	0.118	72.6±10.5	73.2±10.7	0.544	74.7±9.3	72.7±9.5	0.001
TC, mg/dL, mean ± SD	194.3±30.1	200.4±29.7	<0.001	194.6±30.3	194.0±29.8	0.831	201.7±29.6	198.8±29.9	0.123
LDL-C, mg/dL, mean ± SD	113.7±28.5	121.1±26.8	<0.001	114.2±28.3	113.0±28.7	0.659	121.9±26.3	120.2±27.5	0.335
HDL-C, mg/dL, mean ± SD	47.2±12.9	47.9±14.0	0.384	47.2±12.3	47.2±13.6	0.997	47.8±14.1	48.1±13.7	0.749
TG, mg/dL, mean ± SD	170.9±84.0	161.5±82.9	0.049	169.6±84.9	172.6±83.1	0.711	165.6±86.1	156.7±78.9	0.096
Type 2 diabetes, n (%)	263 (58.7)	337 (34.8)	<0.001	143 (57.9)	120 (59.7)	0.699	181 (35.3)	156 (34.2)	0.727
Framingham 10-year CHD risk (%),^Citation11 mean ± SD	21.7±12.3	17.9±10.4	<0.001	22.0±12.0	21.3±12.8	0.606	19.0±10.6	16.7±10.0	<0.001

Notes:

a Treated patients with baseline and one or more postbaseline efficacy measurements

b BP values were measured at baseline (week 0), whereas information on all of the other variables listed were collected during screening.

Abbreviations: bpm, beats per minute; BMI, body mass index; BP, blood pressure; CHD, coronary heart disease; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PA, Pacific Asian; PMI, proactive multifactorial intervention; SBP, systolic blood pressure; SD, standard deviation; TC, total cholesterol; TG, triglyceride; UC, usual care.

Table 2 Distribution of SPAA dose at week 52 by subgroup

	Dose of SPAA (mg/mg)
	5/10	10/10	5/20	10/20
Region
PA, n (%)	210 (83)	43 (17)	0 (0)	0 (0)
Non-PA, n (%)	405 (77)	87 (17)	22 (4)	12 (2)
Sex
Male, n (%)	328 (80)	61 (15)	14 (3)	10 (2)
Female, n (%)	287 (78)	69 (19)	8 (2)	2 (1)
Diabetes status
Diabetes, n (%)	263 (78)	63 (19)	5 (2)	5 (2)
No diabetes, n (%)	352 (79)	67 (15)	17 (4)	7 (2)

Abbreviations: PA, Pacific Asian; SPAA, single-pill amlodipine/atorvastatin.

Figure 2 Relative percentage change in Framingham 10-year CHD risk, from baseline to week 52 for PA and non-PA patients by treatment arm.

Notes: ^aP<0.001. Patients excluded for missing data: PA PMI, n=6; PA UC, n=2; non-PA PMI, n=6.
Abbreviations: CHD, coronary heart disease; CI, confidence interval; LS, least square mean for difference; PA, Pacific Asian; PMI, proactive multifactorial intervention; UC, usual care.

Figure 3 Adjusted mean change from baseline to week 52 in (A) SBP and DBP (mmHg), and (B) TC and LDL-C (%) for PA and non-PA patients.

Notes: ^aP<0.05; ^bP<0.001; ^cP=0.051. Patients excluded for missing LDL-C: PA PMI, n=5; PA UC, n=2; non-PA PMI, n=14; non-PA UC, n=16.
Abbreviations: CI, confidence interval; DBP, diastolic blood pressure; LDL-C, low-density lipoprotein cholesterol; LS, least square mean for difference; PA, Pacific Asian; PMI, proactive multifactorial intervention; SBP, systolic blood pressure; TC, total cholesterol; UC, usual care.

Figure 4 Study-specific BP and LDL-C goal attainment at week 52 for PA and non-PA patients.

Notes: ^aP=0.002; ^bP<0.001; ^cP=0.738; ^dP=0.004. Patients excluded for missing data: dual goal attainment: PA PMI, n=2; PA UC, n=0; non-PA PMI, n=4; non-PA UC, n=4; LDL-C goal attainment: PA PMI, n=4; PA UC, n=2; non-PA PMI; n=4; non-PA UC, n=4.
Abbreviations: BP, blood pressure; CI, confidence interval; LDL-C, low-density lipoprotein cholesterol; OR, odds ratio; PA, Pacific Asian; PMI, proactive multifactorial intervention; UC, usual care.

Table 3 All-causality AEs in PA and non-PA patients

	PA (n=448)a		Non-PA (n=969)a
	PMI arm (n=247)	UC arm (n=201)	PMI arm (n=513)	UC arm (n=456)
Number of AEs, n	354	266	365	327
Patients with AEs, n (%)	137 (55.5)	124 (61.7)	23 (45.2)	172 (37.7)
Serious AEs,b n (%)	19 (7.7)	8 (4.0)	31 (6.0)	13 (2.9)
Severe AEs,c n (%)	13 (5.3)	6 (3.0)	27 (5.3)	10 (2.2)
Discontinued due to AEs, n (%)	7 (2.8)	0 (0.0)	38 (7.4)	4 (0.9)
Dose reduced or temporarily discontinued, n (%)	8 (3.2)	0 (0.0)	16 (3.1)	6 (1.3)
Most frequent AEsd
Edema peripheral, n (%)	15 (6.1)	1 (0.5)	36 (7.0)	10 (2.2)
Hypercholesterolemia, n (%)	0 (0.0)	11 (5.5)	1 (0.2)	1 (0.2)
Headache, n (%)	10 (4.0)	7 (3.5)	13 (2.5)	8 (1.8)
Dyslipidemia, n (%)	0 (0.0)	8 (4.0)	0 (0.0)	3 (0.7)
Nasopharyngitis, n (%)	12 (4.9)	4 (2.0)	10 (1.9)	6 (1.3)
Chest pain, n (%)	13 (5.3)	7 (3.5)	4 (0.8)	3 (0.7)
Increase in TG, n (%)	2 (0.8)	5 (2.5)	9 (1.8)	9 (2.0)
Bronchitis, n (%)	3 (1.2)	0 (0.0)	9 (1.8)	15 (3.3)
Dizziness, n (%)	10 (4.0)	7 (3.5)	6 (1.2)	2 (0.4)
Upper respiratory tract infection, n (%)	16 (6.5)	10 (5.0)	0 (0.0)	4 (0.9)
Increase in creatine phosphokinase, n (%)	4 (1.6)	3 (1.5)	11 (2.1)	2 (0.4)
Dyspepsia, n (%)	3 (1.2)	5 (2.5)	2 (0.4)	5 (1.1)
Constipation, n (%)	6 (2.4)	3 (1.5)	3 (0.6)	1 (0.2)
Arthralgia, n (%)	6 (2.4)	4 (2.0)	3 (0.6)	4 (0.9)
Hyperlipidemia, n (%)	0 (0.0)	9 (4.5)	0 (0.0)	1 (0.2)
Insomnia, n (%)	6 (2.4)	7 (3.5)	2 (0.4)	4 (0.9)
Hypertension, n (%)	2 (0.8)	2 (1.0)	2 (0.4)	10 (2.2)
Pharyngitis, n (%)	2 (0.8)	1 (0.5)	4 (0.8)	12 (2.6)
Palpitations, n (%)	7 (2.8)	3 (1.5)	1 (0.2)	2 (0.4)
Abdominal pain upper, n (%)	6 (2.4)	4 (2.0)	1 (0.2)	3 (0.7)
Chest discomfort, n (%)	5 (2.0)	4 (2.0)	0 (0.0)	0 (0.0)
Osteoarthritis, n (%)	7 (2.8)	3 (1.5)	3 (0.6)	5 (1.1)
Back pain, n (%)	5 (2.0)	5 (2.5)	6 (1.2)	1 (0.2)
Cough, n (%)	7 (2.8)	6 (3.0)	2 (0.4)	2 (0.4)
Hypoesthesia, n (%)	6 (2.4)	0 (0.0)	1 (0.2)	0 (0.0)
Hyperuricemia, n (%)	0 (0.0)	4 (2.0)	0 (0.0)	0 (0.0)
Myalgia, n (%)	2 (0.8)	4 (2.0)	4 (0.8)	1 (0.2)

Notes:

a Safety population: all randomized patients who received at least one dose of study medication

b serious AEs are defined as meeting one of the following criteria: AE resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, or in congenital anomaly or birth defect

c severe AEs are defined as AEs that interfere significantly with a patient’s usual function

d all observed or self-reported AEs that occurred at a rate of ≥2%.

Abbreviations: AEs, adverse events; PA, Pacific Asian; PMI, proactive multifactorial intervention; TG, triglycerides; UC, usual care.

Figure 5 Treatment effect on efficacy measures from baseline to week 52 for men and women in the (A) PA region, and (B) non-PA region.

Note: ^aMean change from baseline to week 52 following treatment with PMI versus UC, adjusted for baseline values.
Abbreviations: CHD, coronary heart disease; CI, confidence interval; LS, least square; PA, Pacific Asian; PMI, proactive multifactorial intervention; UC, usual care.

Figure 6 Treatment effect on efficacy measures from baseline to week 52 for PA and non-PA patients with (A) no diabetes, and (B) diabetes.

Note: ^aMean change from baseline to week 52 following treatment with PMI versus UC, adjusted for baseline values.
Abbreviations: CHD, coronary heart disease; CI, confidence interval; LS, least square; PA, Pacific Asian; SPAA, single-pill amlodipine/atorvastatin; UC, usual care.

WilsonPWD’AgostinoRBLevyDBelangerAMSilbershatzHKannelWBPrediction of coronary heart disease using risk factor categoriesCirculation19989718183718479603539

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