Low-density lipoprotein cholesterol outcomes post-non-PCSK9i lipid-lowering therapies in atherosclerotic cardiovascular disease and probable heterozygous familial hypercholesterolemia patients

Figures & data

Table 1 All ASCVD sample: demographic and clinical characteristics

Demographic and clinical characteristics	All ASCVD, N=186,670
	All ASCVD, index LDL-C value >70 mg/dL N=186,670 (100%)	Index LDL-C value 71–100 mg/dL n=94,323 (50.5%)	Index LDL-C value 101–130 mg/dL n=54,424 (29.2%)	Index LDL-C value >130 mg/dL n=37,923 (20.3%)
Age in years, mean (SD)	68.29 (11.45)	69.66 (10.79)	67.51 (11.85)	66.02 (12.00)
Age groups, %
<18	0.0	0.1	0.1	0.0
18–44	0.8	2.4	4.1	4.8
45–54	2.6	7.3	10.7	13.3
55–64	9.5	18.7	21.4	23.9
>65	20.5	71.7	63.8	58.0
Gender, %
Male	50.3	55.4	48.0	40.9
Female	49.7	44.6	52.1	59.1
Geographic region, %
Northeast	26.9	27.4	26.4	26.2
South	36.8	35.8	37.4	38.5
Midwest	20.6	20.7	20.5	20.7
West	15.7	16.1	15.7	14.5
CCI score, %
0	99.5	99.5	99.5	99.4
>0	0.5	0.5	0.5	0.6
Mean (SD)	0.01 (0.08)	0.01 (0.07)	0.01 (0.07)	0.01 (0.08)
Comorbidities, %
Diabetes	27.3	30.1	25.0	23.8
Hypertension	65.3	68.0	63.8	60.8
Dyslipidemia	68.1	71.1	63.9	66.5
Coronary disease	39.1	41.6	36.6	36.7
Cerebrovascular disease	17.4	16.1	18.5	19.1
Peripheral vascular disease	54.1	54.0	54.6	53.7
Index LDL-C, mg/dL
Mean (SD)	108.12 (31.60)	84.73 (8.52)	113.81 (8.52)	158.12 (26.89)
Number of LDL-C tests, %
1 (index test)	43.5	43.6	44.6	41.6
2	31.2	31.7	30.5	31.1
3	14.6	14.5	14.4	15.3
4	6.5	6.4	6.4	7.1
>4	4.1	3.8	4.2	5.0
Medications, %
Antidiabetic	17.2	19.0	15.8	14.9
Antiarrhythmic	0.5	0.5	0.5	0.4
Antihypertensive	59.9	62.6	58.6	55.4
Index BMI
Patients with BMI, %	91.0	90.9	91.1	91.0
Mean (SD)	29.46 (6.48)	29.44 (6.41)	29.43 (6.61)	29.53 (6.47)

Abbreviations: ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; CCI, Charlson Comorbidity Index; LDL-C, low-density lipoprotein cholesterol.

Table 2 Probable HeFH sample: demographic and clinical characteristics

Demographic and clinical characteristics	Probable HeFH patients
	Index LDL-C value >190 mg/dL n=4,137 (2.2%)
Age in years, mean (SD)	65.32 (11.57)
Age groups, %
<18	0.0
18–44	3.9
45–54	14.6
55–64	26.9
>65	54.7
Gender, %
Male	33.9
Female	66.1
Geographic region, %
Northeast	25.7
South	40.4
Midwest	21.3
West	12.6
CCI score, %
0	99.2
>0	0.8
Mean (SD)	0.01 (0.09)
Comorbidities, %
Diabetes	26.0
Hypertension	62.7
Dyslipidemia	72.0
Coronary disease	40.2
Cerebrovascular disease	18.2
Peripheral vascular disease	52.5
Index LDL-C, mg/dL
Mean (SD)	215.97 (30.92)
Number of LDL-C tests, %
1 (index test)	38.0
2	31.3
3	16.7
4	8.1
>4	5.9
Medications, %
Antidiabetic	16.3
Antiarrhythmic	0.3
Antihypertensive	56.2
Index BMI
Patients with BMI, %	90.8
Mean (SD)	29.63 (6.49)

Abbreviations: BMI, body mass index; CCI, Charlson Comorbidity Index; HeFH, heterozygous familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol.

Figure 1 Summary of post-index treatment and goal achievement, by baseline treated vs not treated.

Abbreviations: ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol.

Table 5 Goal achievement in probable HeFH patients who initiated or modified treatment post-index

Probable HeFH patients (index LDL-C value ≥190 mg/dL) (untreated at index)	n=3,064 (2.8%)	Probable HeFH patients (index LDL-C value ≥190 mg/dL) (treated at index)	n=1,073 (1.4%)
Pts initiating LLT therapy, n (%)	1,540 (50.3)	Pts modifying therapy, n (%)	445 (41.5)
Pts with post-therapy LDL-C, n (%)	896 (58.2)	Pts with post-therapy LDL-C, n (%)	281 (63.2)
Pts with ≥50% LDL-C reduction, % (CI)	31.1 (28.1–34.2)	Pts with ≥50% LDL-C reduction, %	22.1 (17.2–26.9)
Pts with LDL-C ≤70 mg/dL, % (CI)	4.4 (3.0–5.7)	Pts with LDL-C ≤70 mg/dL, %	1.1 (-0.1–2.3)
LDL-C, mean (SD)	136.21 (47.75)	LDL-C, mean (SD)	151.87 (54.37)
Pts initiating statin only, n (%)	1,410 (91.6)	Pts switching statin, n (%)	153 (34.4)
Pts with post-therapy LDL-C, n (%)	815 (57.8)	Pts with post-therapy LDL-C, n (%)	81 (52.9)
Pts with ≥50% LDL-C reduction, % (CI)	32.0 (28.8–35.2)	Pts with ≥50% LDL-C reduction, %	22.2 (13.0–31.5)
Pts with LDL-C ≤70 mg/dL, % (CI)	4.8 (3.3–6.3)	Pts with LDL-C ≤70 mg/dL, %	0.0
LDL-C, mean (SD)	135.12 (48.04)	LDL-C, Mean (SD)	147.40 (49.25)
Pts initiating ezetimibe only, n (%)	90 (5.8)	Pts increasing statin intensity, n (%)	170 (38.2)
Pts with post-therapy LDL-C, n (%)	58 (64.4)	Pts with post-therapy LDL-C, n (%)	109 (64.1)
Pts with ≥50% LDL-C reduction, % (CI)	10.3 (2.3–18.4)	Pts with ≥50% LDL-C reduction, %	26.6 (18.2–35.0)
Pts with LDL-C ≤70 mg/dL, % (CI)	0.0	Pts with LDL-C ≤70 mg/dL, %	1.8 (−0.7–4.4)
LDL-C, mean (SD)	110.93 (32.07)	LDL-C, mean (SD)	152.55 (57.84)
Pts initiating statin + ezetimibe, n (%)	40 (2.6)	Pts decreasing statin intensity, n (%)	81 (18.2)
Pts with post-therapy LDL-C, n (%)	23 (57.50)	Pts with post-therapy LDL-C, n (%)	61 (75.3)
Pts with ≥50% LDL-C reduction, % (CI)	52.2 (30.1–74.3)	Pts with ≥50% LDL-C reduction, %	13.1 (4.4–21.8)
Pts with LDL-C ≤70 mg/dL, % (CI)	0.0	Pts with LDL-C ≤70 mg/dL, %	0.0
LDL-C, mean (SD)	161.45 (38.89)	LDL-C, mean (SD)	164.49 (57.70)

Notes: Only patients with a recorded valid LDL-C measurement from 1 to 12 months after new treatment initiation are shown. The immediate test value post-treatment initiation was used (test values were limited to those observed between 1 and 12 months post-treatment initiation). Baseline statin intensity: among the 1,073 probable HeFH patients treated at baseline, 10.7% were on low statin intensity, 48.6% were on moderate statin intensity, 24.6% were on high statin intensity, and 16.0% were treated with other LLTs.

Abbreviations: HeFH, heterozygous familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapy; Pts, patients.

Table 3 Goal achievement in untreated ASCVD patients initiating treatment

Cohort	ASCVD patients, untreated at index, N=111,147
Index LDL-C value	All patients N=111,147 (100.0%)	71–100 mg/dL n=47,882 (43.1%)	101–130 mg/dL n=34,983 (31.5%)	>130 mg/dL n=28,282 (25.5%)
Pts initiating LLT therapy, n (%)	38,684 (34.8)	17,078 (35.7)	10,561 (30.2)	11,045 (39.1)
Pts with post-therapy LDL-C, n (%)	23,550 (60.9)	10,389 (60.8)	6,474 (61.3)	6,687 (60.5)
Pts with ≥50% LDL-C reduction, % (CI)	7.6 (7.3–8.0)	1.8 (1.6–2.1)	6.8 (6.2–7.4)	17.4 (16.5–18.3)
Pts with LDL-C ≤70 mg/dL, % (CI)	19.1 (18.6–19.6)	26.9 (26.0–27.7)	16.4 (15.5–17.3)	9.7 (8.9–10.4)
LDL-C, mean (SD)	96.29 (32.30)	83.61 (22.94)	96.74 (28.02)	115.54 (38.42)
Pts initiating statin only, n (%)	36,716 (94.9)	16,281 (95.3)	10,051 (95.2)	10,384 (94.1)
Pts with post-therapy LDL-C, n (%)	22,269 (60.7)	9,878 (60.7)	6,132 (61.0)	6,259 (60.3)
Pts with ≥50% LDL-C reduction, % (CI)	7.8 (7.4–8.1)	1.9 (1.6–2.1)	6.9 (6.2–7.5)	17.9 (17.0–18.9)
Pts with LDL-C ≤70 mg/dL, % (CI)	19.1 (18.7–19.7)	26.8 (25.9–27.7)	16.5 (15.6–17.4)	10.0 (9.3–10.7)
LDL-C, mean (SD)	95.78 (31.93)	83.62 (22.87)	96.39 (27.94)	114.37 (38.18)
Pts initiating ezetimibe only, n (%)	1,177 (3.0)	332 (1.9)	339 (3.2)	506 (4.6)
Pts with post-therapy LDL-C, n (%)	752 (63.9)	200 (60.2)	224 (66.1)	328 (64.8)
Pts with ≥50% LDL-C reduction, % (CI)	4.8 (3.3–6.3)	2.0 (0.0–4.0)	6.3 (3.1–9.4)	5.5 (3.0–8.0)
Pts with LDL-C ≤70 mg/dL, % (CI)	12.0 (9.6–14.3)	25.0 (18.9–31.1)	13.8 (9.3–18.4)	2.7 (1.0–4.5)
LDL-C, mean (SD)	114.96 (38.64)	87.31 (27.26)	104.15 (28.38)	139.20 (35.93)
Pts initiating statin + ezetimibe, n (%)	791 (2.0)	465 (2.72)	171 (1.6)	155 (1.4)
Pts with post-therapy LDL-C, n (%)	529 (66.9)	311 (66.88)	118 (69.01)	100 (64.52)
Pts with ≥50% LDL-C reduction, % (CI)	4.9 (4.7–9.0)	1.0 (−0.1–2.1)	5.1 (1.1–9.1)	27.0 (18.1–35.9)
Pts with LDL-C ≤70 mg/dL, % (CI)	24.4 (20.7–28.1)	31.8 (26.6–37.0)	17.0 (10.1–23.8)	10.0 (4.0–16.0)
LDL-C, mean (SD)	91.19 (29.59)	81.15 (21.86)	100.71 (29.71)	111.18 (36.07)

Notes: Only patients with a recorded valid LDL-C measurement from 1 to 12 months after new treatment initiation are shown. The immediate test value post-treatment initiation was used (test values were limited to those observed between 1 and 12 months post-treatment initiation).

Abbreviations: ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapy; Pts, patients.

Table 4 Goal achievement in treated ASCVD patients with post-index therapy modification

Cohort	ASCVD patients, treated at index N=75,523
Index LDL-C value	All patients N=75,523 (100.0%)	71–100 mg/dL N=46,441 (61.5%)	101–130 mg/dL N=19,441 (25.7%)	>130 mg/dL N=9,641 (12.8%)
Pts modifying therapy, n (%)	13,503 (17.9)	5,723 (12.3)	4,440 (22.8)	3,340 (34.6)
Pts with post-therapy LDL-C, n (%)	9,420 (69.8)	4,044 (70.7)	3,120 (70.3)	2,256 (67.5)
Pts with ≥50% LDL-C reduction, % (CI)	5.6 (5.1–6.0)	1.8 (1.4–2.2)	4.6 (3.9–5.4)	13.6 (12.2–15.0)
Pts with LDL-C ≤70 mg/dL, % (CI)	17.8 (17.0–18.6)	26.7 (25.4–28.1)	14.0 (12.8–15.3)	6.9 (5.9–8.0)
LDL-C, mean (SD)	99.03 (34.59)	86.50 (26.39)	99.28 (29.85)	121.17 (41.76)
Pts switching statin, n (%)	4,408 (32.6)	2,012 (35.2)	1,366 (30.8)	1,030 (30.8)
Pts with post-therapy LDL-C, n (%)	3,148 (71.4)	1,462 (72.7)	996 (72.9)	690 (67.0)
Pts with ≥50% LDL-C reduction, % (CI)	5.4 (4.6–6.2)	2.0 (1.3–2.7)	4.1 (2.9–5.4)	14.6 (12.0–17.3)
Pts with LDL-C ≤70 mg/dL, % (CI)	16.2 (14.9–17.5)	23.3 (21.2–25.5)	12.2 (10.1–14.2)	7.0 (5.1–8.9)
LDL-C, mean (SD)	99.47 (33.99)	87.32 (25.09)	101.53 (29.97)	122.24 (42.47)
Pts increasing statin intensity, n (%)	5,723 (42.4)	2,156 (37.7)	2,116 (47.7)	1,451 (43.4)
Pts with post-therapy LDL-C, n (%)	3,920 (68.5)	1,485 (68.9)	1,472 (69.6)	963 (66.4)
Pts with ≥50% LDL-C reduction, % (CI)	6.6 (5.8–7.3)	2.1 (1.4–2.8)	5.2 (4.1–6.4)	15.5 (13.2–17.8)
Pts with LDL-C ≤70 mg/dL, % (CI)	21.1 (19.8–22.3)	34.5 (32.1–36.9)	16.0 (14.1–17.8)	8.2 (6.5–9.9)
LDL-C, mean (SD)	94.79 (33.10)	80.56 (23.52)	94.52 (27.00)	117.13 (41.02)
Pts decreasing statin intensity, n (%)	2,307 (17.1)	1,146 (20.0)	604 (13.6)	557 (16.7)
Pts with post-therapy LDL-C, n (%)	1,588 (68.8)	794 (69.3)	402 (66.6)	392 (70.4)
Pts with ≥50% LDL-C reduction, % (CI)	3.2 (2.3–4.0)	0.5 (0.0–1.0)	4.2 (2.3–6.2)	7.4 (4.8–10.0)
Pts with LDL-C ≤70 mg/dL, % (CI)	10.3 (8.8–11.8)	13.6 (11.2–16.0)	10.5 (7.4–13.5)	3.3 (1.5–5.1)
LDL-C, mean (SD)	108.70 (36.50)	97.70 (29.28)	111.25 (34.53)	128.37 (42.49)
Pts augmenting with ezetimibe, n (%)	1,065 (7.9)	409 (7.2)	354 (8.0)	302 (9.0)
Pts with post-therapy LDL-C, n (%)	764 (71.7)	303 (74.1)	250 (70.6)	211 (69.9)
Pts with ≥50% LDL-C reduction, % (CI)	6.0 (4.3–7.7)	3.0 (1.0–4.9)	3.6 (1.3–5.9)	13.3 (8.7–17.9)
Pts with LDL-C ≤70 mg/dL, % (CI)	23.0 (20.0–26.0)	39.6 (34.1–45.1)	16.0 (11.4–20.6)	7.6 (4.0–11.2)
LDL-C, mean (SD)	98.92 (36.35)	82.23 (28.04)	99.06 (31.01)	122.73 (39.46)

Notes: Only patients with a recorded valid LDL-C measurement from 1 to 12 months after new treatment initiation are shown. The immediate test value post-treatment initiation was used (test values were limited to those observed between 1 and 12 months post-treatment initiation). Baseline statin intensity: among the 75,523 ASCVD patients treated at baseline, 12.18% were on low statin intensity, 58.4% were on moderate statin intensity, 20.6% were on high statin intensity, and 8.8% were treated with other lipid-lowering agents.

Abbreviations: ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; Pts, patients.

Table S1 Stain dose intensity categories (low, moderate, and high)

Statin therapy	Daily dose
	Low intensity	Moderate intensity	High intensity	Intensity classifications of atypical doses
Atorvastatin	<10 mg/day	10 to <40 mg/day	≥40 mg/day	30 mg/day = moderate
Fluvastatin	<80 mg/day	80 mg/day	NA	10 mg/day = low
Lovastatin	<40 mg/day	≥40 mg/day	NA	10 mg/day = low 80 mg/day = moderate
Pitavastatin	<2 mg/day	≥2 mg/day	NA
Pravastatin	<40 mg/day	≥40 mg/day	NA	<10 mg/day = low
Rosuvastatin	<5 mg/day	5 to <20 mg/day	≥20 mg/day	<5 mg/day = low 15 mg/day = moderate
Simvastatin	<20 mg/day	20 to <80 mg/day	≥80 mg/day	<20 mg/day = low >40 to <80 mg/day = moderate ≥80 mg/day = high

Abbreviation: NA, not applicable.