Dose-dependent efficacy of olezarsen in high-risk hypertriglyceridemia: A meta-analysis

Table 1 Tabulated representation of baseline characteristics of included randomized controlled trials

Trial name	Year	Type of study	Location	Total study population	Olezarsen 50 mg (n)	Olezarsen 80 mg (n)	Duration of study
Balance trials[13] 2024	2024	Randomized control trial	United States, Europe and Canada	44	21	23	49 weeks
Bridge-TIMI 73a[11]	2024	Phase 2b randomized control trial	United States	97	58	39	12 months treatment and 13 weeks follow up
Essence-TIMI 73b[12]	2025	Phase 3 randomized control trial	United States	1020	254	766	12 months of treatment and 13 weeks follow up

Table 2 Tabulated representation of baseline characteristic of included population, mean ± SD/n (%)/median (IQR)

Characteristics		Balance trial 2024		Bridge-TIMI 73a 2024		Essence-TIMI 2025
		Olezarsen 50 mg	Olezarsen 80 mg	Olezarsen 50 mg	Olezarsen 80 mg	Olezarsen 50 mg	Olezarsen 80 mg
Age (year)		43.2 ± 12.1	47.7 ± 13.3	63 (54-71)	60 (54-69)	63 (57-69)	64 (56-70)
Female		6 (29)	11 (50)	24 (41)	24 (62)	97 (38.2)	306 (39.9)
Race	White	17 (81)	17 (77)	54 (93)	52 (91)	240 (94.5)	713 (93.1)
	Black	0	2 (9)	3 (5)	5 (9)	2 (0.8)	34 (4.4)
	Hispanic or Latino	3 (14)	1 (5)	21 (36)	23 (40)	67 (26.4)	179 (23.4)
	Asian	3 (14)	3 (14)	1 (2)	0	6 (2.4)	8 (1.0)
BMI (kg/m2)		22.4 ± 3.5	25.1 ± 6.0	32.9	33.0	31.6 (28.3-34.9)	31.5 (28.5-35.9)
DM		3 (14)	7 (32)	37 (64)	30 (77)	151 (59.4)	468 (61.1)
Pancreatitis		15 (71)	17 (77)	2 (3)	0 (0)	-	-
Lipid panel (mg/dL)	ApoC-III	27.7 ± 10.5	27.5 ± 11.6	15.3 (12.0-19.3)	15.8 (13.2-18.7)	15.2 (12.3-18.8)	15.3 (12.9-18.3)
	Triglyceride	2684 ± 1235	2613 ± 1499	230.0 (182.5-331.5)	241.5 (179.5-357.5)	235.3 (186.5-309.5)	237.3 (191.5-306.0)
	LDL cholesterol	17.6 ± 8.5	22.8 ± 14.1	83.8 (59.5-106.0)	81.5 (62.0-104.5)	79.0 (58.0-112.0)	81.0 (60.0-107.3)
	Apolipoprotein B	65.2 ± 13.5	58.4 ± 7.2	90.8 (75.5-105.0)	94.0 (78.0-114.5)	89.5 (73.1-110.3)	90.7 (74.0-109.0)
	Non-HDL cholesterol	307.6 ± 101.8	262.9 ± 100.4	132.2 (103.5-156.5)	134.5 (110.0-161.5)	123.3 (97.5-158.0)	126.0 (99.5-155.5)

BMI: Body mass index; DM: Diabetes mellitus; ApoC-III: Apolipoprotein C-III; LDL: Low density lipoproteins; HDL: High-density lipoproteins.

Table 3 Certainty of evidence assessment using Grading of Recommendations, Assessment, Development, and Evaluation

No of studies	Study design	Certainty assessment					No of patients		Effect		Certainty	Importance
		Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Change in triglyceride level	Placebo	Relative (95%CI)	Absolute (95%CI)
Change in triglyceride level
3	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	845	333	-	SMD 0.72 lower (1.55 lower to 0.12 higher)	High	Critical
Change in HDL
2	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	823	312	-	SMD 0.05 higher (0.08 lower to 0.18 higher)	High	Critical
Change in VLDL
2	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	823	312	-	SMD 0.09 lower (0.22 lower to 0.04 higher)	High	Critical
Change in apolipoprotein C-III level
3	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	845	333	-	SMD 0.26 lower (0.51 lower to 0.01 lower)	High	Critical
Change in apolipoprotein B level
2	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	823	312	-	SMD 0.91 SD lower (2.7 lower to 0.88 higher)	High	Critical
Any adverse events
3	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	695/911 (76.3%)	261/355 (73.5%)	RR = 1.04 (0.96-1.11)	29 more per 1000 (from 29 fewer to 81 more)	High	Critical
Any serious adverse events
3	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	123/911 (13.5%)	34/355 (9.6%)	RR = 1.40 (0.97-2.02)	38 more per 1000 (from 3 fewer to 98 more)	High	Critical
Hypersensitivity reaction
3	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	45/911 (4.9%)	14/355 (3.9%)	RR = 1.71 (0.51-5.75)	28 more per 1000 (from 19 fewer to 187 more)	High	Critical
Renal dysfunction
2	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	44/889 (4.9%)	16/334 (4.8%)	RR = 1.13 (0.62-2.04)	6 more per 1000 (from 18 fewer to 50 more)	High	Critical
Liver dysfunction
3	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	32/911 (3.5%)	15/355 (4.2%)	RR = 1.07 (0.55-2.09)	3 more per 1000 (from 19 fewer to 46 more)	High	Critical
Thrombocytopenia
2	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	29/889 (3.3%)	9/334 (2.7%)	RR = 1.57 (0.28-8.75)	15 more per 1000 (from 19 fewer to 209 more)	High	Critical

RR: Relative risk; HDL: High-density lipoproteins; VLDL: Very low-density lipoproteins; SMD: Standardized mean difference.