Table 1.

Summary of the trials reviewed in this article

Study	Design	Number of participants	Follow-up duration	Principle findings
ODYSSEY HoFH	Randomized, double-blind, placebo-controlled	Alirocumab group (n = 45) Placebo group (n = 24)	12 weeks	At 12 weeks, LDL-C change was −26.9 (4.6)% from baseline (−62.8 [14.0]mg/dL) in the alirocumab group vs. 8.6 (6.3)% from baseline (8.9 [19.0]mg/dL) in the placebo group.
HoFH	Phase 3, randomized, double-blind, placebo-controlled	Evinacumab group (n = 43) Placebo group (n = 22)	24 weeks	At 24 weeks, the evinacumab group showed a LDL-C change of −47.1 (4.6)% from baseline compared with 1.9 (6.5)% in the placebo group.
E3	Randomized, parallel	Nicotine E-cigarettes + counseling (n = 128) Non-nicotine e-cigarettes + counseling (n = 127)	12 weeks	1. At 12 weeks, point prevalence abstinence was 22% in nicotine e-cigarette group vs. 17% in non-nicotine e-cigarette group 2. Relative risk [RR] (95% confidence interval [CI]) of the primary outcome was 2.4 (1.3–4.6) comparing nicotine e-cigarette vs. counseling and 1.9 (1.0–3.8) comparing non-nicotine e-cigarette vs. counseling.
SPYRAL HTN-OFF MED Pivotal trial	Randomized, parallel, sham	Renal denervation (n = 166) Sham (n = 165)	3 months	1. Change in 24-h systolic blood pressure at 3 months was −4.7 mmHg in the renal denervation group compared with −0.6 mmHg in the sham with a mean (95% CI) difference of – 4 mmHg (−6.2 to −1.8) (p < 0.001) 2. Change in office systolic blood pressure at 3 months, was −9.2 mmHg in the renal denervation group compared with −2.5 mmHg in the sham with a mean difference of – 6.6 mmHg (−9.6 to −3.5) (p < 0.001)
VICTORIA	Phase 3, randomized, parallel, double-blind, placebo-controlled	Vericiguat group (n = 2526) Placebo group (n = 2524)	12 months	1. Primary outcome (CV death or heart failure hospitalization) occurred in 35.5% of the vericiguat group compared with 38.5% of the placebo group (hazard ratio [HR] 0.90, p = 0.019). 2. HR (95%) for heart failure hospitalization was 0.90 (0.81–1.00) and for death from cardiovascular causes was 0.93 (0.81–1.06). 3. The composite of death from any cause or hospitalization for heart failure occurred in 37.9% of the vericiguat group and 40.9% in the placebo group with a HR (95% CI) 0.90 (0.83–0.98).
ORION	Pooled analysis of data from the ORION 9, ORION 10 and ORION 11 phase III trials	Inclisiran group (n = 1833) Placebo group (n = 1827)	18 months	1. Inclisiran group had significant lowering of LDL-C compared with placebo (mean difference between groups was −55%, p < 0.0001 at day 510 and − 52%, p < 0.0001 when time-averaged from day 90–540). 2. Similar percentage of patients with at least one TEAE between the inclisiran and placebo groups (78.0% vs. 77.3%, respectively)
REDUCE-IT EPA	Randomized, parallel, double-blind, placebo-controlled (secondary analysis)	N = 8179	4.9 years	1. No heterogeneity of effect on the primary composite endpoint with respect to baseline EPA levels stratified by tertiles (p interaction 0.91) 2. The effect of icosapent ethyl on primary composite endpoint events is independent of triglycerides and other biomarkers evaluated except EPA (HR 1.03, 95% CI 0.91–1.16 after adjustment). 3. High EPA levels correspond to higher risk reduction for primary composite endpoint events (p < 0.001 for all)
Polygenic Risk Score (PGS)	Mendelian randomization	N = 445, 566	Mean 8 years	1. PGS was significantly associated with major coronary events (HR 1.45, 95% CI 1.43–1.47). 2. A stepwise increase in risk for coronary events was further observed across increasing quintiles of PGS (quintile 5 vs. quintile 1: HR 2.77, 95% CI 2.65–2.89). 3. Individuals with high PGS and high exposure to LDL-C and SBP derived the most benefit from LDL-C lowering (ARR 13.02%)