Elderly people also benefit from lipid-lowering therapy for primary prevention

November 26, 2023

LDL-C Reduction With Lipid-Lowering Therapy for Primary Prevention of Major Vascular Events Among Older Individuals

Literature - Andersson NW, Corn G, Dohlmann TL, et al. - J Am Coll Cardiol. 2023 Oct 3;82(14):1381-1391. doi: 10.1016/j.jacc.2023.07.027

Introduction and methods

Background

In elderly people, there is a lack of evidence for the clinical benefit of LDL-c reduction with lipid-lowering therapy for primary prevention [1-4], in part due to underrepresentation of this population in the relevant clinical trials [3,4]. Hence, American and European guidelines provide only weak recommendations for considering initiating statins for primary prevention in older individuals [5,6].

Aim of the study

The authors compared the clinical effectiveness of LDL-c reduction associated with the initiation of lipid-lowering therapy for primary prevention of major vascular events among older and younger individuals in a Danish nationwide cohort.

Methods

Individual-level data were obtained from different Danish national health care and administrative registries to construct a nationwide cohort of individuals aged ≥50 years who initiated new use of lipid-lowering therapy (statins alone or in combination with other lipid-lowering drugs) for primary prevention (i.e., they had no history of ASCVD) between January 2008 and October 2017. All study participants underwent an LDL-c measurement at baseline (≤6 months of index date) and at follow-up (2 weeks to 1 year after index date).

The study cohort comprised 65,190 participants: 16,035 individuals were ≥70 years of age and 49,155 were aged <70 years. Median follow-up time was 2.5 years (IQR: 1.2–5.1).

Outcomes

The primary endpoint was hospitalization for a major vascular event, defined as a composite outcome of ACS, nonhemorrhagic stroke, or coronary revascularization. Secondary endpoints were the individual CV components of the primary endpoint and all-cause mortality.

Main results

  • The median LDL-c reduction was 1.7 mmol/L for both the older (IQR: 1.0–2.2) and younger (IQR: 1.0–2.3) age groups.
  • In individuals aged ≥70 years, each 1 mmol/L reduction in LDL-c level was associated with a 23% lower risk of major vascular events (crude incidence rate: 13.4 per 1000 person-years; adjusted HR: 0.77; 95%CI: 0.71–0.83). This was equal to the relative risk difference in individuals aged <70 years (crude incidence rate: 7.1 per 1000 person-years; adjusted HR: 0.76; 95%CI: 0.71–0.80; P=0.79).
  • For the individual CV components of the primary endpoint, the relative risk differences were of similar magnitude to that observed for the primary endpoint and there were no significant differences in the associations with LDL-c reduction between older and younger individuals (all P>0.05). There was also no significant association with all-cause mortality for individuals aged ≥70 years (adjusted HR: 1.03; 95%CI: 0.98–1.09) and those aged <70 years (adjusted HR: 1.00; 95%CI:0.95–1.06; P=0.46).
  • Subgroup analyses included stratification by sex, baseline LDL-c level, and frailty condition. They did not show any significant differences between older and younger individuals in the risk of major vascular events associated with LDL-c reduction.
  • After further stratification of the older individuals into smaller age groups (70–74, 75–79, 80–84, and ≥85 years), no attenuation of the associated risk of major vascular events per 1 mmol/L LDL-c reduction with increasing age was observed (P=0.61).

Conclusion

This Danish nationwide cohort study showed similar relative clinical benefits of LDL-c reduction associated with the initiation of lipid-lowering therapy for primary prevention of CVD in individuals aged ≥70 years and those aged <70 years. Per 1 mmol/L LDL-c reduction, the risk of major vascular events decreased by 23% in the older age group.

The authors state that as their results are “[b]ased on a substantial sample size representative of a contemporary general population, [they] may contribute to informing future guideline recommendations and clinician-patient discussion on the clinical benefit observed from lowering LDL cholesterol among older individuals for primary prevention of CVD during routine clinical care.”

References

1. Armitage J, Baigent C, Barnes E, et al. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet. 2019;393:407–415.

2. Gencer B, Marston NA, Im K, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020;396:1637–1643.

3. Khan SU, Khan MZ, Raghu Subramanian C, et al. Participation of women and older participants in randomized clinical trials of lipid-lowering therapies: a systematic review. JAMA Netw Open. 2020;3:e205202.

4. Rich MW, Chyun DA, Skolnick AH, et al. Knowledge gaps in cardiovascular care of the older adult population: a scientific statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society. J Am Coll Cardiol. 2016;67:2419–2440.

5. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73: 3168–3209.

6. Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42:3227–3337.

Find this article online at J Am Coll Cardiol.

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