In the JournalsPerspective

Statin therapy reduces CV risks across age groups, including elderly

The use of statin therapy led to notable declines in major vascular events across several age groups, including patients older than 75 years, according to findings published in The Lancet.

Researchers performed a meta-analysis comprised of participant-level data from 22 trials with 134,537 participants and detailed summary data from one trial (n = 12,705) of statin therapy vs. a control group, plus individual participant data from five trials of more intensive vs. less intensive statin therapy (n = 39,612).

Effect on major vascular events

Jordan Fulcher, BSc, MBBS, of the Cholesterol Treatment Trialists’ Collaboration at the University of Sydney NHMRC Clinical Trials Centre, and colleagues estimated effects on major vascular events, cause-specific mortality and cancer incidence as the rate ratio per 1 mmol/L reduction in LDL, with participants divided into six age groups (55 years and younger, 56 to 60 years, 61 to 65 years, 66 to 70 years, 71 to 75 years and older than 75 years).

From the 28 randomized trials, researchers identified 14,483 participants (8%) older than 75 years (median follow-up, 4.9 years).

Fulcher and colleagues identified a 21% proportional reduction in major vascular events per 1 mmol/L reduction in LDL (RR = 0.79; 95% CI, 0.77-0.81) with statin therapy or a more intensive statin regimen. Statin or more intensive therapy yielded a 24% proportional reduction in major coronary events per 1 mmol/L lower LDL (RR = 0.76; 95% CI, 0.73-0.79).

Researchers also identified a 25% proportional reduction in the risk for coronary revascularization procedures with statin therapy or a more intensive statin regimen per 1 mmol/L lower LDL (RR = 0.76; 95% CI, 0.73-0.78), which didn’t differ significantly across age groups (P for trend = .6).

Statin therapy was associated with a 16% proportional risk for stroke of any type (RR = 0.84; 95% CI, 0.8-0.89) and did not differ significantly across any age group (P for trend = .7).

Excluding four trials enrolling only patients with HF or undergoing hemodialysis, smaller proportional trend risk reductions with increasing age persisted for major coronary events (P for trend = .01). The proportional reduction in major vascular events in participants not known to have vascular disease was smaller among older patients compared with younger (P for trend = .05), researchers wrote.

Fulcher and colleagues identified there was a 12% proportional reduction in vascular mortality for 1 mmol/L reduction in LDL (RR = 0.88; 95% CI, 0.85-0.91), with a trend towards smaller reductions with older age (P for trend = .004), but the trend did not persist when trials of patients with HF or on dialysis were excluded (P for trend = .2).

Researchers added that statin therapy had no effect at any age on nonvascular mortality, cancer death or cancer incidence.

“Statin therapy produces significant reductions in major vascular events, irrespective of age,” Fulcher and colleagues wrote. “There is less definitive direct evidence of benefit in the primary prevention setting among patients older than 75 years who do not already have evidence of occlusive vascular disease.”

Weighing risks and benefits

In a related editorial, Bernard M. Y. Cheung, PhD, MA, MB BChir, MRCP, FRCP, FHKCP, FHKAM, and Karen S.L. Lam, MD, MBBS, FHKCP, FHKAM, FRCP, both from the department of medicine at Queen Mary Hospital at the University of Hong Kong, wrote: “When statins are used in people with low cardiovascular risk, the risks and benefits need to be weighed against each other. Statins have been associated with a slight increase in incidence of muscle pain, diabetes and hemorrhagic stroke, but their benefits in prevention of major vascular events are shown to be much greater. The present meta-analysis that includes people older than standard trial populations echoes this conclusion.” – by Earl Holland Jr.

Disclosures: Fulcher reports he receives personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Pfizer and Sanofi. Cheung reports he receives personal fees from Amgen, Pfizer and Roche. Lam reports she receives personal fees from AstraZeneca and Merck Sharpe and Dohme. Please see the study for all other authors’ relevant financial disclosures.

The use of statin therapy led to notable declines in major vascular events across several age groups, including patients older than 75 years, according to findings published in The Lancet.

Researchers performed a meta-analysis comprised of participant-level data from 22 trials with 134,537 participants and detailed summary data from one trial (n = 12,705) of statin therapy vs. a control group, plus individual participant data from five trials of more intensive vs. less intensive statin therapy (n = 39,612).

Effect on major vascular events

Jordan Fulcher, BSc, MBBS, of the Cholesterol Treatment Trialists’ Collaboration at the University of Sydney NHMRC Clinical Trials Centre, and colleagues estimated effects on major vascular events, cause-specific mortality and cancer incidence as the rate ratio per 1 mmol/L reduction in LDL, with participants divided into six age groups (55 years and younger, 56 to 60 years, 61 to 65 years, 66 to 70 years, 71 to 75 years and older than 75 years).

From the 28 randomized trials, researchers identified 14,483 participants (8%) older than 75 years (median follow-up, 4.9 years).

Fulcher and colleagues identified a 21% proportional reduction in major vascular events per 1 mmol/L reduction in LDL (RR = 0.79; 95% CI, 0.77-0.81) with statin therapy or a more intensive statin regimen. Statin or more intensive therapy yielded a 24% proportional reduction in major coronary events per 1 mmol/L lower LDL (RR = 0.76; 95% CI, 0.73-0.79).

Researchers also identified a 25% proportional reduction in the risk for coronary revascularization procedures with statin therapy or a more intensive statin regimen per 1 mmol/L lower LDL (RR = 0.76; 95% CI, 0.73-0.78), which didn’t differ significantly across age groups (P for trend = .6).

Statin therapy was associated with a 16% proportional risk for stroke of any type (RR = 0.84; 95% CI, 0.8-0.89) and did not differ significantly across any age group (P for trend = .7).

Excluding four trials enrolling only patients with HF or undergoing hemodialysis, smaller proportional trend risk reductions with increasing age persisted for major coronary events (P for trend = .01). The proportional reduction in major vascular events in participants not known to have vascular disease was smaller among older patients compared with younger (P for trend = .05), researchers wrote.

Fulcher and colleagues identified there was a 12% proportional reduction in vascular mortality for 1 mmol/L reduction in LDL (RR = 0.88; 95% CI, 0.85-0.91), with a trend towards smaller reductions with older age (P for trend = .004), but the trend did not persist when trials of patients with HF or on dialysis were excluded (P for trend = .2).

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Researchers added that statin therapy had no effect at any age on nonvascular mortality, cancer death or cancer incidence.

“Statin therapy produces significant reductions in major vascular events, irrespective of age,” Fulcher and colleagues wrote. “There is less definitive direct evidence of benefit in the primary prevention setting among patients older than 75 years who do not already have evidence of occlusive vascular disease.”

Weighing risks and benefits

In a related editorial, Bernard M. Y. Cheung, PhD, MA, MB BChir, MRCP, FRCP, FHKCP, FHKAM, and Karen S.L. Lam, MD, MBBS, FHKCP, FHKAM, FRCP, both from the department of medicine at Queen Mary Hospital at the University of Hong Kong, wrote: “When statins are used in people with low cardiovascular risk, the risks and benefits need to be weighed against each other. Statins have been associated with a slight increase in incidence of muscle pain, diabetes and hemorrhagic stroke, but their benefits in prevention of major vascular events are shown to be much greater. The present meta-analysis that includes people older than standard trial populations echoes this conclusion.” – by Earl Holland Jr.

Disclosures: Fulcher reports he receives personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Pfizer and Sanofi. Cheung reports he receives personal fees from Amgen, Pfizer and Roche. Lam reports she receives personal fees from AstraZeneca and Merck Sharpe and Dohme. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Udho Thadani

    Udho Thadani

    Statin therapy reduces the risk for major CV events irrespective of age in patients with established CVD, provided they do not have HF or are on dialysis for end-stage renal disease.

    Use of statins for primary prevention (in those without established CVD) in the elderly irrespective of age may be beneficial but remains to be confirmed in large randomized trials in this group of patients. Statins will be routinely prescribed for secondary prevention irrespective of age, provided patients have no contraindications to their use.

    Evaluation of statins in the elderly with multiple comorbidities and evaluation of their side effects, especially at higher doses, which are currently recommended for the secondary prevention, is needed. Benefits and risks of statins in elderly with no or with only CV risk factors remains to be confirmed.

    Yes, statins should be offered to this population provided they already have evidence of CVD and tolerate the medication without any side effects and there are contraindications to such therapy. 

    Start with a lower dose and, if tolerated, then increase the dose, otherwise discontinuation of treatment will remain a concern.

    Health care providers need to take time to discuss the benefits and possible side effects of statins with elderly patients with CVD so that the patients can make an informed decision and understand that the benefits in general outweigh the risks associated with statin therapy.

    • Udho Thadani, MD, MRCP, FRCPC, FAHA, FCCS
    • Cardiology Today Editorial Board Member
      University of Oklahoma Health Sciences Center and VA Medical Center

    Disclosures: Thadani reports he has served as a local principal investigator for studies supported by grants from Merck and Pfizer and has consulted for and received institutional research grants from various pharmaceutical companies.