Statin therapy lowered the risk of major vascular events for all patients irrespective of age, a meta-analysis found, although the benefit was less certain for patients older than 75 without existing occlusive disease.
Across all ages, statin therapy significantly reduced major vascular events by approximately 21% per 1.0 mmol/L (38.7 mg/dL) LDL cholesterol, during a median follow-up of 4.9 years, reported the Cholesterol Treatment Trialists’ Collaboration with Jordan Fulcher, BSC, MBBS, of the University of Sydney in Australia, as lead author.
For coronary revascularization, there was a reduction of about 25% per 1.0 mmol/L lower LDL, and for stroke a 16% per 1.0 mmol/L reduction in LDL, reported the investigators in The Lancet.
And for major coronary events, the analysis showed a reduction of 24% per 1.0 mmol/L reduction in LDL. Risk continued to decline with age but in smaller proportions. Across all age groups, cancer incidence, cancer death, and non-vascular mortality were unaffected by statin therapy.
The 2018 revised lipid guidelines suggest that PCSK9 inhibitors can be used to treat high-risk atherosclerotic cardiovascular disease patients that have a single event along with multiple high-risk conditions when low-density lipoprotein (LDL) is greater than 70 mg/dL on maximally tolerated ezetimibe (Zetia) treatment and statin or patients that have a number of prior major events.
The guidelines suggest customizing the conversation for adults ages 40 to 75 prior to starting statins for primary prevention, with consideration for risk factors such as comorbidities, history, and 10-year atherosclerotic cardiovascular disease risk calculation, patient values and preferences, possibilities for adverse effects, and costs.
The lipid guidelines “sort of intensified our understanding and our belief that statin therapy is critical. And so this falls in play with that. Saying that if you have high risk populations, high risk phenotypes and your elderly population is at risk, then it’s business as usual,” Robert Biederman, MD, of Allegheny Health Network in Pittsburgh, told MedPage Today.
Biederman noted that “what those guidelines say, and distinctly opposite from [this meta-analysis], is that … additional therapies should be considered such as the PCSK9s.”
There is limited evidence regarding statin therapy for primary prevention among people older than 75 years. Prior research looked at a composite of non-fatal myocardial infarction, coronary death, and fatal and non-fatal stroke as a primary endpoint, which significantly declined in the secondary prevention group but not among those without prior events, noted Bernard Cheung, PhD, and Karen Lam, MBBS, MD, both of the University of Hong Kong in China, in an accompanying editorial.
Other studies assessing statin therapy did not decrease risk in participants ages 70 years or older. However, a trial is underway in Australia assessing the benefits and risks of primary prevention among healthy participants 70 years or older, Cheung and Lam continued.
The present meta-analysis reiterated “the message that statins should be considered for cardiovascular prevention in people at risk, even if they are older in age. Ongoing medical debate exists about whether the risks of statins have been under-recognized or exaggerated,” the editorialists wrote.
Medical professionals should convey benefits and risks in a comprehensible fashion for patients, so that they are well-equipped to make informed decisions, the editorialists noted. “No drug is completely harmless. 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 trialists’ collaboration reviewed 28 trials, with 186,854 patients with a mean age of 63. Participants were divided into age groups: >75, 71 to 75, 66 to 70, 61 to 65, 56 to 60, and ≤55. About 8% were older than 75.
Randomized trials on statin therapy were included if they attempted to recruit at least 1,000 participants and specified a planned statin therapy period of at least 2 years.
The researchers approximated effects on cause-specific mortality, cancer incidence, and major vascular events, like strokes, coronary revascularizations, and major coronary events as the rate ratio per 1.0 mmol/L reduction in LDL cholesterol. They used standard chi-squared tests for heterogeneity to compare proportional risk reductions in two different age subgroups, or trend in instances of more than two groups.
After four trials were excluded that enrolled only participants undergoing renal dialysis or heart failure, the trend was consistently non-significant for major vascular events (P=0.3 for trend) and smaller proportional risk reductions with increasing age persisted for major coronary events (P=0.01 for trend).
For vascular mortality, the investigators found a proportional reduction of 12% per 1.0 mmol/L reduction in LDL cholesterol, as well as a trend towards smaller proportional reduction as age increased (P=0.004 for trend). This trend became nonsignificant after excluding dialysis and heart failure trials (P=0.2 for trend).
“More research in older people is needed to enrich the evidence on the risks and benefits of statins,” the editorialists wrote.
Fulcher disclosed relationships with Amgen, Bayer, Pfizer, Boehringer Ingelheim, Sanofi, and AstraZeneca.
Cheung disclosed relationships with Amgen, Pfizer, and Roche.
Lam disclosed relationships with MSD and AstraZeneca.
Biederman disclosed relationships with Merck.