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16th September 2022
The benefits of statin therapy against cardiovascular disease are life-long because a large share of the benefit occurs later in life according to the results of a modelling study by researchers from Queen Mary University of London, UK and presented at European Society of Cardiology congress in Barcelona, Spain.
According to the 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice, the causal role of LDL-C, and other apo-B containing lipoproteins, in the development of atherosclerotic cardiovascular disease, is demonstrated beyond any doubt by genetic, observational, and interventional studies. Statin therapy is designed to lower LDL-C cholesterol and a 2016 meta-analysis of 26 randomised controlled trials with over 170,000 patients, found that all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction, largely reflecting significant reductions in deaths due to coronary heart disease and other cardiac causes. Despite these clear benefits, there is some uncertainty about when to start and how long to persist, with statin therapy, to optimise the effects. In the present study, the UK researchers estimated the accumulation of benefit from statin therapy, according to age of initiation, using a microsimulation model that was developed using data on 118,000 participants of large international statin trials from the Cholesterol Treatment Trialists’ Collaboration and 500,000 individuals in the UK Biobank population cohort. The model used individual characteristics (e.g. age, sex) and disease histories to simulate the annual risk of heart attack, stroke, coronary revascularisation, diabetes, cancer, vascular death and nonvascular death for each participant. Treatment with a standard dose of statin (40 mg daily) was used to estimate the effect of therapy versus no therapy in these scenarios: (1) lifelong therapy (used until death or 110 years of age if earlier), (2) therapy stopped at 80 years of age, and (3) delayed initiation of therapy by five years in participants under 45 years of age. The benefit of statin therapy was measured in quality-adjusted life years (QALYs), which represents the length of life adjusted by health to reflect quality of life. For example, one QALY is equal to one year of life in perfect health. Benefits were also reported separately according to baseline cardiovascular risk, which refers to the likelihood of having a heart attack or stroke in the next 10 years, and is based on age, blood pressure, cholesterol levels, smoking status, and medical conditions
Statin therapy benefits
The researchers found that a large part of QALYs gained with statin therapy accrued later in life. The higher the participants’ 10-year cardiovascular risk, the larger and earlier the statin benefit accrued. Compared with lifelong statins, stopping therapy at 80 years of age, would erase a large share of the potential benefit, especially for people with relatively low cardiovascular risk.
According to lead author of the study Dr Runguo Wu ‘the study indicates that people in their 40s with a high likelihood of developing cardiovascular disease, and people of all ages with existing heart disease, should be considered for immediate initiation of cholesterol lowering treatment. Stopping treatment, unless advised by a doctor, does not appear to be a wise choice.’
They added that ‘our study suggests that people who start taking statins in their 50s but stop at 80 years of age instead of continuing lifelong, will lose 73% of the QALY benefit if they are at relatively low cardiovascular risk and 36% if they are at high cardiovascular risk – since those at elevated risk start to benefit earlier. Women’s cardiovascular risk is generally lower than men’s. This means that for women, most of the lifelong benefit from statins occurs later in life and stopping therapy prematurely is likely more detrimental than for men.’
It was also important to understand that the benefits of statin therapy was dependent upon an individual’s baseline risk. For example, for some one under 45 years of age at low cardiovascular risk, (i.e., less than 5% likelihood of heart attack or stroke in the next 10 years) a five-year delay in taking statins had little impact – they lost just 2% of the potential QALY benefit from lifelong therapy. However, the impact was larger in people under 45 years of age at high cardiovascular risk, meaning a more than 20% likelihood of heart attack or stroke in the next 10 years – they lost 7% of the potential QALY benefit from lifelong therapy. Dr. Wu said: “Again, this is because people at higher cardiovascular risk start to accrue benefit early on and have more to lose by delaying statin therapy than those at low risk.’
Benefit accrual with cardiovascular disease prevention and effects of discontinuation: a modelling study