Rationale

Cardiovascular disease (CVD) is the leading cause of death globally. The WHO has estimated that 17.5 million people died from CVD in 2012, accounting for 31% of all global deaths.1 Age is the predominant risk factor for CVD with about 70% of adults older than 65 years having either coronary artery disease (CAD) or subclinical atherosclerosis.2 Moreover, older adults (aged ≥65 years) account for more than 80% of the total CVD deaths.3 Thus, reducing mortality and morbidity of CVD in this age group is of paramount importance in reducing related cost and patient’s disability. Additionally, according to the United Nations global demographic report, people aged 60 years or more represented 12.5% of the global population in 2015 and this will increase to an estimated 16.7% in 2030.4 This will undoubtedly increase government expenditure on healthcare. On a population basis, primary prevention is very important for CVD prevention as healthy people represent the largest proportion of the general population. Therefore, the greatest potential for reduction in major adverse cardiovascular events (MACE) resides in this population.5

Statins (hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors) have been shown to reduce MACE and mortality—in both middle-aged and older adults.6 7 The beneficial effect of statins on survival is evident 1–2 years after commencing statin treatment.8 A meta-analysis of observational studies found that about half of patients initiated on statins discontinued their medication within a year. Taking statins for primary prevention was determined to be a main predictor of non-adherence.9 10 Only one in four people aged over 65 years was adherent to statins after 2 years of commencing statin for primary prevention.8 Additionally, statin users aged over 70 years have lower adherence rates than middle-aged adults (50–69 years).10 While there are various reasons for statin discontinuation, two-thirds of the patients reported statin-related adverse effects as the reason.11 Older individuals are more vulnerable to adverse effects of drugs compared with younger individuals due to their physical deconditioning (decreased muscle mass and poorer renal and hepatic clearance), multiple morbidity and polypharmacy.12 13 Recognised statin-associated adverse effects include musculoskeletal dysfunction, hepatotoxicity, new-onset type 2 diabetes and some other rare but significant adverse effects such as cancer, kidney disease and cataract.14–16 Of these, statin-associated muscle symptoms (SAMS), generally defined as all muscle-related complaints such as muscle pain or aching (myalgia), tenderness, stiffness, cramp and weakness, are the most commonly encountered adverse events (AEs) both in clinical studies and daily clinical practice.17 It is estimated that more than 1.5 million people per year experience SAMS.18 Of note, myopathy and rhabdomyolysis, which accompanied with high creatine kinase (CK) level, are two severe statin-related musculoskeletal diseases that rarely happen but are potentially life threatening.

Statins are recommended to be initiated during early middle age for people with clinical atherosclerotic cardiovascular disease (ASCVD) and high estimated 10-year ASCVD risk due to the well-documented benefits in middle-aged adults.2 19 20 Although the beneficial effects of statins in the middle and younger adults are well documented, the older individuals have been under-represented in statin clinical trials, particularly those focusing on primary prevention and drug safety.21 22 There is still no definitive indication of statin therapy in the low-risk elderly due to a lack of evidence from clinical studies or meta-analyses (cited in Class IIb and Level of evidence in European Society of Cardiology guidelines) and making work more challenging in routine clinical practice.19 To our knowledge, one meta-analysis indicated that there is no excess risk of myopathy in older adults who received statins for both primary and secondary prevention, while no prior systematic review has ever primarily investigated the risk of SAMS among older people who received statins for only primary prevention.23 Clearly, studies are required, both randomised controlled trials (RCTs) (such as StaREE: Statins in Reducing Events in the Elderly, which is an ongoing blind, placebo-controlled clinical trial of statin therapy in primary prevention elderly: NCT02099123) and meta-analyses to provide evidence on drug safety of statin therapy prescribed in older adults for primary prevention of CVD and further to facilitate optimal prescribing and management approaches to minimise the side effects.