Statin therapy in primary prevention of cardiovascular disease

Statins are known for reducing cardiovascular risk in people with or at high risk for cardiovascular disease (CVD). However, it is less clear whether the benefits of statins outweigh the risks for primary prevention in older adults and people with intermediate CVD risk. Therefore, studies are needed to provide additional evidence to fill these knowledge gaps and inform evidence-based clinical practice. This thesis aimed to investigate the role of statins for primary prevention in older adults and the value of a novel CVD risk biomarker called coronary artery calcium (CAC) to help refine patient's eligibility to statin therapy. In Chapter 3, a systematic review and meta-analysis of 11 randomised controlled trials was conducted to investigate the safety and tolerability of statin therapy in older adults without overt CVD. The study results showed no significant association between statin use and risk of any adverse events (AE), muscle-related AEs, any treatment discontinuation and discontinuation due to AEs or muscle symptoms. In Chapter 4, a post-hoc analysis of a randomised trial was conducted to investigate the association between statins, disability-free survival (defined as a composite of all-cause mortality, persistent physical disability, or dementia), and risk of CVD in 18,096 healthy community-dwelling adults aged ‚Äöv¢‚Ä¢70 years. The main results suggest that statin use was not associated with improved disability free survival, reduced all-cause mortality and dementia, but was associated with lower risks of persistent physical disability and CVD. In Chapter 5, we performed a qualitative study in the form of semi-structured telephone interviews with 30 participants aged ‚Äöv¢‚Ä¢70 years within an ongoing randomised statin trial. This study aimed to explore the factors contributing to participants' permanent discontinuation of trial medication within two years of trial entry by capturing their experiences and perspectives. Perceived AEs with their impact on participants' daily lives were major factors leading to permanent trial medication discontinuation. For some, concurrent challenging life circumstances further lowered their tolerance to perceived AEs thus making discontinuation of medication more likely. These findings imply that addressing participants' concerns about drug-related side effects at trial entry and offering timely medical assistance if AEs occur may be useful to reduce treatment discontinuation rates. CAC is a potent marker of subclinical atherosclerosis and a powerful predictor of future risk of CVD, independent of traditional risk factors. Chapter 6 investigated the modifying effect of CAC on statin-associated cardiovascular benefits in primary prevention populations. An observational study of 6,301 CVD-free individuals followed for over 14 years found that statin use was associated with a significantly lower risk of CVD only in participants with high CAC burden but not in those with low or no CAC burden. These findings support the role of CAC in identifying best statin candidates in clinical practice, especially in individuals whose indication for statins is unclear. In summary, this thesis offers a valuable insight into the net benefit of statins for primary prevention of CVD in older adults and the role of CAC in helping determine whether primary prevention of statins might help. These results emphasise the necessity of future clinical trials to provide definitive evidence on the net benefit of statins in the certain primary prevention population groups to inform evidence-based clinical decisions about statin prescribing.