This dissertation of Folkert van Bruggen examines the effectiveness and safety of lipid-lowering therapies, with a specific focus on PCSK9 inhibitors.
In Chapter 2, a systematic review and meta-analysis were conducted to evaluate the effects of intensive versus standard lipid-lowering therapies on cardiovascular outcomes, such as heart attacks, strokes, and mortality. The analysis revealed that intensive therapies achieved only a limited reduction in cardiovascular events, with no significant impact on overall mortality.
In Chapter 3, the effects of PCSK9 inhibitors, such as alirocumab and evolocumab, were examined using data from ClinicalTrials.gov. The findings suggested that alirocumab may reduce the risk of serious adverse events, while evolocumab may be associated with an increased risk of mortality and potentially a higher risk of diabetes.
Chapter 4 focused on baseline differences in studies on PCSK9 inhibitors. A meta-epidemiological analysis of 43 studies identified small differences in baseline characteristics between treatment and control groups, with a statistically significant difference in BMI. In most cases, greater standard deviations in baseline characteristics were observed in the treatment group compared to the control group. These findings suggest that the study groups may not have been entirely comparable.
In Chapter 5, the use of preventive cardiovascular medication (PCM) in frail older adults in primary care was investigated. The results showed that a significant proportion of these individuals, particularly those without a history of cardiovascular disease, might benefit from reducing or discontinuing PCM.
Various factors in clinical trials and systematic reviews, such as the choice of effect measure, selection of clinical endpoints, and interpretation of side effects, have influenced the assessment of the importance of intensive cholesterol-lowering therapy for preventing cardiovascular disease. The findings in this dissertation shed new light on this topic. Intensive cholesterol lowering provides limited health benefits. Additionally, there are concerns about side effects.
