Role of Statins in Reducing Cardiovascular Mortality: A Systematic Review of Long-Term Outcomes

Abstract

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, highlighting the critical need for effective preventive therapies. Statins, or HMG-CoA reductase inhibitors, are widely prescribed for their ability to lower low-density lipoprotein (LDL) cholesterol and reduce CV risk. This systematic review evaluates the long-term impact of statins on CV and all-cause mortality across diverse populations, including those with chronic kidney disease, chronic heart failure, and other comorbid conditions. A comprehensive search of major databases identified randomized controlled trials and large observational cohort studies with follow-up periods exceeding one year. Findings demonstrated significant reductions in CV mortality (hazard ratio (HR) range: 0.38-0.76) and all-cause mortality (HR range: 0.55-0.80) with statin therapy, particularly among high-risk groups, such as individuals with elevated LDL-C and moderate chronic kidney disease. Additional benefits were observed in preventing major adverse cardiovascular events (MACEs). Subgroup analyses revealed variations in efficacy based on age, sex, comorbidities, and statin type or dosage, with some populations, such as those with chronic heart failure and chronic obstructive pulmonary disease, showing limited benefit. Geographic and ethnic diversity were underrepresented in the included studies, and data on long-term effects in populations with advanced renal impairment or inflammatory conditions remain insufficient. These gaps underscore the need for methodologically robust studies and tailored approaches to statin therapy that account for individual patient profiles, including comorbidities and demographic factors. Practical steps include integrating statins with newer lipid-lowering agents and developing personalized treatment protocols to maximize their benefits and minimize risks. This review reinforces the critical role of statins in reducing the global burden of CVDs while emphasizing areas for future research.

Keywords: all-cause mortality; cardiovascular mortality; chronic heart failure (chf); chronic kidney disease (ckd); hmg-coa reductase inhibitors; low-density lipoprotein (ldl) cholesterol; major adverse cardiovascular events (maces); primary prevention; secondary prevention; statins.

Figure 1. PRISMA flowchart representing the study selection process.

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses