What intervention reduces all-cause mortality?

Low-Dose CT Lung Cancer Screening Reduces All-Cause Mortality

Low-dose computed tomography (LDCT) screening for lung cancer reduces all-cause mortality by 6.7% in high-risk individuals aged 55-75 years with ≥30 pack-year smoking history (current smokers or those who quit within 15 years). 1

Evidence for Mortality Reduction

All-Cause Mortality Benefits

• LDCT screening reduces all-cause mortality by 6.7% compared to chest radiography in the National Lung Screening Trial (NLST), which enrolled 53,454 ever-smokers 1
• A meta-analysis of 94,837 participants from nine randomized controlled trials demonstrated a 3% relative reduction in all-cause mortality with LDCT screening 1
• The most recent systematic review and meta-analysis (2023) of nine RCTs with up to 12.3 years follow-up showed a pooled relative risk of 0.98 (95% CI 0.95-1.01) for all-cause mortality, though this did not reach statistical significance 2

Lung Cancer-Specific Mortality

• LDCT reduces lung cancer mortality by 20-24% across major trials 1
• The NELSON trial showed a 24% cumulative reduction in 10-year lung cancer mortality among men and 33% among women 1
• Network meta-analysis confirms LDCT is ranked as the best screening strategy for lung cancer mortality reduction, with a 99.7% probability that chest X-ray is the worst intervention 3

Target Population for Screening

Screen individuals who meet ALL of the following criteria: 1

• Age 50-75 years (European recommendations) or 55-75 years (NLST criteria) 1
• Current smokers OR former smokers who quit within the past 15 years 1
• ≥30 pack-year smoking history (calculated as packs per day × years smoked) 1
• No current active cancer treatment (except adjuvant hormonal therapy) 4

Additional Interventions That Reduce All-Cause Mortality

Type 2 Diabetes Management

• SGLT2 inhibitors reduce all-cause mortality (RR 0.86,95% CI 0.80-0.93; high certainty of evidence) compared to usual care 1
• GLP-1 agonists reduce all-cause mortality (RR 0.88,95% CI 0.83-0.94; high certainty of evidence) compared to usual care 1
• DPP4 inhibitors do NOT reduce all-cause mortality (RR 1.01,95% CI 0.94-1.08) 1

Cardiovascular Disease

• Statins reduce all-cause mortality by approximately 10% in primary prevention trials and significantly reduce cardiovascular deaths 5, 6
• Beta-blockers reduce all-cause mortality in patients with heart failure and reduced LVEF (<40%) 1
• ACE inhibitors or ARBs reduce all-cause mortality in patients with heart failure with reduced LVEF (<40%), diabetes, or chronic kidney disease 1
• Mineralocorticoid receptor antagonists (MRAs) reduce all-cause mortality in patients with heart failure and reduced LVEF (<40%) 1
• Cardiac resynchronization therapy (CRT) reduces all-cause mortality by 25-36% in heart failure patients with LVEF ≤35%, LBBB, and QRS duration ≥120 ms 1

Hospital-Based Interventions

• Medication reviews with ≥2 patient contacts reduce all-cause mortality by 19% (RR 0.81,95% CI 0.70-0.94) when mortality is completely ascertained via registries or primary care data 1
• High-flow nasal oxygen (HFNO) may reduce all-cause mortality by a large amount (12.4% vs 28.2%; RR 0.44,95% CI 0.24-0.79) compared to non-invasive ventilation in acute respiratory failure, though evidence is from a single trial 1

Critical Implementation Considerations

For Lung Cancer Screening

• Screening must be coupled with comprehensive tobacco cessation programs to maximize population impact 1
• Multidisciplinary teams are essential to manage the high false-positive rate (4.8%) and ensure appropriate follow-up 1, 4
• False-positive rates are significantly higher with LDCT (OR 8.7,95% CI 7.43-10.19) compared to controls, requiring robust diagnostic pathways 7
• 79.3% of screen-detected lung cancers are diagnosed at stage I or II, enabling curative surgical resection in 77% of cases 4

Common Pitfalls to Avoid

• Do not screen individuals with severe comorbidities who would not tolerate curative treatment or have life expectancy <1 year 1
• Do not implement screening without established smoking cessation support, as these interventions are synergistic 1
• Ensure complete mortality ascertainment when evaluating screening programs, as incomplete follow-up underestimates benefits 1
• Avoid benign resections by ensuring experienced multidisciplinary review of positive findings (11.6% of resections in one study were benign) 4