What interventions reduce all-cause mortality in Coronary Artery Disease (CAD)?

Interventions That Reduce All-Cause Mortality in Coronary Artery Disease

The interventions with the strongest evidence for reducing all-cause mortality in CAD are: statins targeting LDL-C <55 mg/dL, multidisciplinary exercise-based cardiac rehabilitation, ACE inhibitors (or ARBs) in patients with heart failure (LVEF <40%), diabetes, or CKD, beta-blockers in patients with reduced LVEF (<40%), and comprehensive lifestyle modifications including smoking cessation and moderate alcohol use. 1, 2, 3, 4

Pharmacological Interventions with Mortality Benefit

Lipid-Lowering Therapy

• Statins are mandatory for all CAD patients with the goal of reducing LDL-C by ≥50% from baseline AND achieving LDL-C <1.4 mmol/L (<55 mg/dL). 1, 2, 3, 4
• If LDL-C goals are not achieved after 4-6 weeks with maximally tolerated statin dose, add ezetimibe. 1, 2
• If goals still not met after 4-6 weeks on statin plus ezetimibe, add a PCSK9 inhibitor (evolocumab or alirocumab), though these primarily reduce cardiovascular events with minimal mortality impact. 1

ACE Inhibitors or ARBs

• ACE inhibitors (or ARBs if ACE inhibitors not tolerated) reduce all-cause and cardiovascular mortality in CAD patients with: 1, 2, 3, 4
  • Heart failure with reduced LVEF (<40%)
  • Diabetes mellitus
  • Chronic kidney disease
• Do not use if severe renal impairment or hyperkalemia present. 1

Beta-Blockers

• Beta-blockers reduce mortality in CAD patients with: 1, 2, 3, 4
  • Systolic LV dysfunction or heart failure with reduced LVEF (<40%)
  • Previous myocardial infarction
• Beta-blockers also provide symptom control in angina but mortality benefit is specific to reduced LVEF. 1, 2, 3

Mineralocorticoid Receptor Antagonists (MRAs)

• MRAs reduce all-cause and cardiovascular mortality in CAD patients with heart failure and reduced LVEF (<40%). 1

Antiplatelet Therapy

• Aspirin 75-100 mg daily is recommended for secondary prevention but primarily reduces recurrent ischemic events rather than all-cause mortality. 1, 3, 4

Lifestyle and Behavioral Interventions with Mortality Benefit

Exercise-Based Cardiac Rehabilitation

• Multidisciplinary exercise-based cardiac rehabilitation is Class I, Level A recommendation for reducing all-cause and cardiovascular mortality and morbidity. 1, 2, 3
• Home-based cardiac rehabilitation programs show similar mortality benefits to center-based programs for patients unable to access facility-based care. 1
• Cardiac rehabilitation should be initiated during hospitalization with referral prior to discharge. 1

Smoking Cessation

• Smoking cessation reduces all-cause mortality by 36% (RR 0.64,95% CI 0.58-0.71) in CAD patients. 5
• This represents one of the largest effect sizes among lifestyle interventions. 5

Physical Activity

• Increased physical activity reduces all-cause mortality by 24% (RR 0.76,95% CI 0.59-0.98) in CAD patients. 5

Moderate Alcohol Consumption

• Moderate alcohol use reduces all-cause mortality by 20% (RR 0.80,95% CI 0.78-0.83) in CAD patients. 5

Combined Dietary Modifications

• Combined dietary changes (Mediterranean, DASH, or AHA diet patterns) reduce mortality by 44% (RR 0.56,95% CI 0.42-0.74). 2, 3, 5
• Individual dietary components have insufficient data for reliable effect estimates, but combined approaches show substantial benefit. 5

Multidisciplinary Care

• Involvement of multidisciplinary healthcare professionals (cardiologists, general practitioners, nurses, dieticians, physiotherapists, psychologists, pharmacists) reduces all-cause and cardiovascular mortality. 1, 2, 3
• Cognitive behavioral interventions help achieve and maintain lifestyle changes. 1, 2, 3

Blood Pressure Management

Antihypertensive Therapy

• Blood pressure-lowering medications reduce composite cardiovascular events and mortality by 18% (RR 0.82,95% CI 0.71-0.94) in primary prevention, with similar benefits expected in CAD. 6
• Tight blood pressure control reduces events by 34% (RR 0.66,95% CI 0.46-0.96). 6
• Target systolic BP 120-130 mmHg in general CAD population; 130-140 mmHg in older patients (>65 years). 3

Additional Interventions

Influenza Vaccination

• Annual influenza vaccination reduces morbidity, especially in older CAD patients, though mortality data are limited. 1, 2, 3

Psychological Interventions

• Psychological interventions improve depression symptoms and health-related quality of life but lack strong mortality data. 1, 2, 3

Revascularization Considerations

• Myocardial revascularization is indicated when angina persists despite optimal medical therapy, primarily for symptom relief. 1, 2, 3, 4
• In stable CAD, revascularization does not consistently reduce mortality compared to optimal medical therapy alone, except in specific high-risk anatomic subsets (left main disease, severe 3-vessel disease with reduced LVEF). 1, 2, 3
• CABG may reduce mortality in high-risk patients with left ventricular systolic dysfunction, diabetes mellitus, and severe 3-vessel or left main disease. 2, 3

Critical Implementation Points

Common pitfalls to avoid:

• Failing to achieve aggressive LDL-C targets (<55 mg/dL) - this requires combination therapy in most patients. 1
• Underutilizing cardiac rehabilitation - only a minority of eligible patients are referred and enrolled. 1
• Not prescribing ACE inhibitors/ARBs in patients with reduced LVEF, diabetes, or CKD - these have proven mortality benefit. 1
• Discontinuing beta-blockers in patients with prior MI and reduced LVEF - mortality benefit persists long-term. 1

The hierarchy of mortality-reducing interventions:

1. Smoking cessation (36% mortality reduction) 5
2. Combined dietary modifications (44% mortality reduction) 5
3. Statins to LDL-C <55 mg/dL (19% mortality reduction) 6
4. Exercise-based cardiac rehabilitation 1
5. ACE inhibitors/ARBs in appropriate subgroups 1
6. Beta-blockers in reduced LVEF 1
7. Increased physical activity (24% mortality reduction) 5
8. Moderate alcohol use (20% mortality reduction) 5
9. Blood pressure optimization 6