In a 50‑year‑old hypertensive man who smokes one pack per day and has markedly elevated LDL cholesterol, which intervention most effectively reduces cardiovascular disease risk: gradual smoking reduction, low‑intensity statin therapy, bupropion for smoking cessation, or waiting for symptoms?

Immediate Complete Smoking Cessation with High-Intensity Statin Therapy

This patient requires immediate complete smoking cessation (not gradual reduction) combined with high-intensity statin therapy to achieve aggressive LDL-C lowering—these are the two most critical interventions for cardiovascular risk reduction. 1

Smoking Cessation: Complete Cessation, Not Gradual Reduction

Gradual smoking reduction is explicitly not recommended and does not increase the probability of future cessation. 1 The evidence is unequivocal:

• Complete smoking cessation is the single most cost-effective strategy for CVD prevention, with stopping smoking after a cardiovascular event showing a 43% reduction in mortality (RR 0.57 for MI, RR 0.74 for death/MI composite). 1
• Smoking cessation in patients with cardiovascular risk factors reduces premature death by 36% compared to continued smoking. 1
• There is no safe level of smoking—even modest and low levels confer vascular risk. 1
• The benefits begin within 6 months, with CVD risk approaching (but never equaling) never-smokers within 10-15 years. 1

Pharmacological Support for Cessation

Bupropion should be offered as first-line pharmacological therapy for smoking cessation in this patient. 1

• Bupropion increases long-term cessation rates by 62% compared to placebo (RR 1.62), helping 80% more people quit than placebo alone. 1
• Bupropion, nicotine replacement therapy (NRT), and varenicline all have similar efficacy (24% success rate with pharmacotherapy plus behavioral support versus 3-5% with willpower alone). 2
• Combination therapy (NRT plus bupropion) does not appear to offer additional benefit over monotherapy in clinical practice. 3
• Bupropion may be particularly beneficial for patients with depression history, though this patient's history is not specified. 3
• Behavioral counseling combined with pharmacotherapy is essential—professional support increases cessation odds by 66% (RR 1.66). 1

Critical implementation: Start bupropion 150 mg once daily for 3 days, then increase to 150 mg twice daily (second dose before 3 PM to minimize insomnia). 4 Screen for contraindications including seizure history, eating disorders, uncontrolled hypertension, and MAOI use. 4

Lipid Management: High-Intensity Statin Therapy Required

This patient's LDL-C of 8.7 mmol/L (approximately 336 mg/dL) is severely elevated and requires immediate high-intensity statin therapy, not low-intensity treatment. 1, 5

Why High-Intensity Statin is Mandatory

• The 2024 ESC guidelines recommend an LDL-C goal of <1.4 mmol/L (55 mg/dL) with ≥50% reduction from baseline for patients with cardiovascular risk factors. 1
• This patient has multiple high-risk features: 50 years old, 20 pack-year smoking history, hypertension, and markedly elevated LDL-C (8.7 mmol/L).
• Low-intensity statin therapy is inadequate for this degree of LDL elevation and cardiovascular risk burden.

Evidence for Aggressive Statin Therapy

• In the ASCOT trial, atorvastatin 10 mg daily in hypertensive patients with multiple risk factors (similar to this patient) reduced coronary events by 36% (RR reduction, p=0.0005) and revascularization procedures by 42%. 5
• Statin therapy reduces relative cardiovascular risk by 24-37% regardless of baseline LDL level, with benefits seen even in patients with "normal" LDL-C. 6
• More intensive lipid-lowering provides additional clinical benefit—the REVERSAL trial showed atorvastatin 80 mg daily halted atheroma progression compared to moderate-intensity therapy. 6
• Statins are first-line agents for all patients at high cardiovascular risk and should be dosed to achieve guideline-directed LDL goals. 7

Recommended regimen: Start atorvastatin 40-80 mg daily (high-intensity statin) to achieve the target LDL-C <1.4 mmol/L with ≥50% reduction. 1, 5 This patient will likely require 80 mg daily given the baseline LDL of 8.7 mmol/L.

Blood Pressure Management

Optimize antihypertensive therapy targeting systolic BP 120-129 mmHg (provided treatment is well tolerated), as this patient is hypertensive with multiple cardiovascular risk factors. 1

• First-line agents include ACE inhibitors, ARBs, calcium channel blockers, or thiazide/thiazide-like diuretics. 1
• Beta-blockers are less preferred in patients with metabolic risk factors unless specific indications exist (post-MI, angina, heart failure). 1

Why "Waiting for Symptoms" is Dangerous

Waiting for cardiac symptoms to manifest is unacceptable and contradicts all evidence-based guidelines. 1

• This patient already has established high cardiovascular risk based on age, smoking, hypertension, and severe dyslipidemia.
• Primary prevention is most effective when initiated before irreversible organ damage occurs—waiting for symptoms means waiting for a potentially fatal event. 1
• The 10-year fatal CVD risk is approximately doubled in smokers, and this patient has additional risk factors. 1

Implementation Algorithm

1. Today's visit:

   • Prescribe high-intensity statin (atorvastatin 40-80 mg daily)
   • Initiate bupropion 150 mg daily for smoking cessation (after screening for contraindications)
   • Provide smoking cessation counseling and set quit date
   • Optimize blood pressure control

2. Day 3-4:

   • Increase bupropion to 150 mg twice daily (if tolerated)

3. Week 1-2:

   • Follow-up to assess medication tolerance, reinforce smoking cessation, monitor BP

4. 6-8 weeks:

   • Recheck lipid panel to assess LDL-C response
   • Assess smoking status
   • Adjust statin dose if needed to achieve LDL-C <1.4 mmol/L

5. 3-6 months:

   • Continue bupropion for 7-12 weeks total for smoking cessation
   • Verify sustained smoking abstinence
   • Confirm LDL-C at goal

Common Pitfalls to Avoid

• Do not use "gradual reduction" strategies—they are ineffective and delay definitive cessation. 1
• Do not undertreat the dyslipidemia with low-intensity statins—this patient needs aggressive LDL lowering. 1
• Do not wait for symptoms—primary prevention is the goal. 1
• Do not forget behavioral support—pharmacotherapy alone is less effective than combined with counseling. 1, 2
• Monitor for bupropion side effects (insomnia, dry mouth, headache) and contraindications (seizure risk 1/1000). 1, 4