Is there strong evidence for using Xantinol nicotinate (Complamina) to treat Raynaud's disease and Peripheral Artery Disease (PAD) in clinical practice?

Xantinol Nicotinate (Complamina) for Raynaud's and PAD: Evidence Assessment

Direct Answer

There is no strong modern evidence supporting the use of xantinol nicotinate for Raynaud's disease or peripheral artery disease, and this medication is not recommended in any current major clinical practice guidelines.

Guideline Recommendations

For Peripheral Artery Disease

Current evidence-based guidelines make no mention of xantinol nicotinate as a treatment option:

First-line pharmacological therapy for PAD includes:

• Antiplatelet therapy with aspirin (75-100 mg daily) or clopidogrel (75 mg daily) to reduce cardiovascular events 1
• Statin therapy for all PAD patients, targeting LDL-C <55 mg/dL 1, 2
• Antihypertensive therapy, preferably with ACE inhibitors or ARBs, targeting systolic BP 120-129 mmHg 1, 3

For claudication symptoms specifically:

• Supervised exercise therapy is the recommended first-line treatment before considering any pharmacological intervention 1, 2, 4
• Cilostazol (100 mg twice daily) may be added for refractory claudication despite exercise therapy and smoking cessation 1
• Pentoxifylline is specifically recommended against in current guidelines 1

For Raynaud's Phenomenon

While guidelines for PAD do not address Raynaud's specifically, the available evidence suggests:

Recommended treatments include:

• Calcium channel blockers (particularly nifedipine) as the "gold standard" 5
• Simple vasodilators like naftidrofuryl or inositol nicotinate for mild disease 5
• Thymoxamine, prazosin, or nifedipine for severe Raynaud's syndrome 6

Historical Evidence for Xantinol Nicotinate

The only identified study supporting xantinol nicotinate is from 1975 7:

• This single, small double-blind trial (33 patients completing) showed 25/33 patients improved with xantinol nicotinate versus 4/33 with placebo
• However, only 3 of 7 patients under age 50 were helped 7
• Only 3 of 6 diabetics maintained benefit after 6 months 7
• Side effects were common, particularly severe prolonged flushing 7
• The study is nearly 50 years old and has not been replicated in modern trials

Critical Analysis

Major concerns with xantinol nicotinate:

• Complete absence from modern guidelines: None of the major international guidelines (2024 ESC 1, 2017 AHA/ACC 1, 2012 ACCP 1) mention this medication as a treatment option
• Outdated evidence base: The only supporting evidence is from 1975, predating modern standards for clinical trials 7
• Better alternatives exist: Multiple evidence-based therapies with proven mortality and morbidity benefits are now available 1
• Questionable efficacy: A 1998 study concluded that peripheral vasodilators in general "may do more harm than good" for peripheral vascular disease 6

Evidence-Based Treatment Algorithm

For PAD patients, prioritize in this order:

1. Lifestyle modifications (Class I recommendations):

   • Smoking cessation with pharmacotherapy (varenicline, bupropion, or nicotine replacement) 1, 4
   • Supervised exercise therapy: 30-45 minutes per session, 3 times weekly, minimum 12 weeks 1, 2, 4
   • Mediterranean diet rich in fruits, vegetables, and legumes 1

2. Cardiovascular risk reduction (Class I recommendations):

   • Statin therapy for all PAD patients 1, 2
   • Antiplatelet therapy (aspirin or clopidogrel) 1
   • Blood pressure control with ACE inhibitors or ARBs 1, 3

3. Symptom management for claudication:

   • Only after exercise therapy has been attempted 1
   • Consider cilostazol if symptoms remain refractory 1

For Raynaud's phenomenon:

• Nifedipine (calcium channel blocker) remains the evidence-based first choice 5
• Simple vasodilators may be considered for mild disease 5

Common Pitfalls

• Prescribing outdated medications: Using drugs like xantinol nicotinate based on historical practice patterns rather than current evidence 6
• Neglecting proven therapies: Failing to prioritize supervised exercise, which has the strongest evidence for improving claudication 1, 2
• Focusing only on symptoms: Missing the opportunity to reduce cardiovascular mortality with antiplatelet therapy and statins 1
• Inappropriate use of peripheral vasodilators: A 1998 study found 69.6% of peripheral vasodilator prescriptions were for conditions where they lack evidence 6

Bottom Line

Xantinol nicotinate should not be used for PAD or Raynaud's disease in contemporary practice. The medication is absent from all current evidence-based guidelines, relies on a single 50-year-old study, and has been superseded by therapies with proven benefits on mortality, morbidity, and quality of life 1. Clinicians should instead implement guideline-recommended treatments including supervised exercise, antiplatelet therapy, statins, and appropriate antihypertensive therapy 1, 2.