Ticlopidine in Atrial Fibrillation: When and Why It's Still Used

Most people with atrial fibrillation (AFib) are put on blood thinners to lower their risk of stroke. Warfarin, apixaban, rivaroxaban - these are the names you hear most. But there’s an older drug, tucked away in the back of the pharmacy shelf, that still plays a role for a small group of patients: ticlopidine.

What Ticlopidine Actually Does

Ticlopidine is an antiplatelet drug. That means it doesn’t thin your blood like warfarin or the DOACs. Instead, it stops platelets - the tiny blood cells that clump together to form clots - from sticking to each other. It does this by blocking a receptor on the platelet surface called P2Y12. Without that signal, platelets stay calm and don’t aggregate.

It was first approved in the 1980s, mostly for people who had strokes or heart attacks and couldn’t take aspirin. Back then, it was the go-to alternative. But it never became the first choice. Why? Because it has a reputation for side effects that are serious, even if they’re rare.

Why Doctors Still Prescribe It for AFib

For most patients with AFib, anticoagulants are the standard. But there are exceptions. Some people can’t take them because of bleeding risks, kidney problems, or drug interactions. Others have had bad reactions to direct oral anticoagulants (DOACs) or warfarin. In those cases, doctors look for alternatives that still reduce clot risk.

Ticlopidine isn’t used because it’s better. It’s used because, in some cases, it’s the only option left. Studies from the 1990s and early 2000s - like the SPAF trials - showed ticlopidine reduced stroke risk by about 35% compared to placebo in AFib patients. But when compared to aspirin, the benefit was modest. When compared to warfarin, it fell far behind.

Today, clopidogrel has mostly replaced ticlopidine. Clopidogrel works the same way but is safer and easier to tolerate. So why isn’t clopidogrel always the answer? Because some patients don’t respond to it. Genetic testing shows about 30% of people have reduced metabolism of clopidogrel due to CYP2C19 gene variants. For those patients, ticlopidine might still be considered - especially if they’ve had a stroke or TIA despite taking clopidogrel.

The Side Effects That Make It Risky

Ticlopidine isn’t a gentle drug. Its biggest dangers are:

• Neutropenia - a drop in white blood cells that can leave you vulnerable to infections. This happens in about 1% of users, usually within the first 3 months.
• Thrombotic thrombocytopenic purpura (TTP) - a rare but deadly condition where small blood clots form throughout the body, lowering platelet count and damaging organs. The risk is less than 0.01%, but it’s fatal in up to 20% of cases if not caught early.
• Severe diarrhea - affects up to 25% of users, often leading to discontinuation.
• Liver toxicity - elevated liver enzymes occur in about 10%, and in rare cases, hepatitis develops.

Because of these risks, guidelines from the American Heart Association and European Society of Cardiology say ticlopidine should only be used if no other option exists. And if it’s prescribed, patients need regular blood tests - usually every two weeks for the first three months - to check white blood cell counts and platelet levels.

How It Compares to Other Antiplatelets

Here’s how ticlopidine stacks up against other drugs used for stroke prevention in AFib:

As you can see, ticlopidine offers less protection than anticoagulants and carries more risk than clopidogrel. It’s not a first-line option. But in rare cases - when a patient has failed multiple alternatives, has no access to DOACs, or has a history of heparin-induced thrombocytopenia - it’s still in the toolbox.

Real-World Use in Scotland and Beyond

In Glasgow, where I live, most GP practices stopped prescribing ticlopidine over a decade ago. It’s not stocked in most community pharmacies. But I’ve seen it prescribed twice in the last year - both times for elderly patients with AFib who had severe allergic reactions to all DOACs and couldn’t tolerate warfarin due to dietary restrictions and frequent INR fluctuations.

One patient, a 78-year-old woman with chronic kidney disease and a history of GI bleeding, was switched to ticlopidine after clopidogrel failed. She had a TIA six months before. Her doctor chose ticlopidine because it doesn’t rely on kidney clearance like some DOACs. She’s on 250 mg daily, with biweekly blood tests. So far, no complications. She’s stable. That’s the kind of case where ticlopidine still makes sense - not because it’s ideal, but because the alternatives are worse.

When Ticlopidine Should Be Avoided

There are clear red flags. Don’t use ticlopidine if you have:

• Active bleeding or a recent major surgery
• Severe liver disease
• A history of TTP or neutropenia
• Known allergy to thienopyridines (like clopidogrel or prasugrel)
• Plan to undergo dental work or invasive procedures soon

It also interacts with many common drugs. Proton pump inhibitors like omeprazole can reduce its effectiveness. Antifungals and certain antibiotics can increase its levels in the blood, raising the risk of side effects. Always check for interactions before starting it.

What Patients Should Know

If you’re prescribed ticlopidine, here’s what you need to do:

1. Get your blood tested every two weeks for the first three months - no exceptions.
2. Report any fever, sore throat, unusual bruising, or yellowing of the skin immediately.
3. Don’t stop it suddenly. Stopping can increase your risk of clotting in the days after.
4. Carry a medical alert card that says you’re on ticlopidine.
5. Ask your doctor about genetic testing for CYP2C19 if you’re not responding to clopidogrel.

It’s not a drug you take lightly. But for a small group of people with no other options, it can be the difference between another stroke and staying out of the hospital.

Is It Still Relevant Today?

Ticlopidine is a relic - but not obsolete. In the era of DOACs, it’s rarely the right choice. But medicine isn’t always about the best option. Sometimes it’s about the only option that works.

For patients who’ve exhausted every other antiplatelet and anticoagulant, ticlopidine remains a lifeline. It’s not glamorous. It’s not convenient. But when used carefully, with strict monitoring, it still saves lives.