Clopidogrel alternatives: What can I take instead of clopidogrel?

Compare clopidogrel alternatives | Brilinta | Effient | Aspirin/dipyridamole | Cilostazol | Xarelto | Natural alternatives | How to switch meds

In the tenuous situation of a sudden heart attack, known as an acute myocardial infarction, any of us would take whatever medicine the cardiologist suggested. There is a good chance that one of the drugs would be a platelet inhibitor like Plavix, the brand name of clopidogrel. Antiplatelet agents like clopidogrel are vitally important to reverse blood clotting in the field of cardiology, and in treatment of a heart attack, a cardiologist will be the one who decides what agent to use in the critical first hours. 

Beyond that timeframe, clopidogrel can also be used to prevent recurrent blood clotting within the coronary arteries of the heart or to prevent recurrences of blocked arteries elsewhere in the body. These longer timeframes of use enable you to gauge its beneficial and adverse effects. If you are unsatisfied with either, if the expense of the drug is unrealistic, or if you encounter interactions with your other medications, you need to know that you have other options. We will walk you through the alternatives to clopidogrel that are available, detailing how they compare. In the end, you will be well prepared to talk to your healthcare provider about a change.

What can I take in place of clopidogrel?

Plavix inhibits platelets, the blood cells which form clots. As a member of the thienopyridine class, it does so by irreversibly binding to adenosine diphosphate (ADP) at the P2Y12 receptor. Brilinta and Effient are fellow class members and P2Y12 receptor antagonists as well. In the setting of both major types of heart attack, ST-elevation and non-ST-elevation myocardial infarctions (differentiated by presence or lack of ST-segment elevation on electrocardiogram), this drug category can be given as a loading dose to kick start the antiplatelet effect. Each P2Y12 inhibitor has nuances that may be appealing to you.

Platelet inhibition can be achieved by other mechanisms. Aspirin does so by inhibiting cyclooxygenase, dipyridamole by blocking adenosine uptake, and cilostazol by inhibiting phosphodiesterase 3. The end result of all of these is to reduce platelets from sticking together to form a clot. Alternatively, the anticoagulant Xarelto can be used at a low dose as a blood thinner for some of the same medical conditions. Whatever the category or mechanism of action, the important differences for you to consider involve factors like convenience, cost, effectiveness, drug interactions, and side effects.

Top 5 clopidogrel alternatives

The following are some of the most common alternatives to clopidogrel.

1. Brilinta

Plavix and Brilinta have the same mechanism of action, but Brilinta (ticagrelor) has a longer list of approved indications from the Food and Drug Administration (FDA). In particular, use of ticagrelor is approved for the treatment of acute stroke. Ticagrelor has a faster onset and higher potency than clopidogrel, often making Brilinta preferable for treatment of acute conditions like MI and stroke. The potency advantage of Brilinta could be particularly helpful for the percentage of people with genetic resistance to P2Y12 inhibitors. A shorter duration of action also makes Brilinta easier to stop in advance of surgery. Yet another advantage of Brilinta is that it avoids a major drug interaction with certain members of the antacid class proton pump inhibitors (PPIs), like Prilosec (omeprazole), which is a potential concern with Plavix.

Before you jump on the Brilinta train, you should recognize some disadvantages. The lower potency of Plavix is not all bad. It may explain why Plavix has less risk of bleeding side effects, which is noteworthy for anyone at higher risk of bleeding, including seniors. A unique side effect of Brilinta is the tendency to cause shortness of breath. If adverse effects are not enough to cause you to avoid Brilinta, the cost might. Brilinta does not have a generic drug available on the market, so it is typically more expensive than Plavix.

2. Effient

Effient is another fast-acting and highly potent P2Y12 receptor antagonist, reminiscent of Brilinta in that it may be favored over Plavix in an acute coronary syndrome (ACS), a term for when blood supply to the heart is suddenly reduced. Effient was found to be more effective than Brilinta in a randomized clinical trial and in a post hoc analysis involving patients with ACS. These findings need to be confirmed with further studies, but they speak to the efficacy of Effient. 

The effectiveness of Plavix can be undermined by one’s genetics. Your genetics could lessen the drug’s activity by reducing absorption in the intestinal tract or limiting conversion of clopidogrel to its active form by CYP2C19 enzyme. Other medications, such as PPIs, could even impair clopidogrel’s activity. While platelet inhibition may be limited in these scenarios, there may not be a correlation between the reduced platelet inhibition and patient outcomes. Meaning, we do not know how important these drug interactions are. Like Brilinta, Effient avoids some of the drug interactions that can negatively impact Plavix users, and the higher potency of both Brilinta and Effient could reduce the chances of you being a non-responder to P2Y12 inhibition.

Once again, heightened potency is not always a good thing. Effient’s potency comes with an increased risk of major bleeding complications. Which alternative best balances the benefits of antiplatelet therapy with the risk of bleeding is not always an easy decision. Rely on your healthcare provider for medical advice.

Expense could be another element of the decision-making process. Effient is available as the generic prasugrel, similar to Plavix having its generic form clopidogrel. Generic formulations often come at a reduced price. Using a SingleCare discount card at participating pharmacies could help add on additional savings.

3. Aspirin/dipyridamole

Aspirin is commonly used alongside other platelet inhibitors. Dual antiplatelet therapy (DAPT) refers to usage of aspirin with a thienopyridine antiplatelet agent such as Plavix, Brilinta, or Effient. DAPT is often used to prevent stent thrombosis, which is blockage within a previously placed coronary artery stent. Specialized drug-eluting stents may require longer DAPT.

It may also have a short-term role after certain types of stroke as well. Plavix and aspirin are a common choice for DAPT in these circumstances. In follow-up, after short-term DAPT, either single antiplatelet agent is typically continued thereafter. Another long-term option is aspirin/dipyridamole, a combination product with proven efficacy and an advantage over aspirin alone after strokes. Both components of the product have antiplatelet effects. 

Keep in mind that the combination aspirin/dipyridamole is only indicated for preventing stroke recurrence. Accordingly, if coronary event treatment or prevention is your goal, this drug is not really a valid alternative to Plavix for you. The incidence of headache and intestinal side effects also limits aspirin/dipyridamole use, so you may wish to keep looking at other options.

RELATED: How to recognize the signs of a stroke

4. Cilostazol

Cilostazol is another antiplatelet drug with limited indications from the FDA that may not serve your purposes. It is indicated for intermittent claudication, a condition marked by leg pain during walking as a result of blockages within peripheral arteries. Cilostazole’s utility comes from inhibiting phosphodiesterase 3 to decrease platelet aggregation, thereby reducing blood clotting. The drug has also been used off-label for the long-term prevention of a second stroke based on supportive studies from Japan and China. Studies have not proven a benefit in non-Asian ethnic groups, so it does not have a FDA indication for secondary stroke prevention. 

5. Xarelto

If you want an FDA-approved preventive drug, Xarelto is an option. Xarelto belongs to the direct oral anticoagulation family. It is a blood thinner rather than an inhibitor of platelet function, and it prevents blood clots by inhibiting factor Xa enzyme. Xarelto’s most common use is to prevent strokes in those with atrial fibrillation. In a lower dose form, Xarelto can be used along with aspirin for prevention of cardiovascular events, including strokes, in patients with known heart disease or peripheral artery disease. If you have this disease history, low-dose Xarelto coupled with aspirin could be an alternative to Plavix. Adding low-dose Xarelto to aspirin did heighten the risk of hemorrhage however.

RELATED: Xarelto side effects and how to avoid them

Natural alternatives to clopidogrel

Clearly, there is no way to prevent blood clots and not somewhat increase the risk of bleeding. Striking the best balance of benefit to risk is always the goal. This leads to the question of whether a natural alternative could be best. Unfortunately, vitamin D, vitamin E, and omega-3 fatty acids have been studied and not found to be effective. On the other hand, turmeric by way of its principal compound curcumin has shown promise as a blood thinner and potential therapeutic. Its role is yet to be defined.

The lack of a fully demonstrated natural alternative should not prevent you from taking other non-pharmacologic approaches. While they are not a substitute for a recommended antiplatelet agent, a healthy diet, weight loss, and smoking cessation are all worthwhile measures.

How to switch to a clopidogrel alternative

Looking for an alternative to clopidogrel can be an agonizing process. The stakes are high when considering the opportunity to prevent a heart attack or stroke and the chance of a bleeding complication. Your healthcare provider should be directly involved in any decision to change from clopidogrel. Discontinuation of any drug without discussion with a doctor is never advised. Make an appointment, bring your list of current prescription drugs and over-the-counter medications, and expect to reach an informed decision that you can both agree on.