Antiplatelet drugs like Plavix inhibit platelets’ ability to coagulate and form blood clots. They are frequently prescribed to treat individuals with a history of cardiovascular problems related to clotting and is especially well suited for prevention of myocardial infarction (heart attack), unstable angina, stroke, and cardiovascular death.
Plavix is normally administered twice daily in the form of a pill, usually shortly after a meal. Platelets are activated by their P2Y12 receptors. These receptors are directly activated by adenosine diphosphate (ADP), the concentration of which rises in platelets in the presence of proteins from damaged subendothelial cells—cells that lie on the outside of blood vessels and whose proteins normally only appear in the bloodstream if the vessel is damaged.
Platelets coagulate when activated by forming a protein matrix that attracts and binds other platelets, forming a blood clot or a scab. When platelets are activated by an external wound, they form a scab and staunch bleeding, which is clearly a good thing. However, platelets can also be activated by minor internal injuries or even by unfortunate local conditions that can activate their P2Y12 receptors even without any damage to the blood vessels.
Internal platelet activation generates a blood clot that can easily prove dangerous. If the clot moves to another part of the body from its point of origin, it is called an embolus and eventually may lodge itself into the heart, causing a myocardial infarction, into the brain, causing a stroke, or the lungs, causing a pulmonary embolism. If the clot remains at its point of origin and blocks the flow of blood there, it is called a thrombus. Thrombi cause severe damage wherever they form and are particularly dangerous when they occur in the heart, kidneys, and large, deep veins.
Plavix, also known as clopidogrel, is a thienopyridine drug that prevents the formation of clots by binding to and irreversibly inhibiting platelets’ ADP-activated P2Y12 receptors. Plavix in its native form does not actually interact with the P2Y12 receptor, but rather the liver contains an enzyme, CYP2C19, that converts the drug into its active form. This distinction is important for two reasons: inactive Plavix is much more stable than its active form, and a small number of people have livers that do not produce the CYP2C19 enzyme and therefore cannot activate Plavix at all. CYP2C19 deficiency is most prevalent among Asians, between 12 and 23 percent of whom are poor metabolizers for the enzyme, but also is not uncommon in Caucasians, about five percent of whom suffer this condition.
Plavix is frequently prescribed as a primary prevention drug for individuals at risk for thrombus and embolus related maladies like stroke and myocardial infarction. By preventing platelets from forming clots in the first place, it reduces the likelihood of death or permanent damage due to thrombi and emboli. Clinical research done by doctors Huyen Tran, Shamir Mehta, and John Eikelboom demonstrated that Plavix, taken in conjunction with aspirin, itself an effective antiplatelet drug, reduces the risk of recurrent myocardial infarctions by between 20 and 30 percent as compared to using aspirin alone. Another study by Dr. Young Bin Song et al. indicated that clopidogrel reduces the size of myocardial infarctions significantly.
Antiplatelet therapy has also demonstrated value as a method for preventing stroke for at-risk individuals. A review article by doctors Brett Cucchiara and Steven Messé that looked at various studies on aspirin and clopidogrel concluded that clopidogrel reduces the risk of a second stroke after the first occurs by 8.7 percent over aspirin. They also found that combining Plavix and aspirin significantly reduces the risk of bleeding complications as compared to using either drug alone. Another study in the New England Journal of Medicine by Dr. Yongjun Wang et al. found in a study of 5170 patients that only 8.2 percent of patients who took a combination of clopidogrel and aspiring had a recurrent stroke, compared to 11.7 percent of patients in the aspirin-only group.
As a result of its platelet inactivation, Plavix also prevents scabs from forming. Individuals taking the drug will bleed more copiously than they would off of the drug so they should be especially careful not to cause themselves severe bleeding and also be appropriately prepared for accidental injuries that might cause severe external or internal bleeding. Other side effects related to its anticoagulant effects include bruising easily, diarrhea, and upset stomach.
Although very rare, clopidogrel can cause a blood disorder called thrombotic thrombocytopenic purpura, or just TTP, which may include symptoms like severe stomach and abdominal pain, bloody or black stool, fever, elevated heart rate, headaches, bloody vomit, weakness, and seizures. Anyone who experiences these symptoms should cease taking clopidogrel for the time being and seek medical attention immediately to ascertain whether TTP is to blame for those symptoms.
• MedlinePlus: Clopidogrel • Plavix Oral Precautions and Side Effects • Dorsam, Robert; Kunapuli, Satya, “Central Role of the P2Y12 Receptor in Platelet Activation” • Cucchiara, Brett; Messé, Steven, “Antiplatelet Therapy for Secondary Prevention of Stroke” • Horn, John; Hansten, Philip, “Get to Know an Enzyme: CYP2C19” • Song, YB, et al. “A high loading dose of clopidogrel reduces myocardial infarct size in patients undergoing primary percutaneous coronary intervention: a magnetic resonance imaging study.” • Tran, Huyen; Mehta, Shamir; Eikelboom, John, “Clinical Update on the Therapeutic Use of Clopidogrel: Treatment of Acute ST-segment elevation myocardial infarction (STEMI)"