Stroke is the current leading, but preventable, cause of disability in the United States. Earlier, an association was noticed between CYP2C19*2 loss-of-function alleles and poor health outcomes in stroke patients receiving clopidogrel. Recently, scientists in China and United States have found that in stroke treatment, patients with acute minor stroke who are carriers of CYP2C19 loss-of-function alleles are less protected from the subsequent stroke and composite vascular events when treated with clopidogrel and aspirin, in comparison to non-carriers.
The drug clopidogrel is an oral anti-platelet agent which is used to inhibit blood clot formation in coronary heart disease, myocardial infarction and stroke. Clopidogrel, sold under the brand name Plavix by Sanofi and Bristol-Myers Squibb, before its patent expiry, was the second-fastest selling drug in the world. It is also based on the World Health Organization (WHO) Model of Essential Medicines, a list which constitutes the most important drugs needed in a basic health system.
The CYP2C19 gene translates into an enzyme cytochrome P450 2C19 or CYP2C19 which acts on nearly 5-10% of drugs in clinical use nowadays. The drug-metabolizing enzyme helps catalyze the biotransformation of many drugs in the body including clopidogrel, anti-malarial drugs, antitumor drugs and antidepressants.
CYP2C19 genotyping is covered by most private insurers and by Medicare in specific instances. It is widely available in America with a turnaround time of 4 to 5 days.
A Transient Ischemic Attack (TIA) or a minor stroke is also caused by a clot. The only difference between a TIA and a stroke is that in TIA the clot or blockage is temporary.
“By recognizing TIA symptoms and getting to the hospital, the patient can get help in identifying why the TIA occurred and get treatment — either through medication or surgery — that can prevent a stroke from occurring”, says Dr Emil Matarese, Director of the Primary Stroke Center at St. Mary’s Medical Center in Langhorne, Pennsylvania.
A minor stroke often resolves without any specific treatment but drugs such as clopidogrel and aspirin may be given to prevent future strokes. Both of these drugs work by reducing the ability of platelets to stick together and form clots. Moreover, a minor stroke is a warning sign for future attacks, with about a third of patients who experience a minor stroke going on to experience a stroke within a year.
The team of scientists led by Yilong Wang, MD, Phd, from the National Clinical Research Center for Neurological Diseases, Beijing, China, performed efficacy testing of the dual therapy of clopidogrel and aspirin in relation with CYP2C19 loss-of-function alleles.
The randomized clinical trial revealed that when compared with aspirin alone, clopidogrel and aspirin reduced the rate of new stroke in non-carriers of the CYP2C19 loss-of-function alleles, i.e., 6.7% versus 12.4%.
However, the rate of new stroke was not reduced in the carriers of CYP2C19 loss-of-function alleles when compared in different groups receiving the dual therapy and aspirin alone (9.4% versus 10.8%).
These findings suggest a role of CYP2C19 genotype in the efficacy of the dual treatment often used for prevention of strokes.
The results however may not be generalizable to every population as the participants were all from China and of Chinese descent.
Stroke chances vary with race and ethnicity. For example, the risk of a first stroke in African Americans is nearly twice the risk of a first stroke in white races. This is often due to differences in risk of high blood pressure, diabetes and obesity. The stroke risks of Hispanics fall between the risks calculated for blacks and whites. African American, Alaskan Natives and American Indians are more likely to suffer from a stroke.
The trial, named Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE), was registered at clinicaltrials.gov and was funded by the Ministry of Science and Technology of the People’s Republic of China.
The results of the CHANCE trial were published in the Journal of American Medical Association (JAMA) on June 23, 2016.
Nearly 800,000 people in the United States have a stroke every year, of which 87% are ischemic, a condition in which a clot forms in a blood vessel, cutting off blood flow to the brain.
In the United States, someone suffers from a stroke every 40 seconds and every four minutes someone dies because of it.