In limbo after mixed results, Merck blood clot drug stops heart attack with risk of bleeding
In one of the largest heart-drug studies ever conducted, the new drug Vorapaxar showed an impressive efficacy as a blood thinner — but with an increased risk for internal bleeding as a side effect, researchers said on March 24.
The new type of blood clot preventer being tested by Merck & Co has been hounded by bleeding concerns since January 2011. Then, a safety committee overseeing the 26,449-patient study said the new type of anti-platelet drug bore an increased bleeding risk — making it unsuitable for patients who had suffered a stroke.
The latest findings further cloud the future for Vorapaxar, which Merck had hoped might one day be a new blockbuster drug — because it works differently than the popular blood thinner Coumadin or aspirin. The drug is a thrombin receptor antagonist, a new class of experimental platelet-blocker drugs that work by stopping a process that normally allows the blood’s platelets to stick together and form clots.
In people who had had a previous heart attack, the new drug could reduce the risk of dying from a future heart attack or stroke by as much as 20 percent, the large study showed. But it also significantly increased the risk of hemorrhage.
Heart attack, stroke or peripheral artery disease survivors all benefit
Heart attack patients showed the best results, but all the patients studied benefitted — including those with a prior history of stroke or peripheral artery disease. For all study participants, the drug lowered by 13 percent the risk of dying from a heart attack or stroke within three years.
But study participants who suffered a previous stroke and took vorapaxar had significantly more hemorrhage events after three years. To be precise, 4.2 percent of those on the drug suffered from internal bleeding, compared to 2.5 percent of patients taking a placebo.
If Vorapaxar is approved for release on the market, it’s unlikely to be advised for prior stroke victims, as the study showed that the risk of brain bleeding was highest this group of people.
The new data on Vorapaxar — which were the results of a standard therapy in a phase III trial — were presented on March 24 at the American College of Cardiology Conference, a major annual meeting of cardiologists in Chicago. The results were also in the New England Journal of Medicine.
“In the lab, we have seen very compelling science showing the importance of thrombin’s action on platelets causing blood clots in arteries,” said David Morrow, a cardiologist at Brigham & Women’s Hospital in Boston who led the randomized, multinational study. “This is the first study to show definitively that blocking this pathway reduces the risk of suffering another cardiovascular event.”
Dr. Morrow’s team followed for three years 26,449 patients who had heart attack, stroke or leg artery disease.
Will not clinch FDA approval
According to Dr. Steven Nissen, a cardiologist at the Cleveland Clinic who wasn’t involved in the study, the findings are unlikely to be good enough to get U.S. marketing approval. To get the U.S. federal regulator’s nod, new studies proving that vorapaxar can be used in some patients without excess bleeding are needed, he pointed out.
“The bottom line is it’s extremely difficult to make the case that the benefits exceed the risks here,” said Dr. Nissen. “The results are disappointing,” he added.
Merck meets efficacy goal
But Merck Vice President Francis Plat said the company-funded vorapaxar study was “positive” because it achieved its efficacy goal of preventing heart attacks and heart-related deaths.
Speaking to reporters at the sidelines of the cardiology meeting, Plat said his company believes the new medicine might still play a specific role and is discussing this — as well as which patient groups are likely to benefit — with top cardiologists.
Study leader Dr. Morrow thinks that because vorapaxar reduced the risk of heart attacks, strokes and cardiovascular death by 20 percent in the subset of 17,779 patients who had previous heart attacks, the drug’s benefit was compelling in that group.
“There’s potential for benefit in that group that clearly outweighs the risk of bleeding,” Morrow said in a telephone interview with Bloomberg.
All blood thinners have bleeding as a possible side effect
The findings illustrate how tough it is for drugmakers to come up with new blood thinners that work well on top of standard therapy without excessive bleeding, Dr. Nissen said.
“Anything where there’s significantly more bleeding is a difficult sell for doctors,” said Kim Vukhac, an analyst at Credit Agricole Securities in New York, in a telephone interview before the data was released. Investor “expectations are low” for vorapaxar, he said.
Blood thinners reduce the risk of heart attack and stroke by reducing the formation of blood clots in your arteries and veins. If you have some kinds of heart or blood vessel disease — or if you have poor blood flow to your brain — your doctor may recommend that you take a blood thinner. He or she will also prescribe a blood thinner is you have:
• Congenital heart defects
• Heart valve surgery
• An abnormal heart rhythm called atrial fibrillation
Antiplatelet drugs like aspirin prevent blood cells called platelets from clumping together to form a clot. Anticoagulants, such as heparin or warfarin — also known as Coumadin — work on chemical reactions in your body to lengthen the time it takes to form a blood clot.
Common blood thinners and their side effects
Warfarin. More popular by its trade name Coumadin, this drug is used to prevent strokes in people who suffer from atrial fibrillation and blood-clotting disorders, as well as people who have mechanical heart valves.
Warfarin works by decreasing the amount of vitamin K available for use in the body — in turn reducing the body’s blood-clot formation efficiency. But consuming too much foods rich in vitamin K can prevent warfarin from working properly — and leave you temporarily at a high risk of stroke. This is patients who take warfarin should monitor their intake of vitamin-rich foods like asparagus, lettuce, alfalfa sprouts, broccoli, cabbage, cauliflower and spinach.
Doctors also recommend that patients on warfarin maintain a steady level of vitamin K in your body by eating the same amounts of these food items every day.
Abnormal and sometimes profuse bleeding is the most common side effect of warfarin. Bleeding and easy bruising can occur anywhere in the body, but often, the abnormal bleeding can be more dangerous — occurring inside the eye and in the intestines. To watch out for this, patients on warfarin must monitor stool color and seek medical attention if stools become black or tarry.
Warfarin can also cause serious bleeding. To avoid this, people who take this medication must routinely test their INR — or International Normalized Ratio. An international measure of coagulation that attributes a value of 1.0 to people with a normal ability to clot, every increase in INR reflects a lessened likelihood of forming blood clots. To decrease their risk of stroke effectively, patients must maintain an INR of 2-3.
Heparin. Usually given intravenously in hospitals to prevent blood clot formation, heparin enhances the body’s ability to break down existing blood clots. Blood must also be drawn periodically to make sure that its levels fall within a safe margin — allowing heparin to work safely. The blood test performed to do this is called the partial thromboplastin time or PTT.
Bleeding and easy bruising are also the main side effects of heparin. Irritation at the injection site can also occur and in rare instances, heparin can cause an allergic reaction.
Abnormal bleeding is the most common dangerous side effect of heparin. Patients have to look out for black stools, which indicate intestinal bleeding — or for orange, pinkish or smoke-colored urine that shows that there’s blood in the urine.
Aspirin. Commonly used as a blood thinner, aspirin can irritate the stomach and intestines. It can cause indigestion, nausea and vomiting. Difficulty breathing and intestinal bleeding are other less common side effects of aspirin.
If you’re taking aspirin, it’s best to watch out for black or tarry-looking stools, signs of intestinal bleeding. Also, go to the emergency room if you develop difficulty breathing while on aspirin.
Aggrenox. A combination of aspirin and extended-release dipyridamole, this blood thinner causes headache in almost 40 percent of patients taking it. Abdominal pain, indigestion and diarrhea are also common side effects of aggrenox. Stop taking Aggrenox and go to your doctor or to an emergency room if you find black or tarry-appearing stools, as this is a sign of intestinal bleeding.
Natural blood thinners
If you want to go do away with the serious side effects of blood thinners, you can also choose to take salicylates — natural blood thinners that block vitamin K. Many preservatives and flavorings contain salicylates, especially spices and most fruits and nuts.
Here’s a partial list of blood-thinning spices:
• Cayenne pepper
• Curry powder
Fruits high in salicylates include: