In the United States, heart disease is the leading cause of death, and stroke is the fifth-leading cause. A major contributor to these cardiovascular diseases is clogged blood vessels (atherosclerosis), which result from the buildup of fatty deposits or plaque.

Treatment for clogged blood vessels often includes angioplasty. In this procedure, the doctor inserts a small, medical balloon into the damaged blood vessels, and then inflates and removes it. Small tubes, or stents, also may be used to hold open the blood vessels. To prevent further damage from occurring, patients often take multiple blood thinners, such as clopidogrel and aspirin, after stent placement.

Previous research has shown that clopidogrel is less effective in patients with mutations on a specific gene, called CYP2C19, than in patients without the mutations. Whether genetic testing can help guide treatment in clinical practice, however, has remained unclear.

In this study, results showed that genetic testing for CYP2C19 mutations could be used to guide blood-thinner treatment after stent placement. Furthermore, patients with the mutations who received one of two clopidogrel alternatives compared to clopidogrel were more than three times less likely to die or have a heart attack, stroke or other major complications 12 months after treatment. Specifically, major complications occurred among 27 percent of clopidogel patients with the genetic mutations, compared to 8 percent of patients with the mutations who received the alternative medications.

These findings are similar to those of an earlier, multicenter study that found the risk of a major cardiovascular event more than doubled in patients with the genetic mutations who took clopidogrel.

“Using an algorithm based on genetic testing to guide treatment is sustainable and associated with better clinical outcomes in a real-world clinical practice, although it is difficult to consistently maintain,” said Craig R. Lee, Pharm.D., Ph.D., F.A.H.A., associate professor of pharmacy at the University of North Carolina at Chapel Hill Eshelman School of Pharmacy. “Clinicians need to be aware of the increased risk of major adverse cardiovascular events associated with use of clopidogrel in patients receiving stents who carry either one or two copies of the mutation.”

Study participants included 1,193 patients at the University of North Carolina Cardiac Catheterization Laboratory who received stent placement between July 1, 2012, and June 30, 2014. Their average age was 63 years and more than two-thirds were male. Most were white, 21 percent were black, and 1 percent was Asian. Patients identified as high risk, due to decreased blood flow to the heart, received the genetic testing. Follow up was 12 months.

The study has several limitations. For one, the investigators collected information after treatment, so they could not definitively say whether blood-thinner choice and the results of genetic testing caused better patient outcomes. Another limitation includes the use of a single hospital, which may not be applicable to different settings.

“We are using CYP2C19 genetic testing on a daily basis at our institution to help decide in a timely manner which drug to prescribe,” said George “Rick” Stouffer, III, M.D., F.A.H.A., chief of cardiology and co-director of the McAllister Heart Institute at UNC.

Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association’s policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations and health insurance providers are available at www.heart.org/corporatefunding.

About the American Heart Association

The American Heart Association is devoted to saving people from heart disease and stroke – the two leading causes of death in the world. We team with millions of volunteers to fund innovative research, fight for stronger public health policies and provide lifesaving tools and information to prevent and treat these diseases. The Dallas-based association is the nation’s oldest and largest voluntary organization dedicated to fighting heart disease and stroke. To learn more or to get involved, call 1-800-AHA-USA1, visit http://www.heart.org/ or call any of our offices around the country.

The findings come from the ORBITA trial, which stands for “Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina”. (Editor’s note: That is the British spelling of the word “randomized”.) It was a blinded, randomized, placebo-controlled study of 200 patients with stable angina (chest pain or discomfort that most often occurs with activity or stress) in which researchers compared the artery-widening technique (stenting) with a simulated procedure – where a stent was not implanted – for the first time.

A release from Imperial College London explains that results from the trial show that the treatment had no significant additional benefit on patient symptoms or quality of life.

Carried out in the UK and led by researchers at Imperial, the trial provides the first evidence of a direct comparison between stenting for stable angina and placebo, for patients on high quality tablet treatment.

The researchers published their findings in The Lancet and presented them on Thursday, November 2^nd at the Transcatheter Cardiovascular Therapeutics 2017 conference in Denver, Colorado.

The release quotes lead author Dr. Rasha Al-Lamee from the National Heart & Lung Institute at Imperial College London as saying, “The most important reason we give patients a stent is to unblock an artery when they are having a heart attack. However, we also place stents into patients who are getting pain only on exertion caused by narrowed, but not blocked arteries. It’s this second group that we studied. Surprisingly, even though the stents improved blood supply, they didn’t provide more relief of symptoms compared to drug treatments, at least in this patient group.” Dr. Al-Lame is also an interventional cardiologist at Imperial College Healthcare NHS Trust.

“While these findings are interesting and deserve more attention, they do not mean that patients should never undergo the procedure for stable angina. It may be that some patients opt to have an invasive procedure over taking long-term medication to control their symptoms,” she added.

Stable angina is a common condition in adults in which patients feel chest pain as a result of over-exertion due to restricted blood flow to the heart. It is typically caused by the build-up of fatty plaques in the arteries and a hardening of the blood vessel walls, which makes them narrower and less flexible.

Patients can manage the condition with drugs such as beta-blockers or nitro-glycerine. However, some may undergo an invasive procedure, known as angioplasty with stent or Percutaneous Coronary Intervention (PCI). An estimated 500,000 patients around the world undergo PCI each year for stable angina, and the procedure is thought to bring substantial relief from symptoms for patients.

However, since the procedure was introduced it has been unclear whether the relief of symptoms is due to the treatment or to a placebo effect.

As part of the multi-center ORBITA trial, the researchers recruited 200 patients through hospitals in London and the south of England. All patients had stable angina, and had a narrowing in one single coronary vessel. Once enrolled the patients had a six-week phase of intensive medical treatment in which the medications used to treat angina were introduced and increased to maximal doses.

Patients were randomized to receive either a heart stent, or to undergo a placebo procedure in which they had an angiogram procedure, but did not receive the stent.

Of the patient group, half received the stent and half had the placebo procedure. For the next six weeks the patients and their doctors did not know which one they had had.

Both before and six weeks after undergoing the procedure, patients had exercise tests to assess how fast they could walk on a treadmill while their heart and lung function were measured. The key outcome was a change in the amount of time they could exercise after the procedure.

They found the average increase in overall exercise time was 28·4 seconds for patients who had PCI and 11·8 seconds for the placebo group. However, the difference between the groups was not statistically significant, meaning they could not say the effect was down to the stent, or down to chance. There were also no significant differences in patient-reported improvement of symptoms in either group.

Even so the tests did confirm that stenting significantly relieved the narrowing in the coronary artery and improved the blood supply to the heart. This was puzzling as the researchers had expected that exercise capacity and symptoms would improve once the artery had been opened and the blood supply improved.

The researchers explain that they took high doses of medication before the procedure which may not be adhered to in the real-world setting. They also stress that the study group only contained patients with the single-vessel form of disease and that patients with multi-vessel form of disease may get more symptom relief from stenting.

More analysis is expected from the ORBITA trial as the researchers aim to delve deeper into the data to see whether there are subgroups of patients whose angina improves more after stenting.

“It seems that the link between opening a narrowing coronary artery and improving symptoms is not as simple as everyone had hoped,” said Dr Al-Lamee. “This is the first trial of its kind and will help us to develop a greater understanding of stable angina, a disease which affects so many of our patients every day.”

A study led by Bentley Bobrow, MD, professor at the University of Arizona Colleges of Medicine in Tucson and Phoenix and co-director of the Arizona Emergency Medicine Research Center – Phoenix, and his fellow UA emergency medicine researchers, showed that physicians may need to allow comatose cardiac arrest patients much more time to awake before making a prognosis.

More than 400,000 Americans experience out-of-hospital cardiac arrest annually. Survival statistics are bleak: although approximately 50 percent of people who arrest are revived after attempted resuscitation, only about 10 percent of these survive to leave the hospital. Furthermore, almost half of the survivors suffer some level of brain impairment from hypoxia (when the brain is not getting enough oxygen).

While out-of-hospital cardiac arrest is still a leading cause of death in the United States, outcomes have improved dramatically in places like Arizona, where the focus has been on innovative healthcare advances, Bobrow said. Advances include compression-only CPR training for the public, enhanced telephone-CPR instructions and training for 911 dispatchers, implementing high-performance CPR for EMS providers and making sure patients are taken to specialized hospitals that deliver treatments like targeted therapeutic hypothermia to improve brain recovery.

Results from the multicenter study, recently published in the Annals of Emergency Medicine, showed for out-of-hospital cardiac arrest patients, the time it takes to regain consciousness after rewarming from therapeutic hypothermia treatment varies widely and is longer than many had thought.

“Most patients are comatose after resuscitation and accurately predicting those who will wake up can be extremely challenging,” Bobrow said.

“There are many factors involved, but we know that it is common for doctors to try to decide who will and who won’t wake up after 24 to 48 hours of hospitalization. However, our study found that a substantial number of cardiac arrest victims wake up longer than many people would expect. Sometimes they awaken from coma five, six or seven days after being admitted to the hospital and many of these have a good neurological outcome,” he said.

Among 573 out-of-hospital cardiac arrest patients who completed targeted temperature management, 60 woke up at least 48 hours after rewarming. Eight patients became responsive more than seven days after rewarming, six of whom were discharged with good neurological scores. One of the important findings was no predictive factors reliably identified who would awaken early or late.

Bobrow said, “We were surprised by the large proportion of cardiac arrest survivors who woke up more than three days after their arrest and went home with their families.

“While targeted therapeutic hypothermia has been shown to improve outcomes, no validated system currently exists for predicting when patients receiving this treatment will awaken from coma. Physicians and family members may need to wait longer than the traditional three days before making irrevocable decisions about brain function recovery and possible withdrawal of care,” he said.

“Our study quantifies the timing of awakening from a coma after cardiac arrest in the era of targeted temperature management, and this timing is much different than before we had this treatment,” said Daniel Spaite, MD, UA professor and Virginia Piper Distinguished Chair of Emergency Medicine.

“We may be able to save thousands of lives each year across the country by simply giving cardiac arrest victims more time to awaken in the hospital,” said Samuel Keim, MD, professor and chair of the UA Department of Emergency Medicine.

A release from the university notes that therapeutic hypothermia involves decreasing the body temperature to protect the brain when blood flow is reduced from a cardiac arrest, when the heart stops pumping and the patient has no pulse.

Previous studies have shown the therapy effective on patients with so-called “shockable” heart rhythms like ventricular fibrillation. But Perman’s research demonstrates that it’s also effective on patients with “nonshockable” rhythms when there is no pulse and the patient is in a coma.

The release quotes Perman, an assistant professor of emergency medicine at the University of Colorado School of Medicine, as saying,”Prior to our study, there was minimal data to support the use of this treatment on patients with nonshockable rhythms. As a result, the therapy was not widely used with these patients.”

Every year, 530,000 Americans suffer cardiac arrest and 300,000 of them happen outside of a hospital.

Perman, a clinical expert in cardiac arrest and post-arrest care, and her colleagues looked at data from 519 patients who had nonshockable heart rhythms between 2000 and 2013.

They found those who received therapeutic hypothermia were 2.8 times as likely to survive to be discharged from the hospital and 3.5 times more likely to have better neurological outcomes – returning to their baseline mental state – than those who did not have the treatment.

Physicians who use the technique employ cooling wraps to drop the patients’ temperature from approximately 37 degrees Celsius to 33 degrees Celsius (91.4 degrees F). The therapy has shown to reduce damage to the brain following a cardiac arrest, though scientists continue to investigate why this occurs.

Landmark trials in 2002 studying shockable patients found 49 percent of those who received therapeutic hypothermia had good neurological outcomes as opposed to 26 percent who did not receive the treatment. Another trial showed 55 percent of patients with good neurological outcome against 39 percent who didn’t have the therapy.

“Neurologic injury after cardiac arrest is devastating,” said Perman, who like most physicians at CU Anschutz is both an active researcher and practicing clinician. “We have one chance to give some form of neuroprotection, and that’s immediately after the arrest.”

She said therapeutic hypothermia should be more widely used in comatose patients to protect neurological function.

“We know that patients benefit from this therapy,” said Perman, noting the importance of delivering meaningful research from the laboratory directly to the patient. “Therefore, one of our next challenges is to tailor the hypothermia treatment to the patient’s specific injury in order to improve outcomes further.”