CDU

ORLANDO, Florida Cardiovascular Device Update, quite obviously, focuses on devices and instrumentation used in the cardiovascular field, but these areas frequently interlock with both drug and other non-drug technologies.

The variety and tantalizing potential applications for these related technologies are well highlighted at every American College of Cardiology (ACC; Bethesda, Maryland) conference. And these are technologies that device manufacturers and users should be aware of either as early warning for competitive advantage or, more appropriately, for patients and clinicians, since they put on the radar the opportunities for better care and better outcomes at some future time.

Following are a few short notes on some of these technologies reported on at this year's ACC gathering, which took place in early March.

No matter how effective a diagnostic or treatment technology, proper methods of care frequently, follow-on care with medications are considered essential to maximizing opportunity for the best outcomes, meaning reduced death and co-morbidities and improved quality of life.

In this context, electronic medical record programs are being boosted as a way to improve caregiver efficiency. But James Dove, MD, presented research suggesting the need for a dovetailing computer program that provides a method for improved quality-of-care compliance on the physician's part. Dove described a computerized quality improvement program that reminds physicians concerning a list of seven approved cardiovascular treatment guidelines and gives visual alerts if particular guidelines are not checked off as met.

The researchers looked at physician compliance using the computer program in their treatment of 5,000 patients, and 3,000 other patients treated by doctors without the computer program. The study found that when the computer tool was used, 100% of the physicians were compliant in prescribing aspirin - one of the key goals compared to only about 90% without the computer program.

Across all seven guidelines, the computer program was associated with 100% physician guideline compliance, vs. just 26% adherence to all guidelines without it. "Memory fails us," said Dove, offering one reason for the difference. And he noted that with increased documentation of care "there is less and less time to think about how to manage the patient." He said also that this is particularly true in cardiovascular care, with ongoing changing rules of care and the number of team members required to carry out quality care.

Another interesting use of computer technology in quality improvement was demonstrated with the use of the Remind software from Siemens Medical Solutions (Malvern, Pennsylvania). Researchers compared use of the Remind artificial intelligence software, an automated extraction system, with manual chart extraction from an electronic medial record.

Manual extraction and data entry concerning 136 patients required 136 hours compared to three hours using Remind software. A total of l2,289 data elements were identified, with compliance agreement in 1,912 and disagreement in 377 involving 2.5% to 35% of patients for various parameters. Remind was found to be correct in compliance disagreements at 57% and manual extraction was correct in the remaining 43%.

Remind identified adherence at 55.7%, compared to guideline adherence determined by manual extraction at 38.2%. Researchers concluded that Remind can access guideline adherence at least as accurately as manual chart abstraction. And the use of Remind for quality improvement and research can result in improve savings, better resource utilization and may improve data extraction quality, the researchers said.

In other reports:

Autologous myoblast transplantation (AMT) remains efficacious and safe in patients undergoing coronary artery bypass grafting (CABG), according to a U.S. multicenter study that found these goals achieved in a three-year follow-up study. In AMT, skeletal muscle cells, or myoblasts, are taken from the patient's thigh and cultured for several weeks. They are then injected into the heart, at the area of the infarction, to promote the growth of new, viable heart tissue. The ultimate goal of AMT is to heal the heart after myocardial infarction (MI) and improve its pumping ability, said Nabil Dib, MD, of the Arizona Heart Institute (Phoenix).

In this feasibility and safety trial, 24 patients with a prior MI and a left ventricular ejection fraction of less than 40% who were scheduled to undergo CABG were given AMT injections in one of four escalating doses, ranging from 10 million to 300 million cells. Post procedural monitoring included positron emission tomography and MRI.

The PET and MRI scans showed evidence of new heart tissue formation, and heart function was increased from 21% to 34%, an improvement of about one New York Heart Association class, Dib said.

Adding the antiplatelet agent clopidogrel to standard reperfusion therapy for patients with ST-elevation myocardial infarction (STEMI) significantly reduces their rate of blocked culprit coronary artery, death or recurrent MI by the time of angiography. It does this safely, with no increase in bleeding or intracranial hemorrhage, according to a large, multicenter trial. In the Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) Thrombolysis In Myocardial Infarction (TIMI) 28 trial, 3,491 STEMI patients undergoing fibrinolysis were randomized to clopidogrel, followed by another lesser dose, or placebo for an average of four days, until angiography. Standard fibrinolytic agents and anticoagulants were used and all patient received aspirin.

Patients who received clopidogrel had a significantly lower rate of blocked culprit coronary artery, death or recurrent MI than control patients, a benefit seen regardless of age, gender, type of fibrinolytic or type of heparin. By 30 days, patients treated with clopidogrel had a lower rate of death due to cardiovascular causes, recurrent MI or recurrent ischemia leading to the need for urgent revascularization.

Patients with coronary heart disease who took Pfizer's (New York) cholesterol-lowering medicine Lipitor (atorvastatin calcium) and lowered their cholesterol to well below recommended levels experienced significantly fewer heart attacks and strokes than those who only lowered their cholesterol to recommended levels, according to data presented at the meeting. The five-year Treating to New Targets (TNT) trial involved 10,000 patients with established coronary heart disease and elevated LDL, or "bad" cholesterol levels. The study assessed whether high-dose Lipitor patients who aggressively lowered their LDL-cholesterol levels to well below the current guidelines (100 mg/dL) would experience additional cardiovascular benefits compared to Lipitor patients who maintained their LDL-cholesterol at recommended levels.

Patients who received 80 mg doses of Lipitor had 22% fewer cardiovascular events, including CHD death, non-fatal heart attacks, resuscitated cardiac arrest, and fatal or non-fatal strokes compared to patients who took 10 mg of Lipitor. In addition, patients treated with high-dose Lipitor had 25% fewer fatal or non-fatal strokes compared to those treated with just 10 mg of Lipitor. The TNT study demonstrated that the musculoskeletal safety profile of Lipitor at 80 mg dosing was comparable to Lipitor 10 mg doses. The incidence of liver enzyme elevations in both groups was within existing product labeling. TNT is the longest and largest study to date of Lipitor 80 mg efficacy and safety.

TNT is an investigator-led trial coordinated by an independent steering committee and was funded by Pfizer. The study enrolled men and women between 35 and 75 years of age in 14 countries.

New ARIES (African American Rosuvastatin Investigation of Efficacy and Safety) data presented at the meeting showed that AstraZeneca's (London) Crestor (rosuvastatin calcium) at 10 mg and 20 mg reduced levels of C-reactive protein (CRP) by 14% and 19%, respectively, while atorvastatin 10 and 20 mg reduced CRP levels by 8% and 15%, respectively. In a subgroup analysis performed in patients with elevated CRP, Crestor reduced this biomarker of inflammation by 20% and 21% at the 10 and 20 mg doses, respectively, while atorvastatin reduced CRP by 12% and 20%, respectively. CRP is a protein in the body whose level increases when there is inflammation of blood vessels.

"An increasing number of cardiologists believe that CRP may be an important, yet often ignored, diagnostic tool," said Keith Ferdinand, clinical cardiologist and medical director of Heartbeats Life Center and the lead investigator for ARIES. "Through the ARIES trial, we have important new information about the changes caused by Crestor on this potentially critical biomarker in African-Americans."

The ARIES study was the first-ever large-scale, prospective trial exclusively designed to compare the effects of statins in African-American patients. It was randomized, multicenter trial designed to evaluate the efficacy of Crestor and atorvastatin in African- Americans with elevated cholesterol.

Gene therapy is frequently touted as the largest new wave of the future, but one of the studies presented at ACC indicated no efficacy in the exercise improvement of class II to class IV angina patients, although the therapy was safe. The goal of this type of gene therapy is to grow new blood vessels in patients with myocardial ischemia. After earlier trials (AGENT and AGENT-2) showed that intracoronary injections of the adenovirus for fibroblast growth factor 4 (FGFR-4) showed safety and some favorable effects on exercise tolerance and blood flow to the heart in these patients, investigators had high hopes that AGENT-3 would finally demonstrate real improvement in their ability to exercise, said Timothy Henry, MD, of the Minneapolis Heart Institute (Minneapolis).

In AGENT-3, 416 patients at 65 centers in the U.S. were randomized to placebo or low dose and high dose of the adenovirus delivered via intracoronary injection. The patients did not need immediate revascularization for the angina. Patients were then tested on a treadmill at three months and six months to see if their ability to walk had improved. However, walking times remained unchanged in all groups, despite excellent results pertaining to safety. Some improvement was seen in a subset of very high-risk patients, the researchers said, including those with more severe Class III and Class IV angina.

Henry noted: "these results mean that you're not that sick to start with, the gene therapy is not going to make you much better. But it looks as if it is possibly having a better effect in more seriously ill angina patients. In the future, we will probably need to confine this to higher-risk patients."