A study recently conducted by Pfizer has found that patients treated with the arthritis drug valdecoxib after coronary artery bypass graft (CABG) surgery are at an increased risk of adverse cardiovascular events. The final report on the study was submitted to the US Food and Drug Administration (FDA) at the beginning of November.
A total of 1500 patients were included in the study. It was found that approximately 2% of patients suffered a cardiovascular event (including cerebrovascular accident, deep vein thrombosis, myocardial infarction and pulmonary embolism) having been treated with the intravenous form of the drug after CABG, compared with approximately 0.5% of patients who received a placebo. Events also occurred in around 1% of patients who were treated with the oral form of the drug.
As a result, the FDA has added a warning to the drug label that contraindicates its use following CABG. This move follows an increase in information on the cardiovascular risks associated with cyclooxygenase (COX)-2 inhibitors, which, earlier this year, led to Merck withdrawing the drug rofecoxib from the market. Pfizer is also sponsoring a clinical trial of its other COX-2 inhibitor, calecoxib, in osteoarthritis patients with heart disease.
The US regulator said: “Bextra (valdecoxib) is not approved for use in the treatment of postoperative pain of any type; however, the FDA believes that these new findings should be made available to healthcare professionals and patients.”
Electrical stimulation allows heart tissue growth
A group of scientists from the Massachusetts Institute of Technology (MA, USA), have successfully grown tissue in the laboratory that can mimic the beat of the heart. They hope that eventually the tissue will be used to repair the myocardium after a heart attack.
Lead researcher Gordana Vunjak-Novakovic said: “We have been trying to engineer a patch of tissue that has the same properties as myocardium that could be attached over injured myocardium.”
The tissue was grown by placing rat myocytes on a three-dimensional scaffold, which were then stimulated with electrical signals that mimicked those that are involved in the development and function of the heart. The scaffold slowly degraded as the tissue formed. It has not previously been possible to produce cells with the same structure and function as heart tissue.
Another member of the research team, Milica Radisic, said “Initially, we had no idea if this would work. As it turns out, electrical stimulation was crucial for rapid assembly of functional tissue.”
In order to establish the effect of electrical stimulation, control cells were also attached to the scaffold, but did not receive the electric pulses. After 8 days, it was found that those cells receiving the pulses had enhanced alignment and contractile behavior compared with the controls – contraction was seven-times greater and they had reached a ‘remarkable’ level of differentiation.
Charmaine Griffiths of the British Heart Foundation said: “This interesting early research shows that scientists may have developed a functional patch-repair mechanism that might eventually be used to treat damaged heart tissue.”
She added: “Although it is very early days for this approach, developments of this kind using living heart cells may provide help for those with damaged heart tissue in the future.”
Increased myocardial infarction risk with drug discontinuation
Researchers from the University Hospital Basel, Switzerland, have found that the risk of a first acute myocardial infarction (AMI) is greatly increased in the month following nonsteroidal anti-inflammatory drug (NSAID) discontinuation.
“Our results suggest that abrupt discontinuation of NSAID therapy may have to be avoided, and that physicians should carefully review disease status and current medication before terminating a therapy with NSAIDs,” the researchers reported.
“This may be particularly valid for patients with chronic inflammatory diseases and/or for subjects who have used NSAIDs for a long time.”
The researchers examined data from the British General Practice Database, including 8688 patients experiencing a first AMI between 1995 and 2001. They also included 33,923 controls who were matched for age, calendar time, general practice attended and sex. They found that the risk of AMI was increased by 52% in those who had discontinued NSAIDs less than 30 days before the cardiac event. The risk was found to be highest for subjects with rheumatoid arthritis systemic lupus erythematosus (risk increased 3.68-fold) and those who discontinued NSAIDs after long-term use (risk increased 2.6-fold).
The investigators believe that NSAIDs reduce AMI risk by acting on the molecular pathways of inflammation, and potentially by inhibiting platelet aggregation.
The researchers reported: “The results of this large case-control analysis suggest that the risk of developing a first-time AMI is increased for a period of several weeks after discontinuation of NSAID use, particularly in subjects who used NSAIDs on a long-term basis.”
However, no increased risk was associated with current or previous NSAID use (at least 60 days before the cardiac event).
Risk increased with hypertension drug combination
The women’s Health Initiative Observational Study, conducted by scientists at the Albert Einstein College of Medicine, NY, USA, has found that hypertension treatment with calcium channel blockers and diuretics doubles the risk of death from cardiovascular disease (CVD) compared with a combination of β-blockers plus diuretics. Angiotensin-converting enzyme inhibitors plus diuretics did not cause an increased risk. The study included 30,219 women aged 50 to 79 years who were followed for a mean period of 5.9 years; the researchers focused on 11,294 patients who received monotherapy and 4493 patients who received combination therapy.
The found that those patients who received a combination of calcium channel blockers plus diuretics had an 85% greater risk of CVD death than those who received β-blockers plus diuretics. As a monotherapy, calcium channel blockers were associated with a 55% greater risk compared with diuretics.
However, the investigators admitted: “One limitation of our study is that, while prospective, it is an observational rather than a clinical trial; thus, we cannot be certain that we were able to fully control for confounding by indication.”
“Furthermore, our data pertain to postmenopausal women aged 50 to 79 years, and may not be generalizable to younger women or to men.”
Internal mammary artery graft not as superior as thought
A prospective study of CABG patients carried out by scientists at the Southern Arizona Veterans Affairs Healthcare System, AZ, USA, found that long-term patency is higher when an internal mammary artery (IMA) graft is performed, compared with a saphenous vein graft (SVG), but the difference between the two methods may not be as great as was previously thought.
Steven Goldman and colleagues said: “Based on small studies of selected groups of patients, it is generally believed that SVGs have a 40 to 50% 10-year patency and that the IMA graft has a 90 to 95% 10-year patency.”
The study consisted of a 10-year angio-graphic follow-up of CABG patients who took part in two Veterans Affairs Co-operative Trials in the 1980s (that investigated the effect of antiplatelet agents on graft patency). A total of 1074 patients received SVGs, while 457 received a left IMA graft. Serial angiograms were made at 1 week, and 1, 3, 6 and 10 years after surgery. Patency was found to be 61% with SVGs and 85% with IMA grafts (p < 0.001). These values were 68 and 88% for SVGs and IMA grafts, respectively, if the grafts remained open for 1 week after surgery.
Graft patency was increased if the recipient-vessel diameter was greater than 2 mm. Significant predictors of patency included: aspirin use after CABG; older age; lower serum cholesterol; and lowest Canadian Functional Class.
The scientists believe that this data could aid in letting CABG patients know their prognosis. Goldman said: “Clinicians can use our data to tell patients what their long-term chances are of having a patent IMA or vein graft.”
“10-year vein graft patency is better than most people thought, especially when the graft is placed into a larger recipient coronary artery, that is, one with a diameter greater than 2 mm. Also, IMA patency is not as good as people thought.”
FDA approves totally artificial heart
A totally artificial heart (Cardio West™, SynCardia) has been approved by the FDA to bridge patients with nonreversible heart failure to transplant who are not responding to treatment and who are at risk of imminent death. They estimate that approximately 100 of the 4000 patients awaiting transplantation in the USA would be suitable candidates for the device.
In a written statement, the president and CEO of SynCardia, Marvin J Slepian, said: “The FDA’s approval of the first temporary total artificial heart represents a significant milestone in medical history. We will be able to save the lives of many critically ill patients who are in need of, or who are awaiting heart transplants.”
The artificial heart is a pneumatic, biventricular device, with the two ventricles connected to the native atria and greater vessels. A line covered in double-velour material passes from each ventricle to a console. The console sends pulses of pressurized air, and monitors function. The company says the device offers full circulatory support, the shortest blood path and least exposure to artificial surfaces. It also has the highest cardiac output compared with other artificial heart devices.
In order to prove the efficacy of CardioWest, SynCardia presented a study to the FDA panel that compared 81 patients with New York Heart Association class IV heart failure (mean age: 51 years) with 35 control patients. They found that 69.1% of the CardioWest patients were treatment successes (based on predefined criteria), compared with 37.7% of the control patients. However, the CardioWest patients experienced a high rate of adverse events (including infection, renal dysfunction or a neurologic event).
One of the members of the FDA panel, Clyde Yancy, said: “There is certainly a clinical need for this sort of device, but there should be an understanding that there will be an ongoing look at clinical outcomes.”
“It seems to work as well as other devices, but the complication rate is still unacceptably high. If we go forward with approving the device then we need postmarketing data that will show that efforts have been made to bring that rate down.”
SynCardia will need to conduct a postapproval study in order to monitor the device.