Determining the “CADILLAC” of Care
Primary stenting, already accepted as a more effective measure of reducing death, reinfarction, or the need for early recanalization of coronary arteries, is also cost-effective, said primary investigators of the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) trial in a report in this week’s issue of the journal Circulation (Circulation. 2003;108:2857–2863OpenUrl). However, the cost-effectiveness of the glycoprotein IIb/IIIa inhibitor abciximab is equivocal, said the group, led by author Ameet Bakhai, MD, of Harvard Clinical Research Institute in Cambridge, Mass.
In the CADILLAC study, 1703 patients were randomized to stenting versus balloon angioplasty with abciximab versus balloon angioplasty with no abciximab, according to a 2×2 factorial design. The researchers calculated cost per quality-adjusted year of life on the basis of total 1-year costs and lifetime incremental cost-effectiveness ratios. Stenting increased procedural costs by $1148 and initial hospital costs by $1384 over balloon angioplasty. However, stenting also reduced the need for repeat revascularization and reduced follow-up medical care costs by $1215, meaning that at 1 year, the costs for the angioplasty and stent groups were almost the same ($18 690 for angioplasty and $18 859 for stent).
Abciximab increased initial procedural costs by $1122, but most of the drug costs were offset by accelerated discharge from the hospital (0.6 days earlier in the abciximab group). However, the offset did not continue at 1 year, when aggregate costs in the drug group were $1244 more than for those who received standard therapy. Abciximab was cost-effective only if nonsignificant differences in 1-year mortality were included in the analysis.
β-Blockers as Effective as Calcium Antagonists
β-Blockers proved as effective as calcium channel blockers in treating high blood pressure in patients with coronary artery disease in INVEST (International Verapamil–Trandolapril Study), led by Carl J. Pepine, MD, of the University of Florida College of Medicine in Gainesville, according to a report in the December 3, 2003, issue of The Journal of the American Medical Association (JAMA. 2003;290:2805–2816OpenUrlCrossRefPubMed).
INVEST was designed to compare multidrug strategies for reducing blood pressure, because in most people with high blood pressure, more than one drug is necessary to bring blood pressure to desirable levels. A total of 22 576 patients were enrolled in the study, which was carried out at 862 sites in 14 countries. Patients were randomized to a calcium antagonist strategy using verapamil (sustained release) or a β-blocker strategy using atenolol. Patients with diseases such as diabetes, renal failure, or heart failure received hydrochlorothiazide or trandolapril or both, as determined by physicians.
Patients were followed up for 2.7 years on average. During that time, 2269 patients either died or had a myocardial infarction or stroke that did not kill them. In the calcium channel–blocker group, 9.93% of patients had one of those primary outcomes, compared with 10.17% in the β-blocker group. Of the calcium antagonist patients, 71.7% achieved desirable blood pressure below 140/90 mm Hg, compared with 70.7% of patients in the β-blocker group.
The researchers concluded that “lower targets for blood pressure control can be achieved in most hypertensive patients with CAD [coronary artery disease] using a multidrug strategy that includes administration of angiotensin-converting enzyme [ACE] inhibitors to patients with heart failure, diabetes, or renal impairment. The clinical equivalence of the CAS [calcium antagonist] and NCAS [β-blocker] groups in prevention of death, myocardial infarction or stroke supports the use of either strategy in clinically stable patients with CAD who require blood pressure control.”
In an editorial on the study, Michael H. Alderman, MD, of Albert Einstein College of Medicine in Bronx, NY, criticizes the design of INVEST because it allowed manipulation of therapy in a way that reduced the differences between the 2 treatment stratagems (JAMA. 2003;290:2859–2860OpenUrlCrossRefPubMed). Most patients took an ACE inhibitor and a diuretic. He said that diuretics and ACE inhibitors remain the first line of defense in reducing blood pressure.
Gene Mutation Causes Rare Coronary Artery Disease
The deletion of 7 amino acids in transcription factor MEF2A causes an autosomal dominant form of coronary artery disease/myocardial infarction called ad CAD1, said researchers from the Cleveland Clinic Foundation in a report that appeared in the November 28, 2003, issue of the journal Science (Science. 2003;302:1578–1581OpenUrl).
The disease was discovered in genetic analysis of the pedigree of 21 members of an Iowa family, generations of which had suffered abnormally frequent incidents of myocardial infarction, as well as coronary artery disease. Every family member who had had a heart attack also had a risk factor for coronary artery disease. Despite this, by scanning the genomes of all participating family members, researchers in the laboratory of Qing Wang, PhD, found that an area of interest occurred on chromosome 15, in a region that contained an estimated 93 genes. It was in that area that Dr Wang and his colleagues found the large deletion that marked the mutation of the MEF2A gene.
“I couldn’t quite believe it at first. But once we verified this, the real work began to try to determine exactly why the mutation mattered,” said Dr Wang. Because MEF2A governs the production of a regulatory protein controlling gene expression of hundreds of other genes in the endothelium, Dr Wang and his colleagues believe the mutation may weaken that barrier between blood vessels and elements of the blood. Weakened, the epithelium can become prey to monocytes and macrophages, opening the door to the formation of atherosclerotic plaques.
“Finding the gene opens a new avenue through which scientists can track the pathway that leads to coronary heart disease and heart attack,” Dr Wang said in a released statement. “Genes in that pathway then can be used as targets to design new drugs intended to prevent or treat heart disease.”