Repeating Intracoronary Radiation an Option for In-Stent Restenosis, Even After Initial Failure
Using intracoronary radiation as a repeat treatment when it is has previously failed to treat in-stent restenosis successfully is a viable option, said researchers from Washington Hospital Center in Washington, DC, in a report in this week’s issue of Circulation (Circulation. 2003;108:654–656OpenUrl).
In the report led by Ron Waksman, MD, physicians followed up 51 consecutive patients for whom previous radiation treatment had failed to open stenotic areas within the stent. The patients were found to have angina. Angiography showed that they had in-stent restenosis. They were treated with percutaneous coronary intervention and radiation to the segment of the artery that had been treated with radiation previously.
The researchers treated 25 patients with gamma radiation at a dose of 15 Gy. Twenty-six patients received beta radiation with doses of between 18.3 and 23 Gy. Mean cumulative doses were 39.5 Gy (±11.9 Gy).
The outcomes of the patients were compared to those of a cohort of 299 patients for whom radiation did not work in treating in-stent stenosis and who received conventional percutaneous coronary intervention alone. At 9 months, the group that had received the repeat radiation treatment had a lower rate of repeat procedures to the coronary artery that was originally treated (23.5% in the irradiated group versus 54.6% in the percutaneous intervention alone group). The rate of major adverse heart events was also lower in the radiation treatment group (29.4% versus 61.3%). The group that had received repeat radiation had no angiographic evidence of adverse events caused by the radiation, and they had had no clinical problems related to the treatment.
The researchers concluded that repeat radiation is a viable treatment in these patients, although they note that the procedure is a dilemma “involving safety and efficacy issues.”
They also noted that “the introduction of drug-eluting stents has decreased but not eliminated ISR [in-stent restenosis]. While IRT (intracoronary radiation therapy) is currently used as the standard of care for ISR, treatment with DES [drug-eluting stent] for the same indication has yet to be proven as an effective alternative. Meanwhile, reports of late thrombosis for patients who failed IRT and were treated with DES are worrisome and warrant further caution before recommendation for patients who failed IRT.”
Low-Fat Diet From Infancy Reduces Serum Cholesterol and LDL Cholesterol Levels in 7-Year-Old Boys
Finnish researchers found that a diet low in saturated fat lowered serum cholesterol and LDL cholesterol levels in healthy 7-year-olds and reduced LDL particle size in boys. They reported the results of their ongoing study in this week’s issue of the journal Circulation (Circulation. 2003;108:672–677OpenUrl).
This study, led by Tuuli Kaitosaari, MD, of the Research Centre of Applied and Preventive Cardiovascular Medicine at the University of Turku in Finland, also involved researchers from the Research and Development Unit of Social Insurance Institution, the Department of Clinical Chemistry at the same university, and the Hospital for Children and Adolescents. Dietary intervention began when 1062 healthy 7-month-old infants were randomized to the intervention group and the control group. The intervention families received 2 individualized counseling sessions each year. The levels of serum lipids were measured each year.
At age 7 years, the boys in the intervention group had serum cholesterol values that were 0.29 to 0.39 mmol/L lower than those of the control boys. The values did not differ significantly in girls. Similarly, the mean LDL particle size was smaller in intervention boys than in the boys in the control group.
They said they were not sure why the intervention had no effect on girls but hypothesized that it could be caused by gender differences in body composition, serum sex hormone concentrations, and exercise habits.
Another Hit Against Hormone Replacement Therapy
In the latest segment of results from the Women’s Health Initiative, researchers from the federally funded group led by JoAnn E. Manson, MD, of Harvard Medical School and The Brigham and Women’s Hospital, discussed in the August 7, 2003, issue of The New England Journal of Medicine (N Engl J Med. 2003;349:523–534) the results of their study, which demonstrated that not only does the combination of estrogen plus progestin not provide protection against cardiac events, it may even increase the risk of coronary heart disease among healthy, postmenopausal women, especially in the year it is begun.
In the estrogen–progestin arm of the study, 16 608 postmenopausal women ages 50 to 79 years were randomly assigned to receive either 0.624 mg of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate daily or a placebo. After 5.2 years, the project’s data and safety monitoring board advised terminating this arm of the study because the risks exceeded the benefits. The combined hormone replacement therapy was associated with a hazard ratio of coronary heart disease of 1.24. The highest risk was at 1 year, when the hazard ratio was 1.81.
In a second study in the same issue (N Engl J Med. 2003;349:535–545), researchers in the Women’s Estrogen–Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial (WELLHART) reported that 17β-estradiol, given alone or in combination with medroxyprogesterone acetate, did not significantly affect the progression of atherosclerosis in older postmenopausal women who had been diagnosed with coronary artery disease.
The researchers, led by Howard N. Hodis, MD, of the University of Southern California, randomized 226 postmenopausal women aged on average 63.5 years who had at least one coronary artery lesion to usual care, estrogen therapy (17β-estradiol), or 17β-estradiol plus sequentially administered medroxyprogesterone acetate. All patients reduced their low-density lipoprotein cholesterol levels to less than 130 mg per deciliter. After monitoring the patients for a median of 3.3 years, the researchers found that mean change in the percent restenosis in the 169 patients who had a pair of matched angiograms was 1.89 percentage points in the control group, 2.18 in the estrogen-alone group, and 1.24 in the estrogen–progestin group. These results led to the conclusion that the hormone treatment had no effect on the progression of atherosclerosis.
In an accompanying editorial, David M. Herrington, MD, MHS, and Timothy D. Howard, PhD, of the Departments of Internal Medicine/Cardiology and Pediatrics at Wake Forest University School of Medicine in Winston-Salem, NC, noted that the current hormone replacement therapy dilemma provides physicians and patients with many lessons (N Engl J Med. 2003;349:519–521OpenUrlCrossRefPubMed).
“These lessons apply not only to our understanding of estrogen biology and cardiovascular therapeutics, but also to the means by which we should judge any medical intervention. The Roman dramatist Terence once noted that ‘One easily believes what one earnestly hopes for’—a fact that may help to explain the degree of passion felt by so many concerning the putative cardiovascular benefits of estrogen.”
Given this, it was not surprising that the initial results of clinical trials that failed to show a heart benefit were roundly criticized by many physicians. The authors wrote, “The lesson is that belief, no matter how sincerely held, is no substitute for proof in the form of adequately designed randomized clinical trials when it comes to medical interventions, especially long-term interventions that are being contemplated for widespread use in order to prevent disease.”
The second lesson is one of surrogate end points, they wrote. “The story of hormone therapy reminds us that surrogate end points can also be quite misleading. For example, hormone therapy unambiguously lowered the level of low-density lipoprotein (LDL) cholesterol and increased the level of high-density lipoprotein (HDL) cholesterol in both the WHI and the trial by Hodis et al, yet it had no beneficial effect on the development or progression of coronary disease.”
In an editorial perspective (N Engl J Med. 2003;349:521–522), John Bailar, MD, PhD, of the University of Chicago, noted that two years previously the New England Journal had published two studies dealing with the relationship between postmenopausal hormone-replacement therapy and cardiovascular diseases (N Engl J Med. 1985;313:1038–1043; N Engl J Med. 1985;313:1044–1049OpenUrlCrossRefPubMed). One found that women who used hormones had half the risk of those who didn’t. The other found that the risk of hormone users was twice that of those who didn’t.
He noted: “The state of the art has advanced in the 18 years since 1985, the reporting of clinical trial results has also improved, and our understanding of the relevant biology is far ahead of where it was. Perhaps most important, both of the current trials assigned subjects to treatments at random, whereas the earlier studies were observational. Thus, I accept the present results as probably correct and certainly the best basis we now have for making clinical decisions.. . .I believe that the current results are likely to hold up, but it will be interesting to see what we think we know in another 18 years.”