Day: 03/23/2011

Coronary CT angiography: a paradigm shift in the evaluation of coronary artery disease?

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Advances in multidetector CT technology over the past decade, including improvements in spatial and temporal resolution and the introduction of electrocardiographic gating, has made non-invasive visualisation of the coronary arteries feasible. The potential to obtain information non-invasively that is comparable to that provided by invasive coronary angiography has been a major driving force behind the rapid growth and dissemination of coronary CT angiography (CCTA).1 Non-invasive coronary imaging requires a CT system capable of acquiring motion-free, high-resolution images covering the entire heart in a single breath hold. Current-generation 64-detector row systems and more recently introduced CT scanners with 128-, 256- and 320-detector rows fulfil these requirements.1 Most UK radiology departments are in possession of such technology, and many can now provide, or are in the process of setting up, a cardiac CT service.2 In this issue of Postgraduate Medical Journal, Yerramasu et al provide a succinct review of the current status of CCTA technology and its application to the investigation of patients with coronary artery disease (CAD).3

Currently the main strength of CCTA is its extremely high negative predictive value whereby a normal study virtually excludes the possibility of significant CAD with a high degree of confidence (98–99%).4 5 This has been validated in several large clinical trials and has led to the introduction of CCTA into recently published UK guidelines for management of stable chest pain syndromes whereby CCTA is now advocated as a first line test in patients with a low pretest probability of CAD.6 It remains to be seen how widely these guidelines will be implemented and what impact they will have on patient management. Many CT departments across the UK already struggle to meet increasing demands from emergency departments and acute admission units as well as pressure to achieve cancer targets and reasonable waiting times for elective outpatient work. The requirement for on-demand CCTA, linked for example to a rapid-access chest pain clinic, may not be practical or achievable in many hospitals. Several preliminary economic studies have looked at the use of CCTA in the diagnostic evaluation of acute chest pain in the emergency department and suggest that a diagnostic strategy using CCTA may significantly decrease both length of stay and cost, particularly in lower risk patients.7–9 Such an approach has the potential to force a paradigm shift in acute chest pain evaluation, but outcome studies with larger cohorts and longer follow-up times are needed, and again the implementation of such a strategy in the UK would require major resource investment.1

As with any diagnostic test, CCTA has certain technical and patient-related limitations with which users should be familiar, as proper patient selection is important to maximise its diagnostic accuracy. Interpretation is intimately linked to image quality which is dependent on a steady heart rhythm as well as patient compliance with breathing instructions and a number of other factors including body mass index and scan protocol optimisation. Interpretation is challenging in patients with a high volume of calcified atherosclerotic plaque because of a tendency to overestimate disease severity due to calcium-related (blooming) artefact, particularly in smaller and more distal coronary segments.1 CCTA, as with any purely anatomical test (including invasive coronary angiography), is unable to predict the functional impact of a coronary stenosis—that is, the depiction of a stenosis does not imply myocardial ischaemia. Indeed, an analysis of studies comparing results of CCTA with nuclear myocardial perfusion scintigraphy found that only around half of anatomically significant (>50%) lesions had corresponding perfusion defects suggestive of ischaemia.10 A combination of non-invasive anatomical and functional imaging may therefore be the best strategy for identifying patients most likely to benefit from medical therapy (coronary atherosclerosis without ischaemia) or who may be candidates for coronary revascularisation (coronary atherosclerosis with ischaemia).11This further emphasises that the ability of CCTA to provide incremental diagnostic information that alters patient management is heavily dependent on pretest probability of disease, and clinicians should refer to recently published international referral criteria in this respect.

The field of CCTA is advancing at a tremendous rate, with technological evolution at times outpacing research evaluating its incremental benefits, and as a result many important questions remain as yet unanswered. For example, what is the optimal management strategy for incidentally detected non-haemodynamically significant coronary atherosclerotic plaques, and can CCTA provide any insight into prediction of subsequent plaque rupture and acute myocardial infarction?12 In the future, the ability of CCTA to provide such information not currently available from invasive angiography may forge a paradigm shift in how patients with atherosclerotic cardiovascular disease are classified and managed.1 CCTA, although still in its infancy, is already an incredibly powerful tool that is set to have a major impact on the management of CAD for years to come; clinicians must embrace this technology and understand its current limitations for facilitating optimal patient management.

Source: postgraduate journal of medicine

Topotecan for Relapsed Small Cell Lung Cancer: A Systematic Review and Economic Evaluation

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This retrospective analysis looked at prospective studies involving topotecan in patients with relapsed small-cell lung cancer, including cost of treatment and associated quality-of life-years. Obvious…

Background: Topotecan is a relatively new drug for use as a second-line treatment in patients with relapsed small cell lung cancer (SCLC). We performed a systematic review and economic evaluation of topotecan, and consider it here in relation to the NICE end of life criteria.

Methods: Seventeen bibliographic databases (including Cochrane library, Medline and Embase) were searched from 1990 to February 2009, and experts and manufacturers were consulted, to identify relevant randomised controlled trials (RCTs) which were selected according to prospectively defined criteria. An economic evaluation was undertaken to assess cost effectiveness compared with best supportive care (BSC) in the UK.

Results: Five RCTs were included. The clinical evidence indicates a statistically significant benefit of oral topotecan plus BSC compared to BSC alone for overall survival. Intravenous topotecan was similar in efficacy to both oral topotecan and CAV (cyclophosphamide, doxorubicin and vincristine). In the survival model, oral topotecan plus BSC was associated with an average gain in life expectancy of approximately 4 months, resulting in a gain of 0.183 quality-adjusted life years (QALYs). At an incremental cost of approximately £6200 the incremental cost effectiveness ratio (ICER) is £33,851 per QALY gained.

Conclusions: Compared with BSC alone, oral topotecan for patients with relapsed SCLC was associated with improved health outcomes but at increased cost. The ICER is at the upper extreme of the range conventionally regarded as cost effective from an NHS decision making perspective. However, this treatment may fall under supplementary guidance for life extending, end of life treatments.

source: oncoSTAT

Miniaturized Device Puts Nanotechnology to Work in Diagnosing Cancer

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An experimental diagnostic device could be a valuable addition to a pathologist’s tool kit for diagnosing cancer, new research suggests. The miniaturized nuclear magnetic resonance, or micro-NMR, device can diagnose cancer within an hour, using patient samples of just a few thousand cells that are collected using a fine needle and a syringe.

Initial clinical studies by researchers at Massachusetts General Hospital (MGH) indicate that the micro-NMR system, which can quantify multiple protein markers in cells from a single patient sample, may be more accurate than standard diagnostic techniques.

An illustration of cancer cells (and red and white blood cells) passing through one of the coils of a miniaturized nuclear magnetic resonance device used to identify the cancer’s protein signature. (Image courtesy of H. Lee and R. Weissleder, Massachusetts General Hospital) A miniaturized nuclear magnetic resonance (NMR) device can detect cancer cells (dark brown) in a small sample of cells from a patient. The coils generate magnetic fields that excite magnetic nanoparticles attached to antibody-protein complexes, resulting in NMR signals that can be used to identify a cancer protein signature. (Image courtesy of H. Lee and R. Weissleder, Massachusetts General Hospital)

Conventional pathology, which is the current gold standard for diagnosing many cancers, is far from perfect. It takes several days to yield results, may require surgery to provide enough tissue, is technically challenging, and is subject to human interpretation. A biopsy for conventional pathology may be done either with open surgery, which yields samples containing billions of cells, or with a wide or fine needle. A pathologist processes and stains the tissue sample and examines it under a microscope. If enough tissue is available, the pathologist may use immunohistochemistry to visualize specific cancer markers in cross-sections of tissue.

The micro-NMR device uses principles similar to those of magnetic resonance imaging (MRI) to detect magnetic nanoparticles attached to antibodies, which flag protein biomarkers known to be associated with some cancers in patient samples. A physician can operate the portable device from the patient’s bedside with a smart-phone application that displays results on the phone’s screen.

Simplicity, Speed, and Sensitivity

The reactions for coupling the magnetic nanoparticle-antibody complexes to specific target proteins are performed at room temperature, and sample processing is simple and quick, the researchers said. In addition to eliminating waiting time, the rapid processing is an advantage because experiments showed that protein markers in patient samples degrade quickly.

Micro-NMR probably won’t replace conventional pathology and histology completely, but “it would be a good mechanism to triage patients before they undergo more invasive procedures,” said Dr. Cesar Castro, an oncologist and investigator at MGH. Dr. Castro co-led a recent clinical study that was the first to test the micro-NMR and nanoparticle technologies in patient samples.

The entire micro-NMR system costs about $200 and is roughly the size of a cube-shaped box of facial tissue. Developed by Drs. Hakho Lee and Ralph Weissleder at the Center for Systems Biology at MGH, the system is highly sensitive thanks to miniaturization of the device and the chemistry used to bind magnetic nanoparticles to their targets. The device can measure levels of individual tumor markers in a 1-microliter sample containing about 200 cells and—unlike technologies that rely on optical properties—works in nonpurified samples.

Advantages in the Clinic

If validated in larger clinical trials, the micro-NMR system could eventually be used not only to diagnose cancer but also to identify potential patient candidates for targeted therapies and to monitor the response to therapy, Dr. Castro said. When used for diagnosis, this approach could potentially reduce the time that patients are in limbo while waiting for results and provide more information to clinicians, while steering patients away from more invasive procedures and avoiding repeat biopsies, he noted.

“A key advantage of this technique is the ability to look at multiple markers at the same time,” said Dr. Piotr Grodzinski, director of NCI’s Office of Cancer Nanotechnology Research, which helped fund the work. This so-called multiplexing capability is important, he explained, “because cancer is heterogeneous and is not characterized by a single biomarker.”

Components of a diagnostic micro-NMR system, including a mini magnet; chip-sized, microliter-volume sensors; and a smart phone interface (Image courtesy of C. Min, D. Issadore, R. Weissleder and H. Lee) The diagnostic micro-NMR system includes a mini magnet (left); chip-sized, microliter-volume sensors (center); and a user-friendly smart phone interface (right). (Image courtesy of C. Min, D. Issadore, R. Weissleder and H. Lee)

The MGH researchers used micro-NMR to measure levels of nine established cancer-related markers in cells from fine-needle biopsies of deeper lesions, done with guidance from a CT scan or ultrasound. Using a four-protein signature, they were able to diagnose a range of epithelial cancers, including lung, breast, pancreatic, and gastrointestinal, with 96 percent accuracy.

In cell samples from 50 patients who had been referred for clinical biopsies, the four-marker panel correctly diagnosed 48 cases: 44 of 44 malignancies and 4 of 6 benign lesions. In contrast, the accuracy of conventional cytology and histology performed on specimens from the same patients was 74 percent and 84 percent, respectively. The diagnoses were confirmed independently using a combination of clinical, imaging, and pathology data.

The next step for Dr. Castro and his colleagues is to refine the system to identify specific cancers. “Our first endeavor will be customizing the assay with ovarian cancer-specific markers, and we’re enrolling patients treated at the MGH Gillette Center for Gynecologic Oncology for that study,” Dr. Castro said. The researchers hope eventually to apply the technology to blood and other fluids, such as ascites, in which tumor cells are scarce, and they are exploring other cancer applications as well.

Potential for Personalized Medicine

Many cancer researchers and companies recognize the need for diagnostic tools that could be used in tandem with targeted therapies, and in a range of clinical studies needed to develop such therapies.

“To fully achieve the potential of personalized cancer therapy will require noninvasive methods for analyzing genes and proteins in a patient’s tumor or serum, which can be used in real time to determine the best treatment or treatment combination,” said Dr. Roy Herbst, who recently assumed the role of chief of medical oncology at Yale Medical Center. “I think this [micro-NMR system] is clearly an example of a step in the right direction.”

“With this machine, we have the strong potential to start asking more refined and elegant questions in clinical research,” Dr. Castro said. Because the micro-NMR technology is sensitive and minimally invasive, he explained, it could be used in clinical trials that require repeated tumor sampling at various time points. For example, researchers could use micro-NMR to identify and validate new tumor markers for clinical use or to look at how markers change during the course of therapy.

“We consider this to be a platform technology because the markers are very interchangeable,” Dr. Castro explained. “So, as the science evolves, as we get more information from the clinic and from laboratories elsewhere, we can react to that.”

source: NCI bulletin

Incidence Rate of Second Cancer in the Opposite Breast Has Declined in U.S.

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Among women who survive breast cancer, the most frequent new cancer occurs in the opposite, or contralateral, breast. Since 1985, a new study reports, the incidence rate of contralateral breast cancer has declined steadily—at a pace of more than 3 percent per year. Although the causes of this trend are not known, the decline occurred as drugs such as tamoxifen were coming into widespread use to help prevent a recurrence of the disease, researchers reported online in the Journal of Clinical Oncology on March 14.

To assess the incidence rate of contralateral breast cancer over time, Dr. Amy Berrington de González of NCI’s Division of Cancer Epidemiology and Genetics (DCEG) and her colleagues analyzed statistics from the SEER database for the years 1975 to 2006.

The downward trend they observed was driven by declining rates of contralateral breast cancer among women whose first breast cancer tested positive for the estrogen receptor (ER). No clear decrease was seen among women with ER-negative tumors. Although the details of hormone treatments were not available in SEER, the annual declines of more than 3 percent after ER-positive first cancers “suggest an important role for the widespread usage of adjuvant therapies, especially hormone treatments,” the study authors noted.

“We know from randomized trials that drugs like tamoxifen significantly reduce the risk of a contralateral breast cancer, by about 40 percent,” said Dr. Berrington de González. The combination of the trial results, the timing of the decline, and the restriction to cancers following ER-positive first breast cancers all point to adjuvant hormonal therapy as a key factor in the decline, she added.

Tamoxifen was widely adopted in the United States after the results of the Nolvadex Adjuvant Trial were published in 1983. In addition to adjuvant hormone therapies, other factors such as the increased use of chemotherapy may also have contributed to the decline, the study noted. “Newer hormonal therapies like aromatase inhibitors may be even more effective than tamoxifen at reducing contralateral breast cancer rates, and so we would hope to see further reductions in the future,” said Dr. Berrington de González.

Although the decline represents “a notable success,” the study authors cautioned that overall rates of contralateral breast cancer remain high, especially among women whose first breast cancer is ER-negative. “We still need new strategies for reducing risks after an ER-negative cancer, because rates can be as high as 1 percent per year for these women,” said Dr. Berrington de González.

source: NCI bulletin

Thyroid Cancer Risk Persists in People Exposed to I-131 Radiation as Children

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People who were exposed to radioactive iodine (I-131) as children or adolescents after the 1986 Chernobyl nuclear disaster have a long-term increased risk of developing radiation-related thyroid cancer. In a study of more than 12,000 people in three Ukrainian states near the Chernobyl site, researchers found that the risk of radiation-related thyroid cancer doubled for every gray (Gy) of exposure to the thyroid. (A gray is an international measurement used for radiation dose.) This risk did not decrease over 9 years of follow-up during the study.

The findings were published March 14 in Environmental Health Perspectives.

Researchers led by Dr. Alina Brenner of NCI’s Division of Cancer Epidemiology and Genetics, in collaboration with Ukrainian scientists, prospectively studied 12,514 people who were younger than 18 years of age at the time of the accident and were exposed to a wide range of I-131 doses. All participants had direct measurements of thyroid radioactivity taken within 2 months of the accident. Additional data on I-131 exposure included information on diet (the greatest source of exposure was from consumption of contaminated milk) and lifestyle around the time of the accident.

Between the start of the study in 1998 and 2007, all participants underwent screening examinations every 2 years, regardless of their dose. Individuals diagnosed with thyroid cancer during the first examination were excluded from this analysis.

Sixty-five cases of thyroid cancer were discovered during follow-up. Radiation-related risk of thyroid cancer increased with increasing I-131 dose and was greatest for those individuals who were younger at the time of exposure. Risk appeared similar for men and women.

“Our results suggest that thyroid cancers attributable to I-131 exposure continue to occur two decades after exposure,” concluded the authors. In addition, they wrote, the risk per Gy of exposure does not appear to diminish with time, at least not in the amount of time that this cohort has been followed. Since radiation-related cancer risks are known to persist for many decades, the participants will need to be followed for a longer period of time to determine if an eventual decline in risk occurs.

source : NCI bulletin

Smoking Cessation Before Surgery Doesn’t Promote Postoperative Complications

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In fact, evidence suggests smoking cessation lowers risk for complications.

Smokers are at elevated risk for postoperative complications (e.g., delayed wound healing, pulmonary complications, mortality) compared with nonsmokers. However, whether smoking cessation lowers risk for postoperative complications is unclear. Indeed, many clinicians believe that stopping smoking within a few weeks before surgery raises risk for postoperative pulmonary complications (by removing the cough-promoting effect of smoking). Two recent systematic reviews and meta-analyses clarify the effects of smoking cessation on risk for postoperative complications.

One review included six randomized trials (about 600 participants) in which researchers evaluated smoking cessation interventions (e.g., counseling, nicotine replacement, bupropion) and 15 observational studies (about 13,000 participants) in which current versus past smokers were compared. The studies involved surgical procedures at various body sites. In a meta-analysis of randomized trial data, smoking cessation resulted in a 41% relative reduction in total postoperative complications. Each week of smoking cessation significantly increased treatment effect, and trials of 4 weeks’ duration had greater effect than shorter trials. The observational study data revealed similar findings as well as lower risk for specific postoperative complications (wound healing and pulmonary complications).

The other review included nine studies (about 900 participants) in which researchers compared postoperative complications in patients who stopped smoking 8 weeks before surgery (recent quitters) with patients who continued to smoke. Stopping smoking 8 weeks before surgery was not associated with more or fewer total and pulmonary postoperative complications.

Comment: The results of these studies confirm that smoking cessation before surgery does not raise risk for postoperative complications. Furthermore, stopping smoking before surgery might lower risk for postoperative complications, and the benefit probably grows with longer duration of smoking cessation. Smokers should be encouraged to stop smoking — and be offered appropriate treatment — before surgery.

Source:Journal Watch General Medicine

 

Can Ibuprofen Reduce Parkinson Disease Risk?

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Data from two large questionnaire studies suggest a link, but whether it is causal remains unknown.

Increasing evidence suggests that inflammation may play a role in neurodegenerative conditions like Parkinson disease (PD) and that reducing inflammation with nonsteroidal anti-inflammatory drugs (NSAIDs) might reduce this risk. In this prospective study, researchers assessed the PD risk associated specifically with ibuprofen use, compared with use of other NSAIDs, acetaminophen, or aspirin. A total of 136,197 participants from two longitudinal cohorts (the Health Professionals Follow-Up Study and the Nurses’ Health Study) who were free of PD at baseline completed questionnaires on use of these drugs every 2 years.

During 6 years of follow-up, 291 participants developed PD. Individuals who consumed ibuprofen, but not other NSAIDs, aspirin, or acetaminophen, had a significantly (40%) lower risk for PD. The dose-response trend was significant. The association remained significant in analyses adjusted for potential confounding factors (age, smoking, body-mass index, ibuprofen use within 2 years before PD diagnosis, and intake of lactose, alcohol, and caffeine) and after excluding individuals with histories of gout. The prospective nature of the study and the high participation rates minimized the recall and selection bias that are often seen in cohort studies. In a meta-analysis of all published prospective studies assessing ibuprofen use specifically, the PD risk reduction (27%) was still significant.

Comment: These findings suggest that ibuprofen, but not other NSAIDs, might reduce PD risk. Why the differential effect? The authors cite evidence that not all NSAIDs have similar mechanisms of action and that ibuprofen uniquely binds to a specific ligand that acts as an inhibitor of apoptosis and oxidative damage. As editorialists note, this type of association doesn’t prove causation but adds to the growing body of evidence that specific inflammatory factors likely play a role in PD. Clinical trials are now needed to determine if ibuprofen can slow disease progression in patients with PD, but care is needed, as long-term daily use of ibuprofen is not without risks. Given the very low risk for PD in the general population, the risks of long-term ibuprofen couldn’t be justified for primary prevention.

Source :Journal Watch Neurology

 

Allogeneic Stem-Cell Transplantation for Relapsed Lymphoma

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Allogeneic Stem-Cell Transplantation for Relapsed Lymphoma

Patients with relapsed diffuse large B-cell lymphoma after autologous STC benefited from allogeneic STC.

Patients with diffuse large B-cell lymphoma (DLBCL) who relapse after salvage chemotherapy and autologous stem-cell transplantation (SCT) experience poor outcomes and, typically, short survival. Although allogeneic transplantation is a curative option for these patients, long-term data are limited.

Now, investigators have reviewed records from a European transplantation registry to assess outcomes of adult patients with relapsed DLBCL after prior autologous SCT. A total of 101 such patients underwent allogeneic SCT from 1997 to 2006. Of these, 37 (median age, 43) underwent myeloablative conditioning, and 64 (median age, 54) underwent reduced-intensity conditioning (RIC). Matched sibling donors were used for 72 patients; matched unrelated donors were used for 29 patients.

The progression-free survival (PFS) rate at 3 years for the entire cohort was 41.7%, and the overall survival (OS) rate was 53.8%. Nonrelapse mortality at 3 years was higher among patients who underwent myeloablative conditioning versus RIC (41% vs. 20%; P=0.05). Relapse rates were higher for patients who underwent RIC, for those who relapsed within the first year of autologous SCT, and for those who were chemotherapy resistant prior to allogeneic SCT. PFS and OS were unaffected by donor source.

Comment: Even though allogeneic SCT provides a potentially curative option for patients with relapsed DLBCL, clear challenges remain to lower the high rates of nonrelapse mortality as well as the high rates of transplant-related morbidity, given that long-term survivors often experience ongoing complications of graft-versus-host disease. Important unmet needs also exist for patients who experience early relapse after autologous SCT and for those with chemotherapy-refractory disease. Disappointingly, no clear graft-versus-lymphoma effect could be demonstrated in this study, except in patients with DLBCL arising from transformed follicular lymphoma. Ultimately, improved patient selection for allogeneic SCT coupled with more-effective second- and third-line treatment regimens is needed to continue the recent advances in curing DLBCL.

Source:Journal Watch Oncology and Hematology

 

indacaterol:for the once-daily long-term maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema

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Novartis announced today that the US Food and Drug Administration (FDA) has extended the regulatory review period for QAB149 (indacaterol) for the once-daily long-term maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The FDA asked for a three-month extension in order to complete its review of the new drug application (NDA) for QAB149 by July 2011. In its notification, the FDA said it needed more time to examine the data submitted by Novartis in support of the application. The agency did not request additional data.

“This three-month extension reflects discussion at the advisory committee based on the comprehensive clinical program resulting in a large amount of data to be reviewed,” said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. “COPD is a life-threatening lung disease and a major cause of serious long-term disability[1]. We remain committed to bringing new therapies to patients who suffer from this condition.”

Last month the FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) endorsed the safety of both the 75 and 150 mcg doses and voted in favor of approving QAB149 75 mcg in the US, after Novartis presented data showing that QAB149 significantly improved lung function compared to placebo, with improvements seen five minutes after the first dose and lasting for 24 hours[2].

The efficacy of Arcapta Neohaler at 75 and 150 mcg was demonstrated in an extensive clinical trial program in a total of 1,282 COPD patients in five key Phase III trials lasting 12-26 weeks[2].

QAB149 is already approved at 150 and 300 mcg once-daily doses in more than 50 countries worldwide under the brand-name Onbrez® Breezhaler® for the maintenance bronchodilator treatment of airflow obstruction in COPD patients[3]. Incremental efficacy benefits have been observed with indacaterol in escalating doses from 75 mcg up to 300 mcg, with higher doses showing increasing benefit for patients

Source: Novartis release

 

Effect on Clinical Outcome of Lowering Diagnostic Threshold of a Troponin Assay

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Lowering the diagnostic threshold for acute coronary syndrome from a troponin I value of 0.20 to 0.05 ng/mL results in better clinical outcomes, according to a JAMA study.

Researchers examined outcomes in two groups of 1000 patients with suspected ACS during two 6-month periods. (The study was undertaken while their institution started using a more sensitive troponin I assay.) In the first period, troponin results were measured, but only values above the standard diagnostic threshold for ACS — 0.20 ng/mL — were reported. In the second period, the reportable threshold was lowered to 0.05 ng/mL.

After 1 year of follow-up, second-period patients meeting the new 0.05 threshold were more likely than first-period (non-reportable) patients with similar troponin levels to be referred to a cardiologist, receive dual antiplatelet therapy, and undergo coronary angiography. In addition, the rate of death or recurrent myocardial infarction was lower among second-period patients (21% vs. 39%).

Source:JAMA