March 16th, 2011
CABG vs. PCI for Angina Relief: Lessons from SYNTAX
David Cohen, MD MSc
CardioExchange welcomes David J. Cohen, Director of Cardiovascular Research at St. Luke’s Mid America Heart Institute in Kansas City, Missouri, to discuss the latest analysis from the SYNTAX randomized trial. The study has just been published in the New England Journal of Medicine, and Dr. Cohen is the lead author. Questions to Dr. Cohen come from CardioExchange’s Dr. Richard A. Lange and Dr. L. David Hillis.
In SYNTAX, 1800 patients with 3-vessel or left-main coronary artery disease (CAD) were randomized to undergo either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) with a paclitaxel-eluting stent. The score on the angina-frequency subscale of the Seattle Angina Questionnaire (SAQ), the primary endpoint, increased significantly in both groups — but significantly more so in the CABG group. At both 6 and 12 months, the mean SAQ advantage of CABG over PCI was 1.7 points. Rates of freedom from angina were similar between the groups through 6 months, but a significant advantage in the CABG group emerged at 12 months (76.3%, vs. 71.6% with PCI). A maker of paclitaxel-eluting stents funded the trial.
Q: Your team characterized the advantage of CABG over drug-eluting stent PCI (1.7 points on the SAQ) as a “small” benefit in angina reduction. Given that the SAQ is not used in clinical practice, what should we consider a clinically meaningful benefit on that measure?
A: For an individual, a difference of 8 to 10 points on the SAQ angina-frequency score is the smallest amount that would be noticeable. It is difficult to define a “clinically meaningful” benefit for a population of patients. Nevertheless, we can fairly surmise that a mean difference of 1.7 points across the entire trial population suggests a clinically important angina benefit of CABG in only a small fraction of the participants.
Q: The PCI group had a significantly higher rate of repeat revascularization (13.5%, vs. 5.9% in the CABG group) and more often used antianginal medications. Might these differences have mitigated the benefits of CABG?
A: SYNTAX was a strategy trial, so it incorporated all aspects of the treatment strategy, such as an expected higher rate of repeat revascularization procedures to treat restenosis in the PCI group. It is likely that these additional procedures would have bolstered the overall effect of PCI. Similarly, increased use of certain antianginal medications in the PCI group might have mitigated the benefits of CABG. However, given that these are intrinsic components of the PCI strategy, it is not possible to isolate the magnitude of the individual effects with certainty.
Q: Among patients with a high SYNTAX score (a score that represented more-severe angiographically determined CAD), the PCI group had a higher rate of major adverse cardiac or cerebrovascular events than the CABG group. But the SYNTAX score did not predict the effect of treatment (CABG vs. PCI) on symptom relief. Did that surprise you?
A: It did, initially. However, at 1-year follow-up, the main effect of the SYNTAX score in the PCI group was an increased rate of repeat revascularization. Given that most of these events were additional PCI procedures, which are associated with rapid symptom relief and minimal morbidity, it is likely that any effect of restenosis in the PCI group was transient. Thus, by 12 months, we observed only a small difference in angina between the CABG- and PCI-treated patients.
Q: CABG is recommended over PCI in patients with high SYNTAX scores because of a higher rate of major adverse cardiac or cerebrovascular events with PCI. Your study showed that among patients with daily or weekly angina at baseline, the percentage of patients who were free of angina also was greater in the CABG group than in the PCI group at both 6 months (65% vs. 57%) and 12 months (70% vs. 60%). Should we therefore recommend CABG over PCI in patients with daily or weekly angina?
A: I believe that this is a reasonable interpretation of our data. However, even after being provided with this information, many patients may choose an initial PCI strategy to avoid the greater morbidity and more-prolonged recovery after CABG. In our study, the PCI group showed substantial benefits on a variety of measures of health status and quality of life at 1 month, and some patients may value those more-certain (but short-lived) benefits of PCI over the greater long-term angina relief afforded by CABG.
Q: Previous research has shown that patients (and physicians) have an inflated opinion of the benefits of coronary revascularization. How do we integrate the results of your study into clinical practice?
A: Obviously, as a trial that directly compares two different forms of coronary revascularization with each other, SYNTAX does not elucidate the benefits of revascularization per se. Nonetheless, I believe that our results should reassure most patients with 3-vessel or left-main CAD that there are not major differences between a drug-eluting stent PCI strategy and a CABG strategy in terms of overall health status or symptom relief, beyond the initial 1- to 2-month recovery period. In clinical practice, this information (along with relevant data on expected longer-term clinical outcomes) should be explained to help each patient reach a decision that is appropriate for his or her lifestyle, values, and preferences.
March 15th, 2011
Quitting Smoking Shortly Before Surgery: Is It Safe?
Larry Husten, PHD
Quitting smoking soon before surgery is safe, according to a new meta-analysis published in Archives of Internal Medicine. In response to fears that people who stopped smoking within 8 weeks prior to surgery may have had worse outcomes, Katie Myers and colleagues analyzed data from 9 studies and found no association with postoperative complications.
The authors concluded that “patients should be advised to stop smoking as early as possible, but there is no evidence to suggest that health professionals should not be advising smokers to quit at any time prior to surgery.”
But in an accompanying comment, Clara Chow and PJ Devereaux write that although the meta-analysis “provides valuable information it does not definitively answer the question raised” due to the small number of patients enrolled in the studies and other limitations. They recommend that “physicians should ideally try to get their patients to stop smoking several months prior to their surgery” and that advice about “optimal timing of smoking cessation… awaits further research.”
March 15th, 2011
GRAVITAS Editorial: Why Invite the Fox into the Henhouse?
Richard A. Lange, MD, MBA and L. David Hillis, MD
Results from the GRAVITAS randomized trial, presented at the 2010 American Heart Association conference, have just been published in JAMA. They show that high-dose clopidogrel did not improve outcomes after percutaneous coronary intervention (PCI) in patients with “high on-treatment platelet reactivity” (i.e., during clopidogrel therapy), compared with clopidogrel given at conventional doses.
Our interpretation at CardioExchange, reported at the time of the AHA conference, was that assessing platelet reactivity doesn’t effectively identify individuals who are at high risk for a cardiovascular event after PCI. Although 41% of patients were reported to have had high on-treatment platelet reactivity (according to the VerifyNow P2Y12 test), only 2.3% of them had a cardiovascular event in the 6 months after PCI.
In a comment on our post, Dr. Sanjay Kaul bolstered our explanation by noting that 25 of 1080 patients (2.3%) with and 8 of 586 (1.4%) without high on-treatment platelet reactivity had adverse cardiac events. He calculated these statistics:
- sensitivity: 76%
- specificity: 35%
- positive predictive value: 2%
- negative predictive value: 99%
- positive likelihood ratio: 1.17
- negative likelihood ratio: 0.69
- area under the curve: 0.59
In this week’s JAMA, the GRAVITAS article is accompanied by an editorial suggesting that personalized therapy with high-dose clopidogrel was not effective because the cutpoint for defining high on-treatment platelet reactivity (P2Y12 reaction units ≥230) may have been too high. On the contrary, multiple studies have shown that this cutpoint provides the best predictive value of post-PCI ischemic complications, according to receiver-operating-characteristic analysis, and identifies the top tertile of post-treatment reactivity.
Notably, the lead author of the editorial receives grant support from Accumetrics, manufacturer of the VerifyNow P2Y12 test, and is an advocate for its use. We commend the author for disclosing his potential conflict of interest but have difficulty understanding why JAMA invited a major proponent of this platelet-reactivity test to write the editorial. Rather than acknowledging that the test has a negligible impact on risk prediction, the editorial simply calls for different platelet-function cutpoints to be used.
Do you consider this to be a real or merely a perceived conflict of interest? Do you routinely look at the COI disclosures that accompany published studies and editorials?
March 14th, 2011
The Common Thread Among Top-Performing Hospitals
Leslie Curry, PhD, MPH
A qualitative study just published in the Annals of Internal Medicine outlines some important distinctions between hospitals that have the lowest AMI mortality rates in the U.S and those that have the highest. The key factor? A supportive organizational culture. Here, study investigator Leslie Curry, PhD, MPH walks us through what that means and how the findings can be used to improve practice.
Q: What are the key components of a supportive organizational culture? Can you give us some concrete examples?
The participants in our study described five key components of an organizational culture that supports high-quality AMI care: shared organizational values and goals, senior management involvement, broad staff presence and expertise in AMI care, effective communication and coordination among groups, and problem solving and learning.
We heard many concrete examples of these features in the top-performing hospitals. For example, staff reported the vigilant pursuit of ways to improve care, a laser focus on innovation and problem solving without blame, earnest mutual respect for the expertise of diverse team members, and deliberate and systematic attention to the full continuum of AMI care.
Q: What are good first steps for building such a culture?
Building a supportive culture requires first understanding the current culture and the ways in which it is impeding high performance. Key elements in the process of changing an organization’s culture include developing a shared vision for the organization’s objectives, adjusting formal structures and processes to support the desired culture, and working through key opinion leaders to introduce new ways of thinking about and conducting the organization’s work.
Q: What can an individual clinician do differently tomorrow to help shift his or her hospital’s culture?
I asked a clinician on our research team, Erica Spatz, MD, MS, to offer her insight:
Informed and engaged clinicians are central to a culture of quality. At the bedside, clinicians can promote quality by supporting a team approach to patient care. Effective teams communicate openly and exchange ideas. Nurses feel comfortable calling physicians in the middle of the night with a question; cardiologists share newly acquired knowledge with their staff; and clinicians from all phases of AMI care, from EMS to the ED to the cath lab, work together.
Taking a step back from the bedside, clinicians need to be informed about hospital efforts to improve quality — and getting involved in those efforts is even better. A first step is to demand data on outcomes. Most clinicians lack feedback. There is nothing like seeing how you and your hospital are performing compared to a rival hospital down the street or compared to a nationally recognized hospital. These data can help drive clinician-led quality improvement efforts. The success of such efforts can be gauged by internal process measures. But having timely, ongoing access to hospital-level 30-day mortality data can tell you whether you are shifting the quality culture.
Q: Most of the prior work on improving AMI mortality rates has focused on specific interventions, like door-to-balloon time and β-blocker use. How should we balance resources for those types of initiatives versus this one?
A core finding in the D2B and β-blocker studies is that success depends on the presence of an organizational structure and culture that supports the recommended strategies (in the case of D2B, for instance, single call, or in the case of beta blockers, standing orders), so actually our findings here are not inconsistent. We believe that organizational support and culture are fundamental and that investment in these areas will ultimately enhance success both in process measures and in outcomes, such as mortality rates.
March 10th, 2011
Obesity and Cardiovascular Risk: Does Size Matter?
Larry Husten, PHD
A very large new study finds that obesity — no matter how it is calculated — is not an important independent predictor of cardiovascular disease. A report from the Emerging Risk Factors Collaboration published online in the Lancet analyzed individual records from more than 220,000 people without known cardiovascular disease and found that none of the traditional methods to categorize obesity — BMI, waist circumference, and waist-to-hip ratio — provided significant additional information about CV risk beyond that already provided by systolic blood pressure, diabetes, and lipids.
The authors wrote that their finding “does not, of course, diminish the importance of adiposity as a major modifiable determinant of cardiovascular disease” but that “because excess adiposity is a major determinant of the intermediate risk factors… our findings underscore the importance of controlling adiposity to help prevent cardiovascular disease.” The authors also say that their results “reliably refute previous recommendations to adopt baseline waist-to-hip ratio instead of BMI as the principal clinical measure of adiposity.”
In an accompanying comment, Rachel Huxley and David Jacobs Jr. write that “BMI continues to be useful as an indicator of adiposity” and should be “used with good clinical judgment.” However, they note, “size still matters… but not in the way we once thought.”
March 10th, 2011
Howard Bauchner to Replace Catherine DeAngelis as JAMA Editor
Larry Husten, PHD
The AMA announced today that Howard Bauchner will become the next editor-in-chief of JAMA. Bauchner will replace Catherine DeAngelis, who has been the editor for the past 11 years. Bauchner, a professor of pediatrics and community health sciences at Boston University Schools of Medicine, is currently the editor-in-chief of the Archives of Disease in Childhood.
“I have tremendous respect for JAMA and the prestige and stature it has achieved under Dr. DeAngelis,” said Bauchner, in an AMA press release. “JAMA is among the elite medical journals in the world and I am excited and honored by the opportunity to be its new editor.”
March 10th, 2011
Olmesartan Helps Prevent Microalbuminuria, But a Troubling Question Persists
Larry Husten, PHD
Olmesartan can help prevent progression to microalbuminuria in type 2 diabetics, according to results of the ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) trial published in the New England Journal of Medicine. But the positive result was partially offset by the troubling finding of a small but significant increase in fatal cardiovascular events.
Type 2 diabetics (n=4447) were randomized to olmesartan or placebo for 3.2 years. Time to the onset of microalbuminuria — the primary endpoint of the trial — was significantly delayed by olmesartan by 23% (HR 0.77, CI 0.63-0.94, p=0.01). Microalbuminura occurred in 8.2% of olmesartan-treated patients versus 9.8% of placebo-treated patients. Although there were fewer nonfatal cardiovascular events in the olmesartan group (3.6% versus 4.1% in the placebo group, p=0.37), the pattern was reversed for fatal cardiovascular events: 15 patients (0.7%) versus 3 patients (0.1%) (p=0.01).
In an accompanying editorial, Julie Ingelfinger notes that due to ROADMAP and a similar finding in the ORIENT trial, olmesartan is the subject of an ongoing investigation by the FDA. Because of the small number of events it is possible that olmesartan is safe, she acknowledges, but she also speculates that the high 40 mg/day dose of olmesartan used in ROADMAP might have caused an excessive reduction of blood pressure in high-risk patients.
Without taking a firm stance, Ingelfinger writes that “most nephrologists and cardiologists have argued that the benefits of olmesartan outweigh the very small risks,” but that “others would argue that there are many ACE inhibitors and ARBs that have not been associated with a signal of increased cardiovascular death, so why not prescribe one of those agents?”
March 9th, 2011
ACTIVE I Examines Role for Irbesartan in AF Patients
Larry Husten, PHD
The angiotensin-receptor blocker irbesartan does not significantly reduce cardiovascular events in patients with atrial fibrillation, according to the results of the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I), published in the New England Journal of Medicine. Participants had been previously randomized in the ACTIVE A trial or the ACTIVE W trial.
More than 9,000 patients were randomized to irbesartan or placebo and followed for 4.1 years. Although patients treated with irbesartan had a significantly greater drop in blood pressure, there were no significant differences in either the first coprimary endpoint — the composite outcome of stroke, myocardial infarction, or death from vascular causes — or the second coprimary outcome, which consisted of the first composite outcome plus heart failure hospitalization. However, even though most patients were already taking an ACE inhibitor, there were significantly fewer hospitalizations for heart failure in the irbesartan group, a prespecified secondary outcome.
March 8th, 2011
European Study Suggests HDL May Protect Against Colon Cancer
Larry Husten, PHD
In the largest study to date examining the relationship between lipids and colorectal cancer (CRC), a European study has found a strong inverse relationship between HDL cholesterol and colon cancer. Previous smaller studies investigating the relationship had been inconclusive.
In a paper published in Gut, Fränzel JB van Duijnhoven and colleagues report on a nested case-control study from the large European Prospective Investigation into Cancer and Nutrition (EPIC), which includes more than 500,000 participants. The new study focuses on 1238 cases of CRC and the same number of matched controls. After adjusting for other known risk factors, the investigators found a significant inverse association between HDL and apoA and colon cancer. No association was found with rectal cancer.
The authors speculated that a protective role for HDL in colon cancer may involve the effects of HDL on inflammatory pathways or oxidative stress, but they acknowledged that “it still remains to be established whether low HDL concentrations are just correlated with other truly detrimental pathways, whether they are intermediate factors in the colon carcinogenic process or are a true risk factor initiating a mechanistic path on the road to colon cancer.”
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