September 12th, 2013
Colchicine Found Effective in Acute Pericarditis
Larry Husten, PHD
Although colchicine has been shown to be beneficial in patients with recurrent pericarditis, which is thought to have a large inflammatory component related to an immune response, until now its efficacy in a first episode of acute pericarditis has been uncertain, as these episodes are thought to usually have a viral component that might benefit from an inflammatory response.
In a study published in the New England Journal of Medicine, 240 patients with acute pericarditis and receiving conventional therapy with aspirin or ibuprofen were randomized to colchicine or placebo for 3 months. Colchicine was found effective in reducing the rate of incessant or recurrent pericarditis (the primary outcome of the trial), as well as symptom recurrence at 72 hours, the number of recurrences per patient, and the rate of hospitalization:
- Incessant or recurrent pericarditis: 16.7% in the colchicine group versus 37.5% in the control group (relative risk reduction, 0.56; CI 0.30-0.72; number needed to treat, 4; p < 0.001)
- Symptom persistence at 72 hours: 19.2% vs. 40.0% (p = 0.001)
- Recurrences per patient: 0.21 vs. 0.52, (p=0.001)
- Hospitalization rate: 5.0% vs. 14.2% (p=0.02)
There were no significant differences in adverse effects or discontinuation of the study drugs.
Results of the study confirm current European guidelines, which give a class IIa indication for the use of colchicine in acute pericarditis, and an earlier, single-center, open-label trial. The precise mechanism of action of colchicine is uncertain, though the authors point to its high concentration in leukocytes. They conclude that “colchicine, when added to conventional antiinflammatory therapy, significantly reduced the rate of incessant or recurrent pericarditis” in patients with a first episode of acute pericarditis.
In a recent case history published in CardioExchange, the use of colchicine was discussed at some length by a number of well-known clinicians, including James Fang, James de Lemos, Kamalendu Kanu Chatterjee, Thomas Ryan, and Rick Akira Nishimura.
September 12th, 2013
Aspirin Therapy with Anticoagulation in Patients with Afib?
Benjamin A. Steinberg, MD and John Ryan, MD
CardioExchange’s John Ryan interviews Benjamin Steinberg about his group’s recent analysis of data from the ORBIT-AF registry on concomitant aspirin therapy with oral anticoagulation.
THE STUDY
The investigators assessed concomitant aspirin use and its association with clinical outcomes among the >7000 patients in the ORBIT-AF registry who received oral anticoagulation. Thirty-five percent of patients received concomitant aspirin. At 6 months, these patients had significantly higher rates of major bleeding (adjusted hazard ratio, 1.53) and bleeding-related hospitalization (adjusted HR, 1.52) than patients on anticoaguation alone. Rates of ischemic events were low in both groups.
THE INTERVIEW
Ryan: You studied 7347 outpatients with atrial fibrillation who were taking oral anticoagulation and found that 35% were also taking aspirin. Of those patients on the combination treatment, 39% did not have atherosclerotic disease, and 17% had an elevated risk of bleeding. Have you revealed a large group of patients who are being overtreated?
Steinberg: I think we highlighted a large group of patients where the utility of aspirin should be considered very carefully. In patients without manifest atherosclerotic disease, the benefits of aspirin primary prevention are less robust. Furthermore, I think generally we’re more aware that long-term aspirin is not an entirely benign therapy and does carry risk. This point is probably accentuated in patients taking concomitant oral anticoagulation.
Ryan: Should aspirin in these patients be considered a medical error?
Steinberg: I’m not sure we can say that – it’s a judgment call for the physician. What we tried to do was highlight the use of dual therapy in patients that may not warrant it, and provide a glimpse of the potential risks of such an approach.
Ryan: What action should occur as a result of your study?
Steinberg: I think we as providers need to look very closely at our patients on long-term anticoagulation who are also taking long-term antiplatelet therapy (or may be taking it over the counter unbeknownst to us). I’m now much more attuned to patients taking aspirin without a convincing indication. When possible, I try to restrict aspirin use to patients who have a clear reason to be on it, particularly if they’re on other antithrombotic therapy.
JOIN THE DISCUSSION
Will the findings of the ORBIT-AF analysis affect how you approach patients on long-term anticoagulation?
September 11th, 2013
A New Standard For Pulmonary Hypertension Trials
John Ryan, MD
Recently the New England Journal of Medicine published the SERAPHIN trial studying the effects of macitentan, a new endothelin receptor antagonist, in pulmonary arterial hypertension (PAH). This was a well-conducted study in 742 patients with PAH randomized to placebo, a low dose of macitentan (3mg once a day) and a high dose of macitentan (10mg once a day). When compared to placebo, both doses decreased time to the first event related to PAH, a composite endpoint of worsening of PAH, initiation of prostanoids, lung transplantation, atrial septostomy or death.
The primary outcome in the clinical trials of PAH for currently approved therapies has remained the 6-minute walk (6MW) distance since the first randomized controlled trial (RCT) for PAH in 1990. At the time of the design of that study (NEJM 1996), because a survival endpoint would require a much large, long trial, the sponsor and steering committee chose the 6MW test as the primary outcome. Subsequently, almost every trial in PAH has used the 6MW test as the primary outcome. Most of these therapies produce a similar increase in 6MW distance, approximately 30-50 meters. There has been no relationship observed between changes in 6MW distance and mortality, hospitalization for pulmonary hypertension, lung transplantation or escalation of pulmonary hypertension therapy. In fact, 6MW distance may be more reflective of abnormalities and changes in the peripheral vasculature than the pulmonary hemodynamics. In the SERAPHIN study, by choosing a composite clinical endpoint, the authors have broken the mold in PAH trials and introduced a new outcome, which has been proposed for many years (the recent IMPRESS trial used time to clinical worsening as the primary outcome). This represents an important sea change in how PAH trials are conducted.
An important aspect of this trial is where macitentan will fall in terms of clinical options of PAH. In general, most current PAH practice introduces ERAs or PDE5 inhibitors as the first oral options (if patients are not responders to calcium channel blockers) unless there is overt RV failure, where the recommendations are to start prostacyclins. Bosentan and ambrisentan are the most commonly used ERAs. Bosentan is a twice-a-day drug and requires monthly LFTs measurement. Ambrisentan is a once-a-day drug and does not require LFT measurements. In the first bosentan trial (NEJM 2002), elevated LFTs occurred in 4-14% of patients treated with bosentan, depending on the dose used. In the landmark ambrisentan trial (Circulation 2008), no patient receiving ambrisentan developed increased LFTs. In the SERAPHIN study, 3.6% of macitentan patients developed increased LFTs, compared to 4.5% of patients receiving placebo. When it comes to approval and clinical introduction of this agent, what will be important is whether LFT checks will be required in patients once macitentan is initiated. If LFT checks are not required for this agent, then macitentan will be a once a day ERA, akin to ambrisentan but with a more clinical relevant study endpoint.
Whether this composite end point will be enough to change the prescribing patterns of PAH physicians will be interesting to follow, as will be to see if the SERAPHIN study represents a new standard for PAH trials.
September 10th, 2013
Have We Solved The Problem of Ghostwriting?
Harlan M. Krumholz, MD, SM
Several years ago, in the midst of the Vioxx litigation, I became aware of the practice of ghostwriting throughout academic medicine. In general, marketing arms of pharmaceutical companies wanted to seed the peer-reviewed journals with articles published by academics. They would identify an academic and provide him or her drafts of the article. Sometimes they would pay the academic for the review. Sometimes the author was a consultant to the company, and there was no direct payment for the review. The article would typically not acknowledge the relationship — or who actually drafted the article. Joe Ross, Kevin Hill, David Egilman and I wrote about this practice in an article published in JAMA.
Even after publishing that article, I have received invitations to be a first author on review articles that would be drafted for me. I was usually approached by a medical writing company. I have been offered payment for my trouble. I have been told that the effort would not take much of my time. As you might imagine, I do not respond to such inquiries.
In a recent issue of a well-regarded, peer-reviewed journal, I ran across a review article by a prominent academic physician that focused, in part, on a controversial subgroup interaction found in a manufacturer-sponsored clinical trial of a new drug. In my opinion, the content was favorable for the new drug.
The article is completely transparent about its genesis. There is a statement that staff from a medical communications company assisted in drafting the article. The article also states that the manufacturer of the new drug paid for the medical writing support. The author was not paid for the article and disclosed no conflict of interest. However, the disclosure does not explicitly state whether the author had a financial relationship with the pharmaceutical company.
In the past, this article may have been ghostwritten. Now, the connection with the medical writing company is transparent — as is the relationship between the pharmaceutical company and the medical writing company. I wonder if this is progress.
Do you see any problem with this practice?
September 9th, 2013
Clear! CPR in the Hospital Is Not Always Good for the Patient
Larry Husten, PHD
On TV it always seems clear and simple. A patient in the hospital goes into cardiac arrest and the medical team springs into action. After a few tense moments of furious activity, and only after all seems lost, the patient is successfully revived. A few scenes later the smiling and now fully healthy patient thanks the doctor and returns to his or her life as a professional athlete, parent of young children, or criminal mastermind.
Medical professionals know that in real life this is rarely the way it goes. Most patients who undergo cardiopulmonary resuscitation (CPR) are old, frail, and very sick. Many will die and many who survive CPR will die anyway before leaving the hospital. And many survivors will have severe neurological problems.
Now a physician states in JAMA Internal Medicine that hospitals need to change the way they view CPR. When it comes to applying continuous quality improvement processes to CPR, hospitals “tend to focus on the procedural aspects of CPR, such as time to first defibrillation” and the selection of medications, but they “do not regularly scrutinize CPR attempts for appropriate clinical indications.” The author, Jeffrey Berger, is an Associate Professor of Medicine at Stony Brook University School of Medicine and the Director of Clinical Ethics, and the chief of the Section of Hospice and Palliative Medicine at Winthrop University Hospital.
CPR is too often used as a “default action” because of the misconception that there is a “blanket requirement” to use CPR in cases where there is no do-not-resuscitate order, writes Berger. Instead, hospitals should use quality improvement processes to assess when CPR is an appropriate therapeutic option and to avoid CPR when it is inappropriate.
Berger takes issue with the usual, uncritically-held perspective “that cardiopulmonary arrest is itself an indication for attempting CPR” or that CPR is somehow “atypical among medical interventions.”
This perception is evidenced by the use of CPR as a default action rather than within a deliberate treatment plan (e.g., misconstruing presumption of consent in the do-not-resuscitate state law as a blanket requirement to use CPR) and the presentation of CPR as a genuine option even when its therapeutic potential is remote.”
September 9th, 2013
Nontechnical Skills Matter in the Cardiac Operating Room
Joyce Ann Wahr, M.D. and Harlan M. Krumholz, MD, SM
CardioExchange’s Harlan Krumholz interviews Joyce A. Wahr, lead author of the AHA’s new scientific statement on the importance of human factors and teamwork in performing cardiac surgery.
Krumholz: What are the most important insights from this scientific statement?
Wahr: First, we now have strong evidence that nontechnical skills (teamwork and communication) play a critical role in patients’ surgical outcomes. Second, surgical teams can improve these skills and reduce human error with a few simple interventions. The statement reviews the data showing that team training and the use of briefings/checklists can actually improve outcomes. Traditionally, medical and surgical training has focused on development of intellectual acumen and technical skills. We have only recently realized that complex medical environments, in which highly trained subspecialists interact with one another and use sophisticated technology (e.g., cardiac surgery), resemble those in other high-risk, complex industries. In aviation, nuclear power, and the military, the importance of teamwork training and nontechnical skills (such as communication, cooperation, coordination, and conflict resolution) has been emphasized for decades.
Krumholz: Are the findings relevant outside the operating room?
Wahr: The findings are relevant to every healthcare team regardless of its makeup or location in the healthcare system. Although we focused on studies addressing the challenges of reducing human error and improving patient safety in the cardiac and other surgical operating rooms, the concepts in these studies are broadly applicable—they have been studied in emergency departments, obstetrical units, medical intervention suites, and other healthcare settings.
Krumholz: What single change would have the biggest effect on patient safety?
Wahr: We would like to see all unit directors, department chairs, and hospital safety officers institute team training in their units. Excellent healthcare team-training tools exist—they simply need to be used. We also would like to see every cardiac surgeon lead a briefing with his or her team before every operation. Data show that such briefings improve many aspects of teamwork, including team members’ willingness to speak up. Briefings/checklists, together with team training, are the two distinct interventions that have improved surgical patient outcomes in large studies.
JOIN THE DISCUSSION
What’s your view about the potential for team training and presurgical team briefings to improve the safety of cardiac surgery?
September 7th, 2013
Visit-to-Visit Variability in Systolic BP Among Patients with Type 2 Diabetes
John Chalmers, MD phD and John Ryan, MD
CardioExchange’s John Ryan interviews John Chalmers, Jun Hata, Hisatomi Arima, Peter M. Rothwell, and Mark Woodward about their new analysis using data from the ADVANCE trial.
THE STUDY
The investigators analyzed data from 8811 patients with type 2 diabetes who did not die or experience major macrovascular or microvascular events within 2 years after randomization to perindopril + indapamide or matching placebo in the ADVANCE trial. During a median 2.4 years of follow-up after the 2-year visit, visit-to-visit systolic BP variability and maximum SBP each were independent risk factors for major macrovascular events (MI, stroke, CV death) and microvascular events (new or worsening nephropathy or retinopathy). The findings persisted after adjustment for mean SBP and other potentially confounding factors, although the association between maximum SBP and microvascular events did not persist in one adjusted model. SBP variability and maximum SBP were significantly associated with all-cause mortality, whereas mean SBP was not.
THE INTERVIEW
Ryan: The finding that visit-to-visit variability adds prognostic information beyond mean SBP seems to confirm findings from several previous studies. What key knowledge does your paper add?
Chalmers, Hata, Arima, Rothwell, and Woodward: The very new knowledge is that visit-to-visit SBP variability predicts the risk for microvascular complications over and above predicting the risk for death and macrovascular events. The other important finding is that these associations are present and strong in patients with type 2 diabetes.
Ryan: You discuss many potential mechanisms by which the variability might confer increased risk, including medication nonadherence, which seems plausible. Did the variability in SBP correlate with variability in other parameters that might relate to adherence but not to arterial stiffness (your putative mechanism for how variability relates to risk)?
Chalmers, Hata, Arima, Rothwell, and Woodward: We do not have specific information on nonadherence to medication, but we do have data on discontinuation of the randomized study medication—either perindopril/indapamide or placebo. In our sensitivity analyses, the effects of visit-to-visit variability remained significant after excluding patients who discontinued the study medication.
Ryan: What should clinicians do differently as a result of this study? Should they calculate visit-to-visit variability? If so, how do you recommend they do that?
Chalmers, Hata, Arima, Rothwell, and Woodward: These are possibly the most important lessons for the practicing clinician:
1. BP fluctuates widely from visit to visit and across home BP measurements.
2. The occasional high SBP reading (as reflected in the “maximum SBP,” a significant predictor of death and CV events) should prompt immediate action to improve BP control, rather than the more-typical response: “Let’s wait until the next visit to see what your BP is before we increase your medication.” That habit leads to very strong dependence on the mean SBP and ignores the fact that SBP variability constitutes another important and independent predictor or risk factor.
We do not recommend that the average practicing doctor try to calculate one of the various indices used in our formal analyses, such as the standard deviation or the coefficient of variation. Simple common sense should suffice.
JOIN THE DISCUSSION
Will the prognostic value of visit-to-visit variability in systolic BP influence how you manage hypertension in your patients with type 2 diabetes?
September 6th, 2013
Early Surgery vs. Watchful Waiting for Flail-Leaflet Mitral Regurgitation
Rakesh Mark Suri, MD, D.Phil., Maurice Enriquez-Sarano, MD and John Ryan, MD
CardioExchange’s John Ryan interviews Rakesh M. Suri and Maurice Enriquez-Sarano about their research group’s study, published in JAMA, of patients in the Mitral Regurgitation International Database.
THE STUDY
At 6 tertiary care centers in Europe and the U.S., researchers compared the effectiveness of initial medical management (nonsurgical observation) with early mitral valve surgery after diagnosis of mitral regurgitation (MR) due to flail mitral-valve leaflets. Of 1021 consecutive patients without ACCF/AHA class I triggers (heart-failure symptoms or LV dysfunction), 575 were initially medically managed and 446 underwent mitral valve surgery within 3 months after detection of severe MR. At 3 months, the two groups were similar in their rates of mortality and new-onset heart failure; however, at 10 years, the mortality rate was significantly lower among patients who underwent early surgery (14% vs. 31%), as was the long-term risk for heart failure (7% vs. 23%). No advantage in late-onset atrial fibrillation was observed. The findings were confirmed in risk-adjusted models.
THE INTERVIEW
Ryan: Did the decisions about who would have surgery differ between the earlier part of the study, when repair was less frequent, and the later part?
Suri and Enriquez-Sarano: Mitral-valve repair was performed across the MIDA network at a high frequency in both the early surgery and initial medical management groups throughout the study. Given the interim emergence of evidence detailing high repair rates for all categories of leaflet prolapse, improved safety, and excellent durability of repair, referring physicians’ attitudes about early surgical referral may have evolved concurrently.
Ryan: Why do you think some patients underwent surgery and others did not — and did that vary much by center?
Suri and Enriquez-Sarano: Patients who underwent early surgery had larger left-atrial and left-ventricular dimensions, so the existence of adverse remodeling consequences associated with severe MR may have influenced physicians to recommend early surgery. However, despite a greater apparent preoperative effect of MR, as assessed by chamber dimensions in the early surgical group, these patients had better late clinical outcomes, including superior long-term survival and freedom from heart-failure symptoms. Notably, patients with severe, degenerative MR were referred for early surgery at advanced repair centers before heart-failure symptoms or LV dysfunction (class I triggers mandated by practice guidelines) occurred — a strategy that was clearly beneficial.
Ryan: How should this study be integrated into the new guidelines?
Suri and Enriquez-Sarano: This is the largest study of early surgery in asymptomatic patients with severe, degenerative MR in the absence of guideline-based class I triggers for intervention. As such, the study provides sobering evidence that prompt surgical correction of severe MR has important long-term benefits.
We therefore would anticipate that this evidence might lead to the modification of guideline-based recommendations, with the proviso that such patients be referred to advanced repair centers where the likelihood of performing mitral repair safely and effectively is very high (repair rate >90–95%; risk <0.5%; high-quality echocardiography and reoperation rate <1–1.5%/year).
It is also important that (a) echocardiography be used to carefully define MR etiology/severity and (b) the influence of patient comorbidities be considered, to ensure that mitral-valve repair alone will improve life expectancy. We propose the creation of a National Mitral Regurgitation Registry, to ensure that practices and outcomes are continuously tracked, monitored, and reported.
Finally, data-driven discussions regarding the referral of patients for less-invasive surgical options (robotic, thoracoscopic, mini-thoracotomy) should also occur at high-volume referent valve centers. This will ensure that proven techniques are used to perform the technical aspects of the mitral-valve repair itself and that outcomes are followed and reported.
These a priori criteria, necessary for the surgical referral of asymptomatic degenerative severe MR patients, are likely (at least initially) to be most readily applicable in high-volume reference mitral-valve repair centers that have an experienced multidisciplinary heart-valve team.
JOIN THE DISCUSSION
How do the findings from this new analysis affect your view of the value of early surgery in this clinical setting?
September 5th, 2013
Lancet Formally Retracts Jikei Heart Study of Valsartan
Larry Husten, PHD
The Lancet has formally retracted the Jikei Heart Study paper, originally published in 2007. The retraction had been widely anticipated for more than a month, after a series of news reports in Japan made it clear that the long-simmering controversy over scientific misconduct involving the Novartis blood pressure lowering drug valsartan (Diovan) had come to a full boil. (See our earlier story
As reported previously, the current scandal first began to unfold in late 2011 when a Japanese blogger pointed to a number of apparent errors in publications authored by Hiroaki Matsubara. This ultimately led to a series of retractions of Matsubara’s papers and the retraction of the main paper of the Kyoto Heart Study itself by the European Heart Journal.
In the notice of retraction, the Lancet editors outline the chronology of the case, stating that shortly after publication of the Jikei Heart Study in the Lancet they first became aware of concerns in Japan about both the Jikei and the Kyoto Heart studies, both of which studied valsartan and had shared several authors. However, despite the publication of a letter questioning the statistics of the Jikei Heart Study, no further actions were taken until earlier this year.
Following the retraction of the Kyoto Heart Study in February 2013, Jikei University initiated its own investigation. After some delay, and after some prodding from the Lancet after the announcements in the Japanese press, Jikei informed the Lancet editors that blood pressure data in the study had been intentionally altered during the statistical analysis. The person responsible for the data manipulation was Nobuo Shirahashi, whose listed affiliation was “Clinical epidemiology, Osaka City University Graduate School”. Sharahashi, however, was actually an employee of Novartis, and the Osaka City University did not provide statistical analysis for the Jikei Heart Study. A Novartis official told the Lancet that Shirahashi had “obtained an unpaid position in about 2001 with the Osaka City University Graduate School’s Medical Research Faculty as a part-time lecturer in the Department of Medicine. He held the position until 2011.” Shirahashi has now retired from Novartis and has not cooperated with the investigation.
“Taken together,”write the editors, “these findings indicate that there is now sufficient doubt as to the integrity of the Jikei Heart Study and the obfuscation over affiliation of the study statistician for The Lancet formally to retract the paper from the scientific record.”
September 5th, 2013
Should We Be Looking Beyond Door-to-Balloon Time?
Daniel Menees, MD, Hitinder Gurm, MBBS and Brahmajee Kartik Nallamothu, MD, MPH
CardioExchange contributor Brahmajee Nallamothu interviews Daniel Menees and Hitinder Gurm, co-investigators of a New England Journal of Medicine study that calls into question the emphasis on door-to-balloon time for acute MI patients undergoing PCI.
THE STUDY
A door-to-balloon (D2B) time of 90 minutes or less for STEMI patients undergoing primary PCI is a widely used performance measure for quality initiatives. This study found large improvements in D2B times but no significant overall change in unadjusted in-hospital mortality or risk-adjusted in-hospital mortality. The authors conclude that “additional strategies are needed to reduce in-hospital mortality in this population.”
Nallamothu: Although time to reperfusion has been linked to myocardial salvage in experimental models and mortality in numerous observational studies, you found that improvements in D2B time did not correlate with reductions in mortality. Why? Is it something wrong with the measure as we are applying it, or is it that more rapid treatment is unlikely to be beneficial?
Dr. Menees and Dr. Gurm: That is an excellent point. Time to reperfusion is clearly linked with myocardial salvage in animal models, and it makes intuitive sense that more rapid reperfusion should impact outcome. However, D2B time is not “time to reperfusion” — it only measures the delay to reperfusion once the patient reaches a hospital. Myocardial cell death starts soon after arterial occlusion, and the expected myocardial salvage one can expect from reperfusion drops sharply between 2-3 hours; after that time period, the anticipated benefit with respect to myocardial salvage is of limited magnitude. The total ischemic time has come down, but we are still not under that 2-3-hour threshold where we would see the most benefit. With D2B time, we are fixing the part of the process that is easier to fix but constitutes a smaller fraction of the total ischemic time.
There are other benefits of PCI at that point, such as electrical stability, but that is probably less affected by rapid reperfusion. A patient who has VF in the hospital will get defibrillated, and a 10- or even 30-minute difference in getting that artery open probably does not matter that much.
We also would like to address the issue you raised with how we are applying D2B time as a quality measure. D2B time is an attractive metric largely because it is something easily measured and can be applied across all hospital systems. However, in light our data, it is reasonable to question whether D2B time is the best measure of quality of care. Rather, what we are truly measuring is the quality of health systems and their ability to deliver care. We believe there is a subtlety to that distinction that is very important to recognize. Certainly there is a benefit to more efficient healthcare delivery, but we shouldn’t lose sight of the fact that this isn’t the same as improving patient outcomes. So while D2B time may have value, we’re not sure it’s affecting patient care the way we previously expected it to. That said, we’re not sure it’s time to abandon D2B time quite yet. Perhaps the benefit of shorter D2B times will be seen further downstream, in reduced long-term mortality or a decline in heart failure. These aspects still need to be studied.
Nallamothu: How do you think your findings should affect quality initiatives and use of D2B time as a performance measure?
Dr. Menees and Dr. Gurm: We are of the opinion that quality measures should be held to the same standard as new devices or drugs. We cannot perform randomized controlled trials to assess all quality measures, but studies like ours are needed to make sure that we do not become complacent and lose sight of the real goal – improving patient mortality, morbidity, and quality of life.
As far as D2B time is concerned, we probably need to stop focusing on it so much. A goal that almost everyone is meeting should not be a performance measure. We need to focus on total ischemic time, and this will require some innovation on the part of everyone — the general public, the media, community leaders, researchers, and the medical community. Perhaps communities (e.g., by zip codes, counties, etc.) may need to be publicly reporting their total ischemic times; that may possibly effect meaningful change. As everyone knows, prior randomized trials of media campaigns (e.g., the REACT trial) have been negative, and we need to explore alternate approaches.
It may be time to move away from D2B time, or at least recognize its limitations and consider its use in the context of other measures. We need to start trying to track total ischemic time (i.e., onset of symptoms) better, as well as take a closer look at the false activation rates across different regions and hospital systems. We think this is the real message behind our study — it’s time to look beyond D2B times, and we need start looking at other ways we can favorably impact patient outcomes.
Nallamothu: But beyond performance measures, how will these findings influence your own practice when it comes to evaluating and treating individual STEMI patients? Should interventionalists and hospitals still treat these patients as medical emergencies?
Dr. Menees and Dr. Gurm: STEMI is still a medical emergency. We would hate to lose the efficiency and collaboration that the D2B initiative has created. At the same time, physicians should be willing to take a pause when the clinical scenario does not make sense. We have seen an increase in false activations, and patients who have other diagnoses end up in the cath lab before undergoing a thorough evaluation because everyone is focused on the D2B time. Just last year, you diagnosed a perforated bowel in the cath lab in a patient who happened to have a left bundle branch block.
It won’t affect our practice at all. STEMI remains a medical emergency and should be treated as such. The message of our study shouldn’t be that recognizing and treating a STEMI in a timely and efficient matter is no longer of importance. However, we believe it is okay with taking the time to sort out the complex patient, whose diagnosis may be in question, prior to taking that patient emergently to the cath lab, even if it means sacrificing the 90-minute goal.
Nallamothu: Thanks for reminding me of one of my least favorite cases in the cath lab! You are careful to state that “further” efforts to reduce D2B times may not reduce mortality. Do you think we are moving too rapidly at this point?
Dr. Menees and Dr. Gurm: We remain concerned that one possible interpretation one can take from our study is that 90 minutes is not enough, that we need to have a D2B of 60 or 45 minutes. Faster reperfusion is probably always a good idea, but we doubt shaving more time off the D2B time will make much of an impact. We think the focus has to be on the pre-hospital delay.
No one should say after this study that it’s okay to treat a STEMI in 120 minutes. The natural question, though, is should we go even faster? There will clearly never be a randomized controlled trial to assess this issue, which is why we think studies like this are so important. We are worried that we have become too consumed with the “race against the clock,” and findings from our study should give us all pause when thinking about pushing even harder. There definitely comes a point where the pressure to move even faster comes with a consequence, which is namely misdiagnosis and/or medical error. If we are not effecting positive change, then these consequences are amplified even more.
Nallamothu: What are some future directions for measuring time to reperfusion that we should be considering?
Dr. Menees and Dr. Gurm: We need to embrace the concept of total ischemic time, which for most patients is the time from symptom onset to hospital presentation, and believe it should be a quality measure. This is an area on which we need to focus more. Trials of facilitated PCI have largely been disappointing, but perhaps we need to begin exploring reperfusion at the point of health provider contact (pre-hospital) if we are to truly to affect total ischemic times. Hopefully, once we start measuring total ischemic times, we will figure out how to reduce it.
Do you think that less emphasis should be placed on D2B time? Why or why not?
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