August 30th, 2012
Low-Dose Methotrexate to Prevent Recurrent MI and Stroke?
Paul Ridker, MD, MPH
Last week, the National Heart, Lung, and Blood Institute (NHLBI) announced the launch of the Cardiovascular Inflammation Reduction Trial (CIRT), a large clinical trial testing whether treatment with low-dose methotrexate, an anti-inflammatory drug, can reduces rates of cardiovascular events among adults who have had a heart attack within the past five years and who also have type-2 diabetes or metabolic syndrome.
We asked Paul Ridker, who is the principal investigator of CIRT, the Eugene Braunwald Professor of Medicine at Harvard Medical School, and director of the Center for Cardiovascular Disease Prevention at the Brigham and Women’s Hospital, to answer this question about the study:
Why the interest in using low-dose methotrexate (LDM) for prevention of MI and stroke?
I have been thinking about inflammation and cardiovascular disease since the mid 1990s, when we made our first observations about inflammation and cardiac risk, and realized that targeting inflammation might be the key to halting atherosclerosis. At that time, we learned that biomarkers of inflammation predict future heart attack and stroke even when other risk factors are normal, and that aspirin — an anti-inflammatory drug — was more effective at preventing heart disease when levels of inflammation were high.
Over the next decade, we went on to demonstrate that statins are not only powerful lipid-lowering agents, but that they also reduce inflammation. Finally, in our 2008 JUPITER trial we showed that patients with low levels of LDL-C, but increased levels of CRP, clearly benefit from statin therapy in primary prevention. However, there is no way to disentangle the anti-inflammatory effects from the lipid-lowering effects in a statin trial. We believe the time has come to formally test the inflammatory hypothesis of atherosclerosis and see directly whether targeted anti-inflammatory therapies that do not have concomitant effects on lipids and other pathways can reduce vascular-event rates, particularly among those already on statin therapy.
Our group is exceptionally grateful to the NHLBI for funding CIRT, which will compare LDM with placebo in the secondary prevention of heart attack, stroke, and cardiovascular death among high-risk individuals who have had a prior heart attack and who have either diabetes or metabolic syndrome — conditions associated with an enhanced pro-inflammatory response. In addition to all standard therapies, eligible trial participants will be allocated to placebo or to LDM at a target dose of 15 to 20 mg per week. This dose of methotrexate is far lower than that used in combination chemotherapy and is well within the common range used by millions of elderly Americans who take oral methotrexate as first-line treatment for rheumatoid arthritis (RA). Methotrexate in this dose range is well-tolerated and safety guidelines for its use are already in place so that no unknown off-target issues should occur in the trial.
In addition to the core biologic rationale for reducing inflammation as a potential new target, we know from observational studies that RA patients taking LDM appear to have lower vascular-event rates, that LDM reduces CRP and IL-6 levels, and that methotrexate inhibits atherosclerotic progression in animal models. Thus, CIRT will test the fundamental hypothesis of whether or not reducing inflammation with LDM among 7,000 stable post-MI patients will reduce rates of recurrent cardiovascular events and all-cause mortality.
CIRT will begin enrollment in early 2013 at sites across the U.S. and Canada. Physicians interested in serving as a trial site can obtain more details at the trial’s website (theCIRT.org) or by calling (855) 437-9330.
August 29th, 2012
Pilot Study Demonstrates Feasibility of MRI-Guided Catheterization
Larry Husten, PHD
A small pilot study has demonstrated that it may one day be possible to replace x-rays with MRI to guide some cardiac catheterization procedures.
As reported in the European Heart Journal, researchers at the National Heart, Lung, and Blood institute (NHLBI) performed x-ray and MRI-guided transfemoral right heart catheterization in 16 patients (4 with shunt, 9 with coronary artery disease, 3 with other indications). Each patient first underwent catheterization under x-ray guidance, which was then repeated twice with MRI, once using an air-filled balloon-tipped catheter and once using a gadolinium-filled balloon-tipped catheter.
In all but one patient, complete guidewire-free catheterization was successful with both techniques. The researchers said that MRI using gadolinium-filled balloons was “at least as successful as x-ray in all procedure steps, more successful than MRI using air-filled balloons, and better than both in entering the left pulmonary artery.” Procedure time was not significantly longer with MRI. “Catheter conspicuity was best under x-ray and next-best using gadolinium-filled MRI balloons,” the researchers reported.
“This could be the first chapter of a big story,” said Robert S. Balaban, scientific director of the NHLBI’s Division of Intramural Research, in an NHLBI press release. “It provides evidence that clinical heart catheter procedures are possible without using radiation, which could be especially valuable in areas such as pediatrics.”
The authors acknowledge an important limitation of their research: “We do not believe coronary artery interventional procedures are a realistic possibility because of inadequate spatial and temporal resolution. However, we do believe structural heart interventions to be realistic therapeutic targets, including delivery and repair of cardiac valve devices, non-surgical access and closure of large transthoracic cardiac access ports, repair of other cardiac structural defects, and enhanced image guidance of peripheral artery interventions such as recanalization of chronic occlusion.”
August 28th, 2012
WOEST: Get Rid of the Aspirin in Triple Therapy
Larry Husten, PHD
According to current guidelines and clinical practice, PCI patients already taking an oral anticoagulant generally end up on triple therapy comprising the anticoagulant plus clopidogrel and aspirin. However, there is no supporting evidence base for this approach, and the triple-therapy regimen is known to increase bleeding complications. Now a new study — the first randomized trial to address this situation, according to the investigators — may have a large impact on clinical practice by demonstrating that the omission of aspirin in this context appears to be safe and may reduce adverse events.
Results of the WOEST (What Is the Optimal Antiplatelet and Anticoagulant Therapy in Patients with Oral Anticoagulantion and Coronary Stenting) trial were presented by Willem Dewilde at the ESC in Munich today. Investigators in the Netherlands and Belgium randomized 573 patients to triple therapy or dual therapy of an anticoagulant plus clopidogrel for at least 1 month after implantation of a bare-metal stent or 1 year after a drug-eluting stent. Two thirds of the patients were receiving oral anticoagulation for atrial fibrillation.
The primary endpoint, the incidence of all bleeding events, was dramatically reduced in the dual-therapy group at 1 year:
- 44.9% with triple therapy versus 19.5% (HR 0.36, CI 0.26-0.50)
There were three intracranial bleeds in each group. Most of the difference in bleeding occurred in TIMI minor and minimal bleeding. The difference in TIMI major bleeding (3.3% vs. 5.8%) did not achieve statistical significance.
Clinical events, the trial’s secondary endpoint, were numerically lower in the dual-therapy group. The difference in mortality achieved statistical significance.
- Mortality: 7 deaths (2.6%) with dual therapy versus 18 (6.4%) with triple therapy, p=0.027
- MI: 3.3% versus 4.7%, p=0.382
- TVR: 7.3% versus 6.8%, p=0.876
- Stroke: 1.1% versus 2.9%, p=0.128
- Stent thrombosis: 1.5% versus 3.2%, p=0.165
“The WOEST study demonstrates that omitting aspirin leads to less bleedings but does not increase the risk of stent thrombosis, stroke or myocardial infarction,” said Dewilde in an ESC press release. “Although the number of patients in the trial is limited, this is an important finding with implications for future treatment and guidelines in this group of patients known to be at high risk of bleeding and thrombotic complications.”
David Holmes said the trial addressed “an incredibly important issue” and predicted that it would “change the way we practice medicine, it will change practice right away.” Keith Fox said that the evidence base prior to WOEST was extremely limited and that the trial showed that there was no hazard in doing without aspirin. The ESC discussant, Marco Valgimigli, said the trial showed it was safe to drop aspirin and provided another demonstration that “we have hit the wall” with anticoagulation.
August 28th, 2012
‘Rather Than … FAME, Give Me Truth’
Richard A. Lange, MD, MBA and L. David Hillis, MD
In the FAME 2 randomized trial, patients with functionally significant coronary arterial stenoses, as determined by fractional flow reserve (FFR) measurements, who underwent percutaneous coronary intervention (PCI) in combination with the best available medical therapy were less likely to experience death, MI, or urgent revascularization than were patients who received such medical therapy alone. Recruitment was halted prematurely — after only 888 of the 1632 planned patients were enrolled — because of a lower rate of urgent revascularization in those receiving PCI plus medical therapy; the incidence of death or MI was similar in the two groups.
|
Endpoints |
PCI + Medical Therapy |
Medical Therapy Alone |
P value |
| Composite of death, MI, or urgent revascularization |
4.3% |
12.7% |
<0.001 |
| Death |
0.2% |
0.7% |
0.31 |
| Myocardial infarction |
3.4% |
3.2% |
0.89 |
| Urgent revascularization |
1.6% |
11.1% |
<0.001 |
Does this settle the issue that ischemia should guide revascularization? Consider these points:
1. The Data and Safety Monitoring Board halted the study on the basis of differences in the weakest component (urgent revascularization) of a composite endpoint in a setting where referral bias may have influenced the outcome. Interestingly, no formal rules for stopping the study prematurely were specified. How, then, was study termination decided? On average, trials that are stopped prematurely for benefit overestimate that benefit by 30%.
2. Half the patients undergoing urgent revascularization had no objective evidence of ischemia (i.e., elevated biomarkers or ECG changes). Is this really “urgent revascularization” or simply a bias to revascularize subjects with abnormal FFR (vs. those with normal FFR)?
3. The post-PCI diagnosis of MI was established using CK-MB levels (above 5 or 10 times the upper reference limit), whereas the diagnosis of MI in the setting of ACS was established with either CK-MB or troponin levels. Doesn’t this minimize the rate of peri-PCI MI?
4. The sponsor was “involved in the collection and source verification of the data.” What does this mean?
5. Although the study was designed to follow patients for 2 years, the mean follow-up was only 7 months. Come on now — not only was the study terminated prematurely (when only slightly more than half the planned subjects were enrolled), but the follow-up was truncated as well?
6. Demonstration of a pressure gradient across an epicardial coronary stenosis (i.e., abnormal FFR) is not synonymous with ischemia. Instead, ischemia is a consequence of diminished myocardial tissue perfusion and can be identified by ECG changes, regional myocardial perfusion abnormalities during scintigraphy, wall-motion abnormalities on echocardiography, or abnormal tissue perfusion or metabolism on PET imaging. Given that none of these tests was performed in conjunction with the FFR measurements, we cannot know whether an FFR of 0.68 (the mean value in the study) was associated with ischemia. In addition, it’s difficult to compare the FAME 2 patients with the COURAGE patients (85% of whom had documented ischemia).
7. On the basis of the FAME II data, one would perform PCI in 100 patients to prevent 9 “urgent revascularizations,” only 4 of which are for ischemia (i.e., positive biomarkers or ECG changes) — without reducing the incidence of MI or death. This seems to be a long (and expensive) run for a short slide.
Henry David Thoreau asked for truth rather than FAME (or love or money for that matter). What truth do you take from this study? Should we be performing PCI in all stable CAD patients who have abnormal FFR?
August 28th, 2012
FAME 2: Can FFR Save PCI from Medical Therapy?
Larry Husten, PHD
Two sharply divergent views have developed about the value of fractional flow reserve (FFR) in PCI. FFR advocates think the new technology can help identify ischemic lesions that will benefit from PCI, thereby helping to salvage or enhance the reputation of PCI. FFR skeptics think that optimal medical therapy is still the preferred option for most patients with stable angina. Both sides find evidence to support their view in the FAME 2 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) trial presented at the ESC and published simultaneously in the New England Journal of Medicine.
The FAME 2 investigators sought to show that patients who had ischemic lesions as determined by FFR would benefit from the addition of PCI to the best available medical therapy. Patients with stable coronary artery disease under consideration for PCI underwent FFR. Patients who had at least one functionally significant stenosis, defined as FFR 0.80 or less, were randomized to FFR-guided PCI plus medical therapy or medical therapy alone. Patients whose stenoses all had FFRs over 0.80 were observed in a registry and received best medical therapy.
The trial was stopped early, after enrollment of 1220 patients (888 in the randomized portion and 332 to the medical therapy registry), because of a significant reduction in the primary endpoint (the composite of death, MI, or urgent revascularization) in the PCI group:
- 4.3% in the PCI group versus 12.7% in the medical therapy group (HR for PCI 0.32, CI 0.19-0.53, p<0.001)
- 3% of patients in the registry had a primary endpoint event
There was no difference between the groups in the rate of death or MI. The difference in the primary endpoint was driven entirely by the lower rate of urgent revascularization in the PCI group:
- 0.7% in the PCI group versus 9.5% in the medical therapy group (HR 0.07, CI 0.02-0.22)
The FAME 2 investigators wrote that PCI was found to be beneficial in their trial, but not in previous trials like COURAGE, because of the demonstrated presence of ischemia in their randomized population. In addition, they noted that despite receiving the best medical therapy available, there were significantly more unplanned hospitalizations with urgent revascularizations in the medical therapy group.
A very different view of the trial is presented in an accompanying editorial by William Boden, the principal investigator of the COURAGE trial, who asks: “Which Is More Enduring — FAME or COURAGE?” The first FAME trial compared angiographic-guided PCI to FFR-guided PCI but did not include a COURAGE-type arm that received optimal medical therapy alone. FAME 2 was designed to address that question, writes Boden, but it should not be interpreted to mean that FFR-guided PCI is superior to optimal medical therapy. Boden makes the following points:
- There were few “hard” events in FAME 2, and urgent revascularization could be performed without objective evidence of ischemia or positive biomarkers.
- Since the trial was unblinded, “investigators may have had a lower threshold for recommending revascularization” for patients in the medical group.
- Patients in the FFR group did not have noninvasive testing demonstrating ischemia, so some may have had preserved myocardial perfusion.
- Patients in FAME 2 were not at very high risk.
- The short follow-up period (mean, 7 months) did not leave enough time for the risk for restenosis to fully emerge.
Boden is highly critical of the early termination of the study, writing that it leaves “more questions than answers…. but the only enduring finding of the FAME 2 trial appears to be that of a reduced short-term rate of unplanned revascularization with FFR-guided PCI, with little evidence of long-term, incremental benefit on prognostically important clinical outcomes.”
More FAME 2 coverage:
- Interventionalists Rick Lange and L. David Hillis weigh in here.
- Coverage by Howard Herrmann on Journal Watch
August 27th, 2012
When Does a Risk Marker Make the Mark?
J Michael Gaziano, MD, MPH, Amit Khera, MD, MSc and Khurram Nasir, MD MPH
CardioExchange asked three prevention experts to comment on two recent studies of cardiovascular risk markers, published in JAMA.
THE STUDIES
In an analysis of data from 1330 intermediate-risk participants in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium provided “the highest improvement in discrimination” for CHD risk, relative to five other risk markers studied.
In a meta-analysis of 14 studies on carotid intima-media thickness, involving nearly 46,000 patients, adding CIMT to risk prediction provided only a small improvement in net reclassification, which the authors determined “unlikely to be of clinical importance.”
See complete news coverage on CardioExchange.
THE EXPERTS RESPOND
Question: Which, if any, additional risk markers are practical enough to use routinely? How do we determine when a risk marker crosses the threshold of usefulness?
J. Michael Gaziano (Brigham and Women’s Hospital; author of the JAMA editorial on these two studies)
Risk markers have two uses: They can be predictors of risk or targets for intervention. While many novel markers capture various aspects of the atherothrmobotic process and reveal valuable insights about mechanism, they often do not greatly enhance our approach to risk assessment in the clinical setting. Risk assessment using a simple prediction model that incorporates a few easy-to-assess risk factors such as age, sex, smoking, blood pressure, etc. has really stood the test of time. Developed in the 1960s by investigators for the Framingham Heart Study, available risk scores provide estimates that get patients into broad risk categories. For most clinical decisions, that’s good enough. Adding new markers generally does not improve the process for several reasons.
Many new markers are correlated with the older ones; thus, the performance of the models is only modestly improved. While reclassification of patients is used as one metric for improving these models, in clinical practice we are concerned only about reclassification when a patient is near the boundary where a clinical decision is to be made. Improving the accuracy of someone’s risk assessment if that risk is very high or very low may not be useful when it does not alter our clinical decisions for that patient. If a patient is near a decision boundary, we could consider merely repeating the risk assessment score at some point in the future. Repeating a diagnostic test can improve its accuracy and, further, can provide information about its trajectory.
For those few markers that seem to yield a meaningful improvement in the characteristics of the risk modeling, which may be the case for coronary calcium scoring, work remains to be done. We have to weigh the incremental value of the knowledge gained against the costs and the risk of obtaining the results of the novel test. This is needed to better understand for whom and in what situations a novel marker has real utility. Little work in this area has been done. For these reasons, the bar remains high for improving risk-prediction modeling using current risk scores comprising simple, low-cost conventional risk factors.
Amit Khera (UT Southwestern Medical Center)
The move from simple hazard ratios and P values (i.e., statistical associations) to more clinically meaningful metrics, such as the net reclassification improvement (NRI), has been incredibly valuable for evaluating risk markers. By current metrics, coronary artery calcium (CAC) scanning is the clear winner and, in my experience, can be very helpful in treatment decisions for individual patients. However, for routine application, the devil is in the details. Beyond short-term (10-year) risk, CAC scanning is not feasible for people age 30 to 40, for whom preventive efforts offer greater long-term benefits. Fewer than 5% of women are intermediate-risk, so our current algorithms undercut the potential value of additional risk markers in this group. Rather than picking the one best marker, it may be best to use them in combination — and differently in various populations or for predicting specific endpoints (e.g., CAC poorly predicts stroke). Most important, we have no consensus (or good evidence) about the appropriate intervention for a particular level of most markers, including CAC score.
Khurram Nasir (Baptist Health South Florida; Johns Hopkins University)
In my opinion, these studies offer nothing new. The MESA analysis basically confirms the established value of CAC, relative to other biomarkers and risk factors, in terms of prognostication, discrimination, and reclassification of risk for future CVD. The real question is how to gauge whether “novel” risk markers are useful for clinical management. I believe that such markers will cross the critical threshold only when they are able to guide intensity of treatment by identifying which groups are — and which groups are not — likely to benefit from pharmacotherapy, thereby helping to improve decision making about resource allocation. What we need now is a clinical trial comparing the utility and cost-effectiveness of all candidate markers simultaneously. Until then, from the standpoint of clinical equipoise, CAC appears to be the best choice, as it identifies “appropriate” clinical risk and thereby limits under- and overtreatment when only traditional, Framingham-based risk stratification is used.
Which, if any, additional risk makers do you think are ready for routine use in clinical practice?
August 27th, 2012
The Return of Vorapaxar, This Time for Post-MI Patients
Larry Husten, PHD
The once highly promising novel antiplatelet agent vorapaxar, widely thought to be dead on arrival after unacceptably high serious bleeding rates were found in two large clinical trials, has now returned to active duty. On Sunday the drug’s sponsor, Merck, announced that it would seek approval of the drug, with a narrower indication than originally planned, based on new data from a prespecified analysis of the TRA 2P-TIMI 50 trial presented at the ESC and published simultaneously in the Lancet.
Merck said it planned to file applications next year in the United States and Europe for an indication for the prevention of CV events in patients with a history of MI and no history or stroke or TIA.
The new hope for the drug is based on an analysis of the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events trial, which was originally presented in March at the ACC and published simultaneously in the New England Journal of Medicine. In the overall trial, which randomized 26,449 patients with a history of MI, ischemic stroke, or peripheral arterial disease to either vorapaxar or placebo in addition to standard therapy, the rate of CV death, MI, or stroke was significantly reduced by vorapaxar, but a doubling of the rate of intracranial bleeding left many convinced the drug was not commercially viable.
The new analysis, presented at the ESC by Ben Scirica, focused on the subgroup of 17,779 TRA 2P patients — a group larger than usually found in the entire population of most clinical trials, it should be noted — with a history of myocardial infarction. After a median 2.5 years of follow-up, the rate of CV death, MI, or stroke was significantly lower in the vorapaxar group than in the placebo group, although vorapaxar was also associated with an increased risk for bleeding, but not intracranial bleeding:
- Primary endpoint: 8.1% versus 9.7% (HR, 0.80; 95% CI 0.72-0.89, P<0.0001)
- Moderate or severe bleeding: 3.4% versus 2.1% (HR, 1.61; 95% CI, 1.31-1.97, P<0.0001)
- Intracranial hemorrhage: 0.6% versus 0.4%; P=0.076
The authors acknowledged the limitations of subgroup analysis but proposed that vorapaxar might benefit a population with a history of MI but with no history of stroke or TIA, age below 75, and weight over 60 kg.
In an accompanying comment in the Lancet, Stefan James and Claes Held write that the “results support the addition of long-term antithrombotic treatment for patients who have had a myocardial infarction.” But, they ask, “will doctors, patients, health-care providers, and funding agencies accept use of an expensive drug to reduce the risk of myocardial infarction and possibly death in view of the increased risk of severe bleeding?”
August 27th, 2012
IABP Randomized Trial Delivers a Shock
holgerthiele131
We asked the lead author of the IABP-SHOCK II trial to shed further light on his study group’s findings.
THE TRIAL
Six hundred patients patients with acute MI complicated by cardiogenic shock were randomized, in unblinded fashion, to either intraaortic balloon counterpulsation (IABP) or no IABP. All patients were expected to undergo early revascularization (PCI or bypass surgery) and to receive the best available medical therapy.
The 30-day mortality rate (primary endpoint) was 40% in the IABP group and 41% in the control group – a nonsignificant difference. The two groups also did not differ significantly in any other endpoints, including major bleeding, peripheral ischemic complications, sepsis, stroke, renal function, and length of ICU stay.
See news coverage on CardioExchange and analysis from Beat Meyer on Journal Watch.
THE EXPERT RESPONDS
Q: Is it time to overturn – or at least reconsider – the class I guideline recommendation that patients with acute MI complicated by cardiogenic shock undergo IABP? Or should we wait for longer-term mortality data before the guidelines are re-envisioned?
Thiele: I believe that the class I recommendation was always too optimistic because no evidence from randomized trials showed that IABP can improve outcomes. Only registry data have even suggested the possibility of higher mortality if IABP were used in conjunction with primary PCI, and IABP’s benefit was mainly in patients who underwent thrombolysis or no reperfusion. The German/Austrian S3 guidelines, first published in 2011, took this into account and recommended only that the IABP may be used. Those guidelines also stated that we need a randomized trial, which we now have with the IABP-SHOCK II trial, and our findings challenge the current U.S. and European guidelines. I do not believe that at longer follow-up the results of the 30-day outcome will change. Nevertheless, we are very interested in the long-term results.
Q: Was the high number of endpoint events in your trial enough to outweigh the modest sample size of 600 patients? Why or why not?
Thiele: Indeed, we only included 600 patients, which is nonetheless the largest trial performed yet in cardiogenic shock. Trials in cardiogenic shock usually do not need very high patient numbers because of the high event rates. The only minor difference in mortality between the two groups — together with the lack of difference in any of the secondary endpoints or process-of-care measures, – which are usually much more sensitive for detection of meaningful clinical changes — make any clinically relevant effect of IABP unlikely. Therefore, even if we had a larger sample size, a change in the results is extremely unlikely.
Q: As a practical matter, given your finding of no advantage for IABP in acute-MI patients with cardiogenic shock, how would you act tomorrow if confronted with such a patient?
Thiele: What we have learned from IABP-SHOCK II is that approximately 60% of the patients will survive if we treat them according to guidelines — namely, early revascularization in all and dedicated intensive care. The German/Austrian S3 guidelines give very clear recommendations on how to treat cardiogenic shock patients, and we were surprised by the high adherence to the guidelines in our trial. For example, only a few patients were treated with dopamine, and the majority of those patients got norepinephrine plus dobutamine if catecholamines were required. This might be one reason why the mortality was at the lower end of the range that has been reported previously. Another important aspect is that many will now reflexively assume that we will need more and earlier left-ventricular assist devices. I believe that this is not the way to go. We will have to identify patients who might benefit from LVADs, those who might be harmed by these devices, and those who don’t need one at all. We will need good risk scores to predict outcomes for cardiogenic shock patients. This is one of the many areas in which we must move forward in the scientific work on cardiogenic shock.
What’s your view in the IABP SHOCK-II trial results?
August 27th, 2012
ESC: No Benefit of Intraaortic Balloon Counterpulsation in Cardiogenic Shock
Larry Husten, PHD
Despite a lack of evidence, circulatory support with intraaortic balloon counterpulation (IABP) has a class 1 recommendation in the guidelines and is often used in patients in cardiogenic shock following myocardial infarction for whom early revascularization is planned. That situation may change soon, as no benefit was found for the use of IABP in the first large randomized trial of the strategy.
The IABP-SHOCK II (Intraaortic Balloon Pup in Cardiogenic Shock II) was presented at the ESC and published simultaneously in the New England Journal of Medicine. Trial investigators, led by Holger Thiele, randomized 600 acute MI patients in cardiogenic shock to either IABP or no IABP. At 30 days there were no significant differences in mortality, the primary endpoint of the study:
- Mortality: 39.7% in the IABP group versus 41.3% in the control group (relative risk with IABP, 0.96; 95% CI, 0.79-1.17; P=0.69)
There were no significant differences between the groups in secondary endpoints, process-of-care outcomes, or safety endpoints, including stroke and bleeding.
In an accompanying editorial, Christopher O’Connor and Joseph Rogers write that the trial “could have affirmed contemporary clinical practice and guidelines,” but “instead, it revealed surprising results.”
“Members of guidelines committees and clinicians should take note of another example of a recommendation that is based on insufficient data,” they wrote.
