November 26th, 2014
Resolving the Questions About Door-to-Balloon Times
Brahmajee Kartik Nallamothu, MD, MPH
CardioExchange’s John Ryan interviews Brahmajee K. Nallamothu about his research group’s retrospective study of changes, over time, in the relation between door-to-balloon (D2B) times and mortality after primary PCI. The study is published in The Lancet.
Ryan: Why is this study important? Haven’t we figured out D2B time already?
Nallamothu: This study was very important. D2B time is a highly visible performance metric for hospitals that conduct primary PCI. The D2B Alliance and Mission:Lifeline, two large national quality initiatives, have both targeted D2B time in their protocols (or its equivalent “first medical contact-to-balloon”), and the CMS considers D2B one of its core measures for acute MI. However, recent reports using population-level data, including a highly visible NEJM article from last year (Menees et al.), showed that contemporary decreases in D2B time do not correlate with improvements in mortality. According to some observers, this finding suggests that D2B time may not matter for individual patients. If true, that has big implications, as health systems have devoted enormous resources to tackling this problem.
However, Harlan Krumholz and I have been involved in this space for more than a decade now, and we found this interpretation very difficult to understand. It conflicted with prior literature and was inconsistent even with data presented within these reports themselves, which noted consistent individual-level relationships between D2B time and mortality. We felt that resolving this apparent paradox of “shorter D2B times but no change in mortality at the population-level” was important because misinterpretations could lead health systems to pull back from some of the dramatic gains in STEMI care made during the past decade.
Ryan: Did you resolve the contradiction? Could you summarize your findings?
Nallamothu: We did resolve the contradiction at least partially. The key to understanding it was the ecological fallacy that population-level or “aggregate” relationships do not necessarily represent individual-level relationships. For example, the Menees et al. article examined the median D2B time for all the patients who underwent primary PCI in that year and then assigned that value to individuals, regardless of their own D2B time. In such a model, the aggregated median D2B time variable represents many secular factors that were simultaneously changing with year — not just D2B time. What we did was to tease out the individual-level relationship of D2B time with mortality after accounting for the population-level relationship. Our key insight was that the individual-level relationship between D2B time and mortality remained consistent over years, whereas the population-level relationship suggested increased mortality with the population undergoing primary PCI over years. This last finding explains why an overall “null” effect existed at the population-level despite shorter D2B times. The ecological fallacy is something that epidemiologists have long understood and accounted for in their evaluation of population-level data and aggregate relationships. We have not done as good a job in health services research, and this can be dangerous by leading to errors in statistical inference (see Finney et al.).
Ryan: Why is there a trend toward increased mortality with primary percutaneous PCI despite the decrease in D2B time? Why are the patients sicker and more complicated?
Nallamothu: We think it is important to put our findings in the context of what’s been happening in STEMI care during the past decade. Our best estimates suggest that the proportion of STEMI patients who are now treated with primary PCI rather than fibrinolytic therapy has doubled. In addition, the growth of STEMI systems of care are now bringing more STEMI patients to the cath lab who might have died in prior years, as treatment has sped up. Terkelsen and colleagues have called this the “survivor cohort” effect. Both of these facts make it challenging to evaluate the impact of changes at the population-level in D2B time, independent of other unrelated factors in STEMI care that were occurring. This is apparent in our data, where we noted that in a stable cohort of hospitals performing primary PCI, the number of patients treated with primary PCI grew by 55%, and several procedural factors changed over time. Bottom line: The patients who are going to the cath lab with STEMI in 2011 are not the same as those treated in 2006 — and this needs to be appreciated.
Ryan: There appear to be variable rates of usage of drug-eluting stents (DES) vs. bare-metal stents (BMS) in these patients (Table 1 of your article). Please explain this variability.
Nallamothu: This is a great example of what I discuss above: so many moving parts were happening simultaneously in STEMI care, even within this short time period, as both the patients and treatments changed. The variability in DES vs. BMS usage has much to do with the concerns raised about subacute stent thrombosis with DES in 2006, leading to an FDA warning and lots of press about their use relative to BMS. Much of this variability, I believe, is a shift in interventionalists’ views toward those technologies. We see the same patterns in use of antithrombotic medications and devices such as thrombectomy catheters.
Ryan: On a population level, what are the next targets worth pursuing to improve outcomes from STEMI and primary PCI?
Nallamothu: The Menees et al. article is an important study that started a valuable conversation among providers of STEMI care. I agree with them and others that we need to start looking toward new targets for STEMI care but that we also need to safeguard the gains we’ve made in D2B times. We have now established remarkable STEMI systems of care in Europe and North America that can bring more patients, more rapidly, to the right providers. We are also seeing tremendous advances in medical therapy and risk-factor management. I think the major goals of STEMI care continue to be (1) reducing errors in false-activation of STEMI systems to reduce the burden on providers; (2) reducing time from symptom onset to seeking treatment; (3) improving STEMI systems of care in underserved, rural and isolated communities; (4) finding the best mix of pharmacologic and mechanical reperfusion strategies; and (5) developing better options for late presenters who are at risk for reperfusion injury and shock that can lead to early mortality. Pedersen and colleagues recently published data from Denmark showing that patients who survive the first month after STEMI do remarkably well in follow-up (less than a 1.5% annual risk for death from cardiovascular causes). This is highly treatable disease!
JOIN THE DISCUSSION
How does Dr. Nallamothu’s study affect your understanding of the literature about door-to-balloon times?
November 24th, 2014
Selections from Richard Lehman’s Literature Review: November 24th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
JAMA 19 November 2014 Vol 312
Percutaneous Left Atrial Appendage Closure vs. Warfarin for AF (pg. 1988): And now we must turn to the left atrial appendage. As its name suggests, this is a bulge in the left atrium, somewhat fancifully described as “wind-sock shaped.” In non-valvular atrial fibrillation, this is the main site where clot forms. So if you close off the appendage, then you might be able to prevent stroke in AF without the need for anticoagulation. And according to the PROTECT-AF trial, this is indeed the case: “After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.” Once we have better long term data, this could change the routine management of AF.
Association of Inpatient vs. Outpatient Onset of STEMI with Treatment and Clinical Outcomes (pg. 1999): If you have a heart attack in hospital, you are less likely to receive invasive treatment and much more likely to die. This finding emerges from a study of outcomes in 303 hospitals in California, and you can guess at some of the reasons why this should be so. The 5% of myocardial infarction patients who have their event in hospital are older and iller than those who are brought in by ambulance; and those whose MIs are immediately fatal in hospital are going to be counted in the figures, unlike patients who drop dead from heart attacks outside hospital.
Association Between Use of β-Blockers and Outcomes in Patients with HF and Preserved EF (pg. 2008): As you should know by now (since I mention it so frequently), half of old people with the syndrome of heart failure do not have a reduced systolic ejection fraction. The treatments that have some effect on people with impaired systolic function have no effect on them, at least in terms of hospital admission and survival. But a Swedish registry study suggests a possible benefit from β-blockade: “In patients with HFPEF, use of β-blockers was associated with lower all cause mortality but not with combined all cause mortality or heart failure hospitalization. B-blockers in HFPEF should be examined in a large randomized clinical trial.” But why? In these patients, whose mean starting age was 76, the difference in five year survival between those taking β-blockers or not was 45% vs 42%. This just scrapes into apparent statistical significance, provided you don’t round up 0.996 to 1 (hazard ratio [HR], 0.93; 95% CI, 0.86-0.996; P = .04). But consider that this is an observational study, not a randomised trial: people who are able to tolerate β-blockers are not the same as those who cannot; and no amount of propensity scoring can make them so, or balance the groups to a CI of 0.004. And then consider what you would want if you were 76 and had a stiff old heart that was beginning to cause you breathlessness and oedema. Would you want to take an extra pill a day, which might conceivably give you a 3% better chance of living out another five years, at the likely cost of more breathlessness and greater tiredness? My guess (confirmed by several studies) is that you would want something to make you feel better, even at the risk of shortening your remaining life. The drugs that need to be trialled in these patients might be β-adrenergic stimulants, not blockers.
Fixed-Dose Combination Therapy (Polypill) for the Prevention of CVD (pg. 2030): And now think about another therapeutic issue: dosing the entire population so that the herd, on average, can live a few weeks longer. How does individual choice fit in? What number needed to treat are you striving for, and what harms should individuals be asked to trade with it? Not that most real people make their choices this way, but never mind. I am talking, of course, about the polypill. I will just leave you with this summary of the evidence: “Polypills are associated with greater reductions in systolic blood pressure and total cholesterol compared with usual care, placebo, or active comparators, but also with a 19% higher risk of any adverse event. Due to limited power from available evidence, the association of polypills with all cause mortality or fatal and nonfatal CVD events is uncertain.”
Ann Intern Med 18 November 2014 Vol 161
Relation of NSAIDs to Serious Bleeding and Thromboembolism Risk in Patients With AF Receiving Antithrombotic Therapy (pg. 690): I do wish there was a journal series that would remind working doctors—especially in primary care—of the risks they run of poisoning patients with common drugs. I was no saint in this respect myself, but after this week I cannot do any more harm as I shan’t be treating patients. What’s the harm of a bit of ibuprofen in someone with atrial fibrillation? A study of 150 900 Danish patients with AF gives us the answer. “Use of NSAIDs was associated with increased absolute risks for serious bleeding and thromboembolism across all antithrombotic regimens and NSAID types.” By using NSAIDs in these patients (and even more in those with heart failure) you are negating the effects of all the protective treatment they are taking.
Lancet 22 November 2014 Vol 384
Unfractionated Heparin vs. Bivalirudin in Primary PCI (HEAT-PPCI) (pg. 1849): Last week I shrugged my shoulders as I told you about the latest meta-analysis of anticoagulant regimens for use during percutaneous coronary intervention (The BMJ): “In patients undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor and LMWH plus GpIIb/IIIa inhibitor were most efficacious, with the lowest rate of major adverse cardiovascular events, whereas bivalirudin was safest, with the lowest bleeding.” I remarked that these meta-analyses change with each new piece of evidence, and this week’s print Lancet illustrates the point. The HEAT-PPCI trial concludes: “Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially.” OK, so bivalirudin may not be the safest, with the lowest rate of bleeding. Can a mere Toyota owner dispute the findings of a study, which had among its sponsors The Bentley Drivers Club (UK)?
The BMJ 22 November 2014 Vol 349
Decision-Making Tools for Statins: Margaret McCartney’s excellent column this week has the title “We lack the tools to help patients decide about statins.” It’s true that we lack the ideal tool, but there are several which, with suitable tweaking, could be used in real life primary care. The first and most comprehensive is Victor Montori’s from the Mayo clinic.
A single page tool that is easy to use and which incorporates a wide range of risk reducing options has been developed by James McCormack.
The most recent, which compares statins directly with dietary modification and activity, is the Option Grid, which I helped to develop.
Soon there will be a package directly developed by NICE. But what we really need is a two click tool that allows GPs to instantly calculate the figures for individual people, based on their health record, and print off a personalised decision aid that makes sense to users at all levels of education. Long term risk reduction is a matter for shared decision making, not for pronouncements by experts who never see patients.
November 24th, 2014
European Review Confirms Increased Risk with Ivabradine
Larry Husten, PHD
Following a review provoked by troubling findings that emerged from a large clinical trial, the European Medicines Agency (EMA) is making several recommendations intended to lower the risk of heart problems linked to the heart-rate-lowering drug ivabradine. The drug is marketed by Servier in Europe under the brand names of Corlentor and Procoralan and is indicated for the treatment of heart failure and stable angina. The drug is not available in the U.S. but is under development by Amgen for the indication of heart failure.
The review by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) concluded that ivabradine “should only be started if the patient’s resting heart rate is at least 70 beats per minute.” The drug should only be used for the symptomatic relief of angina because it “has not been shown to provide benefits such as reducing the risk of heart attack or cardiovascular death.”
The committee also recommended that ivabradine should not be prescribed along with verapamil or diltiazem, drugs that also lower the heart rate. In addition, patients taking ivabradine should be monitored for atrial fibrillation and if AF develops the physician should re-evaluate treatment with ivabradine.
Concern about ivabradine emerged earlier this year due to results of the very large SIGNIFY study testing a high dose of ivabradine in more than 19,000 patients with stable angina. Although the overall results were neutral, troubling findings occurred in the very large subgroup (more than 12,000 patients) with symptomatic angina. The EMA review concluded that in these patients ivabradine, compared with placebo, had a small but significant increase in the risk of CV death and nonfatal MI (3.4% vs 2.9% yearly incidence rates) and a substantially higher risk of bradycardia (17.9% vs. 2.1%). Also, the rate of AF was 5.3% in the ivabradine group compared with 3.8% in the placebo group. The EMA also examined additional data that confirmed the increased risk of AF in ivabradine patients.
The EMA said that the higher than recommended dose of ivabradine used in SIGNIFY “did not fully explain the findings.” But it repeated its guidance that the initial dose of ivabradine for angina should be no greater than 5 mg twice a day and that the maximum dose should not exceed 7.5 mg twice a day.
November 21st, 2014
Encouraging Results for Two New Drugs for Hyperkalemia
Larry Husten, PHD
Two new agents under development may help curb and prevent hyperkalemia, the common and serious side effect of drugs that inhibit the renin-angiotensin-aldosterone system (RAAS), which are the cornerstones of the treatment of chronic kidney disease and heart failure.
In a phase 3 study, published online in the New England Journal of Medicine, researchers first randomized 753 patients with hyperkalemia to treatment for 48 hours with either placebo or 1 of 4 different dosages of sodium zirconium cyclosilicate (ZS-9), a novel agent from ZS Pharma that captures potassium in the GI tract and rapidly lowers serum potassium. Treatment with ZS-9 was associated with clinically important and statistically significant reductions in potassium during this period. At the highest two dosages the investigators reported normalization of serum potassium, with the highest dosage leading to a mean reduction in serum potassium of 1.1 mmol/liter in patients who had levels greater than 5.5 mmol/liter at baseline.
Patients who achieved normal potassium levels during the initial phase were then randomized in a maintenance phase of the study to continued treatment with ZS-9 or placebo on days 3-14. In the placebo group potassium levels remained elevated above 5.0 mmol/liter, while in the groups taking the two highest dosages of ZS-9 potassium levels were 4.7 and 4.5 mmol/liter. ZS-9 treatment did not lead to an excess of adverse events. The most common complication was diarrhea.
In a second report, also published in the New England Journal of Medicine, investigators first treated 237 chronic kidney disease patients who had elevated potassium levels with patiromer, a nonabsorbed polymer that binds potassium and which is under development by Relypsa. After four weeks of treatment potassium was reduced by 1 mmol/liter and 76% of the patients had reached target levels.
In a second, withdrawal phase of the study, 107 patients were randomized to placebo or patiromer for eight weeks. Hyperkalemia occurred in 60% of patients in the placebo group compared with only 15% of patients in the treatment group. Constipation was the most common adverse event linked to patiromer.
In an accompanying editorial, Julia Ingelfinger states that both agents “appear to offer some promise for the treatment of hyperkalemia in patients with chronic kidney and cardiac disease.” She is concerned, however, about the long-term “durability and side-effect profile of these agents” given the relatively short span of these two studies. “Whether either or both of these agents will permit long-term administration of renoprotective and cardioprotective agents that block the RAAS will require more investigation.”
November 21st, 2014
Encouraging Results For Two New Drugs For Hyperkalemia
Larry Husten, PHD
Two new agents under development may help curb and prevent hyperkalemia, the common and serious side effect of drugs that inhibit the renin-angiotensin-aldosterone system (RAAS), which are the cornerstones of the treatment of chronic kidney disease and heart failure.
…
Click here to read the full post on Forbes.
November 20th, 2014
Intention to Tweet: Does Social Media Exposure Matter for Journal Articles?
John Ryan, MD
Journals increasingly use social media to share medical information. After original research is published, the social media attention it receives correlates with how often it is cited. But does such attention enhance a journal article’s overall impact?
To address this question, my fellow researchers and I randomly assigned 243 consecutive original research articles published in Circulation during the past year to a “social media exposure” arm or a control arm. (Articles that had simultaneous press releases, AHA presentations, or Author profiles were excluded.)
On the day of publication, we tweeted about articles in the social media arm on the official Circulation Twitter page (@CircAHA) and the official Circulation Facebook page. Articles in the control arm received no formal, journal-based social media exposure. Here are examples of a tweet and a Facebook post that we have published during the past year:
With respect to the primary endpoint — article page views within 30 days — articles in the two arms showed no significant difference (median, 409 for social media exposure vs. 392 for control; P=0.80). Among basic science articles, social media exposure showed a trend toward greater page views, but the study was not powered or designed to detect a significant difference.
We think this social media strategy did not affect page views for three reasons:
- Researchers who are interested in articles in Circulation may already be inclined to read them on the journal’s website and not rely on social media to learn about journal articles.
- Cardiology still occupies a minute space on Twitter, where 350 million tweets are posted daily.
- Most Twitter and Facebook users access social media on their phones. In that setting, simply seeing a headline on a newsfeed may suffice, rather than accessing entire papers on the handheld device. Plus, Circulation followers may find our post and the key figure we provide to be enough to satisfy their interest.
According to our work, a social media strategy for Circulation did not increase the number of times an article is viewed. Further research is needed to help us understand and quantify the effect of social media on the reach of published cardiovascular research.
Note: Comments on this news story are closed, but please join the discussion about this topic over at Larry Husten’s discussion of the challenges those in traditional medicine have when using social media to promote research.
November 19th, 2014
U.S. Proposal Would Greatly Expand Transparency of Clinical Trials
Larry Husten, PHD
The U.S. Department of Health and Human Services today proposed new rules that would greatly expand the number of clinical trials that companies and researchers are required to report.
“Medical advances would not be possible without participants in clinical trials,” said NIH Director Francis Collins. “We owe it to every participant and the public at large to support the maximal use of this knowledge for the greatest benefit to human health. This important commitment from researchers to research participants must always be upheld.”
Currently, researchers are required to publish information on ClinicalTrials.Gov, the public database run by the National Library of Medicine, about studies involving drugs, biological products, and devices that are regulated by the FDA, but these regulations do not apply to phase 1 trials of drugs and biological products and small feasibility studies of devices. The new rule would expand the reporting requirements to include all trials of unapproved, unlicensed, and uncleared products. A second proposal would also require the publication of all clinical trials funded by the NIH.
“This is a great day for research in America,” said Harlan Krumholz, who has been an advocate for greater transparency. “NIH is exhibiting extraordinary leadership in exerting their influence to promote the responsible conduct of research for anyone receiving their funds. It’s a day to applaud these actions.”
A statement from the NIH explained the benefits of increased transparency:
Among the primary benefits of registering and reporting results of clinical trials, including both positive and negative findings, is that it helps researchers prevent unnecessary duplication of trials, particularly when trial results indicate that a product under study may be unsafe or ineffective, and it establishes trust with clinical trial participants that the information from their participation is being put to maximum use to further knowledge about their condition.
November 18th, 2014
Losartan No Better Than Atenolol in Marfan’s Syndrome
Larry Husten, PHD
Beta-blockers have been the standard treatment for people with Marfan’s syndrome, a rare inherited connective tissue disorder that affects about 1 in 5000 people. The goal of treatment is to prevent or slow down the dilation of the aorta and avoid aortic dissection, the main cause of death. In recent years, studies have raised the hope that losartan, an angiotensin receptor blocker, might be more effective than beta-blockers in slowing aortic enlargement.
The Pediatric Heart Network Investigators randomized 608 children and young adults with Marfan’s syndrome to the beta-blocker atenolol or losartan. After 3 years of follow-up, they reported no significant difference between the two groups in a measurement of aortic-root growth. There were also no differences between the groups in the rates of aortic surgery, aortic dissection, or death. Results of the trial were presented at the American Heart Association meeting in Chicago and published simultaneously in the New England Journal of Medicine.
One finding of potential importance was that the rate of aortic growth decreased more in younger patients in both treatment groups. “This finding suggests that there is merit in starting therapy at a younger age and at an earlier stage of the disease,” said Ronald Lacro, the principal investigator of the study.
John Elefteriades was the discussant of the trial at the AHA meeting. He said it was unlikely that the trial result was a false-negative, since it enrolled enough patients, gave a sufficient dose of the study drugs, and followed patients for a long enough time. He said that the “therapeutic quiver is not completely empty,” though, as early studies raise the hope that statins may be useful in this condition.
In the accompanying editorial in NEJM, Juan Bowen and Heidi Connolly advise that clinicians “should continue to consider beta-blockers to be the primary medical therapy for aortic protection in Marfan’s syndrome. Losartan appears to be a reasonable treatment option, especially in patients who cannot take beta-blockers.”
November 18th, 2014
Don’t Count the Numbers. HDL Function Looks Like the Key
Larry Husten, PHD
A new study offers important evidence explaining the protective role of HDL cholesterol against cardiovascular disease. Previous studies with drugs that increase HDL levels, including niacin and CETP inhibitors, have not been found beneficial. The new study suggests that simply increasing HDL levels isn’t useful. Instead, cholesterol efflux, the ability of HDL to remove cholesterol from cells — part of the process called reverse cholesterol transport — appears to be the key. The results were presented on Tuesday by Anand Rohatgi at the American Heart Association meeting in Chicago and published in the New England Journal of Medicine.
The investigators followed 2416 people participating in the Dallas Heart Study, who were free of cardiovascular disease at baseline, for 9.4 years. In accord with previous studies, there was a trend suggesting that HDL levels were linked to the development of cardiovascular events, but this association dissolved when other risk factors were considered, so that HDL level did not emerge as a significant independent predictor of cardiovascular disease. By contrast, cholesterol efflux was a strong predictor of outcome, “suggesting that HDL function is associated with cardiovascular risk by means of processes distinct from those reflected by the HDL cholesterol level, HDL particle concentration, or traditional cardiovascular risk factors,” according to the authors.
Daniel Rader, a co-author of the study, was also the discussant at the AHA session. He noted that a previous study had linked cholesterol efflux with prevalent coronary heart disease, but this was the first study to follow people and show that cholesterol efflux was linked to the development of cardiovascular disease over time. Rader expressed optimism about potential roles for cholesterol efflux in the future. According to Rader, efflux may one day be used as a clinical test to assess cardiovascular risk or to assess new therapeutic interventions.
A poster also presented at the AHA meeting provided some of the first results with a therapy intended to enhance cholesterol efflux. CSL112 is a novel formulation of apoA-I, the HDL component that is thought to be the key component in efflux. One study showed that CSL112 significantly increased efflux in 93 people without cardiovascular disease and 44 patients with stable coronary artery disease. This increase occurred in those with both low and high efflux activity at baseline.
November 17th, 2014
Large Japanese Trial Casts Further Doubt on Aspirin for Primary Prevention
Larry Husten, PHD
A large trial from Japan failed to provide any evidence to support the use of routine aspirin in high-risk elderly people to prevent a first cardiovascular event.
The Japanese Primary Prevention Project (JPPP), presented at the American Heart Association meeting in Chicago and published simultaneously in JAMA, enrolled patients between 60 and 85 years of age with hypertension, dyslipidemia, or diabetes. The open label study randomized 14,464 patients to aspirin 100 mg once daily or no aspirin in addition to conventional therapy. Patients were followed for up to 6.5 years for the primary combined endpoint of cardiovascular death, nonfatal stroke, or nonfatal MI.
The trial was designed to accrue enough primary endpoints to make the results meaningful. The independent Data Monitoring Committee discontinued the study after a smaller number than expected endpoints had occurred and it became clear the trial would not be able to reach a statistically significant result.
There was no significant difference in the primary endpoint at any point during the course of the trial (HR 0.94, CI 0.77-1.15, p=0.544). There were 56 fatal events in each arm. Nonfatal events occurred in 137 patients in the aspirin arm versus 151 in the no aspirin arm. The results were consistent across subgroups.
Compared to placebo, aspirin resulted in a significant decrease in nonfatal MI, a marginal reduction in TIA, but a significant increase in serious extracranial hemorrhages. Aspirin also was associated with a big increase in gastrointestinal side effects, including a doubling of duodenal ulcers and a tripling of GI bleeds.
The authors said that although the power of the study was diminished by its early discontinuation, it demonstrates that “the clinical importance of aspirin in the primary prevention of cardiovascular events is less than originally anticipated in this patient population.”
In an accompanying editorial, J. Michael Gaziano and Philip Greenland write that the “results are consistent with those of other primary prevention trials,” with the exception of a higher intracranial hemorrhage rate in the Asian population studied in the trial.
Gaziano and Greenland say that the decision to use aspirin “remains clear in several situations. Aspirin is indicated for patients at high short-term risk due to an acute vascular event and those undergoing certain vascular procedures; patients with any evidence of vascular disease should be given daily aspirin. On the other hand, patients at very low risk of vascular events should not take aspirin for prevention of vascular events, even at low dose.” The decision is more difficult, they write, in people who do not have overt vascular disease but who nevertheless are at very high risk for cardiovascular disease. “It remains likely that there is some level of risk of CVD events that would result in a positive trade-off of benefit and risk for the use of aspirin, but the precise level of risk is uncertain.”
NEJM Journal Watch — Recent Cardiology Articles- To Lower Stroke Risk in Patients Undergoing Atrial Fibrillation Ablation, Is a Device or a Medication Better?
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