February 19th, 2010
Who Does and Who Doesn’t Get Aspirin? Can We Do Better?
Christopher Paul Cannon, MD
Aspirin is the best known and most widely used preventive therapy. A century of clinical experience and randomized trials in over 250,000 patients have proved its benefit in preventing cardiovascular events, and it costs pennies a day. So how can it be that not everyone who needs it gets it?
In a new report, we used prospective, longitudinal data from REduction of Atherothrombosis for Continued Health, a unique registry of outpatients with established atherothrombosis or multiple risk factors, to look at current, “real world” practices of cardiovascular protection. Of more than 25,000 U.S. participants, we found that approximately one quarter of those with vascular disease are not treated with aspirin for secondary prevention, and 15% are not treated with any antithrombotic agent (i.e., aspirin, warfarin, or other antiplatelet agents). Of patients who had risk factors only (i.e, no history of MI, stroke, or peripheral arterial disease), one third were not taking any antithrombotic agent.
So, I see two issues here:
we need to try to make sure that all patients with vascular disease get aspirin (or another antithrombotic agent), and
we need o determine which patients who are at risk for — but have not yet developed — vascular disease should also be receiving such treatment.
1. Secondary prevention. We didn’t ask investigators why they were not treating individual patients with aspirin. Asking that question would be the next step in a quality-improvement initiative to try and extend aspirin treatment to 100% of eligible patients (understanding that some have contraindications). One option for clinicians who use electronic medical records would be to get an automatic reminder that the patient should be on aspirin or another antithrombotic agent whenever we enter a diagnosis of MI, stroke, or PAD or performance of PCI or CABG.
2. Primary prevention. Here, the data are more mixed. A recent analysis by the Antithrombotic Trialists Collaboration found that although patients with only risk factors benefit from treatment, the benefit is very small in low-risk patients: just an 0.25% absolute reduction in cardiovascular death, MI, or stroke per year of treatment. The ATT investigators also reported an increase in bleeding of about half the amount of absolute reduction in occlusive events. Thus, the key question remains: how many patients who do not have cardiovascular disease should be treated with aspirin?
I agree with Drs. Tapp, Shansila, and Lip, the editorialists who commented on the REACH report, who call for a reconsideration of international guidelines regarding aspirin in primary prevention.
What do you do in your practice? Do you prescribe aspirin for 100% of your patients with vascular disease? How do you handle primary prevention? What does your institution need to do to improve antithrombotic use?
February 18th, 2010
Thursday, February 18 News: Renal Outcomes in ACCOMPLISH Published in Lancet
Larry Husten, PHD
The combination of benazepril plus amlodipine was more effective than the combination of benazepril plus hydrochlorothiazide in preventing progression of chronic kidney disease, according to a new report from the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial published online in the Lancet. ACCOMPLISH investigators had previously reported the main results of the trial, which was stopped early when the benazepril/amlodipine combination was found to be more effective in reducing cardiovascular events in 11,506 high-risk patients. In the new report, Bakris et al. write that this substudy “shows that in patients with hypertension at high risk for cardiovascular events, combination treatment with benazepril plus amlodipine reduces progression of chronic kidney disease more effectively than does benazepril plus hydrochlorothiazide.” However, an accompanying comment by Hiddo Lambers Heerspink and Dick de Zeeuw says that the investigators’ conclusion may be unwarranted, and cites problems with the trial design and a result driven by a single component of a combined endpoint.
February 17th, 2010
Which Strategy for Severe Calcific Aortic Stenosis?
Anju Nohria, MD and James Fang, MD
The patient is a 72-year-old man with a history of ischemic cardiomyopathy (LV ejection fraction, 30%–35%) and NYHA class II/III heart-failure symptoms at baseline. Over the previous month, he had experienced recurrent episodes of volume overload and sustained ventricular tachycardia (VT) requiring intravenous diuretics and up-titration of his amiodarone therapy. He then presented in VT storm, requiring intravenous lidocaine in addition to amiodarone, and was transferred to a tertiary care facility for potential VT ablation.
His additional medical history is noteworthy for hypertension, hyperlipidemia, insulin-dependent type II diabetes mellitus, paroxysmal atrial fibrillation, chronic renal insufficiency (serum creatinine, 1.5 mg/dL), mild chronic obstructive lung disease, and Parkinson’s disease. He underwent bypass surgery for coronary atherosclerosis in 2004 and received a biventricular pacemaker/defibrillator in 2005.
At the tertiary facility, an echocardiogram revealed an LVEF of 30%–35% (LV end-diastolic diameter, 5.1 cm) with global hypokinesis. Moderate-to-severe RV dysfunction was identified. The patient had a heavily calcified, trileaflet aortic valve with a peak gradient of 29 mm Hg, a mean gradient of 18 mm Hg, and a calculated valve area of 0.6 cm2. He also had moderate mitral regurgitation (regurgitant volume, 52 mL). His estimated pulmonary-artery systolic pressure was 21 mm Hg + RA.
A subsequent catheterization confirmed severe aortic stenosis and revealed native 3-vessel disease with patent grafts. A FDG-PET scan showed a small area of inferior scar but no ischemia.
Questions:
- Is the patient’s aortic stenosis a major contributor to his recent HF decompensation and recurrent VT?
- Which would better serve the patient: aortic valve surgery or balloon valvuloplasty?
- Should he be considered for an experimental percutaneous valve replacement?
Response:
James Fang, MD
This man appears to have significant aortic stenosis despite his modest gradient. Although the cath lab findings are not reported, they appear to corroborate the echocardiographic findings. No comment is made of assessing contractile reserve, which would help to rule out pseudo-aortic stenosis; this assessment can be done either in the cath lab or using echocardiography. Assuming that such an assessment would confirm severe aortic stenosis, I would recommend surgical aortic valve replacement.
Two other issues should also be resolved before surgery is entertained. The presence of a “porcelain” aorta would temper the enthusiasm for surgical AVR. In addition, the moderate-to-severe RV dysfunction is of concern and needs to be further clarified in the cath lab. The CVP, RVSWI, and TR are not commented on. This degree of RV dysfunction is not typically seen with severe aortic stenosis.
The patient’s comorbidities and the redo nature of an AVR increase his operative mortality. Based on publicly available risk scoring tools, his predicted mortality is in the range of 9% (STS) to 25% (EuroScore). Although these scores have been validated in various populations, they appear, to many clinicians, to overestimate risk in clinical practice. This issue has limited the interpretation of the published TAVI experience, and we await large randomized (albeit not blinded) studies such as PARTNER.
If surgical expertise is not available, a percutaneous AVR could be offered as an alternative but should be done in the context of a clinical trial. The durability of percutaneous valves is not clear and cannot be compared to conventional AVR in this regard at this time. Certainly, the recently published Canadian experience (with both transapical and transfemoral approaches) is encouraging. A “bridging” strategy could include valvuloplasty, with the understanding that the results would be temporary; this approach would primarily serve to reassure the clinicians that AVR of any sort is worth undertaking, while also potentially improving the baseline hemodynamic status of the patient.
There is reasonable evidence that wall stress and decompensated heart failure are arrhythmogenic; the patient’s aortic stenosis appears to be significant enough to contribute to this scenario. It would also be important to assess his CRT. LV stimulation can be pro-arrhythmic in certain substrates — particularly in ischemic heart disease, due to the nature of the scarring involved.
Follow-Up:
The patient underwent aortic valve replacement with a bioprosthetic valve. The total bypass time was 224 minutes with a cross clamp time of 114 minutes. On post-operative day 2, the patient was successfully weaned off pressor and intra-aortic balloon pump support. However, he was massively volume overloaded and remained somnolent, despite lack of sedation, making extubation difficult. An attempt at diuresis with escalating doses of intravenous furosemide was unsuccessful. CVVH was started but diuresis was limited by fever and hypotension. In this context, the patient developed recurrent ventricular tachycardias, requiring anti-tachycardia pacing by his device. Due to the his continued ventilator dependence, a tracheostomy and percutaneous endoscopic gastrostomy tube were placed on post-operative day 12. A chest CT revealed multifocal pneumonia and the patient was treated with broad spectrum antibiotics. He developed a spontaneous pneumothorax, requiring chest tube placement. He then developed progressive hypotension with evidence of Staphylococcus aureus bactermia. Despite escalating support, the patient suffered an asystolic arrest and died on post-operative day 20.
Conclusion:
James Fang, MD
It would be interesting to know what the surgical findings were and the intraoperative course, particularly in light of the close to 4-hour bypass time. If right ventricular dysfunction was an intra- or immediately postop issue, I wonder if RVAD support was entertained, especially since massive volume overload is commented on early after surgery. The prolonged pump time likely played a large role in his postoperative neurologic state. The source of this man’s postoperative infection would also be of interest since it ultimately led to his death. Although the ultimate outcome might temper my preoperative comments, I would still not change my overall preoperative assessment. Valvuloplasty again may have been a reasonable “bridging strategy.”
February 17th, 2010
Wednesday, February 17 News Roundup: Statins & Diabetes; ARTS II at 5 Years
Larry Husten, PHD
Statins & Diabetes: Following the recent observation from JUPITER of an increased risk of developing diabetes among patients taking rosuvastatin, a large meta-analysis in the Lancet by Sattar et al. has found a small but significant increase in the risk of diabetes for all statins. The authors conclude that “the risk is low both in absolute terms and when compared with the reduction in coronary events.” An accompanying comment by Chris Cannon points out that “the benefit in preventing total vascular events to the risk of diabetes is a ratio of about 9:1 in favor of the cardiovascular benefit — the benefit seems to greatly outweigh the risk.”
ARTS II at 5 Years: The ARTS II (Arterial Revascularization Therapies Study II) enrolled 607 patients who received a sirolimus-eluting stent (SES). These patients were then compared with 1205 historical controls from the ARTS I trial who had been randomized to either CABG or a bare metal stent. Serruys and colleagues report the 5-year clinical outcomes in an expedited publication in the Journal of the American College of Cardiology. Having acknowledged the limitations of a nonrandomized comparison with historical controls, the authors report that “SES had a safety record comparable to CABG and superior to BMS, and a MACCE rate that was higher than in patients treated with CABG, and lower than in those treated with BMS.”
February 17th, 2010
The Value of Statistical Modeling?
James De Lemos, MD
In this week’s “The Expert Is In” blog on CardioExchange, I interview Rodney Hayward about his very interesting and soon-to-be controversial paper just published in the Annals of Internal Medicine. Rodney and his coauthors argue that the current lipid guidelines are misguided.
Specifically, the authors show that the NCEP ATP III guideline approach, in which lipid-lowering therapy targets specific goals, is neither evidence-based nor an efficient and effective public health strategy. They argue that a tailored strategy, in which candidates for lipid-lowering therapy are identified based on global CV risk, would more accurately identify individuals who would benefit, would treat more patients, and would improve quantity and quality of life. The study design was….not a randomized controlled trial….not an well-performed observational study….but rather a mathematical model.
It would be difficult to perform randomized controlled trials testing all of the diverse strategies for targeting lipid-lowering therapies. Thus, modeling exercises are becoming increasingly popular strategies for attempting to answer these complex questions.
What you think of this methodology? Have you learned enough about modeling and statistics to be able to interpret these types of data? Are you convinced by the logic of this argument? (As for the important practical question — should this study, and will it, change your practice? — please tell us what you think here.)
February 16th, 2010
Tuesday, February 16 News Roundup: Women & CV Disease — HRT, Genetic Testing, and More
Larry Husten, PHD
HRT & Increased Risk: A new report from the Women’s Health Initiative in the Annals of Internal Medicine finds “no suggestion of a decreased risk for CHD … within the first 2 years” of HRT, even in women who started therapy within 10 years after menopause. For women who started HRT close to menopause, a “possible” cardioprotective effect was observed after 6 years of use.
Genetic Testing in Women: A genetic risk score composed of 101 SNPs (single nucleotide polymorphisms) did not improve cardiovascular risk prediction in more than 19,000 women enrolled in the Women’s Genome Health Study, according to a report by Paynter et al. in the Journal of the American Medical Association. The authors conclude:
“First, genome-wide testing is increasingly available and marketed to the general public. Our study finds no clinical utility in a multilocus panel of SNPs for cardiovascular risk based on the best available literature. Second, our data confirm the utility of intermediate phenotypes such as total cholesterol, high-density lipoprotein cholesterol, and blood pressure in as much as genetic risk scores were no longer significant after adjustment for these phenotypes…. Third, our findings confirm the importance of family history of cardiovascular disease, which integrates shared genetics, shared behaviors, and environmental factors. At the same time, we believe that our data suggest areas for further biomarker research, which may improve prediction.”
Special Issue: The new issue of Circulation: Cardiovascular Quality and Outcomes is a special themed issue on women and CV disease. One report from the Women’s Health Initiative finds that a simplified strategy for assessing cardiovascular risk can predict risk over the following 10 years. Another study confirms that women continue to be underrepresented in research. An accompanying editorial notes that there are still “more questions than answers” in this crucial area.
February 12th, 2010
Stents in the News
Larry Husten, PHD
Bill Clinton’s stent procedure received enormous amounts of attention in the news. Some of the reports even contained various doses of truthful information, though many were riddled with inaccuracies and misperceptions. According to reliable accounts, Clinton had a closed vein graft and received two Xience stents in his left circumflex artery at Columbia-Presbyterian Medical Center in New York. Mark Apfelbaum and Michael Collins implanted the stents. Allan Schwartz, the hospital’s chief of cardiology , said Clinton was walking two hours after the procedure. Clinton went home Friday morning.By sheer coincidence, stents were the subject of a long and thoughtful feature story by Keith Winstein in Thursday’s Wall Street Journal. Winstein explored the reasons why COURAGE didn’t have as big an impact on clinical practice as was initially hoped (or feared). The article quotes a number of well known cardiologists on all sides of the controversy, including William Boden, Sanjay Kaul, Eric Topol, Donald Baim, and Ajay Kirtane.
February 12th, 2010
Statins for Preventing CAD: Is It Better to Tailor Treatment or Treat to Target?
James De Lemos, MD
We welcome Rodney A. Hayward, MD, to this forum to talk about his recent article Optimizing Statin Treatment for Primary Prevention of Coronary Artery Disease (Ann Intern Med 2010; 152:69), which was coauthored by Harlan Krumholz, MD, Editor of CardioExchange. James de Lemos, MD, asked Hayward some key questions. We encourage you to ask yours and to keep the discussion going.
de Lemos: How do you respond to people who might feel that a mathematical modeling study is inherently inferior to real data from real patients?
Hayward: Mathematical models can be compelling or worthless, depending on the strength of the underlying assumptions and evidence. Almost all medical recommendations are, by necessity, based on assumptions that involve extrapolation beyond the results of clinical trials. Unfortunately, the implications of those assumptions are often not formally tested. Such was the case for the NCEP LDL recommendations, which were based on expert opinion. Although supporters of treat-to-target strategies sometimes claim that their recommendations are based on clinical trials, our study clearly demonstrates that the current LDL recommendations are based on many more assumptions from observational analyses than the tailored strategy that we propose. Further, in an intensive review, we found that the best available evidence does not support the key assumptions underlying the LDL-target approach: namely, there is no valid evidence that the degree of patient-level LDL reduction is an accurate predictor of the degree of a statin’s benefit, and the evidence clearly shows that LDL measures in clinical practice are not very reliable measures of patients’ true LDL levels.
de Lemos: Aren’t these types of models suspect because they can’t account for real-world subtleties in patient care?
Hayward: This is a potential problem with all guidelines, regardless of the method used to develop them. We believe that the trend to promote rigid adherence to guidelines (for example, by converting treatment targets into performance measures (A1c <7%, BP <130/80, or LDL <100) has become a problem in medicine. Although our study suggests that tailoring treatment based on a patient’s overall CAD risk is a much better approach than treating that patient to LDL targets, we are not setting rigid cut-points that must always be followed. When doctors talk to patients who have a 5-yr CAD risk that is a little above or a little below 5%, they should always try to consider the patient’s individual circumstances and realize that the decision is not as clear as it would be if the patient’s 5-year risk was 2% (do not treat) or 8% (definitely treat). Further, although excellent CAD risk calculators are available, clinicians may have additional information about their patients that is not included in the formula, and this information could lead them to estimate their patient’s risk differently than the tool would. Guidelines are useful, but good clinicians will occasionally deviate from them, especially when patients are close to recommended treatment cut-points (see Section D of our Appendices for more discussion on this topic).
de Lemos: Are you worried that decreasing the focus on LDL goals might reduce adherence to therapy?
Hayward: We always need to be concerned about medication adherence, since improving that has the potential to dramatically improve patient outcomes. However, a focus on LDL targets does not seem to be a particularly good approach for promoting better adherence. Certainly, current evidence suggests that non-adherence to statins and blood pressure medications is widespread, even in the face of an extreme focus on intermediate measures (LDL, BP and A1c). Although this issue merits empirical study, it is quite possible that we might be able to improve adherence by deemphasizing intermediate measures and instead focusing on the potential of the prescribed medication to prevent heart attacks, strokes, and death. That said, periodically checking lipid levels as a screen for detecting possible non-adherence is certainly a justifiable strategy.
de Lemos: Do you think these results should be incorporated into the next iteration of guidelines? If so, how? If not, what do you think are the critical next steps needed before they can be incorporated? In other words, would you advocate for testing the tailored versus treat-to-target strategies in a clinical trial?
Hayward: We do feel that a tailored approach should be incorporated into the next round of guidelines and that we should not wait for more evidence before making these changes. Inertia is not a valid scientific argument for continuing to follow recommendations that have been demonstrated to be inconsistent with the best available scientific evidence. Our study clearly indicates that tailoring a patient’s treatment based on his or her overall CAD risk is dramatically better than treating to target, regardless of the target (LDL, CRP, or any other risk factor) and even under circumstances that highly favor the treat-to-target approach.
de Lemos: Is there a middle ground where we should consider both tailored and treat-to-target approaches? The tailored approach appears to identify the most appropriate population for treatment, but the intensity of therapy may be greater in the treat-to-target approach. Given that generic atorvastatin is coming soon, and statins have an excellent safety profile at high dosages, what if we used a tailored approach to decide who to treat and then used the target approach to determine how intensively to treat?
Hayward: We examined this issue in our study, and the answer appears to be clear: There is not a role for this combination approach, and it might even lead to net marginal harm. We estimated that 1 QALY would be lost for every 129 tailored-treatment patients who had their statins intensified in pursuit of an LDL target of 100. However, there is a key caveat related to atorvastatin. Although there is good evidence that 80-mg atorvastatin is generally associated with more side effects and lower adherence than 20- to 40-mg simvastatin, there are no head-to-head comparisons (to my knowledge) of 40-mg atorvastatin versus 40-mg simvastatin or pravastatin. If the side effects and risks of 40-mg atorvastatin are comparable to those of a similar dose of other statins, then you could make a strong argument for just using 40-mg atorvastatin as a first choice in all patients who have a 5-year CAD risk of ≥5% (if the costs are similar or if you do not consider costs). However, the current evidence suggests that 80-mg atorvastatin has more side effects and lower tolerance than 40-mg atorvastatin, with only a minimal benefit in potency. Thus, my personal recommendation is to either not use the 80-mg dose or reserve it only for the most high-risk, adherent, and robust of patients.
February 11th, 2010
Study finds significant lesions in one-fifth of patients with zero calcium scores
Larry Husten, PHD
(Note to readers: CardioExchange invited experts with divergent opinions about this study to participate in a debate. The first part of the debate, including comments from PK Shah, Matthew Budoff, and Rita Redberg, is presented at the bottom of this news story.)
A calcium score of zero does not completely rule out significant coronary disease, according to the surprising results of a substudy of the CORE64 multicenter trial, in which patients referred for angiography were also asked to undergo a calcium scan. Ilan Gottlieb and colleagues report in the Journal of the American College of Cardiology on 291 patients enrolled in the study, of whom 72 had a calcium score of zero. 14 of these patients (19%) had at least one lesion with > 50% stenosis. In the study as a whole there were 64 totally occluded vessels, of which 13 (20%) had no calcium. 9 patients with no calcium underwent revascularization.
The authors concluded that “the absence of coronary calcification does not exclude obstructive CAD or the need for clinically indicated coronary revascularization… among patients with a high enough suspicion of CAD prompting an indication for CCA. The absence of coronary calcification should not be used as a gatekeeper and should not prevent a symptomatic patient from undergoing angiography. Furthermore, a large percentage of totally occluded vessels had no evidence of calcium by CT, emphasizing that calcification is not indispensable for plaque rupture and acute coronary events.”
In their report, the authors note that the AHA/ACC Expert Consensus Document states that “for the symptomatic patient, exclusion of measurable coronary calcium may be an effective filter before undertaking invasive diagnostic procedures or hospital admission.”
In an accompanying editorial comment, Rita Redberg notes that calcium scans and angiography “measure different stages of the atherosclerotic process” and that coronary calcification occurs late in the process, so “it is not surprising that significant CAD can occur in the absence of calcification.” Redberg writes: “This apparent lack of predictive value of a CS should be enough to give a clinician pause,” especially in light of the radiation burden associated with the scan.
Until there are more outcomes data for CS with populations at different levels of risk, Redberg argues that “a CS of zero cannot be interpreted as a reassurance of the absence of CAD.” Calcium screening, she writes, “may yet have its place in the clinician’s arsenal for evaluation of patients with chest pain, but until its benefits are clearly established, we must take great care when subjecting patients to it.”
Response
PK Shah, MD
“This is an interesting study confirming prior reports that in a symptomatic population with a high pretest probability of CAD (high enough to warrant invasive coronary angiography) , a negative coronary calcium scan should not be considered reassuring in terms of ruling out obstructive CAD caused by a non-calcified plaque.This is quite different from usefulness of screening coronary calcium scan in asymptomatic low or intermediate pretest probability group where zero coronary calcium predicts an extremely favorable intermediate term prognosis. We should be careful not to extrapolate the results of the current study to the asymptomatic low-intermediate risk group where coronary calcium scoring is likely to be most incrementally useful.”
Response
Matthew Budoff, MD
Coronary Calcium remains an effective filter for invasive angiography. In the paper by Gottlieb et al, the authors question the guidelines and suggest that their small study trumps 25 years of published literature on coronary artery calcium. The guidelines were written based upon multiple studies that were 5-10 times larger than the cohort studied in this issue of JACC. Furthermore, the authors used a pre-determined cutpoint that would, by definition, limit the ability of CAC to predict stenosis. They excluded the 89 patients who were enrolled in CORE64 who had CAC >600. Imagine a paper being published that states that hypertension does not correlate with left ventricular hypertrophy, but the study eliminated the 1/3 of patients who had significant hypertension from the study. Those 89 CORE64 patients, who had CAC scores >600 and angiography, should have been included in the analysis, and clearly that would have significantly changed both the sensitivity and specificity of the study findings.
Furthermore, the authors should not mention prognosis or implications of a negative score, as the literature, with studies published including over 100,000 patients with CAC, clearly demonstrate that a zero score carries an excellent long term prognosis. We followed patients for 8 years after admission to the emergency room, and no patients with a score of zero suffered coronary events.
A bigger issue is how the CORE 64 study is so divergent from almost all published literature on CAC. Almost every published study of CAC, including multicenter trials involving over 2000 participants undergoing both CAC and invasive angiography, demonstrate a high sensitivity (>90%) and lower specificity (<50%). Knez et al. studied 2,115 consecutive symptomatic patients (n = 1,404 men, mean 62±19 years old) with no prior diagnosis of CAD, finding CAC in over 99% of patients with obstructive CAD. No calcium was found in 7 of 872 men (0.7%) and in 1 of 383 women (0.02%) who had significant luminal stenosis on coronary angiography. Seven of these 8 patients with missed obstructive disease and scores of zero were <45 years old. However, the authors present almost exactly the opposite in their small study (a sensitivity of 45% and specificity of 91%), calling into question either the study design or equipment used. The scanner used in CORE64 was demonstrated in the Multi-Ethnic Study of Atherosclerosis to have a significantly worse reproducibility for CAC than all other scanners in the study, and these scanners have been systematically excluded from multicenter trials of lung disease, due to similar technical concerns. To reiterate the concern, results from the ACCURACY multi-center CT trial (using different CT equipment) demonstrated CAC to have a sensitivity of 94% and specificity of 42% for >50% stenosis by quantitative coronary angiography.
Coronary calcium with an effective radiation dose that approaches mammography, remains an effective filter for emergency room patients and those referred for invasive angiography in low to moderate pre-test probability patients. Given rising health care costs, we must strive for cost-effective and easy tests to stratify patients. The literature, with over 1000 published papers on CAC, is clear and even with one exception, consistent. CAC testing should remain a mainstay in both diagnosis and prognosis of the cardiac patient, with more attention on the type of CT scanner used to acquire the data.
Response
Rita Redberg, MD
As I stated in my JACC editorial, none of these articles cited by Budoff give us any information on how the calcium scoring adds incremental information to the traditional predictors for coronary artery disease, such as clinical assessment and stress testing. This apparent lack of predictive value of a calcium score should be enough to give a clinician pause. When combined with the significant radiation risks of coronary artery calcium scans, however, clinicians must use extreme caution when ordering such scans. Whether for a asymptomatic patien for “screening” or for risk stratification or diagnosis in a symptomatic patient, it is essential that the benefits of any test, eg CAC outweigh the risks for patients. That remains to be demonstrated for calcium scoring. CAC does not give us actionable information for screening, or for diagnosis, has the risk of radiation and additional testing to follow up on false positives. The best way to provide this data is via a randomized trial of calcium scoring versus traditional assessment in the populations in question. I hope we can see this soon. None of the many studies that Budoff refers to are randomized trials. The only randomized trial of CAC showed NO benefit (O’Malley JAMA).
Response
PK Shah, MD
I do believe that in selected asymptomatic subjects , identification of subclinical athero by carotid US or EBCT does provide useful information, but I do also agree that the only way to settle this issue once and for all is with a randomized trial and I believe the NHLBI should consider supporting such a trial.
Response
Matthew Budoff, MD
Coronary calcium scanning has been studied in more patients than any other modality in cardiology, save exercise testing. We have more robust data with CAC scanning than stress nuclear testing, stress echocardiography, and invasive angiography. It is true that there is a paucity of randomized controlled trials using one diagnostic strategy against another, but that is true for EVERY modality in cardiology, including Framingham risk assessment, exercise testing, and imaging. The only test validated to improve outcomes is abdominal aortic screening for aneurysms. So, should we abandon all tests due to lack of evidence, or continue to use best practices to take care of our patients? The argument can never be that there are no randomized trials, or cardiology would be paralyzed without any evidence that imaging of any sort improves outcomes. Any clinician recognizes the importance of imaging in practice, to sort out types of chest pain. Without imaging, we would be treating blindly. So far, we have over 16 studies that demonstrate that there is INCREMENTAL value to CAC testing, in that it predicts events better than Framingham, better than nuclear testing, better than stress echocardiography. This incremental value is key to our decision-making. Radiation dose is not high. Dr. Redberg and I published together a guideline in 2004 (Mieres et al.), in which we carefully outlined the low radiation doses with CAC testing (0.7 mSev for EBCT, 1.5 for MDCT). This is comparable to mammography (0.7 mSev per year for annual testing). Since CAC testing is not recommended to repeat over 5 years, the radiation dose for a female undergoing annual mammography is 3.5 mSev, significantly more than a single CAC test. Since more women die of heart disease than breast cancer, clearly the evidence is in favor of screening for heart disease with CAC testing. Remember, Dr. Redberg and I published in 2004 “Coronary calcium, in addition to traditional risk factors, provides independent incremental information in the prediction of cardiovascular outcomes…However for the asymptomatic women with risk factors and an intermediate Framingham risk score of 0.6%-2.0% or higher, screening with EBT can accurately provide evidence of subclinical atherosclerotic coronary disease.” Since data are now more robust after another 6 years of data accumulation, CAC testing remains a robust method of risk stratification, with low doses of radiation and ample clinical evidence.
February 11th, 2010
Thursday, February 11 News: Fulminant Myocarditis in Children with H1N1
Larry Husten, PHD
Myocarditis & H1N1 in Children: In an expedited research correspondence appearing in the Journal of the American College of Cardiology, Bratincsák et al. report four cases of children with H1N1 influenza A virus at Rady Children’s Hospital in San Diego who developed myocarditis, including three with fulminant myocarditis with fatal or near-fatal outcomes. The authors conclude: “Our observations warrant a high index of suspicion for myocarditis in children with H1N1 influenza A infection. Early detection and aggressive management are paramount. Timely intervention with circulatory support may decrease morbidity and mortality, with the potential for a favorable cardiac prognosis.”
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