By: Dr. Geoffrey Modest
A lead article in JAMA was a study of Medicare patients who had an MI with a low ejection fraction (EF) to see what % actually had a cardioverter-defibrillator (ICD) implanted and how the patients did (see JAMA. 2015;313(24):2433-2440). This was a retrospective observational study.
–10,381 patients had an MI with EF<35% from 441 US hospitals, between the years of 2007-2010
–mean age 76, 40% female, 10% nonwhite. 65% had NSTEMIs and 75% had in-hospital revascularization
–cumulative ICD implantation rate by 1 year was 8.1%
–ICDs more often done in patients with prior CABG (31% had ICD vs 20% without); those who had cardiogenic shock (13% had one vs 8% not), and in male patients (38% less likely for females to get ICD).
–the 2-year mortality rate was much lower in those who had ICD placement: 15.3 events per 100 patient-years with ICD (128 deaths in 838 patient-years) vs 26.4 events per 100 patient-years without (3033 deaths in 11479 patient-years), with adjusted HR of 0.64 (0.53-0.78)
There are some important results of the study:
–one likely useful lesson is that those patients with profound LV dysfunction post-MI, should usually receive another echocardiogram 40 days later, and if EF is depressed, should be considered for an ICD. The MADIT-2 trial (N Engl J Med 1996;335:1933-40) did find an impressive 35% decrease in all-cause mortality after only 20 months, at the expense of an increased hospitalization for heart failure, in patients with LVEF<30 and at least 30 days post-MI. It is undoubtedly true that waiting the 40 days, when the patient is an outpatient, will lead to fewer ICDs being implanted (as with statins post-MI: if not started in the hospital, they may never be given later). The recommendations for an ICD are those with an EF<35% from an MI and NYHA class 2-3 after 40 days (and optimal medical therapy), or those with EF<30% and NYHA class 1. The basis for the recommendation to wait 40 days after an MI is a few studies.
–one older article (see Ann Intern Med. 2001;134(6):451) tracked echocardiograms after MIs, finding that 22% of patients with low EF totally normalized their EF, and 36% more had partial functional recovery, with 53% having > 5% improvement of EF over their post-MI baseline. And in the JAMA study above, 75% of those with MIs had revascularization – mostly PCI, which is more likely to lead to high levels of myocardial sparing and recovery over the short-term (after the stunned myocardial wakes up to its new reality). One concern in this Annals study is that there was not optimal medical therapy. Not clear that patients received aspirin, statin or b-blocker (this study was actually one testing the efficacy of ramipril post-MI, beginning on day 14 and with varying doses. So, the myocardial recovery rate they found might have been much higher with our current optimal medical therapy. And the rate of arrhythmias lower.)
–a few trials actually looked at immediate placement of ICDs in patients with MIs and reduced EFs (<35% or <40%): neither the DINAMIT trial (NEJM 2004; 351: 2481) nor the IRIS trial (NEJM 2009; 361: 1427) found any difference in all-cause mortality by implanting ICDs right away
–subgroup analysis in the JAMA study showed that the mortality benefit was the same in patients < and >80 years old, and this suggests pretty strongly that we should still consider ICDs in older patients who were underrepresented in the clinical trials.
But, I do not really trust this study (which basically promotes more patients receiving very expensive devices, for which there are clinically-important adverse effects), and for a variety of reasons:
–this was a quick-and-dirty study, data-mining a large database, but missing important elements: it was not randomized, so those who received ICDs may be very different from those who did not (eg, were some very sick patients excluded from getting ICDs because they were too sick, then only to die without an ICD?). Also, perhaps most importantly, they did not have any data on the EF 40 days after the patients had their MIs
–although the current JAMA study was sponsored by the Agency for Healthcare Research and Quality (AHRQ), the authors had a litany of drug and medical device company affiliations, including to a maker of ICDs (Boston Scientific). And needless to say, if there were a dramatic increase in ICD use, the magnitude of profit increase to these medical device companies would be mind-boggling to us mere mortals and add significantly to our health care costs.
–one last point. Especially in those areas with very rapid diagnostic and therapeutic advances (eg cardiology, or HIV treatments a few years ago), we often confront the problem that by the time a study is published, common practice has already moved beyond the starting point of the study, and the baseline medical management used in the study is no longer relevant. In the current case, the ICD guidelines were based on older studies that did not really answer the questions that we want to know, and typically with suboptimal medical management compared to what we do now. The MADIT-2 study was done in 1996 and 75% of medical controls were on amiodarone, only 2/3 on ACE-I, and a minority on b-blockers. No comment on aspirin or statins. This was not even designed as a post-MI low EF study comparing patients with currently-conceived optimal medical therapy vs the same with ICD. Another big study, the SCD-HeFT trial (N Engl J Med 2005;352:225-37) included patients with both ischemic and nonischemic cardiomyopathy, and there was no clear breakdown of the meds the ischemic group was taking (so hard to know if they had optimal med therapy, though I doubt it given the study was published in 2005), and did not include patients who were NYHA 1 class. So, for example, are ICDs superior to medical management if all of the control patients were on b-blockers (which might prevent arrhythmias — though, the SCD-HeFT study showed no efficacy of amiodarone over placebo), plus aspirin (potentially preventing thrombosis and associated arrhythmias), plus ACE-I (potentially decreasing the vascular remodeling and the direct vasotoxic effects of aldosterone), plus a statin (perhaps preventing thromboses as well as improving endothelial function and being antioxidant, and thereby perhaps decreasing arrhythmias)? So, it is actually hard to know with certainty if, with current aggressive medical management, an ICD would provide significant protection to all patients with persistent low EF post MI, even after 40 days….
So, this article brings up several important issues. One is the role of drug and medical supply companies as drivers for expensive meds/devices, with major input into articles published in our best medical journals, guideline writing, etc. Another issue is that medical management if forever changing, leading to the pretty frequent problem of a moving target: soon after an article is published, medical management may have changed substantially enough that an intervention might not be useful. With all of this lack of certainty, it seems to me appropriate to repeat the echo after 40 days, and if persistently <35%, still to suggest an ICD to the patient. Also, a real concern in the sometimes hectic practice of primary care is to figure out a mechanism to make sure that important issues, including repeating the echo a month or so post-MI, are not lost in the shuffle, amidst the multitude of other issues we deal with pretty much on a daily basis for all patients we see…