ACCEL: ICDs Should be Used More Judiciously in the Primary Prevention Population
Current ACCF/AHA guidelines relating to the use of an ICD for primary prevention state that they are appropriate for consideration in patients with a prior MI or nonischemic cardiomyopathy and an LVEF <35% and NYHA functional class II or III.1 For patients with a prior MI, the guidelines stipulate that ICD use is not recommended until at least 40 days post-infarction; in patients with an LVEF <30%, ICDs may be used in NYHA class I.
There is also an indication to consider an ICD in patients with prior MI, an LVEF <40%, and nonsustained VT or inducible VT at electrophysiology study.
In all cases, the guidelines also note that patients should be on optimal long-term medical therapy and that clinicians, using good clinical judgment, should have assessed the patient and determined that there is a reasonable expectation of survival with good functional status for more than 1 year.
What's the Problem?
These guidelines are based on the results of randomized controlled trials. However, according to Alfred E. Buxton, MD, there are several problems in the application of these guidelines.
Dr. Buxton is a member of the joint AHA/ACCF/ESC committee writing guidelines for care of patients with ventricular arrhythmias/sudden death. Physicians in the United States, he said, tend to simplify the guidelines in practice, using an LVEF <35% as the sole criteria for considering an ICD. Illustrating this point, he pointed to the opening sentence in a paper presenting long-term results of the pivotal trial known as MADIT II (Multicenter Automatic Defibrillator Implantation Trial):
"Current guidelines for device-based therapy of cardiac rhythm abnormalities provide a recommendation for primary ICD therapy in patients with an EF of ≤35%."2
By glossing over the specifics of the guidelines recommendations, said Dr. Buxton, even investigators in this field may not understand the guidelines.
Data published in 2011 certainly suggest there is a problem, too. Using National Cardiovascular Data Registry® (NCDR) ICD Registry™ data between January 1, 2006, and June 30, 2009, investigators reported that among 111,707 patients with ICD implants in this registry, 25,145 (22.5%) did not meet evidence-based criteria for implantation.3
While entry criteria for the pivotal trials may have been more explicit than the opening sentence of the MADIT II results, Dr. Buxton pointed to specific limitations in the application of the current guidelines: Many patients enrolled in the trials had additional risk factors for death, such as a wide QRS complex (50% with a QRS duration >120 ms in MADIT II and 41% of those in SCD-HeFT). Also in MADIT II, 5% of patients were NYHA class IV, despite the fact this was one of the exclusion criteria. "If you have a patient without these major risk factors," Dr. Buxton said, "you should not expect that patient will have a 21% mortality at 2 years, which is what the MADIT II investigators saw in their overall population."
Also, patients enrolled in the trials (like patients seen in practice) are heterogeneous. Consequently, the results of randomized trials do not apply in a straightforward way to individual patients. Even from trial to trial, there are differences in the population studied, which may contribute to the broad relative risk reductions for total mortality seen with ICD therapy: it was 54% in MADIT, 31% in MADIT II, and 23% in SCD-HeFT.
Finally, patients have many attributes that can affect the likelihood of treatment being beneficial or harmful.
In a recent editorial in JACC,4 Dr. Buxton considered another angle on the data: multivariate analyses have demonstrated that in MUSTT and MADIT II, 25-30% of the study populations had 2-year total mortality risk of 5% and 8%, respectively, and in SCD-HeFT, 20% of the study population had 2-year mortality of 5% without ICD therapy. Conversely, in MADIT II and SCD-HeFT, 20% of the study populations had 2-year mortality of 30-50%. The wide variation in risk within these trials translates into vastly different treatment effects; that is, an individual whose baseline risk is 2-3% per year will see much less absolute benefit from treatment than a person with 15-20% annual risk.
The "Sweet Spot"
The challenge is finding the "sweet spot," which he defined as that range of mortality in which the risk for sudden death is high enough—and competing risk for nonsudden death is low enough—that an ICD can affect a significant reduction in mortality.
One approach was published recently in JACC by investigators reporting the development and validation of a practical measure for estimating the probability of survival 1 to 4 years after ICD implantation for the primary prevention of sudden cardiac death.5 The model uses seven clinically relevant and easily assessed covariates:
- 75 years of age or older
- heart failure (NYHA class III)
- chronic obstructive pulmonary disease
- chronic kidney disease
- LVEF ≤20%
- diabetes mellitus
This useful model, based on more than 45,000 primary prevention ICD patients, accurately identifies the 10-20% of patients who are at highest risk for death after device implantation and may significantly influence clinical decision making.
To listen to an interview with Alfred E. Buxton, MD, about ICDs for primary prevention, visit youtube.cswnews.org. The interview was conducted by Patricia A. Pellikka, MD.
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