Real-World Survival on Primary-Prevention ICDs Can Match Clinical Trials

January 03, 2013

CHICAGO, Illinois— Survival with an implantable cardioverter-defibrillator (ICD) was about the same for patients in two major primary-prevention trials as it was for similar real-world registry patients, according to researchers in the January 2, 2013 issue of the Journal of the American Medical Association [1].

Their analysis of patients in the National Cardiovascular Data Registry for ICDs (NCDR-ICD) who were propensity matched to trial patients addresses a longstanding concern about primary-prevention device therapy: whether ICD clinical-trial results are generalizable to clinical practice, where patients are typically older, sicker, and less consistently managed.

The answer appears to be yes, at least for outcomes achieved in two trials that helped establish the ICD in primary prevention, MADIT 2 and SCD-HeFT, according to the authors, led by Dr Sana M Al-Khatib (Duke Clinical Research Institute, Durham, NC). Importantly, the group writes, they saw the same results when considering only patients aged 65 and older.

But the generalizability isn't just about patient selection, Al-Khatib told heartwire . "It's well-known that patients in clinical trials are monitored more closely, told to call if they experience something, and followed very closely. Also, the selection of physicians and other providers who participate in clinical trials--it's not a random process. In general, those who have more expertise, more experience, and better outcomes potentially get selected for the clinical trials." And that, it has been long argued, contributes to better results in trials than in practice.

"But we showed that even if the level of care and monitoring is not as good in clinical practice--and I tell you it's not," she said, "you can still expect to see survival benefits from the defibrillator." Those provider features, however, could still be important to nonmortality outcomes such as hospitalization, complications, or quality of life, Al-Khatib emphasized.

As long reported by heartwire ,MADIT 2 randomized 1232 patients with an LVEF <30% after an MI >40 days previously to receive or not receive an ICD on top of medical therapy; device therapy cut mortality by 31% over a mean of 20 months. In SCD-HeFT, 2521 patients with NYHA class 2–3 heart failure and LVEF <35% were similarly randomized (including to a non-ICD amiodarone group) and showed a 23% mortality reduction over a median 45 months. The principal investigators of both trials are among the authors of the current report.

It compares 2464 NCDR-ICD patients propensity matched with those in MADIT 2 and 3352 registry patients with similarly matched to SCD-HeFT patients, using patient-level data from the trials. Propensity matching derived from baseline demographics, electrocardiographic variables, cardiovascular history, heart-failure class, and medications.

There were no significant differences in adjusted survival between registry and trial patients who received ICDs in either the MADIT 2 or SCD-HeFT analyses.

Propensity-Adjusted Analyses of All-Cause Mortality in All Patients and When Limited to Patients >65 Years

All-cause mortality All patients, HR (95% CI) Aged >65, HR (95% CI)
NCDR-ICD vs MADIT 2 (at 2 y) 1.06 (0.85-1.31), p=0.62 1.02 (0.78-1.33), p=0.88
NCDR-ICD vs SCD-HeFT (at 3 y) 1.16 (0.97-1.38), p=0.11 1.05 (0.81-1.36), p=0.73

In a secondary analysis, registry ICD patients showed significant reductions in mortality compared with patients in both trials, considered separately, who had been randomized to medical therapy.

The current study is a follow-up of sorts to a controversial paper, also based on NCDR-ICD patients and led by Al-Khatib, which concluded that 22.5% of the >100 000-patient-strong cohort had received ICDs without meeting evidence-based guidelines criteria established by the major US and European societies. The report produced a flurry of subsequent letters to the editor contesting or expanding on the findings, including at least one from SCD-HeFT researchers, along with a response from the authors.

Together, Al-Khatib said, the two studies underscore that the ICD improves survival when the patient meets evidence-based guidelines. And although it's known that the ICD is underutilized in such patients, "I hope based on the results of this [current] study that people would feel more confident that what we're doing [with ICDs] is actually beneficial and associated with the expected outcomes based on the clinical trials."

The analysis was supported by a grant from the National Heart, Lung, and Blood Institute (NHLBI). Al-Khatib had no disclosures. Disclosures for the coauthors are listed in the paper. SCD-HeFT was sponsored by Medtronic, Wyeth-Ayerst Pharmaceuticals, and the NHLBI. MADIT-2 was partially funded by Guidant, later bought by Boston Scientific.