DAPA: Early ICD After Primary PCI-Treated STEMI Saves Lives

Liam Davenport

September 04, 2019

PARIS — The early implantation of an implantable cardioverter defibrillator (ICD) in patients with ST-elevation myocardial infarction (STEMI) who have undergone primary percutaneous coronary intervention (PCI) significantly improves survival over medial therapy even a decade later, suggest new trial data.

The Defibrillator After Primary Angioplasty (DAPA) trial randomized 266 high-risk STEMI patients after primary PCI to either ICD implantation or standard medical therapy no more than 40 days after the infarction.

Presenting the findings at the European Society of Cardiology (ESC) 2019 Congress, Arif Elvan, MD, PhD, a cardiologist at Isala Klinieken, Zwolle, the Netherlands, showed early ICD implantation was associated with a 48% reduction in all-cause mortality over standard care.

Elvan told a press conference that the results indicate that "early prophylactic ICD implantation may be considered in selected high-risk patients treated with primary PCI," although he added: "I have to stress that larger studies are needed to confirm our findings."

Speaking to theheart.org | Medscape Cardiology, he explained that it is "actually very feasible" to perform ICD soon after STEMI in high-risk patients after PCI.

However, he cautioned that it should not be done in the first few weeks after a myocardial infarction, as "people die from heart failure or other complications, but if you do it after 30 days it's absolutely feasible."

"The most important part is the risk stratification beyond ejection fraction," he said, which includes TIMI flow and Killip class, and likely also imaging tests, such as MRI.

Elvan also believes that the literature suggests that individuals with an LVEF between 30% and 45% could "gain a lot of benefit" from prophylactic ICD implantation, especially those without heart failure.

To put the findings in context, theheart.org | Medscape Cardiology spoke to Ivor J. Benjamin, MD, immediate past president of the American Heart Association and director, Cardiovascular Center, Medical College of Wisconsin, Milwaukee.

Although he said that the study supported in principle the current practice of ICD implantation in high-risk patients after STEMI and primary PCI, he took issue with the inclusion criteria and warned that they could lead to overtreatment.

Elvan said that the most important determinant for the prophylactic implantation of ICD is currently LVEF, which is primarily based on the results of landmark trials, such as MADIT II.

He pointed out, however, that ICD implantation occurred an average of 6.7 years after myocardial infarction and less than 50% of patients underwent PCI.

Moreover, trials such as DINAMIT and IRIS, in which ICD implantation occurred less than 40 days after myocardial infarction, showed no benefit with ICDs.

Again, rates of revascularization with PCI were relatively low in both trials.

Based on these and other findings, the current recommendations are that ICD implantation take place at least 6 weeks after myocardial infarction in the ESC guidelines and 90 days after revascularization in the US guidelines.

Elvan said that there is, however, a lack of data on the benefit of early ICD implantation in selected high-risk STEMI patients treated with primary PCI.

The team therefore conducted a randomized controlled trial in which patients treated in 12 hospitals in the Netherlands and Poland were randomized 30 to 40 days after their STEMI to either ICD implantation or a control group consisting of medication.

The patients had to have been treated with primary PCI and to have at least one high-risk factor, including:

  • LVEF <30% within 4 days

  • TIMI flow <3 after primary PCI

  • Primary ventricular fibrillation (<24 hours)

  • Killip class ≥2

The study started enrolment in 2004 and so the ICD was programmed with a shock-only protocol, with a VF zone above 190 bpm. Follow-up consisted of 6-monthly clinic visits, and 18-month LVEF reassessment.

Elvan said that "unfortunately, the trial was prematurely terminated due to a slow inclusion rate," with only 38% of the planned number of patients to adequately power the study.

"Back then, there were several reasons that patients weren't included, and one [was] that the participating centers were not motivated after the publication of the IRIS and DINAMIT trials, which were negative," he said.

"We had a different design but nevertheless we saw the doctors weren't motivated to continue the study."

Despite this, the team conducted an additional survival assessment in 2019 following the primary end point of all-cause mortality after 3 years, with secondary end points including cardiac and noncardiac mortality.

The 266 randomized patients had an average age of approximately 60 years, and 77.0% control patients and 79.4% of treated patients were male.

The location of the STEMI was anterior in 84.4% of control to 83.0% of treated patients, and the vast majority received a stent, with less than 6% undergoing coronary artery bypass grafting.

The median time ICD implantation after primary PCI was 50 days (interquartile range, 41 - 60 days). Just 4.6% of patients experienced an implantation-related complication, with local pocket infection being the most common, at 2.3%. There were no device-related deaths.

During the course of the study, 19.3% of control patients ended up having ICD implantation, 6.1% of patients in the ICD group crossed over to the control group, three patients withdrew or refused the intervention, and three devices were removed or switched off.

By the survival assessment in February, 80 (30.1%) patients died over a median follow-up of 9 years (interquartile range, 3 - 11 years.

The researchers found that, after 10 years, the rate of all-cause mortality on intention-to-treat analysis was 24.4% in the ICD implantation group and 35.5% in the control group (hazard ratio [HR], 0.58;95% CI, 0.37 - 0.91; P = .02).

Elvan said that this was primarily driven by differences in cardiac death between the two groups — 11.4% in the ICD group and 18.5% in the control group (HR, 0.52; 95% CI, 0.28 - 0.99; = .04).

In contrast, noncardiac death occurred in 11.5% of ICD patients and 11.9% of control patients.

When the researchers looked at mortality across the course of the study, they found that the difference in all-cause mortality between ICD and control patients showed a trend for significance at 3 years (P = .04), and became significant at 9 years (P = .02).

He added that "one of the interesting findings" was that LVEF assessment at 18 months showed that 46% of ICD and control patients had an improvement in ejection fraction, defined as an increase in LVEF of at least 10%.

"Despite this is LVEF improvement, the benefits of early ICD implantation were preserved during follow-up."

The researchers found that, among the 110 patients whose LVEF was over 30% at 18 months, those who received an ICD had significant lower all-cause mortality at the end of the study than those who did not (HR, 0.47).

Standard of Care

Discussing the findings, Benjamin explained that the "current standard of care is that, if you have a low ejection fraction and you're high-risk after an optimized medical regimen, we still will also recommend an ICD."

In that sense, the "trial is on the same track of what is maybe considered current standard of care," but the central question is: "How do we know that this particular lesion is high-risk?"

He said that the high-risk criteria of LVEF below 30% within 4 days in the study means that the patients are "highly selected."

Benjamin emphasized that the issue with this is that such a short time period is not giving the heart time to recover.

The phenomenon of myocardial ischemic stunning means that, after revascularization, the heart has to be given time to recover, he said.

"My concern with this particular study is that you might be overprescribing ICDs to the tune of $75,000 a person" if the physician does not wait.

They normally give patients about 3 months of recovery time after STEMI and primary PCI, although patients might not necessarily need it, he added.

For Benjamin, the recruitment selection in the study is therefore "far too stringent and it does not address the biology of the ischemic recovery…so, to me, to use this as a criterion for managing patients in 2019 begs some further reconsideration."

Medtronic Inc. was the sponsor of the study and provided financial and technical support. No conflicts of interest declared.

European Society of Cardiology (ESC) Congress 2019: Abstract 6050. Presented September 3, 2019.

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