DANAMI-2: Intermediate results confirm benefit of transfer for primary PCI over thrombolytics for MI

Susan Jeffrey

May 08, 2002

Wed, 08 May 2002 19:21:00

Sydney, Australia - Intermediate results of the DANAMI-2 trial, comparing thrombolysis to referral for primary PCI for patients with ST-elevation MI, continue to support an advantage for the transfer strategy in the reduction of the composite endpoint of death, reinfarction or disabling stroke. With follow-up ranging now from 6 months to 4 years, the results presented here at the XIVth World Congress of Cardiology are very similar to the 30-day outcomes reported earlier this year at the American College of Cardiology Annual Scientific Session.

As with the 30-day results, the benefit from the transfer strategy was driven largely by a reduction in reinfarction, with no significant difference seen in death rates between the groups.

"Based on these data, we conclude that an initial strategy of transferring patients with ST-elevation MI for primary PTCA is superior to accelerated tPA, as long as transfer can be performed within the 3-hour time limit," Dr Henning Rud Andersen (Skejby University Hospital, Aarhus, Denmark) told the meeting here.

"The protocol states that we have to follow the last randomized patient at least 1 year before we can publish...the long-term results, and then we're allowed to look again after 3 years," Andersen said. "But I looked into the database for this meeting, just to give you some idea of the intermediate long-term follow-up."

Early pattern of benefit persists

The Danish Multicenter Randomized Study on Thrombolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction-2 (DANAMI-2) was carried out at 5 centers offering PCI and 22 referring hospitals, with a catchment of about 62% of the Danish population of 5.4 million. Transport distances from the referring hospitals to the invasive centers of up to 95 US miles (150 km) were allowed, but the mean distance for transported cases in this trial was 35 miles (50-55 km).

Andersen and his coinvestigators set out to enroll 1100 patients at the referring hospitals to be divided equally between ambulance transfer for PCI or no transfer, and 800 patients at the invasive centers randomized to fibrinolysis or PCI on site. In November 2001, as reported by heartwire , enrollment in DANAMI-2 had been halted by the trial's safety and efficacy committee after a clear benefit was seen in the PCI patients. At that time, 1129 patients had been enrolled from referring hospitals and only 443 in the invasive centers.

Patients in the transfer arm were randomized within 12 hours of symptom onset, and were allowed 3 additional hours for transport, Andersen said, meaning some patients had PCI up to 15 hours after symptom onset. All had ST-elevation MI >4 mm. No upper age limit was set; the median age was 63, ranging up to 96 years.

Adverse events during transfer were infrequent, and included atrial fibrillation in 2.5%, sustained ventricular tachycardia in 0.2%, ventricular fibrillation in 1.4%, 2.3% developed second- or third-degree AV block. No intubations or deaths occurred.

At 30 days of follow-up, there was a highly significant difference between the groups in the primary endpoint of death, MI, or disabling stroke favoring the primary PCI strategy. The same trend was seen in all 3 components of the endpoint, Andersen said. The pattern of results was similar in the referring and invasive centers, although the number needed to treat to prevent 1 endpoint event fell from 18 to 17 in the invasive centers.

DANAMI-2: Primary endpoint (death, reinfarction, disabling stroke) at 30 days

Endpoint

Fibrinolysis

PCI

p value

NNT

13.7%
8.0%
0.0003
18
14.2%
8.5%
0.002
18
12.3%
6.7%
0.048
17

For this analysis, the investigators now have a median of 600 days follow-up - the last patient included has been followed for 6 months, the first patient for 4 years, Andersen said.

"The pattern is similar to what you saw after 30 days, a highly significant difference favoring primary angioplasty," he said. "In referral hospitals, the result is still highly significant, and the number of patients needed to treat is now only 15, so it seems the long-term results are maintained after 30 days."

DANAMI-2: Primary endpoint at a mean of 600 days (range 6 months to 4 years)


Endpoint

Fibrinolysis

PCI

p value

NNT

24.2%
17.8%
0.002
18
23.3%
16.9%
0.004
15

Andersen also reported the mortality data alone "because everybody is interested in mortality," although he stressed the study was not powered to look at this endpoint. The number needed to treat to save 1 life was 40, and the p value between the 2 groups, similar to that seen at 30 days, was not statistically significant. There was also no significant difference at referral hospitals. "This means you need to put 30 patients into the ambulance and transfer them to save 1 life."

DANAMI-2: Mortality at a mean of 600 days (range 6 months to 4 years)


Endpoint

Fibrinolysis

PCI

p value

NNT

16.0%
13.4%
0.26
40
15.3%
11.9%
0.1
30
To download tables as slides, click on slide logo below

Results causing excitement, but also anxiety

Commenting on the trial during the session, Dr Chris Granger (Duke University Medical Center) called DANAMI-2 a "remarkable feat" for several reasons. First, he pointed out that this is the largest randomized trial of primary angioplasty versus fibrinolysis to date.

"Secondly, it has been done in a country that fundamentally has not been a major advocate of intervention, and especially primary angioplasty," Granger said. "I think that, similar to the FRISC-II results, that that lends it a lot of credibility, and avoids some of the criticism of the earlier trials, that were done by strong advocates who were doing angioplasty so much better than the rest of the world."

Further, it was a trial not of 2 treatments, but of 2 major strategies involving the development of new systems. Prior to the DANAMI-2 trial, only 2 of the 5 invasive centers had done primary angioplasty before; the other 3 had to never done any of these procedures, Andersen noted.

Despite this, Granger noted, door-to-balloon times were comparable and in some cases shorter than those seen at some primary angioplasty centers. However, he pointed out, "I think there's a lot of excitement about the results, but a lot of anxiety about what we should be doing with them. Is this now a mandate, that we shouldn't be satisfied we're providing good care for acute MI unless we have this type of a system in place to provide primary angioplasty?"

 

I think there's a lot of excitement about the results, but a lot of anxiety about what we should be doing with them.

 

Granger raised some questions that he thought should be addressed before this strategy could be seen as mandatory. First, there was no reduction in mortality in this study, something "we would like to see before we bring on expensive new treatments."

In addition, most of the benefit was driven by a reduction in reinfarction with primary PCI, but the rate of reinfarction was 6.3% in the tPA arm. "We know we can lower that with some adjuncts." Finally, he noted that in the tPA arm, there was a low use of urgent or rescue angioplasty that might also have affected the rate of reinfarction.

 

It's really an experiment to put such a patient in an ambulance and drive through the country for 3 hours to reach a cath lab.

 

Andersen appeared to agree that other adjuncts might be useful in reducing reinfarction, but he was clear about the problem of urgent or rescue angioplasty in this setting. "If you have a patient in hospital 150 km away, and you have treated them with fibrinolysis and you think that this treatment actually fails, it's really an experiment to put such a patient an ambulance and drive through the country for 3 hours to reach a cath lab. It's really undocumented that we should do so."

Organizing the system required to accommodate this strategy might be complex, Andersen said, but it can be accomplished. "It's your decision to make, but I think if you can organize a safe transfer, a speedy transfer and you can have the patients arrive in the cath lab within 3 hours, it's a good treatment for the patient."



Related links

1. [HeartWire > News; Mar 20, 2002]

2. [HeartWire > News; Nov 7, 2001]


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