PARIS, FRANCE — Another randomized trial has concluded in favor of complete revascularization in patients with ST-segment-elevation MI (STEMI) and multivessel disease[1], instead of a strategy of PCI limited to the infarct-related artery (IRA)—the latter sometimes called "incomplete" revascularization by those who are not fans.
In the Denmark-based DANAMI-3 PRIMULTI trial, a complete revascularization strategy, staged during the index hospitalization and guided by fractional-flow-reserve (FFR) assessments, was followed by a 44% decline (P=0.004) in risk of the primary end point over >2 years, an end point comprising death by any cause, reinfarction, or repeat ischemia-driven revascularization.
The benefit, relative to the more conservative approach in the randomized trial of >600 patients, was driven by a 69% drop (P<0.001) in repeat revascularization, 40% of which were "urgent," said Dr Thomas Engstrøm (Rigshospitalet, University of Copenhagen, Denmark) when presenting the study here EuroPCR 2015. Neither all-cause mortality nor nonfatal MI were significantly different between the two strategies.
There was a hint that more extensive PCI might be most effective in selected patients. "The effect of complete revascularization on the primary end point was significantly more pronounced in patients with three-vessel disease," Engstrøm observed.
The findings are consistent with at least two other recently reported randomized STEMI trials, he pointed out. In PRAMI there was a 65% reduction (P<0.001) in risk of cardiac death, nonfatal MI, or refractory angina for complete revascularization vs IRA-only PCI. And the CVLPRIT trial showed a corresponding 55% risk reduction (P=0.009) for the end point of total mortality, reinfarction, new heart failure, or repeat revascularization.
Yet contemporary observational studies have shown contrasting results. And current European guidelines from 2014 support IRA-only PCI for STEMI not involving shock or persistent ischemia, according to Engstrøm. But the guidelines do say that staged revascularization of non-IRA lesions "should be considered in STEMI patients with multivessel disease in case of symptoms or ischemia within days to weeks after primary PCI."
In the current trial, 627 patients with STEMI and >50% stenoses in at least one non-IRA coronary artery underwent successful PCI of the culprit lesion only and then were randomized to receive or not receive further revascularization two days later during the same hospitalization.
In both the 313 patients with IRA-only PCI and the 314 going on to complete revascularization, about one-third had triple-vessel disease, about one-third had anterior MI, and about one-quarter had proximal left-anterior-descending coronary stenoses. They were similar in other baseline features (and were ultimately discharged on appropriate medications at the same rates).
The two groups showed no significant differences in complications, with similarly low rates of periprocedural MI, stroke, major bleeding, and contrast-induced nephropathy.
Over a median follow-up of 27 months, the rate of the primary end point was 22% in the IRA-only group and 13% for those getting complete revascularization.
Primary and Secondary Outcomes, by Intention to Treat, for Culprit-Artery PCI vs Complete Revascularization in DANAMI-3
| End points | HR (95% CI) | P |
| Primary end point | 0.56 (0.38 – 0·83) | 0.004 |
| All-cause mortality | 1.4 (0.63–3·0) | 0.43 |
| Nonfatal MI | 0.94 (0.47–1.9) | 0.87 |
| Ischemic-driven revascularization | 0.31 (0.18–0.53) | <0·001 |
| Secondary end points | ||
| Cardiac death or nonfatal MI | 0.80 (0.45–1.45) | 0.47 |
| Urgent PCI | 0.38 (0.16–0·92) | 0.03 |
| Nonurgent PCI | 0.29 (0.13–0·63) | 0.002 |
There was a significant interaction (P=0.046) between the number of coronary vessels with disease and randomization group, Engstrøm observed. There was no significant effect (P=0.3) on the primary end point in patients with two-vessel disease but a 67% drop in risk for complete revascularization vs IRA-only PCI among those with three-vessel disease (P=0.001)
The panel discussion following Engstrøm's presentation of the trial delved into questions of possible confounding bias that he largely deflected. He himself pointed out that patients who knew they had multivessel disease but did not go on to staged complete revascularization might have had an increased likelihood of responding to chest pain by returning for revascularization.
"We thought that there was an established bias in the [trial setup]," he said. But reported relief from angina and angina class were similar in both groups. Readmissions for suspected angina were the same in both groups. And only a fourth of those admissions in both groups actually led to repeat revascularization.
Dr Rosli Mohd Ali (Institut Jantung Negara, Kuala Lumpur, Malaysia) wondered whether there might have been selection bias for the patients who made it into the trial, as physicians may have used discretion in deciding their eligibility, excluding many based on angiographic multivessel disease severity and lesion complexity.
Engstrøm replied that there was very little evidence of selection bias and no sign of sluggish enrollment. He noted, for example, that PRAMI took twice as long as DANAMI 3 to accrue only two-thirds as many patients, and the disparity in CVLPRIT was even greater.
And Dr Gerhard Schuler (University of Leipzig, Germany) proposed that that there may have been bias in selecting patients for urgent revascularization if the clinicians were aware of patients' prior angiographic findings. It varied whether they had such knowledge, Engstrøm said.
A member of the audience asked whether an economic analysis was planned. "If readmission rates for angina were not different, you may argue that the hard outcomes were not different and that the initial conservative strategy was probably less expensive and maybe the preferred route from the health-system perspective."
Engstrøm replied "I think one could argue that." Consistent with that, he had reported that the complete-revascularization cases, unsurprisingly, had longer procedure times and used more stents and contrast agent, all of which cost more.
But, he said, there is strong evidence that patients with a large burden of remaining ischemia raise the risk of later events, and complete revascularization is aimed at remaining ischemic burden. "I think we'll have to wait for large trials with more patients to see if the hard end points can be reached as well."
Engstrøm discloses that he has served as a speaker for St Jude Medical.
Heartwire from Medscape © 2015
Cite this: DANAMI-3 Supports FFR-Based STEMI Complete Revascularization - Medscape - May 22, 2015.
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