Dr Cindy Grines

These are the findings from the Senior Primary Angioplasty in Myocardial Infarction (SENIOR PAMI) study, presented here today at the TCT 2005 meeting. Lead investigator Dr Cindy Grines (William Beaumont Hospital, Royal Oak, MI) noted that the benefits of PCI were confined to patients 70 to 80 years of age, with one analysis revealing strong trends toward benefit in these patients, while those >80 years old did poorly regardless of reperfusion strategy.

"There do appear to be some advantages to primary angioplasty," said Grines. "It clearly avoids intracranial bleeding in the elderly and reduces reinfarction and recurrent ischemia. The benefits of primary PCI, at least in this study, appear to be confined to an age group between 70 and 80 years. The ultraelderly patients, however, do poorly regardless of reperfusion strategy."

Moreover, said Grines, the data should be reassuring to outlying centers where primary angioplasty is not available. If there is going to be a three-hour delay before PCI, thrombolytic therapy with low-dose heparin and rescue PCI is a reasonable strategy in the elderly, Grines said.

Presenting the results of SENIOR PAMI during the late-breaking clinical-trials session, Grines explained that previous PAMI studies have shown that elderly acute MI patients usually have decreased PCI success, increased bleeding rates, increased risk of stroke, and increased risks of renal failure and death than younger patients undergoing PCI. The elderly patients often have more multivessel disease, lower ejection fractions, and a reduced ability to achieve TIMI 3 flow in the infarcted artery, making them particularly challenging PCI cases.

To date, there are limited data comparing angioplasty with thrombolytic therapy in the elderly, with the existing studies showing mixed results. Pooled analyses of randomized trials suggest that younger patients fare well regardless of treatment strategy, but there is an increased risk of death in patients older than 65 years, particularly among those treated with thrombolytic therapy. There is also an increased risk with angioplasty, noted Grines, but this risk does not occur until the patient is close to 80 years old.

With the lack of data, the SENIOR PAMI trial was initiated to compare primary angioplasty with thrombolytic therapy in patients >70 years. All patients had acute myocardial infarction symptoms between 30 minutes and 12 hours and were eligible for lytic therapy. The trial was restrictive in that it excluded patients with a systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg and those taking warfarin.

The study was stopped early because of recruitment issues, 47 patients short of the planned enrollment of 530 patients. Recruitment dwindled in 2004 and 2005 due to a number of published studies showing the superiority of primary angioplasty in the treatment of acute myocardial infarction, said Grines. She noted that enrollment fell sharply in the US, where most clinicians remain convinced of the superiority of mechanical intervention.

The results showed that primary angioplasty was not statistically superior to thrombolytic therapy in this elderly patient population. Although primary angioplasty did not reduce the primary end point of 30-day death or disabling stroke, likely due to an insufficient sample size, said Grines, primary angioplasty was superior to thrombolytic therapy at reducing the combined end point of death, disabling stroke, or reinfarction, a secondary end point.

In a subgroup analysis of patients stratified by age, the SENIOR PAMI investigators did find an advantage of primary PCI over lytic therapy. Among patients 70 to 80 years old, there was a nonsignificant 38% reduction in death, a nonsignificant 36% reduction in death/cerebrovascular accident, and a statistically significant 55% reduction in the combined end point of death/cerebrovascular accident/reinfarction. Among those older than 80 years, there was no advantage of one strategy over the other.

Grines reported that the in-hospital event rates were lower than what might be expected, with a significant advantage of primary PCI over thrombolytic therapy to reduce ischemia, ischemic target vessel revascularization, and reinfarction.

"As an interventional cardiologist, we often get approached with very, very sick, elderly patients—they are demented, they're bed-ridden, they're coming in from nursing homes and often have creatinine levels indicative of kidney disease—and we're being bad guys because we don't want to take them to the cath lab," said Grines, discussing the clinical implications of the study. "Well, now the evidence is there that even if we do our best job, some of them are still going to die, and these are patients who aren't in cardiogenic shock. So I think that as clinicians we need to make some better decisions about who maybe angioplasty isn't that good for, and where maybe thrombolytic therapy would be equally effective."

Grines added that it wasn't that PCI did worse than expected but rather that lytic therapy did better than anticipated, possibly due to the safety of lower-dose heparin (60 µ/kg to a maximum of 4000 µ) as well as the availability of rescue PCI. She said she still believes that primary angioplasty is the preferred strategy in STEMI patients, particularly those <80 years. If primary PCI is not available or transfer times are too long, thrombolytic therapy is a reasonable strategy, she said.

The scheduled discussant for the SENIOR PAMI study, Dr Stuart Pocock (London School of Hygiene and Tropical Medicine, UK), applauded the study investigators for their efforts, saying it is important to determine the answer to the primary PCI/lytic-therapy question in the elderly.

Pocock said the conclusions reached by the SENIOR PAMI investigators, that primary PCI be the preferred treatment strategy in acute myocardial patients <80 years, depends on the context. Not every healthcare system is capable of delivering primary PCI in this timely manner, and further study is needed to determine whether the same results could be achieved in other countries, specifically in Europe.

Noting that he has "been known to attack most subgroup" analyses, Pocock said caution is needed, especially in interpreting the subgroup analysis looking at patients <80 years. Also, regarding the primary end point of death and disabling stroke, Pocock said that by his calculations, study investigators needed nearly four times as many patients. During her presentation, Grines said her group had underestimated the number of patients needed for enrollment, mainly due to the lower-than-expected event rates in the lytic study arm.