ESC 2020 Congress: ISCHEMIA trial suggests invasive approach benefits high risk patients

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Renato Lopes

An invasive approach involving either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) may be beneficial in high risk stable ischaemic heart disease patients with moderate-to-severe ischaemia and a history of heart failure or left ventricular dysfunction. This was the conclusion put forward by Renato Lopes (Duke University, Durham, USA), presenting insights from the ISCHEMIA trial, during a late-breaking science session at the ESC 2020 Congress (Virtual, 29 August–1 September).

However, Lopes cautioned that due to the small number of patients and events in the heart failure and left ventricular dysfunction groups of the study, the results should be interpreted with caution and as “hypothesis generating”, adding that further follow-up is needed to assess potential longer-term benefits of the invasive approach.

The ISCHEMIA trial tested an invasive versus a conservative strategy for patients with stable ischaemic heart disease, and showed that an initial invasive strategy did not reduce the risk of the primary outcome of cardiovascular (CV) death, myocardial infarction (MI), hospitalisation for unstable angina, heart failure or resuscitated cardiac arrest.

According to Lopes, previous studies—including the STICHES trial—have shown that patients with left ventricular ejection fraction (LVEF) lower than 35% or New York Heart Association (NYHA) class III–IV heart failure derive long-term benefit after increased risk from revascularisation with CABG, with a 16% reduction in death at 10 years. However, he said, less is known about patients with heart failure or LVEF between 35-45%. Therefore, the ISCHEMIA trial provided sought to explore the potential benefit of an invasive strategy in this subgroup of patients.

The study team compared the risk of clinical outcomes for patients with and without a history of heart failure or left ventricular dysfunction and used the Cox proportional hazards model, with and without adjustment for key baseline covariates. They also compared outcomes of an invasive versus a conservative strategy across different levels of ejection fraction analysed as a continuous variable, and using a relaxed proportional hazards assumption for treatment variable.

ISCHEMIA enrolled a total of 8,518 patients, 5,179 who had stable ischemic heart disease that was moderate or severe on stress testing were randomised to either an initial invasive treatment strategy (2,588) or to an initial conservative strategy (2,591). “Both groups had similar rates of severe ischaemia at baseline, around 65%, and as expected, patients with heart failure had lower median EF than patients without heart failure, 44% vs 60% respectively,” Lopes said.

“Overall patients with heart failure had worse outcomes, including the primary outcome, cardiovascular death or MI, all cause death, CV death and hospitalisation for heart failure, than patients without heart failure,” he added.

Looking at the association between treatment and outcomes for patients with and without heart failure or left ventricular dysfunction at baseline, Lopes continued, “…we observe that patients with heart failure assigned to an invasive strategy had lower rates of the primary outcome and CV death or MI, than patients assigned to a conservative strategy. This benefit of an invasive strategy over a conservative strategy was not seen in the group of patients without heart failure or left ventricular dysfunction.”

Looking at the cumulative incidence of the primary outcome, Lopes explained that the study team did not find any difference between an invasive and conservative strategy in patients without heart failure. However, in patients with heart failure, the study team observed lower rates of the primary outcome in patients assigned to an invasive strategy, when compared to those assigned to a conservative strategy.

He went on: “In patients without heart failure, we did not find any difference in the rates of the primary outcome between an invasive and a conservative strategy. However, in patients with heart failure we can appreciate that patients assigned to an invasive strategy, who had [a] lower ejection fraction, had lower rates of the primary outcome when compared with patients assigned to a conservative strategy.”

Similar assessment was also done for all-cause death, he said, finding that in patients without heart failure there was no difference between an invasive and a conservative strategy. However, in patients with heart failure and lower EF the study team found lower rates of all-cause death in patients assigned to an invasive strategy when compared with a conservative strategy. Conversely, in patients with heart failure and higher EF, they observed higher rates of all cause death in patients assigned to an invasive strategy when compared to a conservative strategy.

The ISCHEMIA study does have some limitations, Lopes noted, including the possible presence of unmeasured confounding, the small number of patients and events in the heart failure and left ventricular dysfunction groups. “Therefore, our results should be interpreted with caution and as hypothesis generating,” he said.

Finally, he noted, revascularisation in the invasive strategy was a mixture of CABG and PCI, “which may differ in the their acute risks and benefits as well as in their long-term protection from future events”.

In conclusion, Lopes explained: “An invasive approach may be beneficial in this sub group of high risk patients, with moderate-to-severe ischaemia and a history of heart failure or left ventricular dysfunction.

“Further follow-up to provide additional information for the potential longer-term benefits of the invasive approach in this high risk group of patients with heart failure or left ventricular dysfunction is planned,” he finished.


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