The more complicated a primary endpoint is, the greater can be a puzzle for clinicians to interpret the results. It is probably even more difficult for patients, who do not help to choose the events studied in clinical trials, but who are increasingly involved in the influencing management decisions.
This creates an opening for a more patient-centered approach in one of the most influential recent studies in cardiology, ISCHEMIA, which reinforces the case of conservative and medicine-oriented management with a more invasive initial strategy for patients with stability coronary artery disease (CAD) and positive stress tests, the researchers say.
The new pre-specified analysis replaced the conventional main criterion of major adverse cardiac events (MACE) of the trial with one based on “living days out of the hospital” (DAOH) and found an early advantage for the conservative approach, with warnings.
Those assigned to the conservative arm benefited from more days out of the hospital over the next 2 years than those from the invasive management group, due to the early work required by this protocol in the Catholic laboratory with possible revascularization. The difference averaged over 6 days for much of that time.
But DAOH equalized the two groups in the fourth year in the analysis of more than 5,000 patients.
Protocol-determined chair procedures accounted for 61% of group invasive hospitalizations. A secondary analysis of DAOH that excluded these required hospital days, also pre-specified, showed no significant differences between the two strategies during the 4 years, the report notes. published online May 3 Cardiology JAMA.
The DAOH metric has been a much less common consideration in clinical trials compared to clinical events, although in some respects it is a metric as “tough” as mortality, includes a wider range of results, and may matter more. to patients. .
“What patients value most is time at home. So they don’t want to be in the hospital, they don’t want to be away from friends, they want to do recreation, or maybe they want to work,” the lead author explains. This was stated by Harvey D. White, DSc, Green Lane Cardiovascular Services, Auckland City Hospital, University of Auckland, New Zealand. theheart.org | Cardiology Medscape.
“When we need to talk to patients – and us do they need to talk to patients: having a metric of days out of the hospital is very, very important, “he said. Not only is it patient-centered, but it’s” significant in terms of the severity of the events. ” of clinical severity hospitalization, White noted, who is scheduled to present the analysis on May 17 during the 2021 scientific sessions of the American College of Cardiology (ACC) virtual.
How previously reported, ISCHEMIA showed no significant effect on the primary value of cardiovascular mortality (CV), myocardial infarction (MI), or hospitalization for unstable angina, heart attack, or cardiac arrest resuscitated by assignment group for an average of 3.2 years. Angina and improved quality of life measures for invading arm patients.
With an invasive initial strategy, “what we know now is that you don’t get any advantage over the compound endpoint and you will spend another 6 days in the hospital for the first 2 years, with largely no benefits,” White said .
These prospects may apply to four years, the analysis suggests, but could change if DAOH is revalued later, as monitoring of ISCHEMIA continues for what is now a projected total of 10 years.
Meanwhile, current findings could improve discussions between physicians and patients about the trade-offs between the two strategies for individuals whose considerations vary.
“This is a very useful measure for understanding the burden of a patient approach,” noted E. Magnus Ohman, MD, Duke University School of Medicine, Durham, North Carolina, who did not participate in the judges.
With DAOH as an endpoint, “as a physician, you get another aspect of understanding the impact of a treatment on a multitude of endpoints.” Days out of the hospital, he notes, encompass the effects of clinical events that often occur for compound clinical purposes, not death, but nonfatal MI. stroke, need for revascularization and hospitalization CV.
For patients with stable CAD who ask if the invasive approach has merit in their case, finding DAOH “helps you say, at the end of the day, that you will probably spend the same amount of time in the hospital. the starting price is a little higher, but over time, the group receiving conservative treatment will catch up. “
The DAOH result also avoids the limitations of a time-based endpoint to the first event, “no less important,” said White, who only counts the first of what could be multiple events of variable clinical impact. Deceptively, “you may have an event that is a small increase in troponin, but that becomes more important in a person than dying the next day.”
The DAOH analysis was based on 5179 patients from 37 countries with a mean age of 64 years and of whom 23% were women. The end point was considered only overnight stays in hospitals, specialized nursing facilities, rehabilitation centers and residences.
Table. Mean difference in DAOH strategy, conservative versus invasive
|Time since randomization||DAOH (P), conservative versus invasive, has been added||DAOH (P), an invasive conservative, has been added, excluding procedures assigned by protocol|
|1 m||2.4 (<0.001)||0 (.66)|
|1 i||6.3 (<0.001)||1.1 (.11)|
|2 i||6.3 (0.001)||1.1 (.58)|
|4 i||2.8 (.65)||-2.4 (.69)|
DAOH = Living days out of the hospital
There were many more hospital stays or extended care in general in the invasive management group, 4002 vs. 1897 for those who followed the conservative strategy (Pg <.001), but the numbers changed after excluding the procedures assigned by the protocol: 1568 remain in the invasive group compared to 1897 (Pg = .001)
There were no associations between DAOH scores and Seattle Angina Questionnaire 7 – Angina Frequency (SAQ7-AF) or DAOH interactions by age, sex, geographic region, or if the patient had diabetes, previous MI, or heart failure.
The main analysis of ISCHEMIA suggested a possible long-term advantage for the initial invasive strategy in this case, the curves of the two arms crossed after 2 to 3 years, Ohman observed.
Based on this, for younger patients with stable CAD and ischemia on stress tests, “an investment of more days of early hospitalization may be worthwhile in the long run.” But ISCHEMIA, he said, “just suggests it, doesn’t confirm it.”
The study was partially supported by grants from Arbor Pharmaceuticals and AstraZeneca. Devices or medications were provided by Abbott Vascular, Amgen, Arbor, AstraZeneca, Esperion, Medtronic, Merck Sharp & Dohme, Phillips, Omron Healthcare; and Sunovion. White reveals receipt of grants paid to his institution and fees to serve on a board of directors of Sanofi-Aventis, Regeneron, Eli Lilly, Omthera, American Regent, Eisai, DalCor, CSL Behring, Sanofi-Aventis Australia and Esperion Therapeutics ; and personal fees from Genentech and AstraZeneca. The report contains disclosures for the other authors. Ohman reported receiving grants from Abiomed and Cheisi USA and has consulted for Abiomed, Cara Therapeutics, Chiesi USA, Cytokinetics, Imbria Pharmaceuticals, Otsuka Pharmaceuticals, Milestone Pharmaceuticals and XyloCor Therapeutics.
JAMA Cardiol. Published online May 3, 2021. Full text
American College of Cardiology (ACC) 2021 Scientific Sessions. Session 910, Outstanding Original Research: Ischemic Heart Disease and the Year in Review. Summary 910-10. Living days out of the hospital with invasive and conservative initial management in the ISCHEMIA test. It will be presented on May 17, 2021.
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