Factors Associated With Coronary Angiography After Randomization to the Conservative Strategy in the ISCHEMIA Trial
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease.
METHODS
Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use.
RESULTS
Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography.
CONCLUSIONS
Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
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Additional Info
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Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial
Circ Cardiovasc Interv 2024 Apr 17;[EPub Ahead of Print], R Pracoń, JA Spertus, S Broderick, S Bangalore, FW Rockhold, W Ruzyllo, E Demchenko, T Nageh, GB Grossman, K Mavromatis, CN Manjunath, PEP Smanio, GW Stone, GBJ Mancini, WE Boden, JD Newman, HR Reynolds, JS Hochman, DJ MaronFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The debate on the merits of coronary revascularization in addition to optimal medical therapy in patients with chronic coronary syndrome is ongoing. Based on prior research, the indications for coronary stenting or bypass surgery were narrowed mainly to coronary lesions responsible for significant myocardial ischemia and/or persistent symptoms. The ISCHEMIA trial confirmed the presence of improvements in the overall quality of life of patients with the initial invasive strategy but fell short of finding its survival benefits.
The present analysis evaluated the characteristics of patients enrolled in the ISCHEMIA trial who underwent invasive coronary angiography early after randomization to the conservative treatment arm of the trial. Early angiography was defined as coronary angiography performed within 6 months of randomization — a time interval sufficient to optimize medical therapy and schedule invasive procedures, if necessary; but, also a vulnerable period for protocol nonadherent, “cross-over” catheterizations due to a well-known propensity toward invasive procedures despite the conservative treatment arm allocation among some of the patients and study teams.
The analysis showed that the rate of coronary angiography at 6 months after randomization to the ISCHEMIA conservative arm was 8.7% (4.7% for a suspected endpoint event, out of which 2.5% were centrally confirmed; 1.6% for a persistent unacceptable level of symptoms; and 2.6% due to protocol nonadherence). The factors most strongly associated with coronary angiography were symptom-related: daily and weekly angina, new/more frequent angina pre-randomization, and compromised health status as assessed with the Seattle Angina Questionnaire. It is noteworthy that only 35.2% of patients with daily and 16.0% with weekly angina underwent early angiography. A baseline LDL-C level <70 mg/dL was associated with a decreased likelihood of receiving early coronary catheterization. Notably, neither baseline ischemia severity nor the presence of multivessel disease or proximal left anterior descending artery stenosis was associated with early angiography.
These results underscore the methodological stringency of the ISCHEMIA trial in keeping the randomized strategy, irrespective of baseline ischemia severity on imaging or coronary disease severity on baseline CCTA. The other important take-home message is that, although patients with greater symptom burden had a greater chance of ending up in a catheterization lab in the short run, most of them still remained on optimal medical therapy alone, with an invasive treatment option being available to them at a later stage if eventually found necessary. Such a strategy did not affect the survival rates in the ISCHEMIA trial; this finding is crucially important when interpreting other trials testing coronary revascularization versus optimal medical therapy that are often times powered by endpoints such as ischemia-driven or urgent revascularization, not meeting the criteria of myocardial infarction or unstable angina.