Why is this study important?

• ISCHEMIA showed no overall benefit of an initial invasive management strategy of chronic coronary disease as compared to an initial conservative management strategy on cardiovascular events or all-cause mortality at a median of 3.2 years. 
• However, an initial increased risk of procedural MIs was counterbalanced by a reduced risk of spontaneous MI in invasively managed patients. 
• Over time, this trend may result in reduced net cardiovascular events and mortality in the initially invasively managed patients. 

What question was this study supposed to answer?

Does invasive management of chronic coronary disease result in reduced mortality over the longer term?

What did the study show?

• In ISCHEMIA-EXTENDed, ISCHEMIA patients underwent additional follow-up after the end of the main study, resulting in a median follow-up of 5.7 years. Only mortality data was collected. 
• The number of deaths nearly doubled (increasing from 289 to 557) during this additional follow-up period. 
• The 7-year all-cause mortality rate was the same in the invasive and conservatively managed patients (12.7% vs 13.4%, adjusted HR 1.00, 95% CI 0.85-1.18). 
• Invasively managed patients had a lower cardiovascular mortality rate (6.4% vs. 8.6%, adjusted HR = 0.78, 95% CI 0.63-0.95), but a higher non-cardiovascular mortality rate 5.6% vs 4.4%, adjusted HR 1.44, 95% CI 1.08-1.91). 
• Note that causes of death were not adjudicated, and other endpoints (MI, revascularization) were not collected. 

Conclusions: 

• Over the longer term (median 5.7 years), initially invasively managed patients and initially conservatively managed patients with chronic coronary disease experience similar all-cause mortality. 
• An initial invasive management strategy may reduce cardiovascular mortality, but if so, this is counterbalanced by increased non-cardiovascular mortality.