Effects of initial invasive vs. initial conservative treatment strategies on recurrent and total cardiovascular events in the ISCHEMIA trial

Abstract

Aims The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial prespecified an analysis to determine whether accounting for recurrent cardiovascular events in addition to first events modified understanding of the treatment effects. Methods and results Patients with stable coronary artery disease (CAD) and moderate or severe ischaemia on stress testing were randomized to either initial invasive (INV) or initial conservative (CON) management. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and hospitalization for unstable angina, heart failure, or cardiac arrest. The Ghosh–Lin method was used to estimate mean cumulative incidence of total events with death as a competing risk. The 5179 ISCHEMIA patients experienced 670 index events (318 INV, 352 CON) and 203 recurrent events (102 INV, 101 CON). A single primary event was observed in 9.8% of INV and 10.8% of CON patients while ≥2 primary events were observed in 2.5% and 2.8%, respectively. Patients with recurrent events were older; had more frequent hypertension, diabetes, prior MI, or cerebrovascular disease; and had more multivessel CAD. The average number of primary endpoint events per 100 patients over 4 years was 18.2 in INV [95% confidence interval (CI) 15.8–20.9] and 19.7 in CON (95% CI 17.5–22.2), difference −1.5 (95% CI −5.0 to 2.0, P = 0.398). Comparable results were obtained when all-cause death was substituted for cardiovascular death and when stroke was added as an event. Conclusions In stable CAD patients with moderate or severe myocardial ischaemia enrolled in ISCHEMIA, an initial INV treatment strategy did not prevent either net recurrent events or net total events more effectively than an initial CON strategy. Clinical trial registration ISCHEMIA ClinicalTrials.gov number, NCT01471522, https://clinicaltrials.gov/ct2/show/NCT01471522.

Quantitative Flow Ratio or Angiography for the Assessment of Non-culprit Lesions in Acute Coronary Syndromes: Protocol of the Randomized Trial QUOMODO

“…Third, the primary endpoint is assessed at 12 months after protocol-mandated complete revascularization; complaints due to myocardial ischemia, which may occur after a period of more than 1 year, will not be recorded. However, data from the ischemia trial appear to suggest that the incidence of angina remains constant during longer follow-up periods ( 39 ).…”

International Practice Patterns of Dyslipidemia Management in Patients with Chronic Kidney Disease under Nephrology Care: Is it time to review guideline recommendations?

“…Invasive Approaches -Chronic Kidney Disease (ISCHEMIA-CKD) trials found similar effects in reducing all-cause death or myocardial infarction between initial invasive management compared to initial conservative management, which includes aggressive LDL-C therapies as a standard of care, of patients with chronic coronary disease and moderate to severe ischemia on stress testing without or with advanced CKD [19,20]. Also, a post-hoc analysis of the Aggressive Lipid-Lowering Initiation Abates New Cardiac Events (ALLIANCE) Study demonstrated that in patients with coronary heart disease and CKD, intensive LLT with higher doses of atorvastatin to achieve a target < 80 mg/dL reduced the relative risk of time to the rst cardiovascular event by 28% in patients with CKD (HR, 0.72; 95% CI, 0.54 to 0.97; P = 0.02) and 11% in patients without CKD (HR, 0.89; 95% CI, 0.74 to 1.07; P = 0.3) [21].…”

Is non-cardiac death increased with an initial invasive revascularization strategy? Commentary on the ISCHEMIA trial

“…In a recent issue of partner journal from the ESC Journals family, the incidence of cardiovascular adverse events at 4 years of follow-up in the ISCHEMIA trial was reported. 1 In such manuscript, authors did not find any significant differences between initial Invasive (INV) or Conservative (CON) strategies in the number of composite or individual cardiac events.…”

“…However, if we look numbers of cardiovascular death, 3.6% vs. 4.3% with INV and CON strategies, respectively P = 0.176, and all-cause of death 5.6% in both P = 0.944; call to our attention that incidence of non-cardiac death in the INV group would be significant higher compared to the CON ones 2% vs. 1.3%, respectively, P = 0.029 and numbers of non-cardiac death are not reported in the manuscript. 1 Interestingly, most of these were due to cancer accorded to the abstract presentation reported by the same authors in the 2020 American Heart Association meeting. 2…”

“…Introduction of DES in clinical practice significantly reduced incidence of repeat revascularization procedures, however, gap among PCI, CABG, and/or optimal medical treatment did not change in the last 20 years as is reflect by the references of this correspondence letter. 1 , 3 , 4 …”