Guideline-Directed Medical Therapy and Outcomes in the ISCHEMIA Trial.

Summary

In ISCHEMIA participants with chronic coronary disease, early attainment and maintenance of GDMT goals—especially SBP <130 mmHg—was associated with substantially fewer CV deaths/MIs. Achieving all four goals at baseline and maintaining them led to an absolute 16% lower 4-year CV death/MI versus no goals met; each 10 mmHg lower follow-up SBP reduced risk by ~10%.

Key Findings

• At baseline, only 12% met all 4 GDMT goals; those maintaining all goals had 8.7% 4-year CV death/MI vs 24.5% with no goals met.
• SBP target attainment conferred the largest absolute risk reduction in CV death/MI (-5.1%); each 10 mmHg lower SBP over follow-up reduced risk by ~10%.
• Relative contributions: antiplatelet therapy and LDL-C <70 mg/dL provided additional benefit, while smoking abstinence trended favorably.

Clinical Implications

Prioritize early and sustained SBP control (<130 mmHg) alongside antiplatelet therapy, LDL-C <70 mg/dL, and smoking cessation. Implement treat-to-target monitoring and longitudinal goal tracking in CCD clinics to reduce CV death/MI.

Limitations

• Observational, post hoc analysis within a randomized trial—residual confounding possible.
• Goal achievement definitions and care intensity may differ across sites, affecting generalizability.

Future Directions

Prospective, system-level treat-to-target interventions with audit-and-feedback; evaluate digital longitudinal monitoring for GDMT goal maintenance and disparities.