TWILIGHT

Clinical Question

In patients who have undergone PCI and DES placement, is brief initial dual-antiplatelet therapy (Ticagrelor + Aspirin) followed by single antiplatelet therapy (Ticagrelor) superior in regards to clinically relevant bleeding and non-inferior in regards to ischemic events compared to prolonged dual-antiplatelet therapy (Ticagrelor + Aspirin)?

Bottom Line

Brief DAPT followed by antiplatelet monotherapy conferred decreased rates of clinically relevant bleeding compared to prolonged DAPT in patients at high risk of bleeding or ischemic events. It was also non-inferior in regards to a composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke.

Major Points=

Coronary artery drug-eluting stents (DES) is an increasingly common treatment modality in a variety of indications in coronary artery disease. Dual anti-platelet therapy (DAPT) is a necessary concurrent treatment to prevent in-stent thrombosis and restenosis in these stents; optimal duration for this therapy has become a commonly studied question and is dependent on indication for stent placement as well as patient factors. In all situations, however, ischemic reduction benefit of DAPT must be weighed against its resultant risk of bleeding. Recent studies such as STOPDAPT-2 and SMART-CHOICE have shown benefit in shorter durations of DAPT. TWILIGHT expands on this notion and explores bleeding and ischemic outcomes in shortened durations of DAPT in NSTE-ACS, stable angina, and asymptomatic patients who have undergone PCI with DES placement.

Published in 2019, The Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT) trial randomized 7,119 patients in a 1:1 fashion to groups of ASA and ticagrelor for 3 months followed by ticagrelor monotherapy or ASA and ticagrelor for 12 months. The primary outcome was Level 2,3, or 5 bleeding at 12 months follow-up using the Bleeding Academic Research Consortium (BARC) and

Guidelines

There are no major society guidelines based on the results of this study as of December 2019.

Design

* Multicenter, double-blind, parallel-group, randomized, controlled trial

• N=10,251
  • Intensive (n=5,128)
  • Standard (n=5,123)
• Setting: 77 centers in Canada and the United States
• Enrollment: January to June 2001, February 2003 to October 2005
• Mean follow-up: 3.5 years
• Analysis: Intention-to-treat
• Primary outcome:

Population

Inclusion Criteria

• Type 2 diabetes mellitus
• Hemoglobin A1c ≥7.5%
• Age 40-79 years with CAD or 55-79 years with
• Anatomical evidence of significant atherosclerosis
• Albuminuria
• LVH
• ≥2 cardiovascular risk factors (dyslipidemia, HTN, current smoking, obesity)

Exclusion Criteria

• Frequent or recent serious hypoglycemic events
• Unwillingness to perform home glucose monitoring or insulin injections
• BMI >45
• Cr >1.5mg/dl
• Serious illness

Baseline Characteristics

• Mean age: 72 years
• Mean BMI: 28
• Mean HbA1c: 8.8%
• Units of insulin: 14 units/day

Interventions

• Randomized to intensive (targeting HbA1c <6%) or standard (HbA1c 7-7.9%) glycemic therapy

  • Then 46% were randomized to intensive (SBP <120) vs. standard (SBP <140) blood pressure therapy
  • Remaining 54% randomized to fenofibrate vs. placebo; all received statin
• Intensive glycemic control group attended monthly visits for 4 months, then every 2 months, with additional visits and telephone calls as needed
• Standard therapy group had glycemic control visits every 4 months

Outcomes

Comparisons are intensive therapy vs. standard therapy.

Primary Outcomes

Annual rate of nonfatal MI or nonfatal stroke or cardiovascular death

2.11% vs. 2.29% (HR 0.90; 95% CI 0.78-1.04; P=0.16)

Secondary Outcomes

Annual rate of death from any cause

1.41% vs. 1.14% (HR 1.22; 95% CI 1.01-1.46; P=0.04)

Annual rate of cardiovascular death

0.79% vs. 0.56% (HR 1.35; 95% CI 1.04-1.76; P=0.02)