Does premature discontinuation of antiplatelet therapy (DAPT) with medications such as aspirin and a P2Y12 inhibitor (e.g. clopidogrel) in patients with stents increase the risk of both stent thrombosis and in-stent restenosis?

Premature Discontinuation of Antiplatelets and In-Stent Restenosis

No, premature discontinuation of dual antiplatelet therapy (DAPT) does not cause in-stent restenosis—it causes stent thrombosis, which is an entirely different and far more catastrophic complication. The evidence overwhelmingly demonstrates that early DAPT cessation is the leading independent predictor of stent thrombosis, not restenosis 1.

Understanding the Distinction: Thrombosis vs. Restenosis

Stent thrombosis and in-stent restenosis are fundamentally different pathophysiologic processes:

• Stent thrombosis is an acute thrombotic occlusion of the stent, typically occurring when antiplatelet therapy is discontinued prematurely, resulting in death or MI in 64.4% of cases with mortality rates of 20-45% 2
• In-stent restenosis is a gradual proliferative process involving neointimal hyperplasia that develops over months, unrelated to antiplatelet therapy duration 1

The Catastrophic Risk: Stent Thrombosis from DAPT Discontinuation

Premature antiplatelet discontinuation is the single most important predictor of stent thrombosis, not restenosis 2, 3. The evidence is striking:

• 29% of patients who discontinued antiplatelet therapy prematurely experienced stent thrombosis 1
• Hazard ratio of 161 (95% CI: 26-998) for subacute stent thrombosis when DAPT is stopped early 1
• Hazard ratio of 57 (95% CI: 15-220) for late stent thrombosis (>30 days) 1
• 30-fold greater risk of stent thrombosis with premature clopidogrel discontinuation in the first month 1

Critical Timing of Thrombotic Events

The timing of stent thrombosis after DAPT cessation follows a predictable pattern:

• When both antiplatelet agents are stopped simultaneously, the median time to stent thrombosis is exactly 7 days 3, 4
• Among patients who stopped both agents, 75% of thrombotic events occurred within 10 days 4
• If the thienopyridine is stopped but aspirin is maintained, the median time to event extends to 122 days 4
• Only 6% of events occurred within 10 days when aspirin was continued after thienopyridine cessation 4

Mortality Impact of Premature Discontinuation

The mortality consequences are devastating:

• Mortality rate of 7.5% in patients who stopped thienopyridine therapy versus 0.7% in those who continued (hazard ratio 9.0, P<0.0001) 1
• Case fatality rate of 45% when stent thrombosis occurs 5
• 88% risk of death or nonfatal MI when stent thrombosis develops 3

High-Risk Period: First 6 Months

The risk is particularly concentrated in the first 6 months after stenting:

• 35.4% incidence of stent thrombosis when clopidogrel was discontinued in the first 30 days 6
• 11.7% incidence when discontinued within the first 180 days 6
• After clopidogrel discontinuation at 6 months in drug-eluting stents, late stent thrombosis occurred in 2.6% versus 1.3% with bare-metal stents 1

Perioperative Context: Surgical Discontinuation

When DAPT is stopped for noncardiac surgery, the risks are extreme:

• In patients undergoing surgery within 6 weeks of bare-metal stent placement, 7 patients had MI (6 fatal), with 5 of 7 having thienopyridine withheld 1
• Early surgery with DAPT discontinuation resulted in 30.7% major adverse cardiac events (all fatal) versus 0% in those continuing therapy 2
• 13.3% major adverse cardiac events in early surgery versus 0.6% in late surgery 2

Why Restenosis Is Not the Issue

In-stent restenosis is mechanistically unrelated to antiplatelet therapy:

• Restenosis is driven by neointimal proliferation and occurs gradually over months regardless of antiplatelet use 1
• Drug-eluting stents were specifically designed to reduce restenosis through antiproliferative drugs, not through antiplatelet effects 2
• The guidelines and FDA labeling focus exclusively on thrombosis prevention, not restenosis prevention, when discussing DAPT duration 7

Recommended DAPT Duration to Prevent Thrombosis

The American Heart Association and American College of Cardiology recommend:

• Minimum 12 months of DAPT for drug-eluting stents in patients not at high bleeding risk 1, 2, 8
• Minimum 6-12 months as the standard recommendation 2, 8
• For acute coronary syndrome patients, 12 months of DAPT regardless of stent type 8

Critical Management Principles

If DAPT must be interrupted:

• Never stop both agents simultaneously—maintain aspirin if at all possible 3, 4
• If thienopyridine must be stopped, discontinue at least 7 days prior to surgery but continue aspirin 7
• Restart thienopyridine as soon as possible after the procedure 3, 7
• Short-term thienopyridine discontinuation (with continued aspirin) may be relatively safe, but stopping both agents is catastrophic 4

Common Pitfalls to Avoid

• Do not confuse stent thrombosis with restenosis—they are entirely different complications with different mechanisms, timing, and outcomes 1, 2
• Do not assume shorter DAPT is safe based on newer stent data—most studies were underpowered for stent thrombosis and excluded high-risk ACS patients 9, 6
• Do not discontinue DAPT for cost or convenience reasons—the mortality risk far outweighs any perceived benefit 1
• Do not accept "1 month is enough"—this contradicts all major guidelines and is associated with 35.4% stent thrombosis rates 8, 6