The Problem of Anti-Platelet Drug Therapy After A Stent

Long-term treatment is necessary, but problematic

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Over the past 20 years, stents have become very common in the treatment of coronary artery disease. Problems that were seen in the early days of stenting, such as stent dislodgment and a high rate of stent restenosis, have been largely mitigated by advancing technology (in particular, the introduction of drug-eluting stents, which inhibit the tissue growth that is largely responsible for restenosis).

But at least one tenacious problem remains with stents - the risk of stent thrombosis. Stent thrombosis is the sudden formation of a blood clot at the site of a stent, which typically causes rapid and complete occlusion of the coronary artery, often leading to death or significant heart damage from a myocardial infarction.

The risk of stent thrombosis is highest in the weeks and months after stent placement. But over the years it has gradually become apparent to doctors that this risk never entirely disappears, and that “late” stent thrombosis (that is, thrombosis that occurs more than a year after stent insertion) remains a low-incidence, but highly catastrophic, possibility.

Preventing Stent Thrombosis

The risk of stent thrombosis can be greatly reduced when patients are prescribed two anti-platelet drugs to inhibit blood clotting: aspirin, and one of the P2Y12 receptor blockers. The P2Y12 blockers that are used to prevent stent thrombosis are clopidogrel (Plavix - the most commonly used), prasugrel (Effient), and ticagrelor (Brilinta).

Taking one of the P2Y12 drugs plus aspirin is referred to as “dual-anti-platelet therapy,” or DAPT.

How Long Should DAPT Be Used?

DAPT is very effective at lowering the risk of catastrophic thrombosis. Originally, DAPT was used for a month after stent placement, when the risk of thrombosis is highest.

Doctors quickly recognized that DAPT should be used longer, and soon the standard of therapy was to prescribe 6 months of DAPT.

Then, in the early 2000s, the problem of late stent thrombosis was recognized, and many doctors began routinely prescribing DAPT for a full year or more.

Even so, stories began circulating of patients who experienced stent thrombosis soon after DAPT was discontinued, even after long-term treatment. Many doctors worried that DAPT should be continued for a much longer period of time - perhaps for years, perhaps forever. However, little actual data existed to give doctors objective guidance on the optimal duration of DAPT following a stent.

The DAPT Study

The DAPT study was designed to give a final answer regarding the optimal duration of DAPT after stent placement. The study enrolled nearly 10,000 stent patients who had already taken DAPT for 12 months. They were randomized to either to stop DAPT, or continue it for another 18 months (for a total duration of 30 months).

The results, reported in late 2014, showed that 30 months of DAPT was associated with a significantly reduced risk of late stent thrombosis, compared with 12 months of treatment.

Disturbingly, the study also demonstrated that whenever DAPT was discontinued - even after years of use - the risk of stent thrombosis was greatly increased for the next 3 months.

However, patients treated with 30 months of DAPT had more serious bleeding episodes than patients treated for 12 months. And, while most of the investigators appear to believe it to be a spurious finding, patients treated with 30 months of DAPT also had a higher overall risk of death than patients treated for 12 months.

So: the DAPT study indicates that 30 months of DAPT is better than 12 months of therapy at preventing stent thrombosis. It also confirms that there is a significant spike in the risk of thrombosis when discontinuing DAPT, even after long-term use. Finally, it shows there is a trade-off with prolonged DAPT therapy - less stent thrombosis, but more life-threatening bleeding episodes.

Why DAPT Can Be Difficult

Taking DAPT itself poses a risk of major bleeding episodes, and the DAPT study confirmed that the longer a person takes DAPT, the higher the risk of major bleeds. For any person taking DAPT, an episode of moderate trauma (such as a car accident that poses no direct mortal risk) can become lethal because of the bleeding propensity.

Also, because bleeding is so difficult to control on DAPT, most surgeons will not even consider operating on a patient taking DAPT.

This issue regarding surgery creates a major problem for many patients who have stents. On one hand their cardiologist may be telling them to never, ever stop DAPT (because of the acute risk of stent thrombosis); on the other hand, a surgeon may be telling them they are in dire need an operation, and that DAPT must be stopped to allow surgery to proceed. If it should turn out that there is, in fact, an overall increase in mortality with long term DAPT, perhaps avoiding necessary invasive tests and treatments may have something to do with it.

Medical science has not yet devised a solution to this common dilemma. For scientists this is an interesting problem to work on; for some cardiologists it is an unfortunate problem brought on by the patient’s failing to avoid hurting themselves, or failing to avoid the need for surgery; for patients it is a potentially life-altering problem, and one that can be especially frustrating if they have not been adequately informed of the implications of DAPT prior to agreeing to receive a stent.

In most cases if surgery cannot be avoided, every effort is made to continue DAPT for a year after stent placement - or at the very least, for 6 months - before stopping it.

Current Recommendations on DAPT

Most cardiologists insist their stent patients take DAPT for at least 12 months, unless a patient has a clearly increased bleeding risk. After 12 months, a re-evaluation should occur, and if possible, DAPT should be continued for another 18 months.

The Bottom Line

DAPT is necessary after having a stent, but presents its own problems. The medical community is still sorting out the risk-benefit ratio for long-term DAPT, and it is likely to be a while before some consensus is reached.

In the meantime, when a cardiologist recommends stent therapy to a patient, he or she should feel obligated to review with the patient, in great detail, all the implications of the fact that long term DAPT is now an inherent component of stent therapy. All the other treatment alternatives to stent therapy also need to be fully discussed, so that patients can make a truly informed decision.

Sources:

Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014; DOI:10.1056NEJMoa1409312.

Columbo A and Chieffo A. Dual antiplatelet therapy after drug-eluting stents—How long to treat? N Engl J Med 2014; DOI:10.1056/NEJMe1413297.

Spertus JA, Kettelkamp R, Vance C, et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation 2006; 113:2803.

Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011; 124:e574.

Sammy Elmariah, Laura Mauri, Gheorghe Doros, et al. Extended duration dual antiplatelet therapy and mortality: a systematic review and meta-analysis. Lancet 2014; DOI: 10.1016/ S0140-6736(14)62052-3.

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