This systematic review tried to find the optimal duration of dual antiplatelet therapy, usually aspirin and clopidogrel, after coronary stenting. Compared to standard antiplatelet therapy for 12 months, shorter treatment had little impact on stent thrombosis. Treatment for longer than 12 months did, however, reduce thrombosis by 67% (about 7 events per 1000 people). Major bleeding complications were related to duration of therapy, a reduction of about 3 events per 1000 people treated for shorter treatment and an increase of about 7 events per 1000 for longer treatment.
Clinicians may choose to offer shorter duration therapy to many patients (especially those with a higher risk of bleeding) while considering extending treatment beyond 12 months for those with very high ischaemic and low bleeding risks.
Longer treatment duration was also associated with an increase in all-cause mortality (but not cardiovascular mortality) of about 4 per 1000 compared to standard 12 months’ treatment. The reasons are not clear and this finding warrants further investigation.
Why was this study needed?
Coronary heart disease - where the heart’s blood supply is interrupted by blocked arteries - is the leading cause of death in the UK, responsible for more than 73,000 deaths each year. About 1 in 6 men and 1 in 10 women die from heart disease, and 2.3 million people live with the condition in the UK. Stenting, a type of percutaneous coronary intervention, is a procedure that places a wire mesh tube called a stent into the blocked artery in order to hold it open and improve or restore blood flow. In this study drug eluting stents were investigated, these are the most commonly inserted stents in the NHS. These are coated with medication that releases drugs to stop the artery narrowing again.
Dual antiplatelet therapy is currently recommended after a coronary stent has been inserted. It lowers the risk of cardiovascular complications, such as heart attacks and blockages of the stent due to a thrombosis, but increases the risk of bleeding, which may be life-threatening. How long patients should take the drugs for is debated, and current recommendations of a 12 month-long course are based mostly on observational data. This systematic review was designed to assess the benefits and risks of short and long-term drug therapy compared to the currently recommended standard 12 month therapy, following stenting.
What did this study do?
This systematic reviewed identified randomised controlled trials of short-term (three or six month) or long-term (18, 24 or 30 month) drug therapy compared to standard 12 month therapy from January 2002 to February 2015. All participants had heart disease and had undergone angioplasty with the insertion of drug eluting stents.
The main outcomes were cardiovascular mortality, heart attack, blockages of the stent due to a blood clot (stent thrombosis), major bleeding, and overall mortality. Meta-analysis was used to combine the results of the trials. This was a well-designed systematic review, and most of the included trials had only a low risk of bias, meaning the findings should be reliable.
What did it find?
Ten trials were included, with 32,287 participants. Compared to 12 months of drug therapy:
- Short-course drug therapy did not change the number of heart attacks, stent thromboses or deaths due to heart disease or any other cause.
- Long-course therapy halved the number of heart attacks from 3% to 1.5% (OR 0.53; 95% CI 0.42 to 0.66) and reduced the number of definite and probable stent thromboses by over two thirds, from 0.98% to 0.32% (OR 0.33; 95% CI 0.21 to 0.51). This is an absolute reduction of about 7 events per 1000 people treated.
- Short-course therapy reduced the number of major bleeding events by around 40%, though this was a rare event occurring in 0.35% of people in the short-course group and 0.61% in the 12 month group (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.36 to 0.92). This is an absolute decrease of about 3 events per 1000 people treated.
- Long-course therapy increased major bleeding events by about 62%, from about 1.21% to 1.95% (OR 1.62; 95% CI 1.26 to 2.09). This is an absolute increase of about 7 events per 1000 people treated.
- Long-course therapy increased the number of deaths from any cause from 1.42% to 1.84% (OR 1.30; 95% CI 1.02 to 1.66), although it did not increase the number of deaths due to heart disease. This is an absolute increase of about 4 events per 1000 people treated.
What does current guidance say on this issue?
The European Society of Cardiology and the European Association for Cardio-Thoracic Surgery 2014 guidelines recommend dual antiplatelet therapy for 6 to 12 months, followed by taking aspirin on its own.
The 2011 guidelines from the American College of Cardiology and American Heart Association recommend dual antiplatelet therapy for at least 12 months.
What are the implications?
The results of this review suggest that there is no optimal length of dual antiplatelet drug therapy. Instead, individually tailored therapy may provide the best outcomes. Patients with high bleeding risk should receive short durations of drug therapy, while patients with low bleeding risk, but higher risks of heart attack or thrombosis, should receive longer durations of therapy. The observed link between longer duration drug therapy and higher numbers of death due to any cause requires further investigation.
Although this is a systematic review of randomised controlled trials, a generally very reliable study design, the results need to be interpreted with caution. For example, different types of drugs and stents were used across the included RCTs and the length of follow-up for outcomes was not reported. The authors also noted that participants receiving longer duration treatments were randomised only after several months of successful drug therapy, so they would have been a more stable patient population with a lower risk of bleeding.
Navarese EP, Andreotti F, Schulze V, et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ. 2015 Apr 16;350:h1618
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. J Am Coll Cardiol. 2011;58:e44-122
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;371:2155-66.
NHS Choices. Coronary Heart Disease. London: NHS; 2014
Task Force members, Windecker S, Kolh P, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35:2541-619
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