Review question
We set out to determine whether continuing to take antiplatelet drugs before non-cardiac surgery that requires general, spinal or regional anaesthesia increases the risk of experiencing serious bleeding, ischaemic event or death in adults, when compared with stopping antiplatelet drugs for at least five days before non-cardiac surgery.
Background
Antiplatelet drugs such as aspirin or clopidogrel reduce the risk of people getting blood clots, and are routinely prescribed for people who have had coronary stents inserted. They are also recommended for people with unstable angina or heart disease, or people who have had a heart attack, heart surgery or a stroke. Taking antiplatelet therapy introduces an increased risk of bleeding, which could lead to problems if a person needs non-cardiac surgery. Stopping usual antiplatelet therapy a few days before surgery might reduce the risk of serious bleeding during surgery. Not taking these antiplatelet drugs could, however, increase the risk of a heart attack, stroke, or death.
Study characteristics
The evidence from randomized controlled trials is current to January 2018. We included five trials with 666 adults in the review. Three studies are ongoing. All participants were taking antiplatelet therapy (aspirin or clopidogrel) at the start of the study. Two studies stopped antiplatelet drugs for at least five days before surgery, and three studies gave participants a placebo instead of antiplatelet therapy during this time.
Key results
We found low-certainty evidence that either continuing or stopping antiplatelet therapy may make little or no difference to the number of people who died up to 30 days or six months after surgery (five studies, 659 participants). We found moderate-certainty evidence that either continuing or stopping antiplatelet therapy probably makes little or no difference to incidences of bleeding serious enough to need a blood transfusion during or immediately after surgery (four studies, 368 participants). We found low-certainty evidence that either continuing or stopping antiplatelet therapy may make little or no difference to bleeding serious enough to need further surgery (four studies, 368 participants), and may make little or no difference to the number of ischaemic events such as stroke or heart attack (four studies, 616 participants).
Quality of the evidence
Some studies had low risk of bias because they had clearly reported their methods for randomizing people to each group, and three studies used a placebo agent so that people did not know whether or not they were continuing their usual antiplatelet therapy. However, we found few studies with few events, with wide variation in results. To continue or stop taking antiplatelet drugs for a few days before non-cardiac surgery might make little or no difference to the number of people who died, who had bleeding that needed further surgery or who had ischaemic events, and it probably makes little or no difference to bleeding that needed a blood transfusion. We found three ongoing studies which will increase certainty in the effect in future updates of the review.
We found low-certainty evidence that either continuation or discontinuation of antiplatelet therapy before non-cardiac surgery may make little or no difference to mortality, bleeding requiring surgical intervention, or ischaemic events. We found moderate-certainty evidence that either continuation or discontinuation of antiplatelet therapy before non-cardiac surgery probably makes little or no difference to bleeding requiring transfusion. Evidence was limited to few studies with few participants, and with few events. The three ongoing studies may alter the conclusions of the review once published and assessed.
Antiplatelet agents are recommended for people with myocardial infarction and acute coronary syndromes, transient ischaemic attack or stroke, and for those in whom coronary stents have been inserted. People who take antiplatelet agents are at increased risk of adverse events when undergoing non-cardiac surgery because of these indications. However, taking antiplatelet therapy also introduces risk to the person undergoing surgery because the likelihood of bleeding is increased. Discontinuing antiplatelet therapy before surgery might reduce this risk but subsequently it might make thrombotic problems, such as myocardial infarction, more likely.
To compare the effects of continuation versus discontinuation for at least five days of antiplatelet therapy on the occurrence of bleeding and ischaemic events in adults undergoing non-cardiac surgery under general, spinal or regional anaesthesia.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), MEDLINE (1946 to January 2018), and Embase (1974 to January 2018). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles.
We included randomized controlled trials of adults who were taking single or dual antiplatelet therapy, for at least two weeks, and were scheduled for elective non-cardiac surgery. Included participants had at least one cardiac risk factor. We planned to include quasi-randomized studies.
We excluded people scheduled for minor surgeries under local anaesthetic or sedation in which bleeding that required transfusion or additional surgery was unlikely. We included studies which compared perioperative continuation of antiplatelet therapy versus discontinuation of antiplatelet therapy or versus substitution of antiplatelet therapy with a placebo for at least five days before surgery.
Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias and synthesized findings. Our primary outcomes were: all-cause mortality at longest follow-up (up to six months); all-cause mortality (up to 30 days). Secondary outcomes included: blood loss requiring transfusion of blood products; blood loss requiring further surgical intervention; risk of ischaemic events. We used GRADE to assess the quality of evidence for each outcome
We included five RCTs with 666 randomized adults. We identified three ongoing studies.
All study participants were scheduled for elective general surgery (including abdominal, urological, orthopaedic and gynaecological surgery) under general, spinal or regional anaesthesia. Studies compared continuation of single or dual antiplatelet therapy (aspirin or clopidogrel) with discontinuation of therapy for at least five days before surgery.
Three studies reported adequate methods of randomization, and two reported methods to conceal allocation. Three studies were placebo-controlled trials and were at low risk of performance bias, and three studies reported adequate methods to blind outcome assessors to group allocation. Attrition was limited in four studies and two studies had reported prospective registration with clinical trial registers and were at low risk of selective outcome reporting bias.
We reported mortality at two time points: the longest follow-up reported by study authors up to six months, and time point reported by study authors up to 30 days. Five studies reported mortality up to six months (of which four studies had a longest follow-up at 30 days, and one study at 90 days) and we found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to mortality up to six months (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.34 to 4.27; 659 participants; low-certainty evidence); the absolute effect is three more deaths per 1000 with continuation of antiplatelets (ranging from eight fewer to 40 more). Combining the four studies with a longest follow-up at 30 days alone showed the same effect estimate, and we found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to mortality at 30 days after surgery (RR 1.21, 95% CI 0.34 to 4.27; 616 participants; low-certainty evidence); the absolute effect is three more deaths per 1000 with continuation of antiplatelets (ranging from nine fewer to 42 more).
We found that either continuation or discontinuation of antiplatelet therapy probably makes little or no difference in incidences of blood loss requiring transfusion (RR 1.37, 95% CI 0.83 to 2.26; 368 participants; absolute effect of 42 more participants per 1000 requiring transfusion in the continuation group, ranging from 19 fewer to 119 more; four studies; moderate-certainty evidence); and may make little or no difference in incidences of blood loss requiring additional surgery (RR 1.54, 95% CI 0.31 to 7.58; 368 participants; absolute effect of six more participants per 1000 requiring additional surgery in the continuation group, ranging from seven fewer to 71 more; four studies; low-certainty evidence). We found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to incidences of ischaemic events (to include peripheral ischaemia, cerebral infarction, and myocardial infarction) within 30 days of surgery (RR 0.67, 95% CI 0.25 to 1.77; 616 participants; absolute effect of 17 fewer participants per 1000 with an ischaemic event in the continuation group, ranging from 39 fewer to 40 more; four studies; low-certainty evidence).
We used the GRADE approach to downgrade evidence for all outcomes owing to limited evidence from few studies. We noted a wide confidence in effect estimates for mortality at the end of follow-up and at 30 days, and for blood loss requiring transfusion which suggested imprecision. We noted visual differences in study results for ischaemic events which suggested inconsistency.