Oral anticoagulation plus an antiplatelet drug is better than anticoagulants alone for reducing death or blood clots after heart valve replacement

After heart valve replacement oral anticoagulation (a blood thinner) is frequently used to keep blood clots from forming on the valve. These blood clots can block the flow of blood through the valve or break off and cause a stroke. Blood thinners, such as coumadin, reduce the risk of these outcomes and require careful monitoring. Drugs that affect the platelets, such as aspirin, are not effective alone but may add benefit to the blood thinners. This updated review of 13 trials found that oral anticoagulation and antiplatelet drugs were more effective than anticoagulation alone. The addition of antiplatelet drugs to anticoagulants increases the risk of bleeding by about 50%. Low-dose aspirin (less than 100 mg daily) may be associated with the lowest risk of bleeding. However, in general the quality of the included trials tended to be low, possibly reflecting the era when the majority of the trials were conducted (1970s and 1980s when trial methodology was less advanced).

Authors' conclusions: 

Adding antiplatelet therapy, either dipyridamole or low-dose aspirin, to oral anticoagulation decreases the risk of systemic embolism or death among patients with prosthetic heart valves. The risk of major bleeding is increased with antiplatelet therapy. These results apply to patients with mechanical prosthetic valves or those with biological valves and indicators of high risk such as atrial fibrillation or prior thromboembolic events. The effectiveness and safety of low-dose aspirin (100 mg daily) appears to be similar to higher-dose aspirin and dipyridamole. In general, the quality of the included trials tended to be low, possibly reflecting the era when the majority of the trials were conducted (1970s and 1980s when trial methodology was less advanced).

Read the full abstract...

Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of antiplatelet drugs, has been used to minimise this risk. An important issue is the effectiveness and safety of the latter strategy.


This is an update of our previous review; the goal was to create a valid synthesis of all available, methodologically sound data to further assess the safety and efficacy of combined oral anticoagulant and antiplatelet therapy versus oral anticoagulant monotherapy in patients with prosthetic heart valves.

Search strategy: 

We updated the previous searches from 2003 and 2010 on 16 January 2013 and searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 12), MEDLINE (OVID, 1946 to January Week 1 2013), and EMBASE (OVID, 1980 to 2013 Week 02). We have also looked at reference lists of individual reports, review articles, meta-analyses, and consensus statements. We included reports published in any language or in abstract form.

Selection criteria: 

All reports of randomised controlled trials comparing standard-dose oral anticoagulation to standard-dose oral anticoagulation and antiplatelet therapy in patients with one or more prosthetic heart valves.

Data collection and analysis: 

Two review authors independently performed the search strategy, assessed trials for inclusion and study quality, and extracted data. We collected adverse effects information from the trials.

Main results: 

One new study has been identified and included in this update. In total, 13 studies involving 4122 participants were included in this review update. Years of publication ranged from 1971 to 2011. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio (OR) 0.43, 95% confidence interval (CI) 0.32 to 0.59; P < 0.00001) and total mortality (OR 0.57, 95% CI 0.42 to 0.78; P = 0.0004). Aspirin and dipyridamole reduced these events similarly. The risk of major bleeding was increased when antiplatelet agents were added to oral anticoagulants (OR 1.58, 95% CI 1.14 to 2.18; P = 0.006).

For major bleeding, there was no evidence of heterogeneity between aspirin and dipyridamole and in the comparison of trials performed before and after 1990, around the time when anticoagulation standardisation with the international normalised ratio was being implemented. A lower daily dose of aspirin (< 100 mg) may be associated with a lower major bleeding risk than higher doses.