Downloaded from http://heart.bmj.com/ on August 7, 2015 - Published by group.bmj.com
Editorial
Antithrombotic therapy after transcatheter aortic valve implantation Bernard Iung In their Heart paper, Hassell et al1 present an original analysis of four studies comparing single and dual antiplatelet therapy after transcatheter aortic valve implantation (TAVI). There was no difference in the primary endpoint of net adverse clinical and cerebral events combining 30-day rates of mortality, acute coronary syndrome, stroke and major bleeding. However, there was a strong trend, although not statistically significant, towards less major or lifethreatening bleeding at 30 days in patients receiving aspirin alone as compared with those treated using the usual combination of aspirin and clopidogrel early after TAVI. These findings challenge current recommendations and may contribute to improving patient outcome after TAVI. Guidelines consistently recommend dual antiplatelet therapy during 3–6 months after TAVI followed by single antiplatelet therapy (table 1).2–5 This relies mainly on the extrapolation of antithrombotic regimens following coronary stenting. However, despite the common presence of a metallic stent, coronary stenting and TAVI differ by a number of features which may influence thrombus formation, in particular vessel diameter, environment (atheromatous plaques or calcified aortic leaflets), presence of prosthetic leaflets and the frequency of associated atrial fibrillation. Recommended antithrombotic regimens markedly differ between TAVI and surgical aortic valve replacement (AVR) using a bioprosthesis. Anticoagulant therapy was initially recommended during the first 3 months following bioprosthetic AVR, which corresponds to the time delay for endothelialisation of the sewing ring. However, this rationale was challenged by series suggesting that antiplatelet therapy alone may have a better risk:benefit profile.2 This led to changes in ESC/ EACTS and American Heart Association/ American College of Cardiology (AHA/ ACC) guidelines and the ACCP consensus, which now recommend aspirin therapy alone after surgical bioprosthetic AVR, with a class IIa for ESC/EACTS and AHA/ ACC guidelines (table 1).3–5 However, Correspondence to Professor Bernard Iung, Department of Cardiology, Bichat Hospital, AP-HP, DHU Fire and Paris Diderot University, 46 rue Henri Huchard, Paris 75018, France; [email protected]
anticoagulant therapy during the first 3 months remains a class IIb recommendation in AHA/ACC and ESC/EACTS guidelines. This can be explained by the low level of underlying evidence since most data come from observational and often retrospective series. Recent analyses performed in large databases led to contradictory findings on the net clinical benefit of early anticoagulant therapy.2 Uncertainties regarding the optimal antithrombotic therapy after TAVI as well as surgical bioprosthetic AVR illustrate the need for well-designed studies evaluating the risks and benefits of different standardised therapeutic regimens. Both rates of thromboembolism and bleeding are higher during the first month after surgical AVR or TAVI than afterwards.2 6 However, adequately powered controlled trials are lacking in this setting. Although it is no substitute for a large randomised trial, the analysis presented by Hassell et al is an important contribution in the field of TAVI. At the present time, it is the best way to combine available data which are issued from relatively small sample sizes, thereby lacking statistical power to draw conclusions from individual studies. The combination of two randomised trials and two observational series in which propensity-matching limits differences in baseline patient characteristics is an original approach. Its strength is enabling single and dual antiplatelet therapy to be compared in 434 patients, while individual randomised trials included 79 and 120 patients. Of course, propensity-matching does not substitute for randomised trials. Propensity-matching enables single and dual antiplatelet therapy to be compared in patient subgroups in which most characteristics do not differ. However, we cannot exclude residual confounding bias due to covariates not taken into account in the propensity score, as acknowledged by the authors. Thromboembolic complications after TAVI peak during the first few days following the procedure and may be due to different mechanisms which include thrombus formation on the prosthesis, embolisation during prosthesis positioning and deployment and atrial fibrillation. Stroke is the most frequent embolic complication after TAVI and has consequences on functional Iung B. Heart July 2015 Vol 101 No 14
status and mid-term survival. Concerns remain with regards to the most appropriate antithrombotic therapy to decrease the thromboembolic risk according to these different mechanisms. Even in patients who are in sinus rhythm before TAVI, transient atrial fibrillation occurs in as many as 32% after the procedure, is often asymptomatic and therefore overlooked in the absence of systematic electrocardiographic monitoring.7 More importantly, the relationship between transient atrial fibrillation after TAVI and the occurrence of stroke raises the question of the potential usefulness of early anticoagulant therapy after TAVI.7 The efficacy of the different antithrombotic strategies should of course be weighed against the inherent bleeding risk which is a particular concern in the elderly. Major or life-threatening bleeding is a more frequent complication than stroke early after TAVI and it is associated with increased mid-term mortality.8 Bleeding occurring at the access site is likely to decrease with the development of smaller delivery catheters. Smaller catheters reduce vascular injury and expand indications of transvascular approach, thereby leading to a reduction in the rate of transapical approach which is associated with a higher risk of early bleeding.8 Nevertheless, there will remain a risk of early bleeding due to access site and also to other causes of haemorrhage after TAVI and this risk is clearly influenced by concomitant antithrombotic therapy. Therefore, the use of any antithrombotic drug during the early postimplantation period, either singly or even more in combination, should take into account the inherent consequences on the bleeding risk. Beyond the relationship between antithrombotic therapy and 30-day event rates, it is also necessary to pay attention to the risk of late thromboembolism and bleeding after TAVI. After initial dual antiplatelet therapy for 3–6 months, single antiplatelet therapy is recommended lifelong. After surgical AVR, the need for lifelong aspirin therapy using a bioprosthesis is debated and differs between guidelines, which attests to the low underlying evidence (table 1). Although elderly patient candidates to TAVI often have associated atherosclerosis, the risk:benefit ratio of definite aspirin therapy is still a matter of concern. Even low-dose aspirin carries a risk of bleeding, in particular in the elderly. This is of particular importance in case of associated atrial fibrillation, which occurs in at least one-third of patients treated with TAVI. In patients with atrial fibrillation, a combination of anticoagulant and antiplatelet therapy is generally used after TAVI. Such combined therapy is 1089
Downloaded from http://heart.bmj.com/ on August 7, 2015 - Published by group.bmj.com
Editorial Table 1 Current recommendations for antithrombotic therapy after transcatheter aortic valve implantation (TAVI) or surgical bioprosthetic valve replacement TAVI
ESC/EACTS guidelines3
AHA/ACC guidelines4 ACCP consensus5
Bioprosthesis >3 postop. months
Early
Late
3 postop. months
Despite the lack of evidence, a combination of low-dose aspirin and a thienopyridine is used early after TAVI. In patients with AF, a combination of vitamin K antagonist and aspirin or thienopyridine is generally used, but should be weighed against increased risk of bleeding Aspirin (75–100 mg)+clopidogrel (75 mg) for 6 months (IIbC)
Aspirin or a thienopyridine alone
Aspirin (IIaC) VKA (IIbC)
No treatment
Aspirin (75–100 mg) lifelong (IIbC) Long-term aspirin
Aspirin (IIaB) VKA (IIbB) Aspirin (50–100 mg) (2C)
Aspirin (IIaB)
Aspirin (50–100 mg)+clopidogrel (75 mg) for 3 months (2C)
Aspirin (2C)
AF, atrial fibrillation; ACCP, American College of Chest Physicians, AHA/ACC, American Heart Association/American College of Cardiology, ESC/EACTS, European Society of Cardiology/ European Association for Cardio-Thoracic Surgery; VKA, vitamin K antagonists
associated with a 40% increase in major bleeding as compared with vitamin K antagonists alone in randomised trials.9 In patients with atrial fibrillation and stable coronary disease, observational series showed an increased bleeding risk and a lack of benefit on the prevention of thromboembolic events with the combination of aspirin and anticoagulants as compared with anticoagulant therapy alone.10 These findings cannot be extrapolated straightforwardly to patients who have undergone TAVI but should be taken into account as a warning on the bleeding risks of combined antiplatelet and anticoagulant therapies. The burden of longterm bleeding after TAVI is high, as attested by the 27% rate of major bleeding during the 5-year follow-up of the placement of aortic transcatheter valves (PARTNER) trial.11 The need for determining of the best antithrombotic therapy after TAVI expands therefore beyond the early postimplantation period. In addition to the debate between single and dual early antiplatelet therapy, the long-term use of antiplatelet drugs may be reconsidered when anticoagulant therapy is indicated. Direct oral anticoagulants have not been specifically studied in patients with TAVI prostheses, as in those with surgical bioprostheses, and their use if therefore not recommended in these patients in the absence of the results of specific trials. The analysis by Hassell et al does not provide enough evidence to change existing recommendations. However, they have the considerable merit to challenge them and draw attention to the need to optimise each step of the management of
1090
patients undergoing TAVI. Early and late antithrombotic therapies used after TAVI presently rely on low levels of evidence. Randomised trials are ongoing and much needed to provide evidence-based answers to the questions on the respective roles of antiplatelet and anticoagulant therapies in these particular patients who are at high risk for both thromboembolism and bleeding.
4
5
Competing interests BI has received consultant fees from Abbott, Boehringer Ingelheim, Valtech and speaker fees from Edwards Lifesciences. Provenance and peer review Commissioned; internally peer reviewed.
6
7
To cite Iung B. Heart 2015;101:1089–1090. Published Online First 7 May 2015
▸ http://dx.doi.org/10.1136/heartjnl-2014-307053
Heart 2015;101:1089–1090. doi:10.1136/heartjnl-2015-307762
8
9
10
REFERENCES 1
2
3
Hassell MECJ, Hildick-Smith D, Durand E, et al. Antiplatelet therapy following transcatheter aortic valve implantation. Heart 2015;100:1118–25. Iung B, Rodes-Cabau J. The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties. Eur Heart J 2014;35:2942–9. Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease
11
(version 2012): The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2012;33:2451–96. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129:e521–643. Whitlock RP, Sun JC, Fremes SE, et al. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e576S–600S. Tchetche D, Farah B, Misuraca L, et al. Cerebrovascular events post-transcatheter aortic valve replacement in a large cohort of patients: a FRANCE-2 registry substudy. JACC Cardiovasc Interv 2014;7:1138–45. Amat-Santos I, Rodés-Cabau J, Urena M, et al. Incidence, predictive factors and prognostic value of new-onset atrial fibrillation following transcatheter aortic valve implantation. J Am Coll Cardiol 2015;59:178–88. Borz B, Durand E, Godin M, et al. Incidence, predictors and impact of bleeding after transcatheter aortic valve implantation using the balloon-expandable Edwards prosthesis. Heart 2013;99:860–5. Dentali F, Douketis JD, Lim W, et al. Combined aspirin-oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomized trials. Arch Intern Med 2007;167:117–24. Lamberts M, Gislason GH, Lip GY, et al. Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study. Circulation 2014;129:1577–85. Mack MJ, Leon MB, Smith CR, et al. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 2015. Mar 15. pii: S0140-6736(15)60308-7. doi: 10.1016/S01406736(15)60308-7 [Epub ahead of print].
Iung B. Heart July 2015 Vol 101 No 14
Downloaded from http://heart.bmj.com/ on August 7, 2015 - Published by group.bmj.com
Antithrombotic therapy after transcatheter aortic valve implantation Bernard Iung Heart 2015 101: 1089-1090 originally published online May 7, 2015
doi: 10.1136/heartjnl-2015-307762 Updated information and services can be found at: http://heart.bmj.com/content/101/14/1089
These include:
References Email alerting service
Topic Collections
This article cites 10 articles, 5 of which you can access for free at: http://heart.bmj.com/content/101/14/1089#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Interventional cardiology (2819) Drugs: cardiovascular system (8414) Clinical diagnostic tests (4617) Epidemiology (3504)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Editorial
Antithrombotic therapy after transcatheter aortic valve implantation Bernard Iung In their Heart paper, Hassell et al1 present an original analysis of four studies comparing single and dual antiplatelet therapy after transcatheter aortic valve implantation (TAVI). There was no difference in the primary endpoint of net adverse clinical and cerebral events combining 30-day rates of mortality, acute coronary syndrome, stroke and major bleeding. However, there was a strong trend, although not statistically significant, towards less major or lifethreatening bleeding at 30 days in patients receiving aspirin alone as compared with those treated using the usual combination of aspirin and clopidogrel early after TAVI. These findings challenge current recommendations and may contribute to improving patient outcome after TAVI. Guidelines consistently recommend dual antiplatelet therapy during 3–6 months after TAVI followed by single antiplatelet therapy (table 1).2–5 This relies mainly on the extrapolation of antithrombotic regimens following coronary stenting. However, despite the common presence of a metallic stent, coronary stenting and TAVI differ by a number of features which may influence thrombus formation, in particular vessel diameter, environment (atheromatous plaques or calcified aortic leaflets), presence of prosthetic leaflets and the frequency of associated atrial fibrillation. Recommended antithrombotic regimens markedly differ between TAVI and surgical aortic valve replacement (AVR) using a bioprosthesis. Anticoagulant therapy was initially recommended during the first 3 months following bioprosthetic AVR, which corresponds to the time delay for endothelialisation of the sewing ring. However, this rationale was challenged by series suggesting that antiplatelet therapy alone may have a better risk:benefit profile.2 This led to changes in ESC/ EACTS and American Heart Association/ American College of Cardiology (AHA/ ACC) guidelines and the ACCP consensus, which now recommend aspirin therapy alone after surgical bioprosthetic AVR, with a class IIa for ESC/EACTS and AHA/ ACC guidelines (table 1).3–5 However, Correspondence to Professor Bernard Iung, Department of Cardiology, Bichat Hospital, AP-HP, DHU Fire and Paris Diderot University, 46 rue Henri Huchard, Paris 75018, France; [email protected]
anticoagulant therapy during the first 3 months remains a class IIb recommendation in AHA/ACC and ESC/EACTS guidelines. This can be explained by the low level of underlying evidence since most data come from observational and often retrospective series. Recent analyses performed in large databases led to contradictory findings on the net clinical benefit of early anticoagulant therapy.2 Uncertainties regarding the optimal antithrombotic therapy after TAVI as well as surgical bioprosthetic AVR illustrate the need for well-designed studies evaluating the risks and benefits of different standardised therapeutic regimens. Both rates of thromboembolism and bleeding are higher during the first month after surgical AVR or TAVI than afterwards.2 6 However, adequately powered controlled trials are lacking in this setting. Although it is no substitute for a large randomised trial, the analysis presented by Hassell et al is an important contribution in the field of TAVI. At the present time, it is the best way to combine available data which are issued from relatively small sample sizes, thereby lacking statistical power to draw conclusions from individual studies. The combination of two randomised trials and two observational series in which propensity-matching limits differences in baseline patient characteristics is an original approach. Its strength is enabling single and dual antiplatelet therapy to be compared in 434 patients, while individual randomised trials included 79 and 120 patients. Of course, propensity-matching does not substitute for randomised trials. Propensity-matching enables single and dual antiplatelet therapy to be compared in patient subgroups in which most characteristics do not differ. However, we cannot exclude residual confounding bias due to covariates not taken into account in the propensity score, as acknowledged by the authors. Thromboembolic complications after TAVI peak during the first few days following the procedure and may be due to different mechanisms which include thrombus formation on the prosthesis, embolisation during prosthesis positioning and deployment and atrial fibrillation. Stroke is the most frequent embolic complication after TAVI and has consequences on functional Iung B. Heart July 2015 Vol 101 No 14
status and mid-term survival. Concerns remain with regards to the most appropriate antithrombotic therapy to decrease the thromboembolic risk according to these different mechanisms. Even in patients who are in sinus rhythm before TAVI, transient atrial fibrillation occurs in as many as 32% after the procedure, is often asymptomatic and therefore overlooked in the absence of systematic electrocardiographic monitoring.7 More importantly, the relationship between transient atrial fibrillation after TAVI and the occurrence of stroke raises the question of the potential usefulness of early anticoagulant therapy after TAVI.7 The efficacy of the different antithrombotic strategies should of course be weighed against the inherent bleeding risk which is a particular concern in the elderly. Major or life-threatening bleeding is a more frequent complication than stroke early after TAVI and it is associated with increased mid-term mortality.8 Bleeding occurring at the access site is likely to decrease with the development of smaller delivery catheters. Smaller catheters reduce vascular injury and expand indications of transvascular approach, thereby leading to a reduction in the rate of transapical approach which is associated with a higher risk of early bleeding.8 Nevertheless, there will remain a risk of early bleeding due to access site and also to other causes of haemorrhage after TAVI and this risk is clearly influenced by concomitant antithrombotic therapy. Therefore, the use of any antithrombotic drug during the early postimplantation period, either singly or even more in combination, should take into account the inherent consequences on the bleeding risk. Beyond the relationship between antithrombotic therapy and 30-day event rates, it is also necessary to pay attention to the risk of late thromboembolism and bleeding after TAVI. After initial dual antiplatelet therapy for 3–6 months, single antiplatelet therapy is recommended lifelong. After surgical AVR, the need for lifelong aspirin therapy using a bioprosthesis is debated and differs between guidelines, which attests to the low underlying evidence (table 1). Although elderly patient candidates to TAVI often have associated atherosclerosis, the risk:benefit ratio of definite aspirin therapy is still a matter of concern. Even low-dose aspirin carries a risk of bleeding, in particular in the elderly. This is of particular importance in case of associated atrial fibrillation, which occurs in at least one-third of patients treated with TAVI. In patients with atrial fibrillation, a combination of anticoagulant and antiplatelet therapy is generally used after TAVI. Such combined therapy is 1089
Downloaded from http://heart.bmj.com/ on August 7, 2015 - Published by group.bmj.com
Editorial Table 1 Current recommendations for antithrombotic therapy after transcatheter aortic valve implantation (TAVI) or surgical bioprosthetic valve replacement TAVI
ESC/EACTS guidelines3
AHA/ACC guidelines4 ACCP consensus5
Bioprosthesis >3 postop. months
Early
Late
3 postop. months
Despite the lack of evidence, a combination of low-dose aspirin and a thienopyridine is used early after TAVI. In patients with AF, a combination of vitamin K antagonist and aspirin or thienopyridine is generally used, but should be weighed against increased risk of bleeding Aspirin (75–100 mg)+clopidogrel (75 mg) for 6 months (IIbC)
Aspirin or a thienopyridine alone
Aspirin (IIaC) VKA (IIbC)
No treatment
Aspirin (75–100 mg) lifelong (IIbC) Long-term aspirin
Aspirin (IIaB) VKA (IIbB) Aspirin (50–100 mg) (2C)
Aspirin (IIaB)
Aspirin (50–100 mg)+clopidogrel (75 mg) for 3 months (2C)
Aspirin (2C)
AF, atrial fibrillation; ACCP, American College of Chest Physicians, AHA/ACC, American Heart Association/American College of Cardiology, ESC/EACTS, European Society of Cardiology/ European Association for Cardio-Thoracic Surgery; VKA, vitamin K antagonists
associated with a 40% increase in major bleeding as compared with vitamin K antagonists alone in randomised trials.9 In patients with atrial fibrillation and stable coronary disease, observational series showed an increased bleeding risk and a lack of benefit on the prevention of thromboembolic events with the combination of aspirin and anticoagulants as compared with anticoagulant therapy alone.10 These findings cannot be extrapolated straightforwardly to patients who have undergone TAVI but should be taken into account as a warning on the bleeding risks of combined antiplatelet and anticoagulant therapies. The burden of longterm bleeding after TAVI is high, as attested by the 27% rate of major bleeding during the 5-year follow-up of the placement of aortic transcatheter valves (PARTNER) trial.11 The need for determining of the best antithrombotic therapy after TAVI expands therefore beyond the early postimplantation period. In addition to the debate between single and dual early antiplatelet therapy, the long-term use of antiplatelet drugs may be reconsidered when anticoagulant therapy is indicated. Direct oral anticoagulants have not been specifically studied in patients with TAVI prostheses, as in those with surgical bioprostheses, and their use if therefore not recommended in these patients in the absence of the results of specific trials. The analysis by Hassell et al does not provide enough evidence to change existing recommendations. However, they have the considerable merit to challenge them and draw attention to the need to optimise each step of the management of
1090
patients undergoing TAVI. Early and late antithrombotic therapies used after TAVI presently rely on low levels of evidence. Randomised trials are ongoing and much needed to provide evidence-based answers to the questions on the respective roles of antiplatelet and anticoagulant therapies in these particular patients who are at high risk for both thromboembolism and bleeding.
4
5
Competing interests BI has received consultant fees from Abbott, Boehringer Ingelheim, Valtech and speaker fees from Edwards Lifesciences. Provenance and peer review Commissioned; internally peer reviewed.
6
7
To cite Iung B. Heart 2015;101:1089–1090. Published Online First 7 May 2015
▸ http://dx.doi.org/10.1136/heartjnl-2014-307053
Heart 2015;101:1089–1090. doi:10.1136/heartjnl-2015-307762
8
9
10
REFERENCES 1
2
3
Hassell MECJ, Hildick-Smith D, Durand E, et al. Antiplatelet therapy following transcatheter aortic valve implantation. Heart 2015;100:1118–25. Iung B, Rodes-Cabau J. The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties. Eur Heart J 2014;35:2942–9. Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease
11
(version 2012): The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2012;33:2451–96. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129:e521–643. Whitlock RP, Sun JC, Fremes SE, et al. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e576S–600S. Tchetche D, Farah B, Misuraca L, et al. Cerebrovascular events post-transcatheter aortic valve replacement in a large cohort of patients: a FRANCE-2 registry substudy. JACC Cardiovasc Interv 2014;7:1138–45. Amat-Santos I, Rodés-Cabau J, Urena M, et al. Incidence, predictive factors and prognostic value of new-onset atrial fibrillation following transcatheter aortic valve implantation. J Am Coll Cardiol 2015;59:178–88. Borz B, Durand E, Godin M, et al. Incidence, predictors and impact of bleeding after transcatheter aortic valve implantation using the balloon-expandable Edwards prosthesis. Heart 2013;99:860–5. Dentali F, Douketis JD, Lim W, et al. Combined aspirin-oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomized trials. Arch Intern Med 2007;167:117–24. Lamberts M, Gislason GH, Lip GY, et al. Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study. Circulation 2014;129:1577–85. Mack MJ, Leon MB, Smith CR, et al. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 2015. Mar 15. pii: S0140-6736(15)60308-7. doi: 10.1016/S01406736(15)60308-7 [Epub ahead of print].
Iung B. Heart July 2015 Vol 101 No 14
Downloaded from http://heart.bmj.com/ on August 7, 2015 - Published by group.bmj.com
Antithrombotic therapy after transcatheter aortic valve implantation Bernard Iung Heart 2015 101: 1089-1090 originally published online May 7, 2015
doi: 10.1136/heartjnl-2015-307762 Updated information and services can be found at: http://heart.bmj.com/content/101/14/1089
These include:
References Email alerting service
Topic Collections
This article cites 10 articles, 5 of which you can access for free at: http://heart.bmj.com/content/101/14/1089#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Interventional cardiology (2819) Drugs: cardiovascular system (8414) Clinical diagnostic tests (4617) Epidemiology (3504)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
