Professor Francois Schiele, Besancon, France, ESC spokesperson and member of the ESC Press Committee, attended the AHA Scientific Sessions held in Chicago, 14-19 November 2014.
Prompted to comment on the key trials presented this year, he singled out the three following topics that, in his view, will have a direct impact on clinical practice, and that are interesting to compare with European guidelines.
Dual Antiplatelet Therapy
- Use of Dual Antiplatelet Therapy (DAPT) both immediately after inserting a DES and in the very long term (beyond one year and up to 30 months)
- After an ACS with or without DES implantation, with a mandatory minimum DAPT duration of one year
Recent publications question the duration of DAPT after DES implantation and it appears that six months might actually be enough.
Two eagerly awaited DAPT trials were presented by European specialists.
1. ISAR SAFE presented by Prof Stefanie Schulz-Schüpke from the Deutsches Herzzentrum München, Munich, Germany, compared 6 to 12 months DAPT after DES implantation in a large cohort of 4,000 patients, of whom half had ACS
2. ITALIC presented by Martine Gilard, University of Brest, Brest, France was a similar study comparing 6 to 24 months of DAPT after implantation of new generation DES in a similar population also with ACS.
The results of the two studies are quite similar. They show that six months of DAPT is safe, without any increase in the rate of stent thrombosis. Surprisingly, there was no major difference in bleeding rates.
Put in perspective with previous trials, it seems that a short DAPT duration in DES patients (even after ACS) is equally as effective for the prevention of ischemic events and yields a reduction in bleeding.
These results are consistent with the 2014 ESC/EACTS Guidelines on Myocardial Revascularisation regarding the subgroup of stable patients, whereas in ACS, 12 months of DAPT is still recommended.
Conversely, the “DAPT” trial, also presented in Chicago, focused on the clinical benefit of extended DAPT currently recommended by guidelines, comparing twelve months vs 30 months. The study included 9,961 patients treated previously with a drug eluting stent for twelve months.
Interestingly, the results were conflicting. On the one hand, long term DAPT was protective against stent thrombosis and recurrent MI, but on the other hand, DAPT showed a trend towards higher mortality, mostly explained by higher bleeding, more cancer and higher trauma mortality.
Therefore, based on these results, such a long duration of DAPT cannot really be recommended. This is in line with all current ESC guidelines (myocardial revascularisation, STEMI, stable angina).
Check also ESC spokesperson and ESC Press Committee member Prof Freek Verheugt’s video comments here.
Lipids
Lipids were high on the AHA agenda this year with two studies:
- One on primary prevention in diabetic patients
- Another study on secondary prevention post-MI to evaluate the clinical benefit of the Ezetimibe/Simvastatin combination discussed in the IMPROVE IT trial
IMPROVE-IT presented by Prof Christopher Cannon, Brigham and Women's Hospital, Boston, MA, USA was initially designed to assess the clinical benefit of lowering LDL cholesterol below 70mg per dL in post- ACS patients. Therefore patients with an LDL adequately controlled with Simvastatin (LDL level around 70mg) were randomised with an additional 10mg of Ezetimibe vs placebo.
Watch ESC spokesperson Prof Michel Farnier discuss the trial here...
As expected, patients with Ezetimibe achieved a 20% lower LDL, on average 54mg per dL. After six years, investigators observed a 16% reduction in the composite endpoint (CV death, MI, unstable angina, rehospitalisation, coronary revascularization). When a hard composite endpoint was considered (cardiovascular death, non-fatal MI and stroke), there was also a clinical benefit, with a 10% reduction in events, mainly driven by a 13% reduction in MI and a 14% reduction in stroke, without any changes in the mortality rate.
This result confirms the link between a decrease in LDL and a reduction in CV events. It also shows that this applies also to drugs that are not statins, and that decreasing LDL level below 70mg per dL provides additional clinical benefit. This result is fully in line with the European Guidelines on CVD Prevention in Clinical Practice , which advise targeting an LDL level <70 mg/dL in post- ACS patients, and it is not unlikely that a target LDL of 55 mg/dL will be discussed in the next guidelines for these patients.
FACTOR 64 presented by Joseph B Muhlestein, Intermountain Medical Centre; University of Utah, Murray, UT, USA in diabetic patients is discussed here by Francois Schiele.
The aim of the FACTOR-64 study was to assess whether routine screening for CAD by CT-scan in patients with type 1 or type 2 DM deemed to be at high cardiac risk, followed by CT-scan-directed therapy, would reduce cardiovascular risk. 450 patients were randomly attributed to the CT screening group: 31.3% had normal CT examination while the others had mild, moderate or severe lesions on CT-scan. As compared with standard care provided in the control group and in patients with normal coronary arteries, aggressive treatment for four years in patients from the CT-scan group who had coronary lesions did not result in a significant reduction of all-cause mortality, nonfatal MI, or hospitalization for unstable angina.
Despite a high proportion of silent coronary disease observed in diabetics, this study does not support active screening for CAD in stable patients associated with aggressive management in case of CAD. These findings are in line with current 2014 ESC/EACTS Guidelines on Myocardial Revascularisation and 2014 ESC Guidelines on the Management of Stable Coronary Artery Disease.
A new trial showing no benefit of low-dose, once a day aspirin in the primary prevention of cardiovascular events in patients with multiple risk factors, including hypertension, diabetes, and dyslipidemia presented by Dr Kazuyuki Shimada, Shin-Oyama City Hosp, Tochigi, Japan was also of interest. Read more here...
Infective Endocarditis
Another important late breaker was the British registry on infective endocarditis. Renowned expert Prof Gilbert Habib, who was recently elected President of the EACVI at the EuroEcho-Imaging 2014 congress commented on the incidence of infective endocarditis in England from 2000 to 2013, after the presentation of a time-series analysis by Mark J Dayer also as part of the AHA Scientific Sessions 2014.
The authors presented interesting results from the English experience of cessation of antibiotic prophylaxis in infective endocarditis.
Although the 2007 American guidelines and 2009 European guidelines on Infective Endocarditis recommend restricting antibiotic prophylaxis to high-risk subgroups, the NICE recommendations in England took the surprising decision to stop all antibiotic therapy in 2008.
Dr Dayer analysed events from January 1, 2004, to March 31, 2013, and compared the incidence of infective endocarditis before and after the introduction of the NICE guidelines using segmented regression analysis of the interrupted time series.
The main result is that there was a significant decrease in prescriptions of antibiotic prophylaxis for the prevention of infective endocarditis after introduction of the NICE guidance (mean 10 900 prescriptions per month [Jan 1, 2004, to March 31, 2008] vs 2236 prescriptions per month [April 1, 2008, to March 31, 2013], p<0.0001).
The second important result is that starting in March 2008, the number of cases of infective endocarditis increased significantly above the projected historical trend, by 0.11 cases per 10 million people per month (95% CI 0.05–0.16, p<0.0001).
However, this study has several limitations, and the link between the reduction of antibiotic prescription and the increased incidence of endocarditis cannot be deduced from this presentation.
Another indirect conclusion is that, in the coming years, European countries would benefit from greater compliance with ESC guidelines. Proposing individual recommendations creates confusion for both patients and doctors.
The positive consequence of this study is that it emphasizes the need for an international randomized study, in order to correctly answer the important question of the impact of antibiotic prophylaxis in endocarditis. Watch Gilbert Habib discussing the trial here...
Prompted to comment on the key trials presented this year, he singled out the three following topics that, in his view, will have a direct impact on clinical practice, and that are interesting to compare with European guidelines.
Dual Antiplatelet Therapy
- Use of Dual Antiplatelet Therapy (DAPT) both immediately after inserting a DES and in the very long term (beyond one year and up to 30 months)
- After an ACS with or without DES implantation, with a mandatory minimum DAPT duration of one year
Recent publications question the duration of DAPT after DES implantation and it appears that six months might actually be enough.
Two eagerly awaited DAPT trials were presented by European specialists.
1. ISAR SAFE presented by Prof Stefanie Schulz-Schüpke from the Deutsches Herzzentrum München, Munich, Germany, compared 6 to 12 months DAPT after DES implantation in a large cohort of 4,000 patients, of whom half had ACS
2. ITALIC presented by Martine Gilard, University of Brest, Brest, France was a similar study comparing 6 to 24 months of DAPT after implantation of new generation DES in a similar population also with ACS.
The results of the two studies are quite similar. They show that six months of DAPT is safe, without any increase in the rate of stent thrombosis. Surprisingly, there was no major difference in bleeding rates.
Put in perspective with previous trials, it seems that a short DAPT duration in DES patients (even after ACS) is equally as effective for the prevention of ischemic events and yields a reduction in bleeding.
These results are consistent with the 2014 ESC/EACTS Guidelines on Myocardial Revascularisation regarding the subgroup of stable patients, whereas in ACS, 12 months of DAPT is still recommended.
Conversely, the “DAPT” trial, also presented in Chicago, focused on the clinical benefit of extended DAPT currently recommended by guidelines, comparing twelve months vs 30 months. The study included 9,961 patients treated previously with a drug eluting stent for twelve months.
Interestingly, the results were conflicting. On the one hand, long term DAPT was protective against stent thrombosis and recurrent MI, but on the other hand, DAPT showed a trend towards higher mortality, mostly explained by higher bleeding, more cancer and higher trauma mortality.
Therefore, based on these results, such a long duration of DAPT cannot really be recommended. This is in line with all current ESC guidelines (myocardial revascularisation, STEMI, stable angina).
Check also ESC spokesperson and ESC Press Committee member Prof Freek Verheugt’s video comments here.
Lipids
Lipids were high on the AHA agenda this year with two studies:
- One on primary prevention in diabetic patients
- Another study on secondary prevention post-MI to evaluate the clinical benefit of the Ezetimibe/Simvastatin combination discussed in the IMPROVE IT trial
IMPROVE-IT presented by Prof Christopher Cannon, Brigham and Women's Hospital, Boston, MA, USA was initially designed to assess the clinical benefit of lowering LDL cholesterol below 70mg per dL in post- ACS patients. Therefore patients with an LDL adequately controlled with Simvastatin (LDL level around 70mg) were randomised with an additional 10mg of Ezetimibe vs placebo.
Watch ESC spokesperson Prof Michel Farnier discuss the trial here...
As expected, patients with Ezetimibe achieved a 20% lower LDL, on average 54mg per dL. After six years, investigators observed a 16% reduction in the composite endpoint (CV death, MI, unstable angina, rehospitalisation, coronary revascularization). When a hard composite endpoint was considered (cardiovascular death, non-fatal MI and stroke), there was also a clinical benefit, with a 10% reduction in events, mainly driven by a 13% reduction in MI and a 14% reduction in stroke, without any changes in the mortality rate.
This result confirms the link between a decrease in LDL and a reduction in CV events. It also shows that this applies also to drugs that are not statins, and that decreasing LDL level below 70mg per dL provides additional clinical benefit. This result is fully in line with the European Guidelines on CVD Prevention in Clinical Practice , which advise targeting an LDL level <70 mg/dL in post- ACS patients, and it is not unlikely that a target LDL of 55 mg/dL will be discussed in the next guidelines for these patients.
FACTOR 64 presented by Joseph B Muhlestein, Intermountain Medical Centre; University of Utah, Murray, UT, USA in diabetic patients is discussed here by Francois Schiele.
The aim of the FACTOR-64 study was to assess whether routine screening for CAD by CT-scan in patients with type 1 or type 2 DM deemed to be at high cardiac risk, followed by CT-scan-directed therapy, would reduce cardiovascular risk. 450 patients were randomly attributed to the CT screening group: 31.3% had normal CT examination while the others had mild, moderate or severe lesions on CT-scan. As compared with standard care provided in the control group and in patients with normal coronary arteries, aggressive treatment for four years in patients from the CT-scan group who had coronary lesions did not result in a significant reduction of all-cause mortality, nonfatal MI, or hospitalization for unstable angina.
Despite a high proportion of silent coronary disease observed in diabetics, this study does not support active screening for CAD in stable patients associated with aggressive management in case of CAD. These findings are in line with current 2014 ESC/EACTS Guidelines on Myocardial Revascularisation and 2014 ESC Guidelines on the Management of Stable Coronary Artery Disease.
A new trial showing no benefit of low-dose, once a day aspirin in the primary prevention of cardiovascular events in patients with multiple risk factors, including hypertension, diabetes, and dyslipidemia presented by Dr Kazuyuki Shimada, Shin-Oyama City Hosp, Tochigi, Japan was also of interest. Read more here...
Infective Endocarditis
Another important late breaker was the British registry on infective endocarditis. Renowned expert Prof Gilbert Habib, who was recently elected President of the EACVI at the EuroEcho-Imaging 2014 congress commented on the incidence of infective endocarditis in England from 2000 to 2013, after the presentation of a time-series analysis by Mark J Dayer also as part of the AHA Scientific Sessions 2014.
The authors presented interesting results from the English experience of cessation of antibiotic prophylaxis in infective endocarditis.
Although the 2007 American guidelines and 2009 European guidelines on Infective Endocarditis recommend restricting antibiotic prophylaxis to high-risk subgroups, the NICE recommendations in England took the surprising decision to stop all antibiotic therapy in 2008.
Dr Dayer analysed events from January 1, 2004, to March 31, 2013, and compared the incidence of infective endocarditis before and after the introduction of the NICE guidelines using segmented regression analysis of the interrupted time series.
The main result is that there was a significant decrease in prescriptions of antibiotic prophylaxis for the prevention of infective endocarditis after introduction of the NICE guidance (mean 10 900 prescriptions per month [Jan 1, 2004, to March 31, 2008] vs 2236 prescriptions per month [April 1, 2008, to March 31, 2013], p<0.0001).
The second important result is that starting in March 2008, the number of cases of infective endocarditis increased significantly above the projected historical trend, by 0.11 cases per 10 million people per month (95% CI 0.05–0.16, p<0.0001).
However, this study has several limitations, and the link between the reduction of antibiotic prescription and the increased incidence of endocarditis cannot be deduced from this presentation.
Another indirect conclusion is that, in the coming years, European countries would benefit from greater compliance with ESC guidelines. Proposing individual recommendations creates confusion for both patients and doctors.
The positive consequence of this study is that it emphasizes the need for an international randomized study, in order to correctly answer the important question of the impact of antibiotic prophylaxis in endocarditis. Watch Gilbert Habib discussing the trial here...
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