HOT UNE
Hot
line
11
Barcelona, 5 September 2006
In the second hot line session, the results of five trials and one registry were presented. The chairmen of the session were KM. Fox (London, UK) and S.G. Priori (Pavia, Italy).
The WAVE (Warfarin Antiplatelet Vascular Evaluation), a randomised controlled trial testing moderate intensity oral anticoagulation (OAC) and antiplatelet therapy versus antiplatelet therapy alone in patients with peripheral arterial disease (PAD) was presented by S. Anand (Hamilton, CA, US). The first primary endpoint was the composite ofcardiovascular (CV) death, stroke and myocardial infarction (MI). The second primary endpoint was the first primary endpoint plus severe ischaemia of the coronary and peripheral circulation requiring intervention. Safety outcomes included bleeding categorised as life-threatening (fatal, intracranial, requiring more than 4 units of blood or surgical intervention), moderate (more than 4 units of blood) or minor (all other bleeding not requiring transfusion). No difference was observed between the two primary endpoints. However, the incidence of ischaemic stroke was lower and haemorrhagic stroke higher so both effects cancelled each other out. Bleeding (including life-threatening bleeding) was significantly higher in the OAC + antiplatelet therapy group. The conclusion ofthe WAVE trial is that OAC + antiplatelet therapy does not lower the rate of CV events and increases the risk of life-threatening bleeding in patients with PAD. In the discussion that followed, it was mentioned that OAC + antiplatelet therapy has been successful in lowering CV events in other trials (OASIS-2, WARIS-2) with different study populations (MI) and that the reason why this was not successful in the WAVE trial was mainly due to the low risk of CV events in this study population of patients with PAD. Striking is that most studies that found a beneficial effect of OAC were conducted in countries with good compliance to anticoagulation therapy (Norway, the Netherlands).
H.C. Groenewegen P.P. Van Geel Department of Cardiology, University Medical Centre Groningen, Groningen, the Netherlands E-mail: [email protected]
6
Next, the RIVIERA registry was discussed by G. Montalescot(Paris, France). The goal of this registry was to identify current practice guidelines, identify independent risk factors of adverse clinical complications and investigate the use ofunfractioned heparin (UFH) and enoxiparin (low-molecular-weight heparin) in elective and primary percutaneous coronary interventions (PCI). MI, death and life-threatening bleeding were the primary endpoints. Rates of ischaemic and bleeding complications were lower than usually reported in registries and randomised controlled trials. A large number (52%) of the 7962 patients enrolled came from Asia. PCI of the left main trunk was associated with death, PCI of grafts with more bleeding, radial access with less bleeding and ischaemic events. No difference was observed in bleeding complications between enoxiparin and UFH. In the discussion the limited role of registries for definitive conclusions was underlined: trials for evaluation of the risk ofleft main PCI and radial access PCI should be tested in a clinical trial. A meta-analysis ofradial versus femoral approach did not show a difference in major adverse cardiac events (MACE). Although radial approach showed less entry site complications it was also associated with procedural failure. Contrary to the STEEPLE registry, the RIVIERA did not show a lower risk of bleeding with the use of enoxiparin versus UFH. In the RIVIERA registry, however, the patients were younger (59 vs. 64), used less GP IIb/IIIa blockers, radial approach was higher ( 11 vs. 0%) and different definitions were used for bleeding. The SPIRIT II Study, a non-inferiority study of the XIENCE V everolimus-eluting coronary stent versus the TAXUS stent in the treatment of patients with de novo, native coronary artery lesions was reviewed by P. W. Serruys (Rotterdam, the Netherlands). The primary endpoint was in-stent late loss at 180 days. Secondary endpoint was the composite clinical endpoint of death, MI and ischaemic-driven target lesion revascularisation and the safety endpoint of stent thrombosis. In-stent late loss was significantly lower in the XIENCE V stent. The composite clinical endpoint of death, MI and ischaemic-driven target lesion revascularisation was 2.5% in the XIENCE V stent versus 6.5% in the TAXUS stent; however, this difference was not significant and mainly caused by Netherlands Heart Journal, Volume 14, Supplement 2, November 2006
(APC
28th Congress of the European Society of Cardiology / World Congress of Cardiology
ischaemic-driven target lesion revascularisation and non-Q-wave infarction. The XIENCE V stent showed a low incidence of late stent thrombosis of 0.5% compared with 1.3% in the TAXUS stent under dual antiplatelet therapy; however, follow-up was short (53 days). The main issue in the discussion was the safety of drug-eluting stents (DES) with regard to the incidence oflate stent thrombosis. A recent study showed that patients who stopped clopidogrel were at increased risk of myocardial infarction. Data were also presented which suggest significant histological changes in DES compared with bare metal stents (BMS). The following presentation was by G. Veen (Amsterdam, the Netherlands), who discussed the VIAMI (The Viability-Guided Angioplasty after Acute Myocardial Infarction) trial. Patients with MI were tested for viability using low-dose dobutamine echo and randomised to an invasive (infarct-related artery stenting) and a conservative ischaemia-guided strategy. Patients without viability participated as control group. Primary endpoint was the composite of MI, death and unstable angina. The primary endpoint was significantly lower in the invasive strategy group (the difference was driven by unstable angina). The control group (without viability) showed a low incidence ofrecurrent ischaemic events. In the discussion it was pointed out that the population of the VIAMI trial was split into two groups with a different risk profile (acute MI treated with thrombolysis or acute MI without reperfusion therapy). It is not clear in the VIAMI trial which of the two groups (acute MI treated with thrombolysis or acute MI without reperfusion therapy) benefited most from the invasive strategy. The CAPITAL-AMI trial showed the value of post-thrombolysis PCI in a high-risk STEMI population. Furthermore, no significant difference in MI and death existed between the invasive and the conservative group.
The JIKEI Heart Study was presented B. Dabhof (Gothenburg, Sweden) and S. Mochizuki (Minato-ku, Japan). Japanese patients with hypertension and cardiovascular disease were divided into two groups, one received conventional antihypertensive treatment the other valsartan. Primary endpoint was a composite of
q
C
Netherlands Heart Journal, Volume 14, Supplement 2, November 2006
CV mortality and morbidity (death, stroke, TIA, MI, angina pectoris, hospitalisation for chronic heart failure). The study was stopped after three years due to the unequivocal benefit from valsartan. Blood pressure was maintained at 130/80 mmHg and did not differ between the two groups. Stroke, hospitalisation for heart failure and hospitalisation for angina pectoris were significantly lower in the valsartan-treated group. The JIKEI Heart study was conducted in an Asian population so the effects should be confirmed in a European population.
The TROICA (Thrombolysis in Cardiac Arrest) trial was presented by B.W. Boettiger (Heidelberg, Germany). Patients with cardiac arrest were randomised to thrombolysis or placebo. Primary endpoints were 24-hour survival and survival to day 30 or hospital discharge. Thrombolysis did not increase 24-hour survival and survival to day 30 or hospital discharge. Conclusion The WAVE trial: OAC + antiplatelet therapy should not be given to patients with PAD until the risks of bleeding are better controllable (waiting for new oral thrombin inhibitors). The RIVIERA registry: left main PCI might be associated with higher risk ofdeath but this should be confirmed in a randomised controlled trial. The SPIRIT II trial: the question should be raised whether the long-term benefits of DES (by reducing or delaying restenosis) outweigh the disadvantage of a possible increase in stent thrombosis, and the need for a randomised controlled trial was expressed. The VIAMI trial: patients with post-thrombolysis undergoing infarct-related stenting have no reduction in mortality and MI but do have a reduction in angina pectoris. The JIKEI Heart Study: valsartan in association with calcium channel blocker or ACE inhibitor reduces stroke, hospitalisation for angina pectoris and hospitalisation for chronic heart failure. The TROICA trial: thrombolysis should not be given to patients with cardiac arrest unless an indication exists (MI, pulmonary embolism). -
7
Hot
line
11
Barcelona, 5 September 2006
In the second hot line session, the results of five trials and one registry were presented. The chairmen of the session were KM. Fox (London, UK) and S.G. Priori (Pavia, Italy).
The WAVE (Warfarin Antiplatelet Vascular Evaluation), a randomised controlled trial testing moderate intensity oral anticoagulation (OAC) and antiplatelet therapy versus antiplatelet therapy alone in patients with peripheral arterial disease (PAD) was presented by S. Anand (Hamilton, CA, US). The first primary endpoint was the composite ofcardiovascular (CV) death, stroke and myocardial infarction (MI). The second primary endpoint was the first primary endpoint plus severe ischaemia of the coronary and peripheral circulation requiring intervention. Safety outcomes included bleeding categorised as life-threatening (fatal, intracranial, requiring more than 4 units of blood or surgical intervention), moderate (more than 4 units of blood) or minor (all other bleeding not requiring transfusion). No difference was observed between the two primary endpoints. However, the incidence of ischaemic stroke was lower and haemorrhagic stroke higher so both effects cancelled each other out. Bleeding (including life-threatening bleeding) was significantly higher in the OAC + antiplatelet therapy group. The conclusion ofthe WAVE trial is that OAC + antiplatelet therapy does not lower the rate of CV events and increases the risk of life-threatening bleeding in patients with PAD. In the discussion that followed, it was mentioned that OAC + antiplatelet therapy has been successful in lowering CV events in other trials (OASIS-2, WARIS-2) with different study populations (MI) and that the reason why this was not successful in the WAVE trial was mainly due to the low risk of CV events in this study population of patients with PAD. Striking is that most studies that found a beneficial effect of OAC were conducted in countries with good compliance to anticoagulation therapy (Norway, the Netherlands).
H.C. Groenewegen P.P. Van Geel Department of Cardiology, University Medical Centre Groningen, Groningen, the Netherlands E-mail: [email protected]
6
Next, the RIVIERA registry was discussed by G. Montalescot(Paris, France). The goal of this registry was to identify current practice guidelines, identify independent risk factors of adverse clinical complications and investigate the use ofunfractioned heparin (UFH) and enoxiparin (low-molecular-weight heparin) in elective and primary percutaneous coronary interventions (PCI). MI, death and life-threatening bleeding were the primary endpoints. Rates of ischaemic and bleeding complications were lower than usually reported in registries and randomised controlled trials. A large number (52%) of the 7962 patients enrolled came from Asia. PCI of the left main trunk was associated with death, PCI of grafts with more bleeding, radial access with less bleeding and ischaemic events. No difference was observed in bleeding complications between enoxiparin and UFH. In the discussion the limited role of registries for definitive conclusions was underlined: trials for evaluation of the risk ofleft main PCI and radial access PCI should be tested in a clinical trial. A meta-analysis ofradial versus femoral approach did not show a difference in major adverse cardiac events (MACE). Although radial approach showed less entry site complications it was also associated with procedural failure. Contrary to the STEEPLE registry, the RIVIERA did not show a lower risk of bleeding with the use of enoxiparin versus UFH. In the RIVIERA registry, however, the patients were younger (59 vs. 64), used less GP IIb/IIIa blockers, radial approach was higher ( 11 vs. 0%) and different definitions were used for bleeding. The SPIRIT II Study, a non-inferiority study of the XIENCE V everolimus-eluting coronary stent versus the TAXUS stent in the treatment of patients with de novo, native coronary artery lesions was reviewed by P. W. Serruys (Rotterdam, the Netherlands). The primary endpoint was in-stent late loss at 180 days. Secondary endpoint was the composite clinical endpoint of death, MI and ischaemic-driven target lesion revascularisation and the safety endpoint of stent thrombosis. In-stent late loss was significantly lower in the XIENCE V stent. The composite clinical endpoint of death, MI and ischaemic-driven target lesion revascularisation was 2.5% in the XIENCE V stent versus 6.5% in the TAXUS stent; however, this difference was not significant and mainly caused by Netherlands Heart Journal, Volume 14, Supplement 2, November 2006
(APC
28th Congress of the European Society of Cardiology / World Congress of Cardiology
ischaemic-driven target lesion revascularisation and non-Q-wave infarction. The XIENCE V stent showed a low incidence of late stent thrombosis of 0.5% compared with 1.3% in the TAXUS stent under dual antiplatelet therapy; however, follow-up was short (53 days). The main issue in the discussion was the safety of drug-eluting stents (DES) with regard to the incidence oflate stent thrombosis. A recent study showed that patients who stopped clopidogrel were at increased risk of myocardial infarction. Data were also presented which suggest significant histological changes in DES compared with bare metal stents (BMS). The following presentation was by G. Veen (Amsterdam, the Netherlands), who discussed the VIAMI (The Viability-Guided Angioplasty after Acute Myocardial Infarction) trial. Patients with MI were tested for viability using low-dose dobutamine echo and randomised to an invasive (infarct-related artery stenting) and a conservative ischaemia-guided strategy. Patients without viability participated as control group. Primary endpoint was the composite of MI, death and unstable angina. The primary endpoint was significantly lower in the invasive strategy group (the difference was driven by unstable angina). The control group (without viability) showed a low incidence ofrecurrent ischaemic events. In the discussion it was pointed out that the population of the VIAMI trial was split into two groups with a different risk profile (acute MI treated with thrombolysis or acute MI without reperfusion therapy). It is not clear in the VIAMI trial which of the two groups (acute MI treated with thrombolysis or acute MI without reperfusion therapy) benefited most from the invasive strategy. The CAPITAL-AMI trial showed the value of post-thrombolysis PCI in a high-risk STEMI population. Furthermore, no significant difference in MI and death existed between the invasive and the conservative group.
The JIKEI Heart Study was presented B. Dabhof (Gothenburg, Sweden) and S. Mochizuki (Minato-ku, Japan). Japanese patients with hypertension and cardiovascular disease were divided into two groups, one received conventional antihypertensive treatment the other valsartan. Primary endpoint was a composite of
q
C
Netherlands Heart Journal, Volume 14, Supplement 2, November 2006
CV mortality and morbidity (death, stroke, TIA, MI, angina pectoris, hospitalisation for chronic heart failure). The study was stopped after three years due to the unequivocal benefit from valsartan. Blood pressure was maintained at 130/80 mmHg and did not differ between the two groups. Stroke, hospitalisation for heart failure and hospitalisation for angina pectoris were significantly lower in the valsartan-treated group. The JIKEI Heart study was conducted in an Asian population so the effects should be confirmed in a European population.
The TROICA (Thrombolysis in Cardiac Arrest) trial was presented by B.W. Boettiger (Heidelberg, Germany). Patients with cardiac arrest were randomised to thrombolysis or placebo. Primary endpoints were 24-hour survival and survival to day 30 or hospital discharge. Thrombolysis did not increase 24-hour survival and survival to day 30 or hospital discharge. Conclusion The WAVE trial: OAC + antiplatelet therapy should not be given to patients with PAD until the risks of bleeding are better controllable (waiting for new oral thrombin inhibitors). The RIVIERA registry: left main PCI might be associated with higher risk ofdeath but this should be confirmed in a randomised controlled trial. The SPIRIT II trial: the question should be raised whether the long-term benefits of DES (by reducing or delaying restenosis) outweigh the disadvantage of a possible increase in stent thrombosis, and the need for a randomised controlled trial was expressed. The VIAMI trial: patients with post-thrombolysis undergoing infarct-related stenting have no reduction in mortality and MI but do have a reduction in angina pectoris. The JIKEI Heart Study: valsartan in association with calcium channel blocker or ACE inhibitor reduces stroke, hospitalisation for angina pectoris and hospitalisation for chronic heart failure. The TROICA trial: thrombolysis should not be given to patients with cardiac arrest unless an indication exists (MI, pulmonary embolism). -
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