NIHR DC Discover

NIHR Signal Short-duration dual antiplatelet treatment is possible for older people receiving drug-coated stents

Published on 7 March 2018

doi: 10.3310/signal-000566

Drug-eluting stents are more effective than bare-metal stents for preventing repeat procedures to open narrowed heart arteries in older adults with coronary heart disease. In this trial both types of stents were used alongside short courses of dual antiplatelet medication, outcomes for those receiving drug-eluting stents were improved with no difference in bleeding complications or rates of in-stent clots.

This multi-centre European study tested 1,200 people aged 75 years or older. Duration of dual antiplatelet therapy was decided by heart disease severity, rather than the type of stent.

The findings support the idea that people over 75 years can have the benefit of drug-eluting stents, alongside shorter duration dual antiplatelet treatment, like younger adults.

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Why was this study needed?

Coronary heart disease reduces the flow of blood to the heart muscle. It affects 2.3 million people in the UK and causes 70,000 deaths per year.

Stents are devices which can be inserted, via an artery in the arm or groin, into narrowed coronary arteries to keep them open. Stents themselves are a focus for blood clots until the cells that line the artery can cover the “foreign” material. Two anti-platelet drugs are used to reduce clots, but they increase the risk of severe bleeding.

Drug-eluting stents are thought to be better than bare metal stents for keeping the heart arteries open but typically need longer duration dual antiplatelet therapy. Older people have more risk of bleeding, and so drug-eluting stents are usually reserved for younger patients.

The ideal strategy to manage older patients who require percutaneous coronary intervention is unclear as many earlier large trials excluded older patients due to complex illness and comorbidity.

This trial compared the two types of stents in older people.

What did this study do?

The SENIOR randomised trial compared drug-eluting stents with bare-metal stents in 1,200 people aged 75 years or older. The trial was carried out at 44 centres in nine European countries including the UK. Following coronary intervention, the duration of dual antiplatelet was determined according to the patient’s initial presentation – one month for stable cases and six months for unstable cases such as acute coronary syndrome.

The main outcome was a combination of several events, including death, myocardial infarction, and revascularisation (further intervention because the vessel had narrowed) assessed at 30, 180 and 365 days. Other outcomes included bleeding complications and blockage.

This was a well-conducted trial. Patients and the committee assessing outcomes were unaware of the type of stent used, increasing the reliability of the findings.

What did it find?

  • During the first year after the intervention, the main outcome had occurred in 68 (12%) patients who received drug-eluting stents and 98 (16%) patients with bare-metal stents (relative risk [RR] 0.71, 95% confidence interval [CI] 0.52 to 0.94).
  • Revascularisation was less frequent with drug-eluting stents: seven (1%) people with drug-eluting stents needed a repeat procedure by 180 days versus 23 (4%) with bare-metal stents (RR 0.31, 95% CI 0.08 to 0.66). By one year 10 (2%) people with drug-eluting stents had a revascularisation compared to 35 (6%) with a bare-metal stent (RR 0.29, 95% CI 0.11 to 0.54).
  • Type of stent did not affect individual outcomes of death from any cause, cardiovascular death or myocardial infarction.
  • Treatments were equally safe, with no difference in the number of bleeding complications or stent clots.
  • The net clinical benefit, which combines the main outcome with bleeding complications, was in favour of drug-eluting stents at one year. Fourteen percent experienced any of these adverse outcomes compared with 19% of people with bare-metal stents (RR 0.75, 95% CI 0.58 to 0.97).

What does current guidance say on this issue?

The NICE 2008 guidance on drug-eluting stents recommends using them only if the artery to be treated has a diameter smaller than 3mm, or the lesion is longer than 15mm, and the price difference compared with alternatives is not higher than £300.

The NICE guidance on myocardial infarction recommends using dual antiplatelet treatment in people who had a heart attack and have a stent. The guideline recommends dual therapy for one month after bare-metal stents and 12 months after eluting drug stent, followed by aspirin indefinitely.

What are the implications?

Deciding which stent to use for older adults has been challenging, as this population are frequently excluded from trials comparing stents.

The findings suggest that older patients in need of percutaneous intervention for management of coronary heart disease can be treated with drug-eluting stents followed by dual antiplatelet treatment, in the same way as younger people.

Cost effectiveness data from this trial will be available at two years. It will be interesting to see if any additional costs of drug-eluting stents might be offset by the reduced cost of revascularisation.

Citation and Funding

Varenne O, Cook S, Sideris G, et al. Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial. Lancet. 2018;391(10115):41-50.

This project was funded by Boston Scientific.

Bibliography

British Heart Foundation. BHF CVD Statistics Factsheet - UK. London: British Heart Foundation; revised 2017.

NHS Choices. Coronary heart disease. London: British Heart Foundation; 2017.

NICE. Drug-eluting stents for the treatment of coronary artery disease. TA152. London: National Institute for Health and Clinical Excellence; 2008.

NICE. Guidance on the use of coronary artery stents. TA71. London: National Institute for Health and Clinical Excellence; 2003, revised 2008.

NICE. Myocardial infarction: cardiac rehabilitation and prevention of further cardiovascular disease. CG172. London: National Institute for Health and Clinical Excellence; 2013.

Why was this study needed?

Coronary heart disease reduces the flow of blood to the heart muscle. It affects 2.3 million people in the UK and causes 70,000 deaths per year.

Stents are devices which can be inserted, via an artery in the arm or groin, into narrowed coronary arteries to keep them open. Stents themselves are a focus for blood clots until the cells that line the artery can cover the “foreign” material. Two anti-platelet drugs are used to reduce clots, but they increase the risk of severe bleeding.

Drug-eluting stents are thought to be better than bare metal stents for keeping the heart arteries open but typically need longer duration dual antiplatelet therapy. Older people have more risk of bleeding, and so drug-eluting stents are usually reserved for younger patients.

The ideal strategy to manage older patients who require percutaneous coronary intervention is unclear as many earlier large trials excluded older patients due to complex illness and comorbidity.

This trial compared the two types of stents in older people.

What did this study do?

The SENIOR randomised trial compared drug-eluting stents with bare-metal stents in 1,200 people aged 75 years or older. The trial was carried out at 44 centres in nine European countries including the UK. Following coronary intervention, the duration of dual antiplatelet was determined according to the patient’s initial presentation – one month for stable cases and six months for unstable cases such as acute coronary syndrome.

The main outcome was a combination of several events, including death, myocardial infarction, and revascularisation (further intervention because the vessel had narrowed) assessed at 30, 180 and 365 days. Other outcomes included bleeding complications and blockage.

This was a well-conducted trial. Patients and the committee assessing outcomes were unaware of the type of stent used, increasing the reliability of the findings.

What did it find?

  • During the first year after the intervention, the main outcome had occurred in 68 (12%) patients who received drug-eluting stents and 98 (16%) patients with bare-metal stents (relative risk [RR] 0.71, 95% confidence interval [CI] 0.52 to 0.94).
  • Revascularisation was less frequent with drug-eluting stents: seven (1%) people with drug-eluting stents needed a repeat procedure by 180 days versus 23 (4%) with bare-metal stents (RR 0.31, 95% CI 0.08 to 0.66). By one year 10 (2%) people with drug-eluting stents had a revascularisation compared to 35 (6%) with a bare-metal stent (RR 0.29, 95% CI 0.11 to 0.54).
  • Type of stent did not affect individual outcomes of death from any cause, cardiovascular death or myocardial infarction.
  • Treatments were equally safe, with no difference in the number of bleeding complications or stent clots.
  • The net clinical benefit, which combines the main outcome with bleeding complications, was in favour of drug-eluting stents at one year. Fourteen percent experienced any of these adverse outcomes compared with 19% of people with bare-metal stents (RR 0.75, 95% CI 0.58 to 0.97).

What does current guidance say on this issue?

The NICE 2008 guidance on drug-eluting stents recommends using them only if the artery to be treated has a diameter smaller than 3mm, or the lesion is longer than 15mm, and the price difference compared with alternatives is not higher than £300.

The NICE guidance on myocardial infarction recommends using dual antiplatelet treatment in people who had a heart attack and have a stent. The guideline recommends dual therapy for one month after bare-metal stents and 12 months after eluting drug stent, followed by aspirin indefinitely.

What are the implications?

Deciding which stent to use for older adults has been challenging, as this population are frequently excluded from trials comparing stents.

The findings suggest that older patients in need of percutaneous intervention for management of coronary heart disease can be treated with drug-eluting stents followed by dual antiplatelet treatment, in the same way as younger people.

Cost effectiveness data from this trial will be available at two years. It will be interesting to see if any additional costs of drug-eluting stents might be offset by the reduced cost of revascularisation.

Citation and Funding

Varenne O, Cook S, Sideris G, et al. Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial. Lancet. 2018;391(10115):41-50.

This project was funded by Boston Scientific.

Bibliography

British Heart Foundation. BHF CVD Statistics Factsheet - UK. London: British Heart Foundation; revised 2017.

NHS Choices. Coronary heart disease. London: British Heart Foundation; 2017.

NICE. Drug-eluting stents for the treatment of coronary artery disease. TA152. London: National Institute for Health and Clinical Excellence; 2008.

NICE. Guidance on the use of coronary artery stents. TA71. London: National Institute for Health and Clinical Excellence; 2003, revised 2008.

NICE. Myocardial infarction: cardiac rehabilitation and prevention of further cardiovascular disease. CG172. London: National Institute for Health and Clinical Excellence; 2013.

Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial

Published on 6 November 2017

Varenne, O.,Cook, S.,Sideris, G.,Kedev, S.,Cuisset, T.,Carrie, D.,Hovasse, T.,Garot, P.,El Mahmoud, R.,Spaulding, C.,Helft, G.,Diaz Fernandez, J. F.,Brugaletta, S.,Pinar-Bermudez, E.,Mauri Ferre, J.,Commeau, P.,Teiger, E.,Bogaerts, K.,Sabate, M.,Morice, M. C.,Sinnaeve, P. R.

Lancet , 2017

BACKGROUND: Elderly patients regularly receive bare-metal stents (BMS) instead of drug-eluting stents (DES) to shorten the duration of double antiplatelet therapy (DAPT). The aim of this study was to compare outcomes between these two types of stents with a short duration of DAPT in such patients. METHODS: In this randomised single-blind trial, we recruited patients from 44 centres in nine countries. Patients were eligible if they were aged 75 years or older; had stable angina, silent ischaemia, or an acute coronary syndrome; and had at least one coronary artery with a stenosis of at least 70% (>/=50% for the left main stem) deemed eligible for percutaneous coronary intervention (PCI). Exclusion criteria were indication for myocardial revascularisation by coronary artery bypass grafting; inability to tolerate, obtain, or comply with DAPT; requirement for additional surgery; non-cardiac comorbidities with a life expectancy of less than 1 year; previous haemorrhagic stroke; allergy to aspirin or P2Y12 inhibitors; contraindication to P2Y12 inhibitors; and silent ischaemia of less than 10% of the left myocardium with a fractional flow reserve of 0.80 or higher. After the intended duration of DAPT was recorded (1 month for patients with stable presentation and 6 months for those with unstable presentation), patients were randomly allocated (1:1) by a central computer system (blocking used with randomly selected block sizes [two, four, eight, or 16]; stratified by site and antiplatelet agent) to either a DES or similar BMS in a single-blind fashion (ie, patients were masked), but those assessing outcomes were masked. The primary outcome was to compare major adverse cardiac and cerebrovascular events (ie, a composite of all-cause mortality, myocardial infarction, stroke, or ischaemia-driven target lesion revascularisation) between groups at 1 year in the intention-to-treat population, assessed at 30 days, 180 days, and 1 year. This trial is registered with ClinicalTrials.gov, number NCT02099617. FINDINGS: Between May 21, 2014, and April 16, 2016, we randomly assigned 1200 patients (596 [50%] to the DES group and 604 [50%] to the BMS group). The primary endpoint occurred in 68 (12%) patients in the DES group and 98 (16%) in the BMS group (relative risk [RR] 0.71 [95% CI 0.52-0.94]; p=0.02). Bleeding complications (26 [5%] in the DES group vs 29 [5%] in the BMS group; RR 0.90 [0.51-1.54]; p=0.68) and stent thrombosis (three [1%] vs eight [1%]; RR 0.38 [0.00-1.48]; p=0.13) at 1 year were infrequent in both groups. INTERPRETATION: Among elderly patients who have PCI, a DES and a short duration of DAPT are better than BMS and a similar duration of DAPT with respect to the occurrence of all-cause mortality, myocardial infarction, stroke, and ischaemia-driven target lesion revascularisation. A strategy of combination of a DES to reduce the risk of subsequent repeat revascularisations with a short BMS-like DAPT regimen to reduce the risk of bleeding event is an attractive option for elderly patients who have PCI. FUNDING: Boston Scientific.

Expert commentary

Narrowed coronary arteries cause chest pain or a heart attack, and the commonest treatment is to have a stent inserted. To prevent blood clots forming on the stent, blood thinning drugs are given. But as you get older, there is increased risk of these drugs causing bleeding.

Modern stents have a thin drug coating, and this enabled the trialists to reduce the duration of blood thinners to the minimum, reducing the bleeding risk while retaining the benefit of the coating to prevent further narrowing - just like in younger patients.

Julian Gunn, Professor of Interventional Cardiology, University of Sheffield; Honorary Consultant Cardiologist, Lead for Acute Coronary Syndrome Pathways, Sheffield Teaching Hospitals NHS Foundation Trust; Chair, Insigneo Cardiovascular/Respiratory Workgroup, Fellow of the Insigneo Institute for In Silico Medicine