NIHR Signal Routine treatment approaches soon after some types of heart attack, are finely balanced

Published on 30 August 2016

The modest benefits of a routine “angiography first” or “invasive” strategy for patients with some types of chest pain may come at the risk of increased bleeding.

The timing of “invasive” diagnosis and treatments, which include coronary artery catheter investigation and treatment with a stent, is an important part of care for people with heart attacks. In this review, the patients enrolled in eight underlying studies, all had unstable angina or a type of heart attack called non-ST elevation myocardial infarction (NSTEMI).

The routine “invasive” strategy offered early diagnosis and treatment of the narrowed arteries using coronary catheterisation and stents or bypass grafts if required. It was compared to a “selective” or “conservative” strategy. In this alternative approach, routine drug treatment was offered first and coronary angiography plus stent treatment later if symptoms or tests suggested it was needed.

There was no appreciable difference in deaths from all causes or non-fatal heart attack overall when the routine invasive group compared to conservative group. However the risk of a heart attack during the procedure was almost double, and the risk of bleeding as a complication of the catheterisation or treatment was also increased.

The cost and resource implications associated with having angiography and stenting available for everyone was not assessed in this review. There are potential system benefits to consider too, such as the lower readmission rates that were observed in the routine invasive group.

Taking into account a wider range of evidence, clinicians will be able to give more precise estimates of the potential harms and benefits to patients based on this review and an assessment of their risk.

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Why was this study needed?

Both unstable angina (worsening chest pain) and NSTEMI carry a significant risk of recurrent heart attack and death. In 2013/14, there were 45,910 admissions for NSTEMI in England.

In the conservatively strategy arm, the risk of further heart attack was assessed using tools such as the Global Registry of Acute Cardiac Events (GRACE) or other tools. The invasive approach involved routine angiography and revascularisation in most or all patients who have no contraindications, irrespective of the risk score. The researchers wanted to look at all studies that had compared the benefits and harms of these strategies.

New trials have emerged since a 2010 review was published on the same topic. This update was needed to determine if these new trials changed the evidence- base and might warrant a change in guidance and practice.

What did this study do?

This updated Cochrane systematic reviewed eight randomised controlled trials published before August 2015. Five trials were included from an original 2010 review along with three new trials. All trials were carried out in the era in which stents were being used.

The review included 8,915 adults with either an episode of unstable angina, increasing level of resting pain, or tests indicating heart muscle damage without ST elevation on the ECG.

Half of the participants received a conservative management approach whilst the other half received the routine invasive approach.

There were differences in the trials in the time between randomisation and coronary angiography in the routine invasive group, between an average of six hours and four days. Participants varied per study, with some only including people over the age of 65.

What did it find?

At six to 12 months follow up the following events occurred.

  • There was no difference in death from any cause at six to 12 months, with 36 deaths per 1,000 people in the routine invasive approach compared to 42 deaths per 1,000 people for the conservative approach (RR 0.87, 95% CI 0.64 to 1.18).
  • The routine invasive strategy did not appreciably reduce the risk of myocardial infarction at six to 12 months, with 62 episodes per 1,000 people versus 78 per 1,000 people in the conservative strategy (relative risk [RR] 0.79, 95% confidence interval [CI] 0.63 to 1.00) technically a non-significant difference.
  • There were fewer re-hospitalisations with the invasive strategy, 220 per 1,000 people versus 286 per 1,000 people in the conservative strategy (RR 0.77, 95% CI 0.63 to 0.94).
  • The routine invasive strategy increased the risk of bleeding as a complication of investigation or treatment, 42 per 1,000 invasive versus 72 per 1,000 (RR 1.73, 95% CI 1.30 to 2.31) and procedure-related myocardial infarction, at 30 per 1,000 conservative versus 57 per 1,000 in the invasive approach (RR 1.87, 95% CI 1.47 to 2.37).

What does current guidance say on this issue?

NICE’s 2013 guidance on early management of unstable angina and NSTEMI provides recommendations for conservative management and early invasive management. It recommends conservative management without early coronary angiography for patients with a low risk of adverse cardiovascular events (a predicted six-month death of less than 3.0% on GRACE).

The early invasive approach of coronary angiography is recommended within 96 hours of hospital admission for people who have a moderate to high risk of adverse cardiovascular events (a predicted six-month death above 3.0%) and no contraindications. This strategy is also recommended for people initially assessed as at low risk of adverse cardiovascular events if there is ongoing chest pain or evidence of cardiac ischaemia demonstrated on exercise stress testing.

What are the implications?

When looking at a follow up of six to 12 months, this Cochrane review provides evidence that in people with unstable angina and NSTEMI the choice of approach is finely balanced. The authors suggest that the benefits may be more meaningful in a higher risk group and routine invasive approach may be the preferred management strategy for this group.

It is possible that recent changes in therapies or techniques at the time or angioplasty might further reduce the risk of bleeding and tip the balance in favour of invasive treatments for lower risk patients. Careful risk-based patient selection and discussion of possible harms will remain important.

There are resource implications to changing practice including increased availability of angiography and cardiac interventions out of hours. From a system perspective this added cost might be offset by a reduced re-hospitalisation rate.

Citation and Funding

Fanning JP, Nyong J, Scott IA, et al. Routine invasive strategies versus selective invasive strategies for unstable angina and non-ST elevation myocardial infarction in the stent era. Cochrane Database Syst Rev. 2016;(5):CD004815.

This project was funded by The Prince Charles Hospital Foundation, Australia, The University of Queensland Australia and The Cardiac Society of Australia and New Zealand.

Bibliography

NICE. Unstable angina and NSTEMI: early management. CG94. London. National Institute of Health and Care Excellence; 2013.

MINAP. Myocardial Ischaemia National Audit Project: How the NHS cares for patients with heart attack. Annual Public Report April 2013-2014. London: Myocardial Ischaemia National Audit Project; 2014.

Why was this study needed?

Both unstable angina (worsening chest pain) and NSTEMI carry a significant risk of recurrent heart attack and death. In 2013/14, there were 45,910 admissions for NSTEMI in England.

In the conservatively strategy arm, the risk of further heart attack was assessed using tools such as the Global Registry of Acute Cardiac Events (GRACE) or other tools. The invasive approach involved routine angiography and revascularisation in most or all patients who have no contraindications, irrespective of the risk score. The researchers wanted to look at all studies that had compared the benefits and harms of these strategies.

New trials have emerged since a 2010 review was published on the same topic. This update was needed to determine if these new trials changed the evidence- base and might warrant a change in guidance and practice.

What did this study do?

This updated Cochrane systematic reviewed eight randomised controlled trials published before August 2015. Five trials were included from an original 2010 review along with three new trials. All trials were carried out in the era in which stents were being used.

The review included 8,915 adults with either an episode of unstable angina, increasing level of resting pain, or tests indicating heart muscle damage without ST elevation on the ECG.

Half of the participants received a conservative management approach whilst the other half received the routine invasive approach.

There were differences in the trials in the time between randomisation and coronary angiography in the routine invasive group, between an average of six hours and four days. Participants varied per study, with some only including people over the age of 65.

What did it find?

At six to 12 months follow up the following events occurred.

  • There was no difference in death from any cause at six to 12 months, with 36 deaths per 1,000 people in the routine invasive approach compared to 42 deaths per 1,000 people for the conservative approach (RR 0.87, 95% CI 0.64 to 1.18).
  • The routine invasive strategy did not appreciably reduce the risk of myocardial infarction at six to 12 months, with 62 episodes per 1,000 people versus 78 per 1,000 people in the conservative strategy (relative risk [RR] 0.79, 95% confidence interval [CI] 0.63 to 1.00) technically a non-significant difference.
  • There were fewer re-hospitalisations with the invasive strategy, 220 per 1,000 people versus 286 per 1,000 people in the conservative strategy (RR 0.77, 95% CI 0.63 to 0.94).
  • The routine invasive strategy increased the risk of bleeding as a complication of investigation or treatment, 42 per 1,000 invasive versus 72 per 1,000 (RR 1.73, 95% CI 1.30 to 2.31) and procedure-related myocardial infarction, at 30 per 1,000 conservative versus 57 per 1,000 in the invasive approach (RR 1.87, 95% CI 1.47 to 2.37).

What does current guidance say on this issue?

NICE’s 2013 guidance on early management of unstable angina and NSTEMI provides recommendations for conservative management and early invasive management. It recommends conservative management without early coronary angiography for patients with a low risk of adverse cardiovascular events (a predicted six-month death of less than 3.0% on GRACE).

The early invasive approach of coronary angiography is recommended within 96 hours of hospital admission for people who have a moderate to high risk of adverse cardiovascular events (a predicted six-month death above 3.0%) and no contraindications. This strategy is also recommended for people initially assessed as at low risk of adverse cardiovascular events if there is ongoing chest pain or evidence of cardiac ischaemia demonstrated on exercise stress testing.

What are the implications?

When looking at a follow up of six to 12 months, this Cochrane review provides evidence that in people with unstable angina and NSTEMI the choice of approach is finely balanced. The authors suggest that the benefits may be more meaningful in a higher risk group and routine invasive approach may be the preferred management strategy for this group.

It is possible that recent changes in therapies or techniques at the time or angioplasty might further reduce the risk of bleeding and tip the balance in favour of invasive treatments for lower risk patients. Careful risk-based patient selection and discussion of possible harms will remain important.

There are resource implications to changing practice including increased availability of angiography and cardiac interventions out of hours. From a system perspective this added cost might be offset by a reduced re-hospitalisation rate.

Citation and Funding

Fanning JP, Nyong J, Scott IA, et al. Routine invasive strategies versus selective invasive strategies for unstable angina and non-ST elevation myocardial infarction in the stent era. Cochrane Database Syst Rev. 2016;(5):CD004815.

This project was funded by The Prince Charles Hospital Foundation, Australia, The University of Queensland Australia and The Cardiac Society of Australia and New Zealand.

Bibliography

NICE. Unstable angina and NSTEMI: early management. CG94. London. National Institute of Health and Care Excellence; 2013.

MINAP. Myocardial Ischaemia National Audit Project: How the NHS cares for patients with heart attack. Annual Public Report April 2013-2014. London: Myocardial Ischaemia National Audit Project; 2014.

Routine invasive strategies versus selective invasive strategies for unstable angina and non-ST elevation myocardial infarction in the stent era

Published on 27 May 2016

Fanning, J. P.,Nyong, J.,Scott, I. A.,Aroney, C. N.,Walters, D. L.

Cochrane Database Syst Rev Volume 5 , 2016

BACKGROUND: People with unstable angina and non-ST elevation myocardial infarction (UA/NSTEMI) are managed with a combination of medical therapy, invasive angiography and revascularisation. Specifically, two approaches have evolved: either a 'routine invasive' strategy whereby all patients undergo coronary angiography shortly after admission and, if indicated, coronary revascularisation; or a 'selective invasive' (also referred to as 'conservative') strategy in which medical therapy alone is used initially, with a selection of patients for angiography based upon evidence of persistent myocardial ischaemia. Uncertainty exists as to which strategy provides the best outcomes for these patients. This Cochrane review is an update of a Cochrane review originally published in 2006, to provide a robust comparison of these two strategies in the early management of patients with UA/NSTEMI. OBJECTIVES: To determine the benefits and harms associated with the following.1. A routine invasive versus a conservative or 'selective invasive' strategy for the management of UA/NSTEMI in the stent era.2. A routine invasive strategy with and without glycoprotein IIb/IIIa receptor antagonists versus a conservative strategy for the management of UA/NSTEMI in the stent era. SEARCH METHODS: We searched the following databases and additional resources up to 25 August 2015: the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library, MEDLINE and EMBASE, with no language restrictions. SELECTION CRITERIA: We included prospective randomised controlled trials (RCTs) that compared invasive with conservative or 'selective invasive' strategies in participants with acute UA/NSTEMI. DATA COLLECTION AND ANALYSIS: Two review authors screened the records and extracted data in duplicate. Using intention-to-treat analysis with random-effects models, we calculated summary estimates of the risk ratio (RR) with 95% confidence intervals (CIs) for the primary endpoints of all-cause death, fatal and non-fatal myocardial infarction (MI), combined all-cause death or non-fatal MI, refractory angina and re-hospitalisation. We performed further analysis of included studies based on whether glycoprotein IIb/IIIa receptor antagonists were used routinely. We assessed the heterogeneity of included trials using Pearson chi(2) (Chi(2) test) and variance (I(2) statistic) analysis. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and the GRADE profiler (GRADEPRO) was used to import data from Review Manager 5.3 (Review Manager) to create Summary of findings (SoF) tables. MAIN RESULTS: Eight RCTs with a total of 8915 participants (4545 invasive strategies, 4370 conservative strategies) were eligible for inclusion. We included three new studies and 1099 additional participants in this review update. In the all-study analysis, evidence did not show appreciable risk reductions in all-cause mortality (RR 0.87, 95% CI 0.64 to 1.18; eight studies, 8915 participants; low quality evidence) and death or non-fatal MI (RR 0.93, 95% CI 0.71 to 1.2; seven studies, 7715 participants; low quality evidence) with invasive strategies compared to conservative (selective invasive) strategies at six to 12 months follow-up. There was appreciable risk reduction in MI (RR 0.79, 95% CI 0.63 to 1.00; eight studies, 8915 participants; moderate quality evidence), refractory angina (RR 0.64, 95% CI 0.52 to 0.79; five studies, 8287 participants; moderate quality evidence) and re-hospitalisation (RR 0.77, 95% CI 0.63 to 0.94; six studies, 6921 participants; moderate quality evidence) with routine invasive strategies compared to conservative (selective invasive) strategies also at six to 12 months follow-up.Evidence also showed increased risks in bleeding (RR 1.73, 95% CI 1.30 to 2.31; six studies, 7584 participants; moderate quality evidence) and procedure-related MI (RR 1.87, 95% CI 1.47 to 2.37; five studies, 6380 participants; moderate quality evidence) with routine invasive strategies compared to conservative (selective invasive) strategies.The low quality evidence were as a result of serious risk of bias and imprecision in the estimate of effect while moderate quality evidence was only due to serious risk of bias. AUTHORS' CONCLUSIONS: In the all-study analysis, the evidence failed to show appreciable benefit with routine invasive strategies for unstable angina and non-ST elevation MI compared to conservative strategies in all-cause mortality and death or non-fatal MI at six to 12 months. There was evidence of risk reduction in MI, refractory angina and re-hospitalisation with routine invasive strategies compared to conservative (selective invasive) strategies at six to 12 months follow-up. However, routine invasive strategies were associated with a relatively high risk (almost double the risk) of procedure-related MI, and increased risk of bleeding complications. This systematic analysis of published RCTs supports the conclusion that, in patients with UA/NSTEMI, a selectively invasive (conservative) strategy based on clinical risk for recurrent events is the preferred management strategy.

People with prolonged or recurrent chest pain may have a condition called unstable angina or suffer a certain type of heart attack called non-ST elevation myocardial infarction (NSTEMI) signifying damage to the heat muscle but not complete blockage.

People with either of these two conditions have treatment options. One of two treatment strategies are often considered:

  • The routine invasive strategy. In this approach patients have a catheter (a long tube) inserted into the arteries that bring blood to the heart muscle. The main objective behind inserting this catheter is to look for thickening and hardening of the vessel. If a significant narrowing is found, then the narrow artery may be opened by inflating a balloon catheter to open the vessel and improve blood flow. The vessel is held open by inserting a metallic stent. In some cases, the region of vessel narrowing is not amenable to this approach and surgery to bypass it is required.
  • The conservative or ’selective invasive strategy’. For this strategy, patients are initially treated with drugs, and only those who continue to suffer further chest pain or who demonstrate evidence of ongoing coronary artery narrowing via other non-invasive tests, undergo coronary angiography and revascularisation if indicated.

Revascularisation interventions included percutaneous coronary intervention or coronary artery bypass graft (CABG), dependant on the angiographic findings.

Prediction of death within six months is calculated using risk scoring systems such as the Global Registry of Acute Cardiac Events (GRACE). This system combines age, clinical history, blood pressure, heart rate, ECG findings and various blood test results. A score of less than 3% is considered low risk, 3% to 6% intermediate risk and more than 6% high risk.

Expert commentary

Routine invasive strategy reduces repeat myocardial infarction, refractory angina and rehospitalisation compared to a conservative (selective invasive) strategy, with a trend to also decreasing all-cause mortality after a short period of follow-up. The authors conclude that a conservative strategy is preferable because a routine invasive strategy will expose more patients to the risks of intervention. However, this risk is incidentally diminishing with evolving practice, e.g. through the use of radial access. But the invasive approach improves patient outcomes and diminishes readmission which also has an economic impact not addressed by this meta-analysis.

Dr Stephen Hoole, Consultant Interventional Cardiologist, Papworth Hospital NHS Foundation Trust, Cambridge