Remote Ischaemic Postconditioning
Objective Determine whether remote ischaemic postconditioning (RIP) protects against percutaneous coronary intervention-related myocardial infarction (PCI-MI).
Design Single-centre, randomised, blinded to the researchers, clinical trial. ClinicalTrials.gov (NCT 01113008).
Setting Tertiary hospital centre.
Patients 232 patients underwent elective PCI for stable or unstable angina.
Interventions Patients were randomised to RIP (induction of three 5-min cycles of ischaemia in the arm after the PCI) versus placebo.
Main outcome measures The primary outcome measure was the peak 24-h troponin I level. PCI-MI was defined by an elevation of troponin values >3 or >5 of the 99th percentile according to the classical or the new definition. The secondary outcome measure was hospital admission, PCI for stable angina or acute coronary syndrome and mortality after 1 year of follow-up. The use of RIP in diabetic patients was specifically studied.
Results The mean age was 64.6 years, and 42% were diabetic. The peak troponin in the RIP patients was 0.476 vs 0.478 ng/mL (p=0.99). PCI-MI occurred in 36% of the RIP patients versus 30.8% in the placebo group (p=0.378). Diabetic RIP patients had more PCI-MI (new definition): OR 2.7; 95% CI 1.10 to 6.92; p=0.027. The secondary outcome measure was seen in 11.7% of the RIP patients versus 10.8% in the placebo group (p=0.907).
Conclusions RIP did not reduce the damage associated with elective PCI or cardiovascular events during the follow-up. The diabetic population who underwent RIP had more PCI-MI.
Ischaemic heart disease is one of the main causes of death in industrialised countries. Percutaneous coronary intervention (PCI) is a very efficient therapeutic approach for this disease, particularly in patients with acute coronary syndrome. However, PCI in patients with stable coronary disease has failed to show any clear improvement in the prognosis of the heart disease over and above that already achieved with medical therapy. This may, at least in part, be explained by the myocardial damage associated with the procedure (periprocedural myocardial injury, PMI); myocardial damage, as evidenced by postprocedural measurement of troponins, occurs in up to 30% of cases. PMI seems to be associated with an unfavourable late clinical course, and even greater mortality.
Much interest now surrounds PMI as various different strategies have been identified that could limit its extent. Some of these seek to stimulate the innate mechanisms of cell protection and are based on the concept of ischaemic preconditioning, which involves brief episodes of non-lethal ischaemia reperfusion applied to an organ or tissue and that confers this with a certain degree of protection against another sustained episode of a lethal ischaemia-reperfusion injury. These brief episodes of ischaemia, given before, during or even after the myocardial ischaemic insult (preconditioning, periconditioning or postconditioning, respectively), are applied to the ischaemic myocardium itself or to a distant tissue (remote conditioning). Thus, remote ischaemic preconditioning (application of controlled cycles of ischaemia in the limbs before performing coronary angioplasty) appears to reduce the myocardial damage in patients who undergo elective PCI. Remote postconditioning may be of greater clinical applicability as it is simple to administer. Though favourable results have been reported in experimental animal studies, remote ischaemic postconditioning (RIP) has not yet been evaluated in humans.
Diabetes mellitus is a risk factor with an increasing incidence and a negative prognosis for patients who undergo PCI. These patients benefit from particular treatment strategies that are generally more aggressive. In addition, diabetic patients seem to behave differently to the phenomena of conditioning. Diabetes mellitus may affect the mechanisms for cell protection against ischaemia, reducing the protective effect attributed to ischaemic conditioning.
The aim of this study, which used a harmless and simple protocol, was to assess for the first time in humans the effect of RIP on the PMI of persons undergoing elective PCI. Special attention was given to the diabetic patients. The primary endpoint was to determine whether an RIP protocol reduced the myocardial damage associated with the RIP measured by the maximum elevation of troponin I during the first 24 h as compared with a control group.
The secondary endpoint was the analysis of the clinical course of the patients, recording such data as readmission, new revascularisation due to acute coronary syndrome or stable angina, and mortality at 1 year of follow-up.
Abstract and Introduction
Abstract
Objective Determine whether remote ischaemic postconditioning (RIP) protects against percutaneous coronary intervention-related myocardial infarction (PCI-MI).
Design Single-centre, randomised, blinded to the researchers, clinical trial. ClinicalTrials.gov (NCT 01113008).
Setting Tertiary hospital centre.
Patients 232 patients underwent elective PCI for stable or unstable angina.
Interventions Patients were randomised to RIP (induction of three 5-min cycles of ischaemia in the arm after the PCI) versus placebo.
Main outcome measures The primary outcome measure was the peak 24-h troponin I level. PCI-MI was defined by an elevation of troponin values >3 or >5 of the 99th percentile according to the classical or the new definition. The secondary outcome measure was hospital admission, PCI for stable angina or acute coronary syndrome and mortality after 1 year of follow-up. The use of RIP in diabetic patients was specifically studied.
Results The mean age was 64.6 years, and 42% were diabetic. The peak troponin in the RIP patients was 0.476 vs 0.478 ng/mL (p=0.99). PCI-MI occurred in 36% of the RIP patients versus 30.8% in the placebo group (p=0.378). Diabetic RIP patients had more PCI-MI (new definition): OR 2.7; 95% CI 1.10 to 6.92; p=0.027. The secondary outcome measure was seen in 11.7% of the RIP patients versus 10.8% in the placebo group (p=0.907).
Conclusions RIP did not reduce the damage associated with elective PCI or cardiovascular events during the follow-up. The diabetic population who underwent RIP had more PCI-MI.
Introduction
Ischaemic heart disease is one of the main causes of death in industrialised countries. Percutaneous coronary intervention (PCI) is a very efficient therapeutic approach for this disease, particularly in patients with acute coronary syndrome. However, PCI in patients with stable coronary disease has failed to show any clear improvement in the prognosis of the heart disease over and above that already achieved with medical therapy. This may, at least in part, be explained by the myocardial damage associated with the procedure (periprocedural myocardial injury, PMI); myocardial damage, as evidenced by postprocedural measurement of troponins, occurs in up to 30% of cases. PMI seems to be associated with an unfavourable late clinical course, and even greater mortality.
Much interest now surrounds PMI as various different strategies have been identified that could limit its extent. Some of these seek to stimulate the innate mechanisms of cell protection and are based on the concept of ischaemic preconditioning, which involves brief episodes of non-lethal ischaemia reperfusion applied to an organ or tissue and that confers this with a certain degree of protection against another sustained episode of a lethal ischaemia-reperfusion injury. These brief episodes of ischaemia, given before, during or even after the myocardial ischaemic insult (preconditioning, periconditioning or postconditioning, respectively), are applied to the ischaemic myocardium itself or to a distant tissue (remote conditioning). Thus, remote ischaemic preconditioning (application of controlled cycles of ischaemia in the limbs before performing coronary angioplasty) appears to reduce the myocardial damage in patients who undergo elective PCI. Remote postconditioning may be of greater clinical applicability as it is simple to administer. Though favourable results have been reported in experimental animal studies, remote ischaemic postconditioning (RIP) has not yet been evaluated in humans.
Diabetes mellitus is a risk factor with an increasing incidence and a negative prognosis for patients who undergo PCI. These patients benefit from particular treatment strategies that are generally more aggressive. In addition, diabetic patients seem to behave differently to the phenomena of conditioning. Diabetes mellitus may affect the mechanisms for cell protection against ischaemia, reducing the protective effect attributed to ischaemic conditioning.
The aim of this study, which used a harmless and simple protocol, was to assess for the first time in humans the effect of RIP on the PMI of persons undergoing elective PCI. Special attention was given to the diabetic patients. The primary endpoint was to determine whether an RIP protocol reduced the myocardial damage associated with the RIP measured by the maximum elevation of troponin I during the first 24 h as compared with a control group.
The secondary endpoint was the analysis of the clinical course of the patients, recording such data as readmission, new revascularisation due to acute coronary syndrome or stable angina, and mortality at 1 year of follow-up.