Abstract
To test whether remote ischaemic conditioning (RIC) as adjuvant to standard of care (SOC) would prevent progression towards heart failure (HF) after ST-elevation myocardial infarction (STEMI). Single-centre parallel 1:1 randomized trial (computerized block-randomization, concealed allocation) to assess superiority of RIC (3 cycles of intermittent 5 min lower limb ischaemia) over SOC in consecutive STEMI patients (NCT02313961, clinical trials.gov). From 258 patients randomized to RIC or SOC, 9 and 4% were excluded because of unconfirmed diagnosis and previously unrecognized exclusion criteria, respectively. Combined primary outcome of cardiac mortality and hospitalization for HF was reduced in RIC compared with SOC (n = 231 and 217, respectively; HR = 0.35, 95% CI 0.15–0.78) as well as each outcome in isolation. No difference was found in serum troponin I levels between groups. Median and maximum follow-up time were 2.1 and 3.7 years, respectively. In-hospital HF (RR = 0.68, 95% CI 0.47–0.98), need for diuretics (RR = 0.68, 95% CI 0.48–0.97) and inotropes and/or intra-aortic balloon pump (RR = 0.17, 95% CI 0.04–0.76) were decreased in RIC. On planned 12 months follow-up echocardiography (n = 193 and 173 in RIC and SOC, respectively) ejection fraction (EF) recovery was enhanced in patients presenting with impaired left ventricular (LV) function (10% absolute difference in median EF compared with SOC; P < 0.001). In addition to previously reported improved myocardial salvage index and reduced infarct size RIC was shown beneficial in a combined hard clinical endpoint of cardiac mortality and hospitalization for HF. Improved EF recovery was also documented in patients with impaired LV function.
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Abbreviations
- ACEi/ARB:
-
Angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker
- AUC:
-
Area under the curve
- BMI:
-
Body mass index
- BP:
-
Blood pressure
- CABG:
-
Coronary artery bypass grafting
- CI:
-
Confidence intervals
- CIN:
-
Contract-induced nephropathy
- CRT:
-
Cardiac resynchronization therapy
- EF:
-
Ejection fraction
- HB:
-
Hospital de Braga
- HF:
-
Heart failure
- HR:
-
Hazard ratio
- IABP:
-
Intra-aortic balloon pump
- ICD:
-
Implantable cardioverter–defibrillator
- IHD:
-
Ischaemic heart disease
- IRI:
-
Ischaemia–reperfusion injury
- ITT:
-
Intention-to-treat
- LV:
-
Left ventricle
- MACCE:
-
Major adverse cardiovascular and cerebrovascular events
- MI:
-
Myocardial infarction
- PCI:
-
Percutaneous coronary intervention
- RCT:
-
Randomized controlled trial
- RIC:
-
Remote ischaemic conditioning
- RR:
-
Risk ratio
- SOC:
-
Standard of care
- STEMI:
-
ST-elevation myocardial infarction
- TIMI:
-
Thrombolysis in myocardial infarction study group grading of coronary flow
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Acknowledgements
We would like to thank all the nurses and interventional cardiologists engaged in the study at Hospital de Braga.
Funding
This work was supported by the Portuguese Foundation for Science and Technology (Projects PEst-C/SAU/UI0051/2011 and EXCL/BIM-MEC/0055/2012) through the Cardiovascular R&D Unit, by the European Commission Grant FP7-Health-2010 (MEDIA-261,409) and by Project DOCnet (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). European Structural and Investment Funds (ESIF), under Lisbon Portugal Regional Operational Programme and National Funds through Foundation for Science and Technology under project POCI-01-0145-FEDER-016385. This work was supported by a grant from José de Mello Saúde.
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A comment to this article is available at https://doi.org/10.1007/s00395-018-0673-2.
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Gaspar, A., Lourenço, A.P., Pereira, M.Á. et al. Randomized controlled trial of remote ischaemic conditioning in ST-elevation myocardial infarction as adjuvant to primary angioplasty (RIC-STEMI). Basic Res Cardiol 113, 14 (2018). https://doi.org/10.1007/s00395-018-0672-3
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DOI: https://doi.org/10.1007/s00395-018-0672-3