Effect of remote ischemic preconditioning in patients with STEMI during primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials

Reviews in Cardiovascular Medicine  2020, Vol. 21 Issue (1): 103-112     DOI: 10.31083/j.rcm.2020.01.10 Effect of remote ischemic preconditioning in patients with STEMI during primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials En Chen1, Wei Cai1, Danqing Hu1, Lianglong Chen1, *() 1 Department of Cardiology, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fujian Institute of Coronary Artery Disease, Fujian Institute of Geriatrics, Fujian,
350001, P. R. China Abstract:

Remote ischemic conditioning is usually associated with cardioprotective intervention against ischemia-reperfusion. However, the effect of remote ischemic preconditioning (RIC-pre) completed before myocardial reperfusion with intermittent limb ischemia-reperfusion in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) is unclear. PubMed, EMBASE, and the Cochrane Library were fully searched from the beginning of each database up to September 2019 to find seven RCTs, a total of 2796 patients with STEMI undergoing PPCI with RIC-pre and 2818 patients with STEMI undergoing PPCI alone. No significant discrepancy in cardiac death was observed between RIC-pre and control groups (RR 1.03, 95% CI [0.76-1.41], P = 0.83, I2 = 40%). The incidences of hospitalization for heart failure (RR 1.03, 95% CI [0.85-1.25], P = 0.77, I2 = 0%), myocardial infarction (RR 0.86, 95% CI [0.59-1.26], P = 0.44, I2 = 0%), and stroke (RR 1.04, 95% CI [0.62-1.77], P = 0.87, I2 = 0%) were not decreased in RIC-pre group when compared with control group. Subgroup analysis revealed similar risk in clinical adverse events at long- and short-term follow-up between two groups. However, peak of creatine kinase-myocardial band (CK-MB) was reduced in RIC-pre group (SWD -0.42, 95% CI [-0.77, -0.07], P = 0.02, I2 = 34%). RIC-pre tended to a low peak of CK-MB in patients with STEMI undergoing PPCI, but lacked significant beneficial effects on improving clinical outcomes at long- and short-term follow-up.

Submitted:  02 February 2020      Accepted:  10 March 2020      Published:  30 March 2020      Fund: 
81370311/National Natural Science Foundation of China
81670332/National Natural Science Foundation of China
2016Y9030/Scientific and Technological Innovation Project of Fujian Province *Corresponding Author(s):  Lianglong Chen     E-mail:  lianglongchenfj@126.com Service E-mail this article Add to citation manager E-mail Alert RSS Articles by authors En Chen    Wei Cai    Danqing Hu    Lianglong Chen   

Figure 1.  Flow diagram showing the process of study selection including eligibility against the inclusion and exclusion criteria set out in the methods section of this meta-analysis. The number of studies is the bottom of the flowchart was the selected studies that were considered eligible for inclusion in this meta-analysis.


Figure 2.  The quality of included randomized controlled trials shows the risks of bias, including random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias.


Figure 3.  A forest plots represents the statistical effect of clinical outcomes in the follow up time between the RIC-pre and the control group, including cardiac death, hospitalization for heart failure, myocardial infarction and stroke.


Figure 4.  Subgroup analysis according to the time of follow-up (long-term vs. short-term) on cardiac death, hospitalization for heart failure, myocardial infarction and stroke between the RIC-pre and the control groups.


Figure 5.  A forest plots represents the statistical effect of EF after procedure and the peak of CK-MB between the RIC-pre and the control groups. Abbreviation: CK-MB: creatine kinase-myocardial band; EF: ejection fraction

Table 1.  Characteristics of the 7 included studies.

StudyYear of publicationRegionFollow-upRIC-preControlRIC protocolMain findings( RIC-pre group vs. Control group)Bøtker2010Denmark30
days126125Intermittent arm ischemia through four cycles of 5-min in?ation and 5-min de?ation of a blood-pressure cuffMyocardial salvage index: 0.75 (0.50-0.93) vs. 0.55 (0.35-0.88), P = 0.0333; Final infarction size (% of left ventricle): 4% (1-14) vs. 7% (1-21), P = 0.10Hausenloy2019UK, Denmark, Spain, Serbia12 months25462569Applying to the arm through four alternating cycles of cuff inflation for 5 min to 200 mm Hg and deflation for 5 minCardiac death 3.1% vs. 2.7%, P = 0.46; Hospitalization for heart failure 7.6% vs 7.1%, P = 0.55Liu2016China12 months5960Four cycles inflating a pneumatic cuff above the upper arm to 200 mm Hg for 5 min and then followed by a 5-min deflationMyocardial infarction size (% left ventricle): 14.2 ± 6.1 vs. 16.6 ± 6.7, P = 0.042; MACCE: 5.1% vs. 13.3%, P = 0.116Munk2010Denmark30 days123119Intermittent arm ischemia through four cycles of 5-min in?ation and 5-min de?ation of a blood-pressure cuffMyocardial area at risk % left ventricle: 26 ± 14% vs. 27 ± 16%, P = 0.9; EF:54 ± 8% vs. 53 ± 10%, P = 0.42Prunier2014France3 days1817Three cycles of 5-min inflation to 200 mmHg and 5-min deflation of an upper arm blood-pressure cuff inflation to 200 mmHg and 5-min deflation of an upper armPeak of CK-MB (U/L): 267 ± 168 vs. 415 ± 195, P = 0.016Sloth2013Denmark5 years126125Intermittent arm ischemia through four cycles of 5-min in?ation and 5-min de?ation of a blood-pressure cuffMACCE: 13.5% vs. 25.6%, P = 0.018; All-cause mortality:4% vs. 12%, P = 0.027Yamanaka2015Japan30 days4747Three cycles of the upper arm achieved by 5 min cuff inflation at 200 mm Hg followed by 5 min of complete cuff deflationMACCE:4% vs. 14%, P = 0.07; Peak of CK-MB(IU/L): 238 ± 159 vs. 303 ± 267, P = 0.15

Table 2.  Clinical baseline characteristics of 7 included studies (RIC-pre/Control).

StudyYear of publicationAgeMale(%)Diabetes
(%)Hypertension (%)Smoker(%)Hypercholeste
rolemia (%)Symptom to balloon time, minInfarct-related coronary artery(non-LAD,%)Occluded vessel on arrival TIMI 0-1,(%)Bøtker201062 ± 12/63 ± 1176.0/75.09.0/9.038.0/24.056.0/57.015.0/19.0190 (134-305)/188 (134-309)61.0/57.056.0/61.0Hausenloy201963.9 ± 12.1/63.1 ± 12.276.0/77.611.9/10.443.7/40.140.5/40.928.0/27.2178 (130-278)/177 (128-279)59.1/56.973.7/74.8Liu201662.1 ± 12.1/62.6 ± 11.976.3/81.720.3/20.045.8/40.039.0/46.732.2/28.3420 ± 174/402 ± 15652.5/58.366.1/75.0Munk201062 ± 11/62 ± 1177.0/78.09.0/8.038.0/24.056.0/57.015.0/18.0190 (134-304)/185 (129-299)62.0/58.058.0/61.0Prunier201466.1 ± 16.2/61.7 ± 14.078.0/76.011.0//12.050.0/41.022.0/47.033.0/35.0227 ± 103/241 ± 7561.0/59.0NA/NASloth201362 ± 12/63 ± 1176.0/75.09.0/9.038.0/24.056.0/57.015.0/19.0190 (134-305)/188 (134-309)61.0/57.056.0/61.0Yamanaka201567 ± 12/67 ± 1576.0/76.031.0/37.061.0/65.059.0/51.051.0/53.0326 ± 278/360 ± 27460.0/56.0NA/NA [1] Bahr Hosseini, M.,Hou, J.,Bikson, M.,Iacoboni, M.,Gornbein, J. and Saver, J. L. 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