More than 10,000 patients worldwide have completed clinical trials involving RIC, and another 20,000 are enrolled in ongoing trials. The first human clinical trial of RIC was conducted by Dr. Redington in pediatric patients undergoing heart surgery at the Hospital for Sick Children. The patients treated with RIC prior to surgery exhibited less heart damage, as measured by the biomarker troponin, as well as less need for supportive drugs. This trial was followed by others measuring the effects of RIC on rates and outcomes of heart attacks, heart failure, stroke, and cardiothoracic intervention. Heart attacks In multiple randomized controlled trials,<unk>  reduced infarct size in ST-elevation myocardial infarction (STEMI) patients when used in the ambulance or emergency department as an adjunct therapy to primary percutaneous coronary intervention (PCI), or when used with thrombolytic drugs. In seven trials comprising 2,372 STEMI patients, infarct size—a measure of damage to the heart—was reduced by 17–30% on average, and the reduction was greatest (~60%) in the largest infarcts. Further analysis of a Danish study (CONDI-1), in which patients were treated in the ambulance, showed that those who received RIC did not show a decline in myocardial salvage index (a measure of a healthy heart) when they experienced a delay in treatment, while the control group experienced a significant decline in salvage index. The RIC treatment therefore resulted, effectively, in an extension of the "golden hour", the period in which medical treatment for heart attacks is most effective. Infarct size is a predictor of future cardiovascular events as well as mortality, and researchers doing long-term follow-up on STEMI patients treated with RIC found that the reduction in heart damage at the time of the heart attack resulted in clinical improvement four years later: MACCE (major adverse cardiovascular and cerebrovascular event) rates were reduced by 47% (13.5% vs. 25.6%, p=0.018). This improvement resulted in mean cumulative cardiovascular medical care costs that were €2,763 lower in the RIC-treated group than in the control group (€12,065 vs. €14,828)—savings of approximately 20%. There are currently two large randomized controlled trials of RIC treatment in STEMI patients ongoing in Europe, both of which will examine the effects of RIC treatment on coronary death and hospitalization for heart failure after one year. Percutaneous coronary intervention<unk>  significantly reduced heart damage (as measured by troponin elevations) in four randomized controlled trials involving 816 elective (non-emergency) PCI patients. The myocardial damage and troponin elevations seen in elective PCI patients are less than that in emergency STEMI patient, because there is less acute reperfusion injury in elective PCI, and damage instead results from distal embolization and side-branch occlusion. Nevertheless, myocardial damage during elective PCI remains a significant predictor of morbidity and mortality, as patients exhibiting any increase in troponin are at a significantly increased risk of future cardiovascular events. Researchers at Papworth Hospital in Cambridge conducted the first large study of RIC in elective PCI patients (the CRISP study) and found that patients treated with RIC prior to stenting showed a 62% reduction in troponin levels, less chest discomfort, and reduced six-month hospitalization rates. Long-term follow-up of the CRISP study showed that this single RIC treatment resulted in a 35% reduction in six-year MACCE rates. Cardiac and oncological imaging RIC has been shown to reduce Contrast-induced nephropathy (CIN) and contrast-induced acute kidney injury (CI-AKI), two serious complications that can occur when patients are given contrast media during imaging or invasive procedures such as angioplasty or percutaneous aortic valve replacement. The incidence of CIN is 13% in an unselected population and can be as much as 57% in patients with poor kidney function and congestive heart failure. The development of CIN after percutaneous coronary intervention is independently associated with an increased risk of short- and long-term<unk>  and hemorrhagic events. RIC provided a statistically significant benefit in five randomized clinical trials comprising 480 patients. The first report was in an observational study of patients in the United States, and the first randomized clinical trial to show a benefit in patients at extremely high risk of injury (those with Stage 3 or 4 kidney disease, diabetes, or heart failure) was done in Germany. The German study showed a reduced incidence of CIN (a 70% reduction, from 40% to 12%, p=0.002), with no patients in the treated arm needing in-hospital dialysis (compared with 14% in the control group), and reduced six-week readmission rates (a 60% reduction, from 36% to 14%). Similar protection was seen in cancer patients undergoing contrast-enhanced computed tomography (CECT): Researchers found a 35% reduction in CIN across the population, and the patients at highest risk benefited the most, with a 60% reduction. These results, confirmed in subsequent clinical trials involving cardiac patients, show that RIC can protect the kidneys as well as the heart. Coronary surgery Yetgin and colleagues conducted a systematic review and analysis of RIC in cardiac surgery, examining thirteen trials involving 891 patients, and found that RIC treatment reduced troponin levels by 21% to 49%. In addition, they concluded that trials in which the primary measure was a validated biomarker (e.g., 72-hour cardiac troponin AUC) showed a benefit from RIC treatment, while trials in which a non-validated biomarker (e.g., 24-hour troponin AUC) was the primary measure did not show a benefit. In the first prospectively designed trial to examine the effect of RIC on clinical outcomes in coronary artery bypass grafting (CABG), Thielmann and colleagues showed that RIC treatment reduced troponin levels and improved long-term morbidity and mortality. However, while patients who received the anesthetic isoflurane benefited from the treatment, the anesthetic propofol blocked the effects of RIC. Investigations in Dr. Gerd Heusch's lab showed that propofol abolishes the phosphorylation of STAT5, a key survival molecule that is activated by RIC. Two other trials in CABG surgery (ERICCA and RIP-HEART) reported neutral results for the clinical benefit of RIC, but both of these trials used propofol as the initiating anesthetic. In a viewpoint letter that followed the publication of the ERICCA and RIP-HEART trials, Heusch and Dr. Bernard Gersh wrote that the use of propofol rather than volatile anesthesia appeared to be a common denominator in all studies that failed to find protection with RIC. A 2015 trial in high-risk CABG patients showed a reduced incidence of surgical acute kidney injury in RIC-treated patients (37.5% vs. 52.5%, p=0.02), a reduced need for dialysis, and shorter stays in the intensive care unit. This study did not use propofol, and a three-month follow-up found that RIC treatment improved clinical outcomes.
Remote ischemic conditioning
Transmyocardial revascularization
Ischemic preconditioning
Pericardial window
Cardiomyoplasty
Vagal maneuver
Hybrid coronary revascularization
Graded exercise therapy