Does intra-aortic balloon support for myocardial infarction with cardiogenic shock improve outcome?

Expanded abstract Citation Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, Richardt G, Hennersdorf M, Empen K, Fuernau G, Desch S, Eitel I, Hambrecht R, Fuhrmann J, Böhm M, Ebelt H, Schneider S, Schuler G, Werdan K; IABP-SHOCK II Trial Investigators: Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012, 367:1287-1296. Background In the current international guidelines, intra-aortic balloon pump (IABP) counterpulsation is considered a class I treatment for acute myocardial infarction complicated by cardiogenic shock. However, evidence is based mainly on registry data, and there is a paucity of randomized clinical trials. Methods Objective To test the hypothesis that IABP counterpulsation, as compared with the best available medical therapy alone, results in a reduction in mortality among patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization is planned. Design Randomized, prospective, open-label, multicenter trial. Setting Thirty-seven centers in Germany. Subjects All adults had acute myocardial infarction complicated by cardiogenic shock and were expected to undergo early revascularization (by means of percutaneous coronary intervention or bypass surgery). Intervention After enrollment, 600 patients were randomly assigned to intra-aortic balloon counterpulsation (IABP group, 301 patients) or no IABP counterpulsation (control group, 299 patients). Outcomes The primary efficacy endpoint is 30-day all-cause mortality. Results At 30 days, 119 patients in the IABP group (39.7%) and 123 patients in the control group (41.3%) had died (relative risk with IABP, 0.96; 95% confidence interval, 0.79 to 1.17; P = 0.69). There were no significant differences in secondary endpoints or in process-of-care measures, including the time to hemodynamic stabilization, the length of stay in the intensive care unit, serum lactate levels, the dose and duration of catecholamine therapy, and renal function. Conclusions The use of IABP counterpulsation did not significantly reduce 30-day mortality in patients with acute myocardial infarction complicated by cardiogenic shock for whom an early revascularization strategy was planned.


Background
In the current international guidelines, intra-aortic balloon pump (IABP) counterpulsation is considered a class I treatment for acute myocardial infarction complicated by cardiogenic shock. However, evidence is based mainly on registry data, and there is a paucity of randomized clinical trials.

Methods
Objective: To test the hypothesis that IABP counterpulsation, as compared with the best available medical therapy alone, results in a reduction in mortality among patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization is planned. Design: Randomized, prospective, open-label, multicenter trial. Setting: Th irty-seven centers in Germany. Subjects: All adults had acute myocardial infarction complicated by cardiogenic shock and were expected to undergo early revascularization (by means of percutaneous coronary intervention or bypass surgery).

Results
At 30 days, 119 patients in the IABP group (39.7%) and 123 patients in the control group (41.3%) had died (relative risk with IABP, 0.96; 95% confi dence interval, 0.79 to 1.17; P = 0.69). Th ere were no signifi cant diff erences in secondary endpoints or in process-of-care measures, including the time to hemodynamic stabilization, the length of stay in the intensive care unit, serum lactate levels, the dose and duration of catecholamine therapy, and renal function.

Conclusions
Th e use of IABP counterpulsation did not signifi cantly reduce 30-day mortality in patients with acute myocardial infarction complicated by cardiogenic shock for whom an early revascularization strategy was planned.

Commentary
Cardiogenic shock complicates 7% to 10% of patients with acute myocardial infarction and carries a mortality rate approaching 70% to 80% [1]. Intra-aortic balloon pump (IABP) counterpulsation has been used routinely as an adjuvant treatment for myocardial infarction compli cated by cardiogenic shock on the basis of evidence that it is associated with hemodynamic improvements [2]. Given the lack of randomized clinical trials, recommendations for adjunctive therapy in this high-risk population have been based only on pathophysiological assumptions and expert opinion.
An IABP is a device placed in the descending thoracic aorta that infl ates with diastole, increasing upstream coronary perfusion, and that defl ates with systole, decreas ing left ventricular (LV) afterload and, in turn, overall myocardial oxygen demand for a given cardiac output in the setting of cardiogenic shock. Th e use of IABPs as a bridge to support LV function originated in the 1960s, when coronary artery bypass surgery was just becoming available. Today, IABP counterpulsation is considered one of the most widely used mechanical assist devices in hemodynamically unstable cardiac patients.
Th e international guidelines endorsed the use of IABP in treating cardiogenic shock post-myocardial infarction with class 1 recommendation [3,4], despite the lack of adequately powered randomized trials and the recent metaanalysis data that show limited effi cacy of IABP use [5].
Th e Intra-aortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial was a prospective multicenter randomized trial conducted at 37 German medical centers over a 3-year period. Six hundred patients with acute myocardial infarction complicated by cardiogenic shock were randomly assigned in a 1:1 ratio to either IABP or no IABP. Th ere were no signifi cant diff erences between the groups in terms of baseline characteristics or clinical course before random assignment. Th e major outcome was 30-day all-cause mortality. At 30 days, there was no signifi cant diff erence in relative risk for death between the two groups (relative risk of death with IABP, 0.96; 95% confi dence interval, 0.79 to 1.17; P = 0.69). Th ere were no signifi cant diff erences in secondary endpoints and process-of-care outcomes (that is, lactate, C-reactive protein levels, renal function, and Simplifi ed Acute Physiology Score II). Importantly, IABP was not associated with any signifi cant increase in adverse events, including similar rates of reinfarction, stent thrombosis, bleeding, sepsis, or stroke. Th is multicenter randomized controlled study was well designed in the setting of cardiogenic shock with excellent recruitment of subjects based on eligibility.
However, general issues with this trial deserve consideration. Th e control and IABP groups had similar low mortality rates of 40% compared with previous registries and randomized clinical trials, which reported mortality rates of over 65%. Th is suggests that the patients studied in this trial had less severe cardiovascular de com pen sa tion and may not represent the highest-risk patient cohort with severe cardiogenic shock. Second, there was crossover of 10% of the control group to IABP therapy and a more frequent use of left ventricular assist devices (LVADs) in control patients (7.4% versus 3.7%), and both of these factors might decrease the control group mortality if IABP and LVAD use is benefi cial. Th ird, the timing of IABP insertion was not controlled for. Fourth, the study reports only short-term results. Clearly, cardiac mortality is best assessed by 6-and 12-month mortality rates, if not longer. For example, the SHOCK trial did not show survival diff erences at 30 days but did see a survival benefi t at 6 months [6]. Th ose longer-term results from this trial are needed to confi rm the neutral eff ect of IABP treatment.

Recommendation
In view of the lack of prior controlled clinical trials or other convincing evidence, this study challenges the current level I guideline recommendations for the use of IABP counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock. In this setting, the routinely used IABP counterpulsation need not be the default therapeutic approach.