N Engl J Med 2017;377:2419-2432
Background: A small fraction of patients with acute myocardial infarction (5-10%) have cardiogenic shock. These patients have a high baseline mortality. Early revascularization had been established as better than initial stabilization with medical therapy. Many patients with cardiogenic shock due to acute myocardial infarction (AMI) have multivessel disease. The question arises about whether to do culprit-only percutaneous coronary intervention (PCI) or more complete PCI at the time of the initial intervention.
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The Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was designed to test the hypothesis that PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, would result in better clinical outcomes than immediate multivessel PCI among patients who have multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock.
Patients: The trial enrolled 706 patients with acute myocardial infarction (ST-segment elevation or non-ST-segment elevation) complicated by cardiogenic shock who had multivessel coronary artery disease. Cardiogenic shock was defined as SBP < 90 mmHg for more than 30 minutes or requiring pressors, clinical signs of pulmonary congestion, and signs of organ hypoperfusion (altered mental status, cold/clammy skin, oliguria, or lactate > 2 mmol/L).
Exclusion criteria were extensive and designed to exclude patients with extremely poor prognosis: prolonged resuscitation, no intrinsic heart action, fixed dilated pupils, an indication for urgent CABG, a mechanical cause of shock, age > 90 years, massive pulmonary embolism, or severe renal insufficiency at baseline.
Baseline Characteristics: The median age was 70 years, and approximately 75% were male. About 63% of patients had three-vessel disease. More than half the patients had ST-segment elevation myocardial infarction (about 62%), and anterior ST-segment elevation MI accounted for approximately 54% of these cases. About 53% of patients required resuscitation before randomization. The median left ventricular ejection fraction was between 30-33%.
Procedures: In the culprit-lesion-only PCI group, only the culprit lesion was treated during the initial procedure, with staged revascularization encouraged based on residual ischemic lesions. In the multivessel PCI group, PCI of all major coronary arteries with >70% stenosis was performed, including attempts to recanalize chronic total occlusions. Crossover from the culprit-lesion-only PCI group to the multivessel PCI group occurred in 12.5% of patients, while crossover in the opposite direction happened in 9.4% of patients. The overall dose of contrast material was significantly higher and the duration of fluoroscopy significantly longer in the multivessel PCI group. Other interventional therapeutic measures were allowed, independent of the assigned treatment strategy.
Endpoints: The primary endpoint was a composite of death from any cause or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Secondary endpoints included the individual components of the primary endpoint, recurrent myocardial infarction, rehospitalization for heart failure, repeat revascularization, time to hemodynamic stabilization, catecholamine therapy duration, ICU stay duration, and measurements of renal and myocardial injury. Safety end points included bleeding, which was defined as type 2, 3, or 5 on the Bleeding Academic Research Consortium (BARC) scale.
Trialists estimated an event rate of the composite primary endpoint of 38% in the culprit-only group vs 50% in the complete group. Using a global type I error level of 0.05, the authors calculated that a sample of 684 patients would give the trial 80% power to rule out the null hypothesis of no difference between the two treatment groups in the event rate for the primary end point.
Results: At 30 days, the composite primary endpoint occurred in 45.9% of patients in the culprit-lesion-only PCI group versus 55.4% in the multivessel PCI group (relative risk, 0.83; 95% CI, 0.71 to 0.96; P=0.01). Death occurred in 43.3% of the culprit-lesion-only PCI group versus 51.6% of the multivessel PCI group (relative risk, 0.84; 95% CI, 0.72 to 0.98; P=0.03). The rate of renal-replacement therapy was 11.6% in the culprit-lesion-only PCI group and 16.4% in the multivessel PCI group (relative risk, 0.71; 95% CI, 0.49 to 1.03; P=0.07).
Rates of recurrent myocardial infarction, rehospitalization for heart failure, bleeding, and stroke did not differ significantly between groups. Subgroup analyses showed consistent results across all prespecified subgroups. The time to hemodynamic stabilization, the use of catecholamine therapy and the duration of such therapy, the duration of the ICU stay, and the use of mechanical ventilation and the duration of such therapy also did not differ significantly between the two groups.
Conclusion: In patients with myocardial infarction and cardiogenic shock, culprit-only PCI was superior to multivessel PCI. Both components of the primary endpoint, death and severe renal failure were lower in the culprit-only arm.
The authors and editorialists speculate why these findings contrast with trials in hemodynamically stable myocardial infarction patients, where early multivessel PCI showed benefit over culprit-only PCI.
If you accept the thesis that multi-vessel PCI was superior to culprit-only PCI in stable AMI patients, the likely reason for the disparate results are that patients with cardiogenic shock differ substantially from stable patients. The sicker patients with cardiogenic shock benefit from a less-is-more approach where culprit-only PCI reduces treatment harm relative to multivessel PCI.
We at CardiologyTrials, however, find the evidence for complete revascularization in stable AMI patients less than clear. The COMPLETE trial found benefit from multivessel PCI over culprit-only, but both composite endpoints were driven largely by non-fatal MI. CV death was not substantially different. The difference in MI could have been related to excluding procedure-related MI.
What’s more, the FULL-REVASC trial, which also compared culprit-only and multivessel PCI, failed to replicate the COMPLETE trial results. In FULL-REVASC the rates of the composite primary outcome of death, MI or unplanned revascularization were not significantly different. Sadly, FULL-REVASC was stopped early when COMPLETE results were published, which led to a possible loss of power.
It’s possible, likely even, that the null results of CULPRIT-SHOCK are not really that disparate from prior trials in patients with more stable AMI.
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