CULPRIT-SHOCK

Published

Thiele H, et al. "PCI strategies in patients with acute myocardial infarction and cardiogenic shock". New England Journal of Medicine. 2017. epub 2017-10-30:1-13.
PubMed • Full text • PDF

Clinical Question

In patients with acute myocardial infarction (MI) complicated by cardiogenic shock found to have multivessel CAD on angiography, is multivessel percutaneous coronary intervention (PCI) superior to culprit-only PCI?

Bottom Line

In patients with acute MI complicated by cardiogenic shock found to have multivessel CAD on coronary angiography, culprit-only PCI is associated with 9.5% absolute reduction in the rate of death or renal replacement therapy at 30 days. This was driven primarily by a 7.3% absolute reduction in all-cause mortality with culprit-lesion only PCI.

Major Points

There has been substantial investigation into whether patients presenting with acute MI found to have multivessel obstructive coronary artery disease on angiography should undergo PCI of the culprit lesion only or complete revascularization. The previous DANAMI-3-PRIMULTI, PRAMI, and CvLPRIT trials have suggested that there may be benefit to complete revascularization, with a meta-analysis of these trials demonstrating lower rates of composite major adverse cardiac events with complete revascularization. On the strength of these data, the 2015 ACC/AHA/SCAI guidelines on primary PCI for ST elevation MI now include PCI of non-culprit lesions in "selected patients with STEMI and multivessel disease who are hemodynamically stable, either at the time of primary PCI or as a planned staged procedure" as a class IIb recommendation. Whether these findings extend to patients with severe enough MI to cause hemodynamic instability and cardiogenic shock is unclear, and is of particular interest since patients with cardiogenic shock complicating MI are far more likely to have multivessel rather than single-vessel CAD. In these cases, it remains unknown whether the benefit of improved perfusion and myocardial function afforded by more complete revascularization is offset by the risks inherent to a longer procedure time, increased contrast load, and possible induction of further ischemia from complex intervention.

The 2017 Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) randomized 706 patients presenting with either STEMI or NSTEACS complicated by cardiogenic shock with an identifiable culprit lesion to either immediate multivessel PCI (including chronic total occlusions, which were present in 24% of patients) or culprit lesion-only PCI with the option of staged revascularization. Importantly, patients with an primary indication for urgent coronary artery bypass were excluded from the trial. At 30 days, there was a 9.5% absolute reduction in the rate of the primary endpoint of death or renal replacement therapy in patients randomized to culprit-lesion only revascularization. This difference was driven largely by a 7.3% absolute reduction in all-cause mortality with culprit-lesion only revascularization. Rates of procedural complications were similar between the groups, although there was a trend toward more BARC 2,3, or 5 bleeding with multivessel revascularization. Of note, 21.5% of patients randomized to culprit-lesion only revascularization subsequently underwent staged or urgent repeat revascularization.

In summary, the results of CULPRIT-SHOCK provide strong evidence that a culprit-lesion only PCI strategy (with option of staged revascularization of non-culprit lesions) is preferred in patients presenting with cardiogenic shock found to have multivessel coronary disease on angiography, acknowledging that up to 1 in 5 of these patients will end up requiring staged or urgent revascularization in the short term. Although the cause of improved outcomes with culprit-lesion only PCI is not entirely clear, it is likely related to shorter procedure time as well as lower contrast load (190cc vs. 250cc). Given short duration of follow-up in CULPRIT-SHOCK, further studies are needed to confirm the long-term stability of these results.

Guidelines

ESC/EACTS myocardial revascularization (2018, adapted)

• If cardiogenic shock, recommend against revascularization of non-infarct related artery lesions identified during PCI (class III, LOE B)

Design

• Multicenter, open-label, randomized trial
• N=706
  • Culprit lesion-only PCI (n=351)
  • Immediate multivessel PCI (n=355)
• Setting: 83 centers in Europe
• Enrollment: April 2013 - April 2017
• Duration of follow-up: 30 days
• Analysis: Intention-to-treat
• Primary Outcome: Death from any cause or severe renal failure leading to renal replacement therapy

Population

Inclusion Criteria

• Planned early revascularization by PCI
• Multivessel CAD with identifiable culprit lesion
• Shock defined as either of:
  • SBP < 90mmHg for > 30 minutes
  • Catecholamines required to maintain SBP > 90mmHg during systole
• Signs of pulmonary congestion
• Signs of impaired perfusion with at least one of:
  • Altered mental status
  • Cold, clammy skin and extremities
  • Oliguria with urine output <30mL/h
  • Lactate > 2.0mmol/L

Exclusion Criteria

• Resuscitation > 30 minutes
• No intrinsic heart action
• Cerebral deficit with fixed dilated pupils (not drug-induced)
• Need for primary urgent bypass surgery (to be determined after diagnostic angiography)
• Single vessel disease
• Mechanical cause of cardiogenic shock
• Onset of shock > 12h
• Massive lung emboli
• Age > 90 years
• Shock of other cause (bradycardia, sepsis, hypovolemic, etc)
• Other severe concomitant disease with limited life expectancy < 6 months

Baseline Characteristics

From the culprit lesion only group.

• Demographics: Age 70 years, male 75%
• Comorbidities: BMI 27, smoker 25%, HTN 59%, HLD 33%, DM 30%, previous MI 18%, previous stroke 9%, PAD 13%, previous PCI 19%, previous CABG 6%
• Cardiac: Heart rate 90, LVEF 33%, any mechanical support 29%, resuscitation 52%, STEMI 62%
• Laboratory Measures: creatinine 1.17,
• Coronary disease: 2-vessel disease 36%, 3-vessel disease 64%, chronic total occlusion 22%
• Procedural: femoral access 83%, radial access 18%, DES 94%, contrast dose 190cc, fluroscopy time 13min, staged PCI of non-culprit lesions 17%, staged CABG 0.3%
• Medications: aspirin 98%, clopidogrel 46%, prasugrel 34%, ticagrelor 40%, glycoprotein IIb/IIIa inhibitor 22%, cangrelor 2%, UFH 80%, LMWH 15%, bivalirudin 5%, statin 94%, beta blocker 93%, ACE inhibitor/ARB 90%

Interventions

• Patients randomized 1:1 to one of two initial revascularization strategies
  • Immediate multivessel PCI
  • Culprit lesion-only PCI, with the option of staged revascularization of nonculprit lesions
• Patients randomized immediately after coronary angiography
• In patients randomized to culprit lesion-only PCI, staged revascularization was encouraged on the basis of residual ischemic lesions (on noninvasive testing or using fractional flow reserve), symptoms, and clinical and neurologic status
• In patients randomized to multivessel PCI, PCI of all lesions with ≥ 70% angiographic stenosis was mandated
  • This included patients with chronic total occlusions during the acute phase
• A total dose of IV contrast dye ≤ 300mL was recommended in all cases
• All other interventional therapeutic measures were allowed, including use of mechanical circulatory support, at the discretion of the primary operator

Outcomes

Comparisons are culprit-lesion only vs. multivessel revascularization

Primary Outcomes

Death from any cause or renal replacement therapy

158 (45.9%) vs. 189 (55.4%) [RR 0.83; 95% CI 0.71-0.96; p=0.01]

Secondary Outcomes

Death from any cause

149 (43.3%) vs. 176 (51.6%) [RR 0.84; 95% CI 0.72-0.98; p=0.03]

Renal replacement therapy

40 (11.6%) vs. 56 (16.4%) [RR 0.71; 95% CI 0.49-1.03; p=0.07]

Recurrent myocardial infarction

4 (1.2%) vs. 3 (0.9%) [RR 1.32; 95% CI 0.30-5.86; p=1.00]

Staged or repeat revascularization

74 (21.5%) vs. 13 (3.8%) [RR 7.43; 95% CI 3.61-15.31; p<0.001]

Stroke

12 (3.5%) vs. 10 (2.9%) [RR 1.19; 95% CI 0.52-2.72; p=0.68]

Subgroup Analyses

Results for the primary endpoint did not differ on the basis of sex, age, diabetes, hypertension, infarct type, location of STEMI, presence of previous infarction, number of affected vessels, or presence of chronic total occlusion.

Adverse Events

BARC 2,3, or 5 bleeding

57 (16.6%) vs. 75 (22.0%) [RR 0.75; 95% CI 0.55-1.03; p=0.07]

Criticisms

• Open label nature of the study allows for bias in the ascertainment of outcomes and may affect the incidence of more subjective secondary outcomes. For example, patients known to be randomized to culprit lesion-only PCI may be more likely to undergo urgent revascularization due to treating providers' knowledge that initial revascularization was incomplete.
• 30 day follow-up endpoint limits assessment of the long-term stability of the results.
• 43 patients crossed over from culprit-lesion only PCI to multivessel PCI (for reasons including lack of hemodynamic improvement, discovery of new lesions after initial PCI, and plaque shifts), potentially leading to bias toward including more complex and comorbid patients in the multivessel PCI group. This may lead to overestimation of the benefit of culprit-lesion only PCI.
• Due to ethical reasons, patients with an indication for urgent coronary artery bypass were excluded from the study, limiting generalizability of findings to this population.
• 24% of patients in the multivessel CAD arm had a chronic total occlusion for which revascularization was attempted (successful in 81%). The benefit of revascularization of chronic total occlusions is unclear particularly in the cardiogenic shock setting, and so mandated revascularization of these lesions may have contributed to the worse outcomes observed in the multivessel PCI arm.

Funding

• NHLBI at the NIH
• Several authors with multiple ties to industry