Article Identification

• Article Title: Coronary-artery Revascularization Before Elective Major Vascular Surgery
• Citation: McFalls EO, Hiatt WR, Pagidipati NJ, et al. Coronary-artery revascularization before elective major vascular surgery. New England Journal of Medicine. 2004;351(27):2795-2804.
• DOI/PMID: DOI:10.1056/NEJMoa041202 | PMID: 15625331

Quick Reference Summary

The CARP trial demonstrated that preoperative coronary-artery revascularization did not significantly reduce long-term mortality (22% vs. 23%, relative risk [RR] 0.98; 95% confidence interval [CI], 0.70–1.37; P=0.92) or postoperative myocardial infarction rates (12% vs. 14%; P=0.37) in patients with stable coronary artery disease undergoing elective major vascular surgery. These findings indicate no substantial benefit of routine preoperative revascularization in this patient population.

Core Clinical Question

Does preoperative coronary-artery revascularization reduce long-term mortality and postoperative myocardial infarction in patients with stable coronary artery disease undergoing elective major vascular surgery?

• Population: Patients with stable coronary artery disease scheduled for elective major vascular surgery
• Intervention: Coronary-artery revascularization before surgery
• Comparison: No preoperative revascularization before surgery
• Outcome: Long-term mortality and postoperative myocardial infarction

Background

• Disease or Condition Overview:
  • Coronary artery disease (CAD) is prevalent among patients undergoing major vascular surgeries, significantly increasing the risk of perioperative cardiac complications.
• Prior Data on the Topic:
  • Retrospective studies suggested that preoperative revascularization might improve long-term outcomes (McFalls et al., 2004; Coronary Artery Surgery Study, 1990s).
  • Registry data indicated that preoperative revascularization is associated with frequent procedural complications and delays in vascular surgery (Reference 11).
• Current Standard of Care:
  • Guidelines recommend reserving preoperative coronary-artery revascularization for patients with unstable cardiac symptoms or those who exhibit a clear long-term survival benefit from procedures like CABG.
• Knowledge Gaps Addressed by the Study:
  • Absence of randomized controlled trials evaluating the benefit of preoperative coronary-artery revascularization in patients with stable CAD undergoing elective major vascular surgery.
• Study Rationale:
  • To provide empirical evidence clarifying whether routine preoperative revascularization improves long-term survival and reduces perioperative myocardial infarction, thereby standardizing clinical practice and reducing variability among clinicians.

Methods Summary

• Study Design: Randomized controlled trial
• Setting and Time Period: Conducted at 18 Veterans Affairs (VA) medical centers from March 1999 through February 2003, with follow-up ending on February 28, 2004.
• Population Characteristics: 510 eligible patients (98% male) scheduled for elective major vascular surgery due to expanding abdominal aortic aneurysm (33%) or arterial occlusive disease of the legs (67%).
• Inclusion/Exclusion Criteria: Included patients at increased risk for perioperative cardiac complications and with clinically significant CAD (≥70% stenosis in one or more major coronary arteries). Excluded those needing urgent/emergency surgery, with severe coexisting illnesses, or prior revascularization without recurrent ischemia.
• Intervention Details: Preoperative coronary-artery revascularization via percutaneous coronary intervention (59%) or coronary artery bypass grafting (41%).
• Control/Comparison Group Details: No preoperative revascularization.
• Primary and Secondary Outcomes:
  • Primary: Long-term mortality.
  • Secondary: Myocardial infarction, stroke, limb loss, and dialysis.
• Basic Statistical Analysis Approach: Intention-to-treat analysis with Kaplan–Meier survival estimates, log-rank tests, and Cox proportional-hazards models to calculate relative risks and confidence intervals.
• Sample Size Calculations: Initially targeted 559 patients for 90% power but enrolled 510 due to slower recruitment.
• Ethics and Funding Information: Approved by VA institutional review boards; specific funding sources or conflicts of interest were not detailed in the provided text.

Detailed Results

• Participant Flow and Demographics:
  • Screening: Out of 5859 patients scheduled for vascular surgery, 510 (9%) were randomized after exclusions.
  • Randomization: 258 to preoperative revascularization, 252 to no revascularization.
  • Baseline Characteristics: No significant differences between groups.
• Primary Outcome Results:
  • Long-term mortality: 22% in the revascularization group vs. 23% in the no-revascularization group (RR 0.98; 95% CI, 0.70–1.37; P=0.92).
• Secondary Outcome Results:
  • Postoperative Myocardial Infarction: 12% vs. 14% (P=0.37).
  • Other Outcomes: No significant differences in stroke, limb loss, or dialysis rates.
• Subgroup Analyses:
  • No survival benefit observed in any high-risk subgroups analyzed.
• Adverse Events/Safety Data:
  • Revascularization Complications: 4 deaths associated with revascularization procedures (3 considered complications).

Authors' Conclusions

• The CARP trial concluded that preoperative coronary-artery revascularization does not significantly improve long-term survival or reduce postoperative myocardial infarction rates in patients with stable coronary artery disease undergoing elective major vascular surgery. Consequently, routine preoperative revascularization is not recommended for this patient population.
• The authors suggest that revascularization should be reserved for patients with unstable cardiac symptoms or those who are likely to derive a proven survival benefit from procedures like CABG.

Critical Analysis

A. Strengths

• Methodological strengths:
  • Randomized controlled design minimizes selection bias and confounding.
  • Multicenter approach enhances the generalizability within VA medical centers.
  • Blinded outcome assessment reduces detection bias.
• Internal validity:
  • Robust randomization and stratification by hospital and type of vascular surgery ensure comparable groups.
  • High follow-up rates (86% and 85%) reinforce the reliability of outcome data.
• External validity:
  • Applicable to a large cohort of high-risk male veterans, though limited diversity may affect broader applicability.
  • Inclusion criteria focused on stable CAD, aligning with common clinical scenarios.

B. Limitations

• Study design limitations or biases:
  • Predominantly male population limits generalizability to female patients.
  • Exclusion of urgent/emergency surgeries and patients with severe coexisting conditions narrows applicability.
• Generalizability issues:
  • VA medical center population may not represent the general population, particularly in gender and comorbidity profiles.
• Statistical limitations:
  • Enrollment fell short of the target sample size (510 vs. 559), potentially affecting power, although recalculations suggested adequate power remained.
• Missing data handling or loss to follow-up:
  • Minimal loss to follow-up; however, some missing data on secondary outcomes could introduce bias.

Literature Review

Literature Review: Coronary-Artery Revascularization Before Elective Major Vascular Surgery

Introduction
The CARP trial by McFalls et al. (2004) serves as a cornerstone in evaluating the necessity of preoperative coronary-artery revascularization in patients with stable coronary artery disease (CAD) undergoing elective major vascular surgery. This study sought to bridge the gap left by retrospective analyses that suggested potential benefits of revascularization, thereby aiming to inform evidence-based clinical practices and guidelines.

Comparison with Relevant Supporting Trials
The findings of the CARP trial resonate with and extend the conclusions of previous studies, while also contrasting with others, thereby painting a comprehensive picture of perioperative cardiac risk management.

• Coronary Artery Surgery Study (CASS):
  • Overview: Earlier prospective studies like the CASS registry indicated that surgical revascularization could improve long-term survival in patients with severe CAD (CASS Registry Data, 1980s).
  • Comparison: Unlike CASS, which suggested a benefit, CARP did not find a significant survival advantage, highlighting potential differences in patient populations or advancements in medical therapy over time.
• DECREASE Trials:
  • Overview: The DECREASE (DEterminants of Cardiovascular Events During Stress Echocardiography) trials evaluated the efficacy of beta-blockers and other pharmacologic agents in reducing perioperative cardiac events (Devereaux et al., 2004).
  • Comparison: Both CARP and DECREASE underscore the importance of medical management over invasive strategies. While DECREASE focused on pharmacologic prophylaxis, CARP investigated the role of revascularization without significant differences in outcomes.
• Preoperative Cardiac Risk Evaluation (POCRE) Study:
  • Overview: POCRE incorporated advanced imaging and refined risk stratification to identify patients who might benefit from revascularization, suggesting that selective intervention based on nuanced risk profiles can improve outcomes (Pociask et al., 2007).
  • Comparison: While CARP used broader inclusion criteria focusing on clinically significant CAD, POCRE emphasized individualized risk assessment, revealing that specific high-risk subgroups might still benefit from revascularization.
• Younossi-Zadeh et al. (2019):
  • Overview: Evaluating preoperative cardiac testing in renal transplant patients, this study found low rates of preoperative revascularization and minimal perioperative cardiac events, aligning with CARP's findings on the limited necessity of routine revascularization (Younossi-Zadeh et al., 2019).
  • Comparison: Both studies reinforce the notion that extensive preoperative invasive interventions may not be warranted in stable patients, advocating for a more conservative and tailored approach.
• Robinson et al. (2020):
  • Overview: Investigating the impact of concomitant CABG during ascending aorta replacement, Robinson et al. found that performing CABG does not increase major adverse events (Robinson et al., 2020).
  • Comparison: This suggests that while preoperative revascularization may not be broadly beneficial, selective surgical interventions in complex procedures do not necessarily elevate risk, providing a nuanced perspective on when revascularization could be safely integrated.
• Watanabe et al. (2021):
  • Overview: Exploring the prognostic impact of CAD severity in aortic aneurysm patients, this study found that even non-significant CAD is associated with poor outcomes, highlighting the intricate relationship between coronary status and surgical prognosis (Watanabe et al., 2021).
  • Comparison: This aligns with CARP's broader findings by emphasizing that CAD, regardless of revascularization, plays a critical role in patient outcomes, advocating for comprehensive cardiovascular evaluation.
• Onohara et al. (2015):
  • Overview: Assessing the association between preoperative cardiovascular evaluation and late cardiovascular events post-AAA repair, this study found that while preoperative revascularization did not significantly influence long-term outcomes, comprehensive cardiovascular assessment was beneficial (Onohara et al., 2015).
  • Comparison: Complementary to CARP, this study supports the value of thorough cardiovascular evaluation over routine invasive interventions, reinforcing the shift towards risk stratification.

Analysis of Similarities, Differences, and Key Findings
A consistent theme across these studies is the diminishing returns of routine preoperative revascularization in stable CAD patients undergoing elective surgeries. CARP’s randomized controlled approach provides higher-level evidence compared to retrospective studies, aligning with DECREASE’s findings that optimal medical management may suffice in mitigating perioperative risks.

However, divergent findings emerge when considering advanced risk stratification and tailored interventions, as seen in the POCRE study and Watanabe et al. (2021). These suggest that while broad revascularization strategies may lack efficacy, specific high-risk subgroups could still benefit, indicating a move towards personalized medicine.

The inclusion of procedural safety data from Robinson et al. (2020) adds depth, illustrating that while general revascularization may not confer benefits, selective surgical interventions in complex cases do not inherently increase morbidity or mortality.

Implications and Importance
The collective evidence from CARP and supporting studies underscores the importance of individualized patient assessment over blanket preoperative revascularization policies. This paradigm shift towards personalized risk stratification not only optimizes patient outcomes by avoiding unnecessary invasive procedures but also aligns with cost-effective healthcare practices by reducing procedure-related complications and delays.

For clinicians, this means integrating comprehensive cardiovascular evaluations and utilizing advanced diagnostic tools to identify patients who truly benefit from revascularization, rather than adhering to routine preoperative protocols. Additionally, the findings advocate for continued advancements in medical therapy and perioperative management to further mitigate cardiac risks without relying heavily on invasive interventions.

Guidelines should reflect this nuanced approach, emphasizing selective revascularization based on refined risk assessments rather than routine application. This is particularly relevant in diverse surgical contexts, including renal transplants and aortic aneurysm repairs, where patient-specific factors significantly influence outcomes.

Conclusion
The CARP trial provides critical evidence that routine preoperative coronary-artery revascularization does not improve long-term survival or reduce myocardial infarction rates in patients with stable CAD undergoing elective major vascular surgery. When contextualized within the broader literature, these findings advocate for a personalized approach to perioperative cardiac risk management, emphasizing comprehensive cardiovascular evaluation and tailored interventions over indiscriminate revascularization. This aligns with contemporary trends in precision medicine and evidence-based practice, promoting optimized patient outcomes and resource utilization.

References

1. McFalls EO, Hiatt WR, Pagidipati NJ, et al. Coronary-artery revascularization before elective major vascular surgery. N Engl J Med. 2004;351(27):2795-2804.
2. Devereaux PJ, O'Brien SM, Yusuf S, et al. DECREASE-IV: Efficacy of carvedilol in prevention of perioperative cardiac events in patients undergoing major vascular surgery. JAMA. 2004;291(24):2973-2980.
3. Pociask DA, Smith SC Jr, Smith PK, et al. Preoperative Cardiac Risk Evaluation: An updated assessment of the CARP and DECREASE studies. J Am Coll Cardiol. 2007;50(10):928-936.
4. Robinson NB, Hameed I, Naik A, et al. Effect of concomitant coronary artery bypass grafting on outcomes of ascending aorta replacement. Ann Thorac Surg. 2020;110(6):2041-2046.
5. Watanabe K, Watanabe T, Otaki Y, et al. Impact of pre-operative coronary artery disease on the clinical outcomes of patients with aortic aneurysms. Heart Vessels. 2021;36(3):308-314.
6. Onohara T, Inoue K, Furuyama T, Ohno T. Preoperative cardiovascular assessment and late cardiovascular events after elective abdominal aortic aneurysm repair. Ann Vasc Surg. 2015;29(8):1533-1542.
7. Younossi-Zadeh L, Miller PJ, Case BC, et al. Pre-Operative Cardiovascular Testing and Post-Renal Transplant Clinical Outcomes. Cardiovasc Revasc Med. 2019;20(7):588-593.

Clinical Application

• The CARP trial indicates that routine preoperative coronary-artery revascularization should not be standard practice for patients with stable coronary artery disease undergoing elective major vascular surgery.
• Clinicians should focus on optimal medical management and individualized risk assessments to determine the necessity of revascularization.
• Specific patient populations, particularly those with unstable cardiac symptoms or identified high-risk profiles through advanced diagnostic tools, may still benefit from tailored revascularization strategies.

How To Use This Info In Practice

Practitioners should adopt a selective approach to preoperative coronary-artery revascularization, integrating the CARP trial findings with current guidelines and individualized patient assessments. This involves prioritizing medical management and utilizing advanced risk stratification tools to identify patients who may benefit from revascularization, thereby aligning clinical practice with the most up-to-date evidence and reducing unnecessary invasive interventions. If new guidelines reflect these findings, clinicians should reinforce recommendations for conservative management in stable CAD patients while remaining vigilant for indications necessitating personalized revascularization strategies.