Medicolegal Issues

In the Literature


Coronary-Artery Revascularization Before Elective Major Vascular Sugery

McFalls EO, Ward HB, Moritz TE, et al. Coronary-artery revascularization before elective major vascular surgery. N Engl J Med. 2004;351:2861-3.

Cardiac risk stratification and treatment prior to non-cardiac surgery is a frequent reason for medical consultation, and yet the optimal approach to managing these patients remains controversial. National guidelines, based on expert opinion and inferred from published data, suggest that preoperative cardiac revascularization be reserved for patients with unstable coronary syndromes or for whom coronary artery bypass grad ing has been shown to improve mortality. Despite these recommendations, there remains considerable variability in clinical practice, which is compounded by a paucity of prospective randomized trials to validate one approach over another.

In this multicenter randomized controlled trial, McFalls et al. studied whether coronary artery revascularization prior to elective vascular surgery would reduce mortality among a cohort of patients with angiographically documented stable coronary artery disease. The investigators evaluated 5859 patients from 18 centers scheduled for abdominal aortic aneurysm or lower extremity vascular surgery. Patients felt to be at high risk for perioperative cardiac complications based on cardiology consultation, established clinical criteria, or the presence of ischemia on stress imaging studies were referred for coronary angiography. Of this cohort, 4669 (80%) were excluded due to subsequent determination of insufficient cardiac risk (28%), urgent need for vascular surgery (18%), severe comorbid illness (13%), patient preference (11%), or prior revascularization without new ischemia (11%). Of the 1190 patients who underwent angiography, 680 were excluded due to protocol criteria including: the absence of obstructive coronary artery disease (54%), coronary disease not amenable to revascularization (32%), led main artery stenosis ≥ 50% (8%), led ventricular ejection fraction <20% (2%), or severe aortic stenosis (AVA<1.0 cm2) (1%).

Of the 510 patients who remained, 252 were randomized to proceed with vascular surgery with optimal medical management, of which 9 crossed over due to the need for urgent cardiac revascularization. Two hundred fifty-eight patients were randomized to elective preoperative revascularization; 99 underwent CABG, 141 underwent PCI, and 18 were excluded due to need for urgent vascular surgery, patient preference, or in one case, stroke. Both groups were similar with respect to baseline clinical variables, including the incidence of previous myocardial infarction, congestive heart failure, diabetes mellitus, led ventricular ejection fraction, and 3vessel coronary artery disease. They were also similar in the use of perioperative betablockers (~ 85%), statins, and aspirin.

At 2.7 years after randomization, mortality was 22% in the revascularization group and 22% in the medical management group, the relative risk was 0.98 (95% CI 0.7-1.37; p=.92), which was not statistically significant. The median time from randomization to vascular surgery was 54 days in the revascularization group and 18 days in the medical management group not undergoing revascularization (p<.001). Although not designed to address short-term outcomes, there were no differences in the rates of early postoperative myocardial infarction, death, or hospital length of stay. It is also worth noting that 316 of the 510 patients who were ultimately randomized had undergone nuclear imaging studies, of which 226 (72%) had moderate to large reversible perfusion defects detected. These outcome data suggest that the presence of reversible perfusions defects is not in itself a reason for preoperative revascularization.

This well-designed study demonstrates that in the absence of unstable coronary syndromes, led main disease, severe aortic stenosis, or severely depressed led ventricular ejection fraction, there is no morbidity or mortality benefit to revascularization among patients with stable coronary artery disease prior to vascular surgery. Because vascular surgery is the highest risk category among non-cardiac procedures, it may be reasonable to extend these findings to lower risk surgeries as well, and in this sense this study is particularly relevant to consultative practice. While this study provides clear evidence on how to manage this cohort of patients, it remains unclear what the optimal strategy is to identify and manage those patients who were excluded from the trial. (DF)

Amiodarone or a Implantable Cardioverter-Defibrilator for Congestive Heart Failure

Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005 20;352:225-37.

Ventricular arrhythmias are the leading cause of sudden cardiac death in patients with systolic heart failure. Treatment with antiarrhythmic drug therapy has failed to improve survival in these patients, due to their proarrhythmic effects. Unlike other antiarrhythmics, amiodarone is a drug with low proarrhythmic effects. Some studies have suggested that amiodarone may be beneficial in patients with systolic heart failure. Conversely, several primary and secondary prevention trials have demonstrated that placement of an implantable cardioverter-defibrillator (ICD) confers a survival benefit in patients with ischemic cardiomyopathy. However, the role of ICDs in nonischemic heart failure remained unproven.

Bardy and colleagues developed the Sudden Cardiac Death in Heart Failure Trial (SCDHeFT) to evaluate the hypothesis that treatment with amiodarone or a shock-only, single-lead ICD would decrease death from any cause in a population of patients with mild to moderate heart failure. They randomly assigned 2521 patients with New York Heart Association (NYHA) class II or II heart failure (and a led ventricular ejection fraction (LVEF) of 35% or less to conventional medical therapy plus placebo, conventional therapy plus treatment with amiodarone or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD.

Fifty-two percent of patients had ischemic heart failure and 48% had nonischemic heart failure. Placebo and amiodarone were given in double-blind fashion. The primary endpoint was death from any cause with a median followup of 45.5 months. The results were as follows:

Placebo Group - 244 deaths (29% Death Rate)

Amiodarone Group - 240 deaths (28% Death Rate)

ICD Group - 182 deaths (22% Death Rate)

Patients treated with amiodarone had a similar risk of death as those who received placebo (hazard ratio, 1.06; 97.5% CI: 0.86–1.30; p=0.53). Patients implanted with an ICD had a 23% decreased risk of death when compared with those who received placebo (0.77; 97.5% CI: 0.62–0.96; p=.007). This resulted in an absolute risk reduction of 7.2% at 5 years. The authors concluded that in patients with NYHA class II or III heart failure and a LVEF of 35% or less, implantation of a single-lead, shock-only ICD reduced overall mortality by 23%, while treatment with amiodarone had no effect on survival. The benefit of ICD placement reached or approached significance in both the ischemic (hazard ratio .79, CI: 0.60–1.04, p= .05) and nonischemic (hazard ratio 0.73, CI: 0.50–1.07, p= 0.06) subgroups.

It is important to note that an additional subgroup analysis showed that ICD therapy had a significant survival benefit only in NYHA class II patients but not in NYHA class III patients. Amiodarone therapy had no benefit in class II patients and actually decreased survival in class III patients compared to those receiving placebo. In light of results from previous trials that demonstrated a greater survival benefit from ICD placement with worsening ejection fraction in patients with ischemic heart failure, the authors were unable to explain whether the differences in subclasses were biologically plausible.

This study is important for several reasons. First, it suggested that patients with systolic heart failure due to either ischemic or non ischemic causes would benefit from placement of an ICD. Second, these results support the conclusions of previous trials that demonstrate a survival advantage of ICD placement in patients with ischemic heart failure. Finally, this study also demonstrates that amiodarone therapy offers no survival benefit in this population of patients. (JL)

Clopidogrel versus Aspirin and Esomeprazole to Prevent Recurrent Ulcer Bleeding

Chan F, Ching J, Hung L, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005;352:238-44.

The optimal choice of antiplatelet therapy for patients with coronary heart disease who have had a recent upper gastrointestinal hemorrhage has not been well studied. Clopidogrel has been shown to cause fewer episodes of gastrointestinal hemorrhage than aspirin, but it is unknown whether clopidogrel monotherapy is in fact superior to aspirin plus a protonpump inhibitor. In this prospective, randomized, doubleblind trial, Chan and colleagues hypothesize that clopidogrel monotherapy would “not be inferior” to aspirin plus esomeprazole in a population of patients who had recovered from aspirin-induced hemorrhagic ulcers.

The study population was drawn from patients taking aspirin who were evaluated for an upper gastrointestinal bleed and had ulcer disease documented on endoscopy. Patients with documented Helicobacter pylori infection were treated with a 1-week course of a standard triple-drug regimen. All subjects, regardless of H. pylori status, were treated with an 8-week course of proton-pump inhibitors (PPI). Inclusion criteria included endoscopic confirmation of ulcer healing and successful eradication of H. pylori, if it was present. The location of the ulcers was not specified in the study.

Exclusion criteria included use of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, anticoagulant drugs, corticosteroids, or other anti-platelet agents; history of gastric surgery; presence of erosive esophagitis; gastric outlet obstruction; cancer; need for dialysis; or terminal illness.

Subjects who met the inclusion criteria were randomized to receive either 75 mg of clopidogrel and placebo or 80 mg of aspirin daily plus 20 mg of esomeprazole twice a day for a 12 months. Patients returned for evaluation every 3 months during the 1-year study period. The primary endpoint was recurrence of ulcer bleeding, which was predefined as clinical or laboratory evidence of gastrointestinal hemorrhage with a documented recurrence of ulcers on endoscopy. Lower gastrointestinal bleeding was a secondary endpoint.

Of 492 consecutive patients who were evaluated, 320 met inclusion criteria and were evenly divided into the clopidogrel plus placebo or the aspirin plus esomeprazole arms. Only 3 patients were lost to followup. During the study period, 34 cases of suspected gastrointestinal hemorrhage (defined as hematemesis, melena, or 2 g/dL decrease of hemoglobin) were identified. During endoscopy,14 cases were confirmed to be due to recurrent ulcer bleeding. Of these, 13 ulcers were in the clopidogrel arm (6 gastric ulcers, 5 duodenal, and 2 both) and 1 ulcer (duodenal) in the aspirin plus esomeprazole arm, a statistically significant difference (p=.001).

Fourteen patients were determined to have a lower gastrointestinal hemorrhage. Interestingly, these cases were evenly divided between the clopidogrel group (7 cases) and the aspirin plus esomeprazole (7 cases). This finding suggests the effect of esomeprazole in this study may be specific in preventing recurrent upper gastrointestinal ulcer formation and hemorrhage. The 2 groups had equivalent rates of recurrent ischemic events.

This study addresses an important clinical question, frequently encountered by hospitalists. The recommendation that clopidogrel be used instead of aspirin in patients who require antiplatelet therapy but have a history of upper gastrointestinal hemorrhage is based on studies using high-dose (325 mg) aspirin and excluded patients on acid-suppressing therapy. However, this study failed to prove noninferiority of clopidogrel to aspirin and esomeprazole for this indication. Although this study was not designed to show superiority of aspirin and esomeprazole over clopidogrel, these results indicate that this may be the case, and such a study would be timely. (CG)

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