Jeptha P. Curtis, MD; Harlan M. Krumholz, MD, SM Keeping the Patient in View Defining the Appropriateness of Percutaneous Coronary Interventions (Circulation 2004;110:3746-3748. 12-21-04)

What are the benefits of PCI?

Current evidence would suggest that outside the setting of an acute myocardial infarction, the principal, if not the only, benefit of PCI is to reduce angina and improve quality of life. Randomized trials of PCI versus medical therapy in patients with chronic stable angina suggest that routine revascularization has no effect on the risk of death or myocardial infarction and that its benefits are restricted to reducing angina and improving exercise tolerance.4,5

These findings are supported by a meta-analysis of all randomized trials of PCI versus medical therapy in which PCI was associated with a significant reduction in angina but nonsignificant increases in the risk of myocardial infarction, death, and bypass surgery.6 The counterintuitive notion that opening tight stenoses does not extend life or prevent myocardial infarction has been explained by the paradigm of plaque rupture, wherein the majority of culprit lesions arise from previously noncritical stenoses.7 At present, the Asymptomatic Coronary Ischemia Pilot study is unique in its support of the contention that routine revascularization of patients with stable coronary disease reduces the risk of myocardial infarction and death.8 [Comment: The ACIP trial (1995) is felt by some to have very serious shortcomings.] It is important to keep in mind, however, that the study was small and intended to serve as a precursor to a larger, more definitive trial. Cardiologists are familiar with trials in which a surprising mortality benefit in a pilot study was not supported by a larger, appropriately sized study.9 In addition, more contemporary trials have demonstrated the potential superiority of intense medical therapy, incorporating either exercise training or aggressive lipid-lowering therapy, in improving event-free survival as compared with PCI.10,11

This study quantifies what should be obvious: If a person has few or no symptoms at the outset, then significant improvement will not be seen after PCI, even if the procedure is technically successful. What was striking, however, was that >10% of asymptomatic patients reported moderate or large decreases in quality of life after PCI. It cannot be shown that these changes were the result of the procedure, but this finding raises concerns and emphasizes the need to understand the determinants of these decrements in health status. The study also reveals the high frequency with which minimally symptomatic patients undergo PCI. Of the 1518 patients included in the analysis, 46% experienced little or no physical limitations from their coronary artery disease, 23% had no angina, and 46% experienced angina less than once a week. Thus, the majority of patients were asymptomatic or had minimal symptoms and, according to the experience at this center, experienced little improvement in health status after the procedure. It seems likely that this patient series is representative of patients referred for cardiac catheterization in the United States. Why are so many asymptomatic or minimally symptomatic patients undergoing PCI, an invasive procedure that carries small but real risks of life-threatening complications? One piece of missing information is the denominator: We do not know how many patients with significant coronary stenoses did not undergo PCI, and we do not know how such patients would have differed from those included in the analysis. In addition, the authors do not provide detailed information about the indications for angiography, although it is likely that most patients were referred in response to symptoms or an abnormal stress test and underwent PCI on the basis of angiographic findings. Nevertheless, the question remains: What benefits do clinicians and patients anticipate when the decision is made to proceed with PCI in the absence of clinically significant symptoms? Research into clinician expectations has not been performed, but we do have some insight into patients’ knowledge and expectations. Investigators have demonstrated that almost 75% of patients with stable coronary disease undergoing PCI believe that the procedure would prevent a future myocardial infarction or improve their longevity, whereas <50% could name a single potential procedural complication.17 Clearly, a discrepancy exists between patient expectations and the available evidence, which can only be communication and ensure that patients are truly aware of both the risks and benefits of PCI.

Optimal Medical Therapy with or without PCI for Stable Coronary Disease. Boden WE et al. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

Background In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events.

Methods We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6).

Results There were 211 primary events in the PCI group and 202 events in the medical-therapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P=0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P=0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33).

Conclusions As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657 [ClinicalTrials.gov] .)

Link to free article. Link to free editorial.

Wish List and REALITY
Choice of Stents and End Points for Treatment of De Novo Coronary Artery Lesions
Sorin J. Brener, MD JAMA. 2006;295:937-938.

Because there was no expectation that either stent would prevent myocardial infarction or cardiovascular death, the lack of such a difference also is not unexpected. Nevertheless, the absence of unexpected findings does not negate the importance of a well-performed study and the additional contributions it makes to current collective knowledge.

The choice of the primary end point needs careful consideration. Because angiographic restenosis and TLR apparently track in nonlinear fashion,⁵ clinically indicated or ischemia-driven TLR might have been a better choice than measurement of diameter stenosis. Indeed, only half of the TLR procedures in REALITY were clinically indicated, while the other half were the direct result of protocol-mandated angiography in largely asymptomatic patients. These data are identical to large US postmarketing registries. For example, the 1-year incidence of TLR was 5.4% among 2458 patients treated with paclitaxel-eluting stent in the ARRIVE 1 Registry⁶ and 3.7% with sirolimus-eluting stent in the T-Search Registry.

Ischemia, Revascularization, and Perioperative Troponin Elevation After Vascular Surgery* Debabrata Mukherjee, MD, FACC, Kim A. Eagle, MD, FACC Ann Arbor, Michigan

J Am Coll Cardiol. 2004 Aug 4;44(3):576-8.

Finally, one needs to consider the suboptimal use of beta blockers (_40%) and statins (30%) in this cohort, both of which have been demonstrated to reduce periprocedural events in patients undergoing vascular surgery (17,18). Whether coronary revascularization reduces periprocedural troponin elevation and clinical events in the presence of optimal medical therapy is not yet known. Until then, the indications for coronary revascularization should include patients with poorly controlled ischemic symptoms despite excellent medical therapy or patients with a large ischemic burden (>25% of the left ventricle) on stress perfusion imaging (19). In patients with such extensive ischemia, effective beta-blockade may not be sufficient to reduce the rate of perioperative cardiac complications (20). Whether coronary revascularization is offered or not, aggressive medical and preventive therapies are essential to improve long-term outcomes.

Coronary-Artery Revascularization

before Elective Major Vascular Surgery

N Engl J Med 2004;351:2795-804. 12-30-04

background

The benefit of coronary-artery revascularization before elective major vascular surgery

is unclear.

methods

We randomly assigned patients at increased risk for perioperative cardiac complications

and clinically significant coronary artery disease to undergo either revascularization or

no revascularization before elective major vascular surgery. The primary end point was

long-term mortality.

results

Of 5859 patients scheduled for vascular operations at 18 Veterans Affairs medical centers,

510 (9 percent) were eligible for the study and were randomly assigned to either

coronary-artery revascularization before surgery or no revascularization before surgery.

The indications for a vascular operation were an expanding abdominal aortic aneurysm

(33 percent) or arterial occlusive disease of the legs (67 percent). Among the patients

assigned to preoperative coronary-artery revascularization, percutaneous coronary intervention

was performed in 59 percent, and bypass surgery was performed in 41 percent.

The median time from randomization to vascular surgery was 54 days in the revascularization

group and 18 days in the group not undergoing revascularization (P<0.001).

At 2.7 years after randomization, mortality in the revascularization group was 22 percent

and in the no-revascularization group 23 percent (relative risk, 0.98; 95 percent

confidence interval, 0.70 to 1.37; P=0.92). Within 30 days after the vascular operation,

a postoperative myocardial infarction, defined by elevated troponin levels, occurred in

12 percent of the revascularization group and 14 percent of the no-revascularization

group (P=0.37).

conclusions

Coronary-artery revascularization before elective vascular surgery does not significantly

alter the long-term outcome. On the basis of these data, a strategy of coronary-artery revascularization

before elective vascular surgery among patients with stable cardiac symptoms

cannot be recommended.

Coronary Angiography and the Extent (and hazard) of Coronary Artery Atherosclerosis (from: Assessment of Coronary Artery Disease by Cardiac Computed Tomography: A Scientific Statement From the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology Matthew J. Budoff, Stephan Achenbach, Roger S. Blumenthal, J. Jeffrey Carr, Jonathan G. Goldin, Philip Greenland, Alan D. Guerci, Joao A.C. Lima, Daniel J. Rader, Geoffrey D. Rubin, Leslee J. Shaw, and Susan E. Wiegers. Circulation 2006 114: 1761 – 1791.)

Coronary angiography has traditionally served as the principal imaging modality to evaluate CAD. However, both necropsy and coronary intravascular ultrasound (IVUS) studies have consistently shown that angiographically “normal” coronary artery segments may contain a significant amount of atherosclerotic plaque and that coronary angiography consistently underestimates the amount of coronary atherosclerosis. (234,235) Furthermore, previous angiographic studies have shown that most MIs result from the rupture of a vulnerable plaque in the absence of a significant luminal stenosis. These rupture-prone plaques, which are 7 times more likely to cause disruption than the more severe, extensive plaques, are not visible on 2-dimensional x-ray angiography. (236,237)

234. Roberts W, Jones AA, Nissen SE. Coronary intravascular ultrasound: implications for quantitation of coronary arterial narrowing at necropsy in sudden coronary death. Am J Cardiol. 1979;44:39–44.

235. Mintz GS, Painter JA, Pichard AD, Kent KM, Satler LF, Popma JJ. Chuang UC, Bucher TA, Sokolowicz LE, Leon MB. Atherosclerosis in angiographically “normal” coronary artery reference segments: an intravascular ultrasound study with clinical correlations. J Am Coll Cardiol. 1995;25:1479 –1485.

236. Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988;78:1157–1166.

237. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657– 671.

Long-term outcome of prophylactic coronary revascularization in cardiac high-risk patients undergoing major vascular surgery (from the randomized DECREASE-V Pilot Study). AM J Cardiol. 2009 Apr 1;103(7):897-901. Epub 2009 Feb 7.

Schouten O, van Kuijk JP, Flu WJ, Winkel TA, Welten GM, Boersma E, Verhagen HJ, Bax JJ, Poldermans D; DECREASE Study Group.

Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands.

Overview: Prophylactic coronary revascularization in vascular surgery patients with extensive coronary artery disease was not associated with an improved immediate postoperative outcome. However, the potential long-term benefit was unknown. This study was performed to assess the long-term benefit of prophylactic coronary revascularization in these patients.

Methods: Of 1,880 patients scheduled for major vascular surgery, 430 had > or =3 risk factors (age >70 years, angina pectoris, myocardial infarction, heart failure, stroke, diabetes mellitus, and renal failure). All underwent cardiac testing using dobutamine echocardiography or nuclear stress imaging. Patients with extensive stress-induced ischemia (> or =5 segments or > or =3 walls) were randomly assigned to additional revascularization. In total, 101 patients showed extensive ischemia and were assigned to revascularization (n = 49) or no revascularization (n = 52).

Results: After 2.8 years, the overall survival rate was 64% for patients randomly assigned to no preoperative coronary revascularization versus 61% for patients assigned to preoperative coronary revascularization (hazard ratio [HR] 1.18, 95% confidence interval [CI] 0.63 to 2.19, p = 0.61). Rates for survival free of all-cause death, nonfatal myocardial infarction, and coronary revascularization were similar in both groups at 49% and 42% for patients allocated to medical treatment or coronary revascularization, respectively (HR 1.51, 95% CI 0.89 to 2.57, p = 0.13). Only 2 patients assigned to medical treatment required coronary revascularization during follow-up. Also, in patients who survived the first 30 days after surgery, there was no apparent benefit of revascularization on cardiac events (HR 1.35, 95% CI 0.72 to 2.52, p = 0.36).

Conclusions: Preoperative coronary revascularization in high-risk patients undergoing major vascular surgery was not associated with improved postoperative or long-term outcome compared with the best medical treatment.