Long-term Outcomes in Patients Undergoing Percutaneous Coronary Intervention with Drug-eluting Stents

Roberta Rossini; Giuseppe Musumeci; Alessandro Aprile; Orazio Valsecchi

Disclosures

Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(1):49-61. 

In This Article

DES versus Medical Therapy & DES versus CABG for Nonacute CAD

Meta-analyses suggest that PCI improves outcomes in high-risk patients with acute coronary syndromes (ACS) and ST-elevation MI. However, their role in the management of patients with nonacute CAD has been controversial. Despite the sequential testing of PTCA versus medical therapy, BMS versus PTCA, and DES versus BMS, the cumulative benefits of technological innovations after 20 years of clinical trials in this area have not been systematically assessed.

The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial was designed to determine whether PCI coupled with optimal medical therapy reduced the risk of death and nonfatal MI in patients with stable CAD compared with optimal medical therapy alone.[25] It demonstrated that PCI added to optimal medical therapy did not reduce the primary composite end point of death and nonfatal MI or reduce MACEs compared with optimal medical therapy alone, during follow-up of 2.5–7.0 years, despite a high baseline prevalence of clinical coexisting illnesses, objective evidence of ischemia, and extensive CAD as seen on angiography.

Trikalinos et al. have recently published a systematic overview of RCTs comparing PTCA, BMS and DES with each other and with medical therapy in patients with nonacute CAD.[3] A total of 61 eligible trials (25388 patients) investigated four out of six possible comparisons between the four interventions; no trials directly compared DES with medical therapy or PTCA. In all direct or indirect comparisons, succeeding advancements in PCI did not produce detectable improvements in deaths or MI. The risk ratio (RR) for indirect comparisons between DES and medical therapy was 0.96 for death and 1.15 for MI. By contrast, sequential significant reductions in TLR or TVR with BMS compared with PTCA (RR: 0.68) and with DES compared with BMS (RR: 0.44) were recorded. The RR for the indirect comparison between DES and PTCA for TLR or TVR was 0.30. The present data suggest that each technological innovation became the de facto standard for trials of future innovations, although no clear advantage in terms of hard clinical outcomes had been shown compared with medical therapy. In these cases, an indirect comparison suggests that DES substantially reduces the relative risk for TVR or TLR by roughly 70% compared with balloon angioplasty. A likely reason for the apparent failure of PCI to reduce these outcomes in nonacute CAD is that PCI remains a local therapy, which is typically targeted at a few hemodynamically compromising lesions. However, CAD is a diffuse disease process that frequently involves the entire coronary vasculature, making it more likely to respond to systemic treatments such as medical therapy. Additionally, radiographically detected restenotic lesions that can lead to revascularization in nonacute CAD might often be stable and less prone to cause MI or death. However, although some patients treated medically might eventually need PCI for symptom relief, many seem able to avoid the risk and expense of PCI, without any higher risk of mortality or MI. The one caveat to this tenet is that initial PCI with DES could reduce the need for CABG, compared with initial medical therapy; this finding, however, should be confirmed in a head-to-head comparison.

The two primary interventions for patients with multivessel CAD are CABG and PCI. Several RCTs and observational studies have compared the long-term outcomes of these two interventions, but these studies all preceded the introduction of DES. Consequently, the findings of these studies are outdated and may no longer reflect current relative outcomes. Hannan et al. compared the rates of death, cardiac death or MI, and subsequent revascularization in patients receiving DES and those undergoing CABG in (NY, USA), between 2003 and 2004.[26] In comparison with treatment with a DES, CABG was associated with lower 18-month rates of death and of cardiac death or MI both for patients with three-vessel disease and for patients with two-vessel disease. Among patients with three-vessel disease who underwent CABG, compared with those who received a stent, the adjusted survival rate was 94.0 versus 92.7% (p = 0.03), with an adjusted rate of survival free from MI of 92.1 versus 89.7% (p < 0.001). Among patients with two-vessel disease who underwent CABG, as compared with those who received a stent, the adjusted survival rate was 96.0 versus 94.6% (p = 0.003), with an adjusted rate of survival free from MI of 94.5 versus 92.5% (p < 0.001). Patients undergoing CABG also had lower rates of repeat revascularization. Patients with ejection fractions below 40% and patients who were at least 80 years old who underwent CABG had significantly lower rates of death or MI.

The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial was a 1800-patient trial conducted in Europe and the USA, randomizing patients to either CABG or PCI using PES.[27] The 1-year results showed that the primary end point (major adverse cardiac and cerebrovascular events: death, cerebrovascular events, MI and repeat revascularization) occurred significantly more often among PCI-treated patients than among CABG-treated patients (17.8 vs 12.1%; p = 0.002) with a 7.7% difference driven by repeat procedures in the PCI group. For the composite, 'harder' safety end point of death/cerebrovascular events/MI, rates were almost identical between the two groups, whereas the stroke rate, by contrast, was higher in the CABG-treated patients. Of note, however, stroke rates were analyzed on an intention-to-treat basis, and almost half of the strokes in the CABG arm actually occurred prior to surgery, but postrandomization, while patients were awaiting a surgery date. At 2 years major adverse cardiac and cerebrovascular event rates were significantly different between the two groups (23.4 vs 16.3%; p < 0.001), driven by a repeat revascularization rate in PCI-treated patients that was more than double that of the CABG-treated group (17.4 vs 8.6%; p < 0.001) [KAPPETEIN AP, PERS. COMM.]. MI also increased after 1 year among PCI-treated patients (5.9 vs 3.3%; p < 0.01). The significantly higher rate of strokes seen in CABG-treated patients at 1 year was evident also at 2-year follow-up, but the difference appeared to be a carryover from the first 12 months, since very few strokes occurred between the 1- and 2-year mark in either group. For the hard end point of death/stroke/MI, there were no significant differences between the two groups.

Long-term data are warranted, as the time domain is critical in determining the relative benefits of CABG and PCI. In general, the mortality and morbidity in CABG revascularization peaks within the first few months and then is relatively silent until vein grafts start failing, whereas stenting has a benign early course with a gradual attrition with time, due to stent thrombosis.

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