Interventional Cardiology. Группа авторов

by permission of Oxford University Press.

Percutaneous coronary intervention for stable angina

      Several randomized trials have compared the outcomes following PCI with medical management for stable angina [8–11]. These include the studies from the balloon angioplasty era such as the second Randomized Intervention Treatment of Angina (RITA‐2) [9] and the Angioplasty Compared to Medicine (ACME) trials [10]. The studies and meta‐analyses of the randomized trials [12,13] demonstrates that PCI does not reduce the likelihood of death or myocardial infarction, but is more effective in relieving angina in patients with single and multivessel disease. Notably, there was an early hazard associated with PCI due to a greater likelihood of periprocedural myocardial infarction, a consistent finding in subsequent interventional trials. In addition, balloon angioplasty was associated with a high rate of emergency CABG, but this is no longer the case in contemporary practice due to the routine use of stents.

      The COURAGE trial randomization 2287 patients to either optimal medical therapy alone or PCI with bare metal stents (with optimal medical therapy) [14]. Approximately two‐thirds had multivessel disease). The inclusion criteria were either a coronary stenosis ≥80% and classic angina without provocative stress testing, or a stenosis ≥70% in at least one proximal epicardial coronary artery and objective evidence of myocardial ischemia. A large number of patients were excluded from the trial because of high risk features such as a strongly positive stress test, persistent CCS class IV angina, an ejection fraction of <30%, refractory heart failure or cardiogenic shock, revascularization within the previous six months, and those with coronary anatomy unsuitable for PCI. During a median follow‐up duration of approximately five years, there was no difference in the primary composite endpoint of death and nonfatal myocardial infarction. These findings must be interpreted in light of the facts that less than 10% of the patients screened met eligibility criteria for enrolment, 85% of patients were male, and that randomization was performed in the cardiac catheterization laboratory following angiography, which may have contributed to selection bias. Revascularization rates during follow‐up were lower in the PCI arm (21.1% vs 32.6%) and may have been lower had drug‐eluting stents (DES) been used. PCI was associated with a small reduction in the requirement for anti‐anginal therapy and greater likelihood of freedom from angina; however, this benefit diminished over time. Crossover to PCI in the medical arm was due to inadequate control of symptoms.

      The importance of risk stratification based on the magnitude of ischemic burden has been investigated in the ISCHEMIA trial. 5179 patients with at least moderate ischemia were randomized to an initial invasive strategy of angiography and revascularization (PCI or CABG), if feasible, in addition to optimal medical therapy or optimal medical therapy initially with revascularization reserved for failure of medical therapy. Importantly, enrollment into the trial was prior to diagnostic angiography to reduce selection bias. There was no significant difference in the primary composite endpoint of cardiovascular death, nonfatal MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure (HR:0.93, CI:80‐1.08;p=0.34) during approximately three year follow‐up. Patients in the invasive‐strategy group had more procedure related myocardial infarctions, but fewer nonprocedural infarctions during follow‐up. The incidence of death from any cause was low and similar in the two groups. These data suggest that an ischemic burden based strategy for revascularization is not superior medical therapy[15]. However, this conclusion needs to be interpreted in light of the facts that the statistical power of the trial was decreased due to lower than planned recruitment and lower event rates than expected, duration of follow‐up was relatively short, high‐risk patients with significant left main disease (on CT angiography), low ejection fraction, severe heart failure, or severe symptoms despite optimal medical interventions were excluded.

Measurement of fractional flow reserve (FFR) appears to be beneficial in the triage of patients with an intermediate stenosis who have not had a stress test prior to the angiogram. In the DEFER trial, patients with single vessel disease and an intermediate stenosis, an FFR ≥0.75 identified a low risk group of patients who did not benefit from angioplasty at a follow‐up of five years. In the more recent Fractional Flow Reserve vs Angiography for Multivessel Evaluation 2 (FAME 2) trial, the clinical utility of FFR measurement in patients with stable coronary artery disease being angiographically evaluated for PCI was assessed [16]. FFR was measured across all lesions with a ≥50% diameter reduction in a major native epicardial coronary artery with a diameter of at least 2.5 mm and supplying viable myocardium. Patients with at least one stenosis with an FFR of ≤0.80 were randomized to FFR‐guided PCI of all stenoses with FFR ≤0.80 with DES plus optimal medical therapy, or optimal medical therapy alone. The primary endpoint was a composite of death, myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 24 months. The study was stopped prematurely by the data and safety monitoring board. After a mean duration of follow‐up of 213 days, after randomization of 888 of the planned 1632 patients, the primary endpoint occurred in 4.3% who had PCI compared to 12.7% who were managed medically (hazard ratio [HR] 0.32, 95% CI 0.19–0.53). The difference persisted at 2‐year follow‐up. The reduction was driven by a lower rate of urgent revascularization in the PCI group. Though “urgent revascularization” is considered a “soft” endpoint, the definition used to define the events met criteria for an acute coronary syndrome and 50% of the patients had objective evidence of ischemia. Limitations of the FAME 2 include the premature termination of the trial, lack of non‐invasive stress test documentation of ischemia prior to angiography, and the absence of double blinding of the assigned strategy such that the results of FFR measurement in the medical arm may have biased the patient’s and/or physician’s decision for preceding with crossover to PCI. Nevertheless, the findings of FAME 2 suggest that PCI is appropriate in patients with functionally significant stenosis involving a moderate or greater myocardial territory, and this is reflected in current guidelines (Table 11.2). Most interventionist use a FFR‐guided strategy for intermediate (50–70% diameter stenosis) lesions in the absence of objective documentation of at least moderate ischemic burden in the coronary territory of interest or unclear results from stress testing.

      The Medicine, Angioplasty, or Surgery Study (MASS) and MASS II trials have compared medical therapy with PCI and CABG in stable angina. The MASS trial enrolled patients with single vessel disease (>80% proximal left anterior descending artery stenosis) [17]. While balloon angioplasty and medical therapy were associated with greater need for revascularization, there was no difference in rate of death or myocardial infarction in the three groups during follow‐up. The trial was conducted in the pre‐stent era without modern medical therapy which limits the applicability of the findings to contemporary practice. The MASS II trial, however, was conducted in patients with multivessel disease, and had a similar design except that PCI was performed with bare metal stents in most patients, and more contemporary medical therapy was implemented. At five years, the results were similar to the MASS trial in that there was no difference in death or myocardial infarction between the three treatment strategies, but the need for revascularization for refractory angina during follow‐up was much higher with medical therapy and PCI [18].

      The ORBITA trial randomized 230 patients with CCS class II and III angina and single‐vessel disease (≥70% stenosis) to PCI or a sham procedure. The placebo procedure in the control arm and blinding of patients as well as the care team following the procedure are unique features of this trial. At six weeks follow‐up, there was no difference between the groups for the primary end point of exercise time increment (28.4 versus 11.8 seconds, p = 0.2), though the trend favored PCI. Other exercise variables and angina severity also was not different. The very small sample size, surrogate endpoints, exceedingly short duration of follow‐up, and exclusion of patients with complex disease are major limitations of the trial [19].

A significant number of patients with CAD have asymptomatic or “silent” ischemia which is associated with an increased risk of cardiovascular events. The Asymptomatic Cardiac Ischemia Pilot (ACIP) study investigated the efficacy of three treatment strategies among patients with stable disease who had angina or silent ischemia from single or multivessel disease. Patients were randomized to angina‐guided medical therapy, angina plus ischemia‐guided medical