Medical treatment, PCI, or CABG for Stable CAD ?

8/2/2016

• Medical treatments of coronary artery disease have improved in the past decade because of the availability of statins, effective blood pressure lowering drugs and antiplatelet agents.

• In addition, improvements in PCI have revolutionised the management of high risk people with acute myocardial infarction (primary PCI and rescue PCI), non-ST elevation myocardial infarction and unstable angina.

• The use of stents, together with antiplatelet and antithrombotic treatments, has reduced procedural complications and made PCI safer.

• DESs have reduced restenosis after PCI, although they increase late stent thrombosis, for which long term dual antiplatelet treatment is required.

• Improvements in coronary artery bypass (CABG) surgery have been slow because only a few randomised controlled trials have been performed.

• Surgeons still debate the benefits of off-pump CABG (beating heart surgery) versus on-pump surgery, and whether double internal mammary artery grafts are superior to single internal mammary grafting.

• IHD represents as a dynamic continuum of disease with a variable natural history that may, over decades, encompass many phases of clinical expression ranging from asymptomatic periods, development of chronic exertional angina, subsequent quiescent periods, progression to accelerating angina, and culmination in unstable angina, acute MI, or sudden cardiac death.

• Therefore the approach to treatment should be tailored to the individual patient’s clinical status.

Risk Stratification Based on Noninvasive Testing

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/ STS guideline for the diagnosis and management of patients with stable ischemic heart disease: Circulation. 126:e354, 2012.

(Data from Califf RM, Armstrong PW, Carver JR, et al: Task Force 5: Stratification of patients into high-, medium-, and low-risk subgroups for purposes of risk factor management. J Am Coll Cardiol 27:964, 1996.)

Patient Selection for Revascularization

• Each of the following considerations may be used to guide decisions regarding the indications for as well as the approach to revascularization:

– Presence and severity of symptoms– Physiologic significance of the coronary lesions and other anatomic

considerations– Extent of myocardial ischemia and the presence of LV dysfunction– Other medical conditions that influence the risks associated with

percutaneous or surgical revascularization.

PCI vs OMT

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).

Subgroup Analysis

Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary end-point event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001).

• All patients were prescribed aspirin at a dose of 80 to 325 mg daily, metoprolol at a dose of 50 to 200 mg daily (or any other beta-1–selective blocker, alone or in combination with a calcium-channel blocker or a long-acting nitrate), lisinopril (≥5 mg daily, or another angiotensin-converting–enzyme [ACE] inhibitor or an angiotensin II–receptor blocker if the patient had unacceptable side effects with the ACE inhibitor), and atorvastatin (20 to 80 mg daily, or another statin of similar potency alone or in combination with ezetimibe, to reduce the low-density-lipoprotein [LDL] level to less than 70 mg per deciliter [1.8 mmol per liter]).

12 randomized clinical trials enrolling 7182 participants who fulfilled our inclusion criteria. For the primary analyses, when compared with OMT, PCI was associated with no significant improvement in mortality (risk ratio [RR], 0.85; 95% CI, 0.71-1.01), cardiac death (RR, 0.71; 95% CI, 0.47-1.06), nonfatal myocardial infarction (RR, 0.93; 95% CI, 0.70-1.24), or repeat revascularization (RR, 0.93; 95% CI, 0.76-1.14), with consistent results over all follow-up time points. However, for freedom from angina, there was a significant improved outcome with PCI, as compared with the OMT group (RR, 1.20; 95% CI, 1.06-1.37), evident at all of the follow-up time points.

Extended survival information was available for 1211 patients (53% of the original population). The median duration of follow-up for all patients was 6.2 years (range, 0 to 15); the median duration of follow-up for patients at the sites that permitted survival tracking was 11.9 years (range, 0 to 15). A total of 561 deaths (180 during the follow-up period in the original trial and 381 during the extended follow-up period) occurred: 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (adjusted hazard ratio, 1.03; 95% confidence interval, 0.83 to 1.21; P=0.76).

PCI vs CABG

The CABG group had significantly lower mortality than the medical treatment group at 5 years (10.2 vs 15.8%; odds ratio 0.61 [95% CI 0.48-0.77], p = 0.0001), 7 years (15.8 vs 21.7%; 0.68 [0.56-0.83], p < 0.001), and 10 years (26.4 vs 30.5%; 0.83 [0.70-0.98]; p = 0.03). The risk reduction was greater in patients with left main artery disease than in those with disease in three vessels or one or two vessels (odds ratios at 5 years 0.32, 0.58, and 0.77, respectively).

Impact of Coronary Artery Bypass Surgery versus Medical Therapy on Survival

Effects of CABG on Survival

Left Main Disease

Major adverse cardiac and cerebrovascular event rates at 1 year in LM patients were similar for CABG and PCI (13.7% versus 15.8%; Delta2.1% [95% confidence interval -3.2% to 7.4%]; P=0.44). At 1 year, stroke was significantly higher in the CABG arm (2.7% versus 0.3%; Delta-2.4% [95% confidence interval -4.2% to -0.1%]; P=0.009]), whereas repeat revascularization was significantly higher in the PCI arm (6.5% versus 11.8%; Delta5.3% [95% confidence interval 1.0% to 9.6%]; P=0.02); there was no observed difference between groups for other end points. When patients were scored for anatomic complexity, those with higher baseline SYNTAX scores had significantly worse outcomes with PCI than did patients with low or intermediate SYNTAX scores.

Major adverse cardiac and cerebrovascular event rates at 5 years was 36.9% in PCI patients and 31.0% in CABG patients (hazard ratio, 1.23 [95% confidence interval, 0.95-1.59]; P=0.12). Mortality rate was 12.8% and 14.6% in PCI and CABG patients, respectively (hazard ratio, 0.88 [95% confidence interval, 0.58-1.32]; P=0.53). Stroke was significantly increased in the CABG group (PCI 1.5% versus CABG 4.3%; hazard ratio, 0.33 [95% confidence interval, 0.12-0.92]; P=0.03) and repeat revascularization in the PCI arm (26.7% versus 15.5%; hazard ratio, 1.82 [95% confidence interval, 1.28-2.57]; P<0.01). Major adverse cardiac and cerebrovascular events were similar between arms in patients with low/intermediate SYNTAX scores but significantly increased in PCI patients with high scores (≥33).

Unresolved Questions

• ISCHEMIA is an NHLBI-funded international randomized controlled trial comparing the effectiveness of two initial management strategies in 8,000 patients with moderate or severe ischemia: an invasive strategy with cardiac catheterization and optimal revascularization plus OMT versus a conservative strategy with OMT alone and cath reserved for patients who fail medical therapy.

• The primary aim of the ISCHEMIA trial is to determine whether the invasive strategy will reduce cardiovascular death or nonfatal myocardial infarction as compared with the conservative strategy.

• Patients who qualify on the basis of ischemia and have normal renal function will undergo blinded coronary CT angiography (CCTA) to exclude left main disease and to confirm the presence of obstructive coronary artery disease prior to randomization.

• Eligible patients are then randomized to the invasive or conservative strategy

• Accrual is projected to last 4 years with a minimum 1.5 years and maximum 6 years of follow-up.

• Patients randomized to the invasive group will undergo optimal revascularization—PCI or CABG—as recommended by the local interventional cardiologist and cardiovascular surgeon based on protocol recommendations.

• Patients randomized to the conservative strategy will be permitted to undergo invasive management as needed for refractory angina or acute coronary syndrome.

• The protocol is designed to minimize unnecessary cath in patients randomized to the conservative strategy.

• The primary outcome measure is time to cardiovascular death or nonfatal MI.

• Secondary outcome measures will include quality of life, cost-effectiveness, and cardiovascular hospitalizations.

• Enrollment began in late 2012.

Revascularization to Improve Survival Compared With Medical Therapy

Revascularization to Improve Survival Compared With Medical Therapy

Revascularization to Improve Survival Compared With Medical Therapy

Revascularization to Improve Symptoms With Significant Anatomic (>50% Left Main or >70% Non–Left Main CAD) or

Physiological (FFR <0.80) Coronary Artery Stenoses

Conclusions

• In patients with multivessel coronary disease, CABG does not only lead to a dramatic reduction in repeat revascularization and MACCE but also leads to a 27% reduction in long-term all-cause mortality and a 42% reduction in MIs compared with PCI.

• The benefits were not only observed in trials of diabetic patients but also in trials where the great majority of patients were nondiabetic.

• Use of bare-metal or drug-eluting stents did not alter the mortality benefit.

• The three approaches should complement one another, not compete.