**3.4. Advances in surgical techniques**

From the standpoint of CABG, we have over the years learned the benefits of arterial grafting with the internal mammary artery (IMA) in improving survival [26]. A high long-term patency rate of left internal mammary artery (LIMA) after revascularization of the LAD is well established and is estimated at 88 percent at 10 to 15 years [26]. More recently, to circumvent particular risks associated with sternotomy, there has been some investigation of revasculari‐ zation of the LAD with the LIMA using a minimally invasive direct coronary artery bypass (MIDCAB) technique [26]. In the setting of multivessel disease (MVD), there has been some discussion of a hybrid approach with MIDCAB for the LAD and PCI of the other vessels. However, the evidence supporting this approach is still limited; the most recent European Society of Cardiology (ESC) Guidelines give a *Class IIb recommendation* to this approach *(Level of Evidence B) for those "patients with conditions likely to prevent healing after sternotomy"* [26]. This approach does have significant promise and further research is required before it is adopted on a population level.

There was an overall statistically significant survival benefit with an **absolute risk reduction (ARR) 5.6% at 5 years, 5.9% at 7 years and 4.1% at 10 years** [Figure 1] [27]. This was likely an overall underestimate of the total treatment effect as there was a 36.4% cross over from the medical group to CABG over that time period whereas 93.7% of those assigned to the surgical group underwent CABG [27]. Subgroup analysis revealed that benefit was largely in those that had *three-vessel disease (3VD) and those with involvement of the proximal LAD* with each of those groups demonstrating a 42% relative risk reduction (RRR) in mortality [27]. In contrast, revascularization in two-vessel disease (2VD) in the absence of involvement of the proximal LAD did not result in a significant mortality benefit [27]. Randomized data is fairly consistent with that of registry data, demonstrating survival benefit for revascularization over medical therapy in those with 3VD; its support for benefit in those with 2VD even in those with proximal left anterior descending (LAD) involvement was non-significant [28].

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Many of the earlier studies comparing surgical revascularization with medical therapy was during a period in cardiology where the BB and nitrates were the mainstay of medical therapy. Although antiplatelets were available, these were only taken by approximately 20% of the patients at the time [27]. It may hence be important to interpret these results in the context of current medical practice, which include contemporary treatments (standard secondary prevention with antiplatelets, statin therapy, BB and ACEi) that have all made further

ASA for secondary prevention has an estimated RRR of 18 percent in total serious vascular events (including stroke and major coronary event) with an **annual ARR of 1.5 percent**; the decrease in major coronary event (non-fatal myocardial infarction (MI) and cardiovascular death) is estimated at **annual ARR of 1.0 percent** [29]. As an adjunctive antiplatelet clopidogrel has further reduced death from cardiovascular causes, non-fatal MI and stroke in patients with Non ST elevation acute coronary syndromes (NSTEACS) with an **ARR of 2.1 percent**[30]. Most recently, newer agents such as prasugrel and ticagralor have both shown benefit compared to clopidogrel in patients with acute coronary syndromes (ACS). Prasugrel compared with clopidogrel in PCI treated ACS has demonstrated an **ARR of 2.2 percent** with regards to death from cardiovascular causes, nonfatal MI or non-fatal stroke over the 6-15 month follow up period [31]. Ticagralor has shown similar reduction in the same composite endpoint in patients with ACS over clopidogrel with an **ARR of 1.9 percent** [32]. In addition, ticagralor also showed

BB's have a longstanding history in the management of CAD [7]. Although BB's can be used in patients post-MI with a normal ejection fraction (EF), the evidence for this is not as strong as that for those with significant Left Ventricular (LV) dysfunction [8]. It was previously shown that Carvedilol compared with placebo in patients with chronic heart failure (HF) and severe LV dysfunction (average EF 22-23 percent**) reduces all cause mortality with an ARR of 4.6**

The latter may be related to improvements in medical therapy.

**4. Changing landscape in the treatment of CAD**

advancements in the survival and prognosis of patients with CAD [7].

an overall **reduction in all cause mortality with an ARR of 1.4 percent** [32].

**percent** [33].

#### **3.5. Evidence of survival benefit for revascularization in stable ischemic heart disease (SIHD)**

The current framework for patient selection in treatment strategy for MVD is largely shaped by early studies comparing medical therapy and CABG. This body of evidence has been best synthesized by a meta-analysis performed by Yusuf et al in the Lancet in 1994 [27]. This metaanalysis was an individual patient data analysis of 2549 patients derived from three large randomized controlled trials, the Coronary Artery Surgery Study (CASS), Veterans Adminis‐ tration (VA) study and the European Coronary Surgery Study (ECSS) as well as four other smaller randomized studies [27]. The population studied consisted of patients with stable symptomatic coronary artery disease of a wide spectrum of severity [27]. However, only 10 percent were single vessel disease (1VD); the remainder consisted of MVD with 59.4% affecting the proximal LAD [27].

**Figure 1.** Survival curve for medical therapy versus coronary artery bypass grafting (CABG). Reproduced with permis‐ sion from Yusuf S. et al. Lancet 1994. 344;8922:563-568

There was an overall statistically significant survival benefit with an **absolute risk reduction (ARR) 5.6% at 5 years, 5.9% at 7 years and 4.1% at 10 years** [Figure 1] [27]. This was likely an overall underestimate of the total treatment effect as there was a 36.4% cross over from the medical group to CABG over that time period whereas 93.7% of those assigned to the surgical group underwent CABG [27]. Subgroup analysis revealed that benefit was largely in those that had *three-vessel disease (3VD) and those with involvement of the proximal LAD* with each of those groups demonstrating a 42% relative risk reduction (RRR) in mortality [27]. In contrast, revascularization in two-vessel disease (2VD) in the absence of involvement of the proximal LAD did not result in a significant mortality benefit [27]. Randomized data is fairly consistent with that of registry data, demonstrating survival benefit for revascularization over medical therapy in those with 3VD; its support for benefit in those with 2VD even in those with proximal left anterior descending (LAD) involvement was non-significant [28]. The latter may be related to improvements in medical therapy.
