Lifestyle modification is a mainstay of any treatment program beginning before the diagnosis of diabetes is even made. One randomized trial of 3234 high-risk nondiabetic individuals found that a lifestyle intervention of 7 % weight loss and 150 min of physical activity per week decreased the incidence of diabetes by 58 % [11]. Similarly in the CAD population, many studies have confirmed long term mortality benefits for participation in cardiac rehabilitation programs that focus on increasing physical activity and promoting optimal dietary habits [12, 13]. Therefore, diabetic CAD patients have multiple reasons to develop healthy lifestyle habits. However, an analysis from the 2008 National Health and Nutrition Examination Survey found that less than 1 % of US adults exhibited ideal cardiovascular health for seven predefined metrics (diet, physical activity, body mass index, smoking, blood pressure, total cholesterol, and fasting blood glucose) [14].

Aside from the difficulty in achieving optimal control of health behaviors, recent trial data do not support reduction in hard cardiovascular outcomes with successful lifestyle interventions. The multicenter Look AHEAD (Action for Health in Diabetes) trial randomly assigned 5145 diabetes patients between the ages of 45 and 75 with a body mass index of 25 or greater to lifestyle modification with decreased caloric intake and increased physical activity designed to promote weight loss versus control (diabetes support and education) [15]. At a median follow up of 9.6 years, the investigators found no difference between groups in the composite outcomes of cardiac death, nonfatal MI, nonfatal stroke, or hospitalization for angina (403 intervention vs. 418 control; hazard ratio in the intervention group, 0.95; 95 % CI, 0.83–1.09; p = 0.51). This was despite greater weight loss in the intervention group compared to control (8.6 % vs. 0.7 % at 1 year; 6.0 % vs. 3.5 % at study end). With difficulties in adherence and unclear long-term efficacy, lifestyle modification remains only an adjunct strategy in diabetic patients with CAD. Further management relies on medical therapy and/or invasive revascularization.

Primary and secondary prevention efforts for CAD have evolved quite considerably over the last 25–30 years. The first therapy proven to reduce long-term mortality post acute coronary syndrome (ACS) was aspirin. In the early 1980s, a randomized controlled trial of 1266 patients diagnosed with unstable angina or non ST elevation myocardial infarction (NSTEMI) were enrolled to aspirin versus placebo on hospital discharge. They found a 51 % mortality reduction in the aspirin group compared to placebo [16]. Since this landmark study, multiple medications have been approved for the secondary prevention of coronary artery disease. Aside from aspirin, angiotensin converting enzyme inhibitors, beta blockers, and statins have all subsequently become guideline-recommended approved therapies for secondary prevention in diabetic patients with coronary artery disease [17].

As diabetic patients tend to have a more aggressive form of CAD, they particularly benefit from adherence to established medical therapies aimed at the secondary prevention of CAD [18, 19]. However, adherence that translates into obtaining objective measurements of risk factor control is difficult even under the most rigorous of circumstances. An analysis of three large randomized controlled trials that promoted strict risk factor control pooling data from over 5000 diabetic patients found that reaching optimal target levels of 4 important risk factors: glycemic control, systolic blood pressure, low density lipoprotein cholesterol, and smoking cessation ranged from only 8–23 % across the studies [20] (Fig. 4.1).

It has been well established that revascularization improves mortality and reduced the incidence of subsequent myocardial infarction in all subsets of patients presenting with acute coronary syndromes [21]. Furthermore, early data from the Coronary Artery Surgery Study (CASS) study revealed that stable CAD that includes left main and proximal left anterior descending stenosis also benefited from revascularization [22–24]. The issue that was less clear was whether significant stenoses (≥70 %) in patients with stable CAD benefited from revascularization compared to medical management.

The pivotal trial examining the comparative effectiveness of medical therapy versus percutaneous coronary intervention (PCI) for the management of stable coronary artery disease is the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial released in 2007 [25]. In this trial 2287 patients with stable CAD were randomized to a strategy of optimal medical therapy versus optimal medical therapy plus PCI. They included patients with stable ischemic heart disease and stenosis in one or more epicardial vessel of ≥ 70 %. After excluding high-risk patients, including those with persistent angina, depressed ejection fraction, and markedly positive stress tests; almost one half of patients were asymptomatic or Canadian Cardiovascular Society (CCS) I. Over a median follow up of 4.6 years, the primary outcome, a composite of nonfatal myocardial infarction (MI) and all-cause mortality, occurred in 211 (19 %) patients in the PCI arm versus 202 (18.5 %) patients in the optimal medical therapy group (P = 0.62). Although there was a statistically significant improvement in rates of freedom from angina in the PCI group relative to the medical therapy group, this trial demonstrated no benefit for stenting with regards to MI or death.

Approximately 34 % percentage of patients in COURAGE had diabetes. Subgroup analyses did not demonstrate any appreciable difference in this subset [26]. Expanding on these results by focusing solely on diabetic patients, the multinational Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study investigated the questions of medical management versus revascularization for diabetic patient with stable CAD [27]. The investigators randomized a total of 2368 patients from almost 50 sites to elective revascularization (PCI or coronary artery bypass grafting (CABG) at the discretion of the treating physician) plus aggressive medical therapy versus medical therapy alone. Mortality was similar between the two groups (11.7 % vs. 12.2 % p = 0.97) as well the composite outcome of death, stroke, or myocardial infarction (MACE) (22.8 % vs. 24.1 % p = 0.70). Interestingly, those who underwent CABG had a lower major cardiovascular event (MACE) rate compared to the medical therapy group (22.4 % vs. 30.5 % p = 0.01). Since this group was naturally higher risk with more extensive underlying disease compared to those selected for the PCI group, there appeared to be a signal indicating beneficial effects of surgical revascularization in high-risk diabetic patients. Of note, less than half the patients received contemporary drug eluting stents (DES) and there was significant crossover of the patients in the medical therapy arm to revascularization.

Whereas medical therapy has not proven inferior in low risk patients, those with aggressive multivessel CAD benefit from revascularization. The first large trial to look at this question in diabetic patients was the Bypass Angioplasty Revascularization Investigation (BARI) trial which looked at 1928 patients with multivessel CAD randomizing them to PCI with percutaneous coronary angioplasty (PTCA) or CABG [28]. Between group 5-year survival rates were similar (86.3 % PTCA vs. 89.3 % CABG, p = 0.019), despite significantly higher rates of revascularization in the PTCA arm (54 % vs. 8 %). In a subgroup analysis looking only at diabetic patients, CABG offered a substantial mortality benefit with survival rates of 80.6 % versus 65.5 % in the PTCA group (p = 0.03). This dramatic reduction in mortality led to a National Heart Lung and Blood institute alert recommending CABG for as the preferred method for revascularization in diabetic patient with multivessel disease [29].