Medical and Revascularization Management of Stable Ischemic Heart Disease: An Overview

Abstract

Stable ischemic heart disease (SIHD) affects approximately 10 million Americans with 500,000 new cases diagnosed each year. Patients with SIHD are primarily managed in the outpatient setting with aggressive cardiovascular risk factor modification via medical therapy and lifestyle changes. Currently, this approach is considered as the mainstay of treatment. The recently published ISCHEMIA trial has established the noninferiority of medical therapy in comparison to coronary revascularization in patients with moderate to severe ischemia. Percutaneous coronary intervention is currently recommended for patients with significant left main disease, large ischemic myocardial burden, and patients with severe refractory angina despite maximal medical therapy.

Stable ischemic heart disease (SIHD) affects approximately 10 million Americans with 500,000 new cases diagnosed each year. ¹ Patients with SIHD are primarily managed in the outpatient setting with aggressive cardiovascular risk factor modification via medical therapy and lifestyle changes. Currently, this approach is considered as the mainstay of treatment. The recently published ISCHEMIA trial has established the noninferiority of medical therapy in comparison to coronary revascularization in patients with moderate to severe ischemia. Percutaneous coronary intervention (PCI) is currently recommended for patients with significant left main disease, large ischemic myocardial burden, and patients with severe refractory angina despite maximal medical therapy. ²

Review

Coronary artery disease (CAD) is characterized by the narrowing of coronary arteries due to the deposition of fat, cholesterol, and other materials into the inner walls of the vessels. This mechanism leads in turn to the formation of a fatty plaque with a surrounding fibrous layer, a phenomenon known as atherosclerosis. Detrimental effects due to atherosclerosis can range from none (asymptomatic or subclinical disease) to decreased oxygen supply to the heart (SIHD) to plaque rupture with overlying thrombus formation and subsequent infarction (acute coronary syndrome or ACS). In this review we focus our attention on the management of patients with SIHD.

Atherosclerosis and Plaque Composition in Patients with SIHD

The regions of the coronaries most susceptible to plaque formation are those with a disturbed flow. These areas have low endothelial shear stress and are localized at inner curvatures and near branch-points of the arteries. The proposed mechanism for this observation is that regions with low shear stress have disturbed flow with complex directional changes that fail to induce endothelial cells alignment in the direction of the flow. ^{3 4} These regions are also susceptible to multiple inflammatory responses that increase the permeability of the intima layer and induce the expression of receptors and cytokines which recruit leukocytes. In other terms, a causal relationship exists between low shear stress and the upregulation of endothelial genes and proteins that promote atherosclerosis. These findings have been confirmed in multiple in vitro studies. ^{3 4 5}

Atherosclerosis occurs in three distinct phases: fatty streaks formation, followed by the formation of atheroma and atherosclerotic plaques. Fatty streak formation is initiated by the deposition of lipoproteins particles into injury-prone intimal layers with endothelial dysfunction. Among these particles, cholesterol-rich low-density lipoproteins (LDLs) have a particularly higher atherogenic potential due to their ability to infiltrate into the endothelium via endocytosis and to bind extracellular matrix proteins (proteoglycans). As opposed to patients with normal plasma LDL levels, those with elevated plasma LDL levels have an increased expression of proteoglycans which have a high affinity to bind LDL particles. ⁶ This, in turn, leads to increased trapping of LDL particles into the intimal layers. Therefore, LDL levels can be used as an indirect marker of atherogenesis in clinical settings. ⁷ The trapped LDL particles will then undergo oxidation and, along with cytokines, attract T lymphocytes and monocytes into the intimal layer via the upregulation of leukocytes adhesion molecules. Monocytes will then undergo differentiation into macrophages, which will take up oxidized LDL particles and form foam cells. ⁸ Oxidized LDL also serve as antigens to T lymphocytes which, when activated, release cytokines that activate macrophages. The accumulation of foam cells along the arterial walls forms the fatty streaks. The apoptosis of some foam cells leads to the formation of the characteristic necrotic lipid core of the developing atherosclerotic plaque.

Atheroma formation occurs following cytokine-induced migration of smooth muscle cells from the media to the intima layer, which in turn differentiate into synthetic phenotype and produce collagen, elastin, and proteoglycans. This fibrous cap is composed of a fiber-rich extracellular matrix in addition to smooth muscle cells, macrophages, and T lymphocytes. Macrophages secrete meta-proteinase which can weaken the extracellular matrix, while T lymphocytes secrete TNF-α that prevents the production of collagen by the smooth muscle cells. These mechanisms, in turn, lead to the weakening of the fibrous cap and its exposure to platelets with subsequent blood clot formation and sudden blockage of the involved artery. The mature atherosclerotic plaque consists of a lipid-rich core and a surrounding fibrous cap. The formed plaque will protrude into the vessel lumen and cause a decrease in the blood flow to the vessel. It will also be subject to remodeling mediated by mechanical factors. In particular, the atherosclerosis-induced areas of low blood flow and shear stress are subject to high strain which increase the vulnerability of plaques to rupture. Plaques with lipid-rich core and thin fibrous caps are at a higher risk of rupture. Finally, it is important to note that the formation of the atherosclerotic plaque involves a complex interaction between multiple processes, which in turn leads to heterogeneous plaque morphology, unpredictable plaque progression rate, and different clinical outcomes. ⁹

Evaluating the Risk in SIHD: Stress Testing, Stress Imaging, and CT Angiography

The 2019 European Society of Cardiology guidelines recommend to start with noninvasive stress/functional testing to diagnose and risk stratify patients with obstructive CAD. ¹⁰ Data from the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) which randomized 10,003 patients to a strategy of computed tomography angiography (CTA) first or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography [ECG]) found that abnormal CTA (including an abnormal calcium score) in patients younger than 65 years was associated with an increase in cardiovascular death myocardial infarction (MI) than in patients older than 65 years. For patients older than 65 years of age, only a positive functional test was associated with an increased risk of cardiovascular death/MI. Thus, the role of CTA as a diagnostic test for stable CAD seems promising among younger patients whereas functional testing is likely the most cost-effective test for risk stratification among those over 65 years of age. ¹¹

Although exercise ECG is an appropriate test in patients who are able to exercise and with interpretable baseline ECG, its diagnostic accuracy is reduced compared with stress imaging tests (nuclear or ECG). In a recent randomized study, ¹² stress Echocardiography was more efficacious and had better cost-savings when compared with exercise ECG in patients with no known CAD but with new onset of stable angina. Also, stress imaging remains preferred in patients with an intermediate likelihood of disease in whom revascularization is contemplated and in patients with baseline uninterpretable ECG (such as the presence of LBBB, left ventricular hypertrophy, or digitalis). ¹³ Furthermore, pharmacological stress testing requires the use of imaging (nuclear, echo or cardiac MRI and cannot rely on ECG alone for diagnosis. Rarely will one test drive a decision for therapy, but rather the integration of data from several risk-stratification modalities will provide the most complete assessment and, therefore, the most appropriately guided therapeutic decisions.

Evaluating the Risk of SIHD in the Cardiac Catheterization Laboratory: iFR, FFR, and IVUS

PCI is usually performed for severely stenotic lesions (>70% stenosis) and avoided for mildly stenotic ones (<40% stenosis). Intermediate lesions (40–70% stenosis) are more difficult to evaluate for significance on plain angiography and several tools (fractional flow reserve [FFR], intravascular ultrasound [IVUS] and instantaneous wave-free ratio [iFR]) have been developed to further characterize and risk stratify such lesions.

FFR is defined as the ratio of maximum flow through a stenotic area in a vessel to the maximum flow through a nonstenotic area in the same vessel. It is identified as a pressure ratio of the pressure distal (Pd) and proximal (Pa) to the stenotic area (FFR = Pd/Pa). ¹⁴ FFR is a guidewire-based procedure that is performed during a diagnostic cardiac catheterization and is usually performed in a state of maximal blood flow or hyperemic state. This is usually achieved by injecting intravenous adenosine and is then followed by measuring the proximal and distal pressures across a stenotic lesion. A ratio of >0.8 indicates a nonischemic producing lesion with medical therapy currently recommended for such lesions. A ratio of <0.75 indicates an ischemic producing lesion with revascularization/PCI recommended as the choice of treatment. A ratio of 0.75 to 0.8 is a gray area with no definitive treatment guidelines, therefore, patients' preference, ischemic burden, ejection fraction, severity of symptoms should be taken into consideration. ¹⁵ The Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) trial in 2009 was the first major study that compared outcomes in patients with multivessel stable CAD on optimal medical therapy (OMT) who were undergoing FFR-guided PCI or angiography-guided PCI. This study showed that the 1-year event rate (rate of death, nonfatal MI, and repeat revascularization) was significantly reduced in patients who have undergone FFR-guided PCI. ¹⁶ Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) trial then followed in 2011 and compared the outcomes of PCI versus OMT in patients with single or multivessel stable CAD and lesions with FFR less than or equal to 0.8. The rate of the primary end point (composite of death from any cause, nonfatal MI, or urgent revascularization within 2 years) was significantly less in the FFR-guided PCI group. ¹⁷

The iFR is another guidewire-based assessment tool that allows us to identify ischemia producing stenotic lesions and limitation of blood flow. This is achieved by following the same concept of measuring the ratio of Pd to Pa, however, without the use of the hyperemia-inducing agent, adenosine. iFR isolates a wave-free period in diastole where microvascular resistance is at its lowest and measures the resting pressure gradient across a stenotic lesion. iFR <0.89 is considered to be an ischemic producing lesion and revascularization/PCI is the ideally pursued among most cardiologists. Two major studies, the Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization (DEFINE-FLAIR) and the Instantaneous Wave-free Ratio versus Fractional Flow Reserve in Patients with Stable Angina Pectoris or Acute Coronary Syndrome (iFR-SWEDEHEART) trials, revealed that iFR-guided PCI was noninferior to FFR-guided PCI with regards to the rate of composite events (death from any cause, nonfatal MI, or unplanned revascularization) at 1 year. ^{18 19}

IVUS has also been introduced as a complimentary diagnostic tool for better characterization of the vessel plaques and optimization of stent deployment. ²⁰ IVUS utilizes a piezoelectric transducer located at the tip of the catheter that generates soundwaves when electrically stimulated, which in turn propagate into different tissues and produce a reflection image based on the acoustic properties of that tissue. IVUS can measure the luminal diameter and cross-sectional area, the diameter and area of the vessel wall, and evaluate the shape, morphology, and size of the plaque. Initially, the gray-scale IVUS classified plaques according to its visual appearance, by comparing the echogenicity of the plaque to its surrounding adventitia. This has been possible with the use of 20 to 40 Hz transducers. The plaques were classified into four groups: (1) soft plaque, (2) fibrous plaque, (3) calcified plaque, and (4) mixed plaques. With the ongoing technological advancements in the medical field, virtual histology-IVUS (VH-IVUS) was developed to better assess and characterize the histological composition of the vessel plaque by analyzing an additional low radiofrequency (RF) content. This RF signal in addition to the gray-scale signal, is processed using an autoregressive model and matched to color-coded histological databases to classify plaques according to their morphological composition: (1) fibrous tissue, (2) fibrofatty tissue, (3) necrotic core, and (4) dense calcium. Two new RF-based IVUS modalities have evolved and include iMAP-IVUS and integrated backscattered IVUS (IB-IVUS) that use more sophisticated software algorithms and thus leading to better tissue characterization. ²¹ The ATHEROMA-IVUS study assessed the prognostic value of RF-IVUS in patients with CAD undergoing coronary revascularization in the setting of ACS or SIHD. This study revealed that IVUS-derived luminal area and plaque burden were able to predict major adverse cardiovascular events (MACE) over a mean follow-up period of 4.7 years, however, there was no correlation between RF-IVUS derived compositional plaques and MACE. ^{21 22 23}

The Providing Regional Observation to study Predictors of Events in the Coronary Tree (PROSPECT) trial revealed that major cardiovascular events during follow-up in patients who initially presented with ACS can be predicted based on plaque burden, minimal luminal area, and plaque composition all of which are detected by IVUS. ²⁴ It is important to note that patients with SIHD were not included in the PROSPECT study.

Pharmacologic Treatment of SIHD

The treatment strategy for patients with SIHD is aggressive control of risk factors and the use of OMT to control symptoms and improve morbidity. Revascularization is mostly reserved for those with poorly controlled symptoms or those with high-risk anatomical or functional findings on noninvasive testing or abnormal invasive assessment of functional flow reserve. The pharmacologic treatment of patients with SIHD can be classified into anti-ischemic drugs, antiplatelets, anticoagulants, lipid-lowering drugs, and newer SGLT2 inhibitors, and glucagon-like peptide-1 receptor (GLP) agonists in patients with type 2 diabetes.

Beta Blocker

Beta-blocker (BB) has been shown to reduce angina in patients with SIHD. Their effect is mostly through reducing myocardial oxygen demand. There is no evidence that BB in SIHD without prior MI or underlying heart failure reduces mortality. ^{25 26 27} In patients with MI a recent analysis showed that BB following the event has a positive effect on reducing mortality (hazard ratio or HR 0.68, 95% confidence interval or CI 0.50–0.91; p  = 0.01), cardiovascular death (HR 0.52, 95% CI 0.37–0.73; p  = 0.0001), and cardiovascular death/nonfatal MI (HR 0.69, 95% CI 0.52–0.93; p  = 0.01). ²⁸

Nitrates

Nitrate formulations provide relief from angina by acting as a substrate to nitric oxide which activates cGMP resulting in smooth muscle relaxation with afterload and preload reduction and decreasing left ventricular tension and end-diastolic pressure. The mainstay relief in acute angina is achieved with sublingual or with spray route of administration. The oral ingestion has longer duration of effect with slower onset and should be considered as second-line therapy for angina relief when initial therapy with a BB or calcium channel blocker (CCB) is contraindicated, poorly tolerated, or insufficient to control symptoms. There is no known mortality benefit from the use of nitrates despite its wide application for angina relief. ²⁶ Tolerance/tachyphylaxis can develop over long periods of treatment with nitrates and nitrate-free period is needed for the drug to remain effective. Contraindications to nitrates include hypertrophic obstructive cardiomyopathy, severe aortic stenosis, and co-administrations of phosphodiesterase inhibitors. ²⁹

Calcium Channel Blockers

CCBs are classified into two classes, dihydropyridines (DHP) (nifedipine and amlodipine) and nondihydropyridines (verapamil and diltiazem). Dependent on the class of CCB, they exert their antianginal effect by reducing myocardial oxygen demand and/or increase myocardial blood supply. CCBs have not been shown to reduce mortality but they are effective antianginal drugs. ²⁶ CCBs are recommended as monotherapy for relief from angina when BBs are not tolerated or are contraindicated. ¹² Non-DHP can be combined with BB in selective patients; however, risk of bradycardia and worsening heart failure need to be considered. ¹³ DHPs are better used in patients with bradycardia at baseline as they have minimal effect on reducing heart rate.

Ranolazine

Ranolazine is a late sodium channel influx (late INa) inhibitor, resulting in a decreased intracellular sodium concentration which reduces ventricular wall tension and subsequently oxygen consumption and improves anginal symptoms. Ranolazine has been evaluated in numerous randomized trials both as a monotherapy and add-on therapy in angina management of SIHD patients, with proven efficacy and also a dose–response decrease in anginal severity. Guidelines do recommend using ranolazine as add-on therapy to BB therapy and also as monotherapy when BB therapy is not tolerated. ²⁶ Ranolazine has no effect on the risk of mortality or MI.

Antiplatelet Therapy

Treatment with an antiplatelet drug is recommended in all patients with SIHD to prevent MI and death. Aspirin, 75 to 162 mg daily, has a Class I recommendation for this indication. A comprehensive meta-analysis documented a 37% reduction in the risk of serious vascular events, including 46% decrease in risk for unstable angina and 53% reduction in the need for revascularization, among patients with SIHD taking aspirin. In patients with contraindications to aspirin, clopidogrel 75 mg daily is a reasonable option. The CAPRIE (Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events) trial compared clopidogrel 75 mg daily with aspirin 325 mg daily in patients with atherosclerotic vascular disease (ischemic stroke, recent MI, or symptomatic peripheral artery disease) and found that clopidogrel provided superior secondary prevention of atherosclerotic vascular events by a small margin, with most benefit noted in patients with peripheral artery disease. ³⁰ Dipyridamole is an antiplatelet drug with coronary vasodilatory effect. In the PARIS (Patterns of nonadherence to Antiplatelet Regimen in Stented patients) trial, the combination of aspirin plus dipyridamole was not superior to aspirin alone for secondary prevention of MI. Moreover, dipyridamole can provoke exercise-induced ischemia and is not recommended for secondary prevention of MI in patients with SIHD (Class III). ¹³

Several trials have investigated dual antiplatelet therapy (DAPT) in stable CAD. In the CHARISMA trial (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance), patients were randomized to aspirin monotherapy versus DAPT of clopidogrel and aspirin. ³¹ At 28-month median follow-up, there was no reduction in MI, stroke, or death from cardiovascular causes in the DAPT when compared with aspirin. Post hoc analysis suggested a benefit in symptomatic atherothrombosis and a harm in patients with only multiple cardiac risk factors. In the PEGASUS-TIMI 54 trial, stable patients with high-risk features 1 to 3 years post-MI were randomized to either DAPT (with ticagrelor 60 mg or 90 mg twice daily) or continued aspirin monotherapy. At mean follow-up period of 33 months, ticagrelor significantly reduced the risk of cardiovascular death, MI, or stroke (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75–0.96; p  = 0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74–0.95; p  = 0.004) but increased the risk of major bleeding. ³² Currently, DAPT is not recommended in patients with SIHD without prior stent implantation and with no history of acute coronary syndrome.

Anticoagulant Therapy

In the COMPASS trial, ³³ patients with stable CAD and peripheral artery disease were randomly assigned to rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily) with a mean follow-up of 23 months. The primary outcome was a composite of cardiovascular death, stroke, or MI. Low-dose rivaroxaban plus aspirin had better cardiovascular outcomes than those assigned to aspirin alone (hazard ratio, 0.76; 95% confidence interval [CI], 0.66–0.86; p  < 0.001). Major bleeding, however, occurred more with the rivaroxaban-aspirin group (hazard ratio, 1.70; 95% CI, 1.40–2.05; p  < 0.001) but no significant difference in intracranial or fatal bleeding was seen between these two groups. The rivaroxaban-alone group did not show a significant reduction in outcome when compared with the aspirin-alone group and resulted in more major bleeding events. Currently, a low-dose rivaroxaban-aspirin can be considered in patients with SIHD, particularly those with prior MI and multiple vessel disease when there is no contraindication to anticoagulation.

Lipid-Lowering Drugs

Statins, the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, lowers serum LDL cholesterol up to 50% from baseline. High intensity statins are important in the treatment of patients with SIHD and have been shown to reduce significantly the risk of cardiovascular events by 15 to 37%. ³⁴ The addition of ezetimibe to statins lower further LDL and cardiovascular risk as seen in the IMPROVE-IT trial. ³⁵ Recently, PCSK9 inhibitors have lowered LDL by an additional 50% approximately on top of statins and also has been shown to reduce cardiovascular events. The lower the LDL, the lower the cardiovascular events of patients with SIHD. ^{36 37}

SGLT2 Inhibitors and GLP Agonists

The presence of both diabetes and cardiovascular disease increases the risk of death significantly. Diabetes is associated with a twofold- to fourfold increase in the risk of coronary heart disease and death. GLP1 agonists have been shown to reduce the combined end point of cardiovascular death, nonfatal strokes, and nonfatal MI among patients with type II diabetes and established atherosclerotic heart disease. ³⁸ They have not been shown to reduce readmission from heart failure. SGLT2 inhibitors also reduced the combined end point of cardiovascular death, nonfatal strokes, and nonfatal MI in patients with atherosclerotic disease and diabetes. ³⁹ Empagliflozin has also been shown to reduce cardiovascular death as a secondary end point in the Empa-Reg trial. ⁴⁰ As a class, SGLT2 inhibitors seem to reduce heart failure readmissions in diabetics or nondiabetics. ^{41 42} The addition of SGLT2 inhibitors and/or GLP agonists is now warranted in patients with type 2 diabetes and atherosclerotic heart disease if no contraindications exist to their administration.

Revascularization Treatment of SIHD

Multiple trials have compared revascularization with PCI and or coronary artery bypass graft (CABG) to medical therapy over the course of the last 3 decades.

Until recently, studies that compared PCI only to medical therapy were limited by their inclusion of single-vessel CAD or less complex multivessel disease with a relatively low to moderate ischemic burden. Recently, the ISCHEMIA trial ⁴³ tested an invasive strategy with PCI or CABG versus medical therapy in patients with moderate to severe ischemic burden with a mean number of diseased coronaries of more than two. No difference was noted in the primary outcome (cardiovascular death, MI, hospitalization with unstable angina, heart failure, or resuscitated cardiac arrest) between the two groups. However, this trial was not powered enough to detect overall mortality difference, especially that the final number of participants enrolled was lower than initially planned. Also a high crossover rate to PCI was seen in patients treated with an initial strategy of medical treatment. A recent metanalysis comparing PCI to medical therapy in SIHD included the recently published ISCHEMIA trial which also found no added benefit of PCI in improving all-cause death, cardiovascular mortality, or MI when compared with guideline-directed medical therapy alone. This metanalysis focused on trials with contemporary medical therapy and in which use of stents was more than 50% in PCI. ⁴⁴ Although the ISCHEMIA trial supported the conservative approach to treatment of SIHD, it did not exclude an aggressive approach with revascularization as both modalities had equivalent outcomes. Also, it is clear that patients with refractory angina did benefit from revascularization by reducing their angina attacks and improving their quality of life. Also the trial excluded very high risk patients, particularly those with left main disease by screening CT angiography prior to randomization to the conservative versus the revascularization approach. These high risk patients are more likely to benefit from revascularization rather than conservative medical therapy. It should be also noted that physiologic testing in the laboratory had a major impact on outcomes in those with abnormal invasive functional testing and undergoing revascularization. Angiography with functional assessment in the cardiac catheterization laboratory remains an important step to evaluate symptomatic patients with moderate CAD.

CABG on the other hand is a superior treatment to medical therapy in reducing adverse outcomes in patients with left main and extensive triple-vessel disease and particularly diabetes. ⁴⁵ However, advances in techniques, stents, and ventricular support devices, have allowed at present the treatment of high-risk complex coronary disease with PCI. The recent application of the SYNTAX (Synergy between PCI with Taxus and cardiac surgery) scoring system has offered interventionalists a more objective way to predict procedural complications and outcomes with PCI or surgery in these complex patients. ⁴⁶ The SYNTAX score relies on location and extent of disease involvement in coronary vessels with higher score signifying more extensive CAD burden. In patients with baseline SYNTAX scores of 0 to 22 the outcomes were similar for CABG and PCI patients. CABG was associated with lower event rates with SYNTAX scores greater than 22. ⁴⁷ Finally, in the BARI-2D trial, patients with diabetes and multivessel disease demonstrated a better outcome with CABG compared with medical treatment (22.4 vs. 30.5%, p  = 0.01), whereas no difference in death and major cardiovascular events was found between the groups that received PCI versus medical therapy. ⁴⁸

Patients with SIHD can be evaluated also in the cardiac catheterization laboratory where moderate lesions (40–70%) can be functionally tested using FFR or iFR. The 5-year follow-up of the FAME trial ⁴⁹ showed that revascularization with PCI guided by FFR in SIHD patients yielded a significantly lower rate of the primary composite end point of death, MI, or urgent revascularization than medical therapy alone (13.9 vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34–0.63; p  < 0.001). The main difference was driven by reduction in urgent revascularizations in the FFR guided PCI group (6.3% PCI group vs. 21.1% medical-therapy group; hazard ratio, 0.27; 95% CI, 0.18–0.41).

Conclusion

Management of SIHD has evolved considerably over the past several years. Medical and preventative therapies have become the mainstay of treatment. Revascularization should be tailored to vascular complexity, degree of ischemia, presence of diabetes, other co-morbidities, and patients' preference. A cardiovascular team approach is important to come to a consensus to the optimal treatment in complex cases.

Funding Statement

Funding N.W.S. receives educational and research grants from Boston Scientific, Bard, Intact Vascular, VentureMed Group and is on the speaker bureau of Janssen, Boehringer Ingelheim, Novartis, and Zoll Medical.