Impact of DPP4 Inhibition on Survival in Patients With Metastatic Renal Cell Carcinoma and Type 2 Diabetes Mellitus.

BACKGROUND: Dipeptidyl peptidase IV (DPP4) is a cell surface receptor that possesses numerous substrates implicated in tumor growth and metastasis. Prior studies have suggested an association between DPP4 inhibition and increased progression-free survival (PFS) and overall survival (OS) in colorectal and lung cancers but no benefit in breast or pancreatic cancers. However, no studies to date have explored the impact of DPP4 inhibitors (DPP4i) in patients with metastatic renal cell carcinoma (mRCC). In this study we present a first-time analysis examining the impact of DPP4i use on PFS and OS in patients with mRCC and type 2 diabetes mellitus. METHODS: We performed a retrospective analysis of patients with diabetes and mRCC at the University of Virginia. The study group comprised those whose diabetic regimen included a DPP4i during mRCC treatment. The control group comprised patients whose diabetic regimen did not include a DPP4i during treatment. Cox regression analysis was utilized to determine the hazard ratios of progression and death between groups. RESULTS: Fifty-nine patients were eligible for the study, with 11 in the DPP4i group and 48 in the control group. Cancer progression occurred in 81.8% of patients in the DPP4i group and 66.7% in the control group. No statistically significant differences on PFS (HR: 1.60 [95% CI, 0.75-3.43]) or OS (HR: 0.69 [95% CI, 0.28-1.70]) were found between groups. CONCLUSIONS: This retrospective study explored the effect of DPP4i on outcomes in patients with mRCC and diabetes. DPP4i have been shown to have favorable effects on PFS and OS in some cancers but not in others. The results of this study suggest that DPP4i do not confer clinical benefit in patients with mRCC. Larger studies are warranted to better elucidate the effect of DPP4i in mRCC and the mechanisms underlying differential tumor response to these agents in different malignancies.

Impact of Angiotensin Converting Enzyme Inhibitors on Pathologic Complete Response With Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer.

INTRODUCTION: The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. We examined the association of RAS inhibitors (RASi)-namely angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB)-with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) preceding radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively investigated concurrent RASi use with NAC prior to RC in 302 patients with MIBC from 3 academic institutions. Outcomes included pathologic complete response (pCR) and overall survival (OS). Pathologic features, performance status (PS), clinical stage, type/number of cycles of NAC, and toxicities were collected. RESULTS: Overall pCR rate was 26.2% and 5-year OS was 62%. Concurrent ACEi intake with NAC approached significance for association with pCR (odds ratio [OR] = 1.71; 95% CI, 0.94-3.11; P = .077). Patients with cT3/4N0-N1 disease receiving ACEi had higher pCR rates (30.8% vs. 17.7%, P = .056) than those not on ACEi. Female sex had a statistically significant favorable interaction for pCR with ACEi intake (P = .044). ACEi intake was not associated with OS, while pCR, PS and lower clinical stage were significantly associated with improved OS. CONCLUSION: ACEi intake is potentially associated with increased pCR in patients with MIBC receiving NAC prior to RC, and this association is more pronounced in patients with higher clinical stage of disease at the initiation of therapy and female sex. Our data suggest the potential relevance of the RAS as a therapeutic target in aggressive MIBC.

Impact of Institutional Universal Microsatellite-Instability (MSI) Reflex Testing on Molecular Profiling Differences Between Younger and Older Patients with Colorectal Cancer.

INTRODUCTION: DNA mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC) is found in about 15% of early-stage diseases and 5% of metastatic diseases. We reviewed a large, single-institutional database after implementation of universal reflex dMMR/MSI-H testing in CRC to compare profiles of younger (≤50) and older (>50) patients. PATIENTS AND METHODS: Between 2009 and 2017, all patients diagnosed with CRC at the University of Florida underwent reflex somatic tumor testing for dMMR by immunohistochemistry (MLH1, PMS2, MSH2, MSH6), MSI by PCR, and Next-Generation Sequencing. Statistical analysis was conducted with 2-sample comparison tests and logistic regression models. RESULTS: There were 375 patients included in the final analysis. Patients were grouped as younger (ages ≤50 years-old; n = 80) or older (>50 years-old; n = 295). Compared to tumors from older patients, tumors from younger patients were less likely to be dMMR/MSI-H (12.5% vs. 21.4%, P = .013) and less likely to have a BRAF mutation (1.5% vs. 16.1%, P = .002). BRAF mutation status was highly associated with MMR status; BRAF-mutated tumors were 29.7 times more likely than BRAF-WT tumors to be dMMR/MSI-H (P = < .001, 95% CI 11.3-78.3). CONCLUSIONS: Tumors of younger patients were less likely than tumors of older patients to have a dMMR/MSI-H or BRAF mutation. Universal MMR/MSI testing in our dataset identified a relatively large population of older patients with sporadic CRC who were eligible for immunotherapy.

A Comprehensive Review of Randomized Clinical Trials Shaping the Landscape of Rectal Cancer Therapy.

Colorectal carcinoma is the second leading cause of cancer-related deaths in the United States, with rectal cancer accounting for approximately one third of newly diagnosed cases. Surgery remains the cornerstone of curative therapy, with total mesorectal excision being the standard of care. Although minimally invasive procedures might be appropriate for a subset of patients with early-stage, superficial tumors, the standard of care for medically operable patients with nonmetastatic rectal cancer includes a comprehensive multimodality approach of neoadjuvant chemoradiotherapy, surgery with total mesorectal excision, and systemic chemotherapy. However, the morbidity and mortality related to both local and distant organ relapse have remained challenging. In the present review, we have discussed the trial-level evidence that has shaped the current clinical practice patterns in the treatment of curable, nonmetastatic rectal cancer. In addition, we have discussed the anticipated results of ongoing clinical trials and outlined pragmatic opportunities for future investigation to optimize the current status quo and, hopefully, provide prospective validation of novel approaches in the treatment of rectal cancer.

A Novel Case of Leflunomide-Induced Thrombotic Thrombocytopenic Purpura.

Leflunomide has not been previously associated with thrombotic thrombocytopenic purpura (TTP), a rare life-threatening clinical syndrome characterized by thrombotic microangiopathy (TMA) due to inability to cleave ADAMTS13. Here, we present the first case of leflunomide-induced TTP. Our patient developed encephalopathy, thrombocytopenia, anemia and hyperbilirubinemia 2 months after starting leflunomide. Schistocytes were noted on peripheral smear and ADAMTS13 activity was low (< 5%), consistent with acquired TTP. He received therapeutic plasma exchange, corticosteroids, rituximab and caplacizumab with normalization of hemolysis labs and ADAMTS13 activity. However, pancytopenia persisted, raising the suspicion for leflunomide toxicity. Oral cholestyramine treatment was empirically started before teriflunomide (a leflunomide metabolite) level was found to be elevated. Blood counts normalized after cholestyramine and have remained normal at last follow-up over a year later. This is the first reported case of TTP precipitated by leflunomide. Our case highlights the importance of recognizing drugs as an etiology of TMA and adds leflunomide to this list.

Systematic Analysis of Extracting Data on Advance Directives from Patient Electronic Health Records (EHR) in Terminal Oncology Patients.

BACKGROUND: Advance directives are legal documents that include living wills and durable health care power of attorney documents. They are critical components of care for seriously ill patients which are designed to be implemented when a patient is terminally ill and incapacitated. We sought to evaluate potential reasons for why advance directives were not appropriately implemented, by reviewing the electronic health record (EHR) in patients with terminal cancer. METHODS: A retrospective analysis of the EHR of 500 cancer patients from 1/1/2013 to 12/31/2016 was performed. Data points were manually collected and entered in a central database. RESULTS: Of the 500 patients, 160 (32%) had an advance directive (AD). The most common clinical terminology used by physicians indicating a terminal diagnosis was progressive (36.6%) and palliative (31%). The most common clinical terminology indicating incapacity was altered mental status (25.6%), and not oriented (14%). 34 (6.8%) patients met all criteria of having a terminal diagnosis, a documented AD, and were deemed incapacitated. Of these patients who met all of these data points, their ADs were implemented on average 1.7 days (SD: 4.4 days) after which they should have been. This resulted in a total of 58 days of additional care provided. DISCUSSION: This study provided insight on to how ADs are managed in day to day practice in the hospital. From our analysis it appears that physicians are able to identify when a patient is terminal, however, it is typically later than it should have been recognized. Further studies should be performed focusing on harnessing the power of the EHR and providing physicians formative and evaluative feedback of practice patterns to ensure that ADs are honored when appropriate.

Reduction of immunosuppression for post-transplant lymphoproliferative disorder (PTLD): a single-center experience of allograft survival outcomes.

Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication of hematopoietic stem cell transplant and solid organ transplant. While reduction in immunosuppression (RIS) is the first-line treatment for PTLD, outcomes of allograft function as a result of RIS remain understudied. In this retrospective study, we examine rates of allograft rejection and graft failure after RIS in 141 patients diagnosed with PTLD at the University of Florida. Compared to prior literature demonstrating around 32-40% rate of allograft rejection as result of RIS, our institutional analysis revealed a much lower treatment-related allograft rejection rate of 18.4%. Out of the patients who experienced acute allograft rejection, 23.1% ultimately progressed to allograft failure. Interestingly, acute allograft rejection episodes during PTLD treatment were not statistically found to impact overall survival. RIS remains an overall beneficial treatment modality of PTLD due to its low allograft rejection rate relative to treatment rate.

Emerging Treatment Options for the Treatment of Metastatic Urothelial Cancer: Therapeutic Potential of Enfortumab Vedotin.

Enfortumab vedotin (EV) is an antibody-drug conjugate with humanized anti-Nectin-4 antibody linked with a microtubule-disrupting agent called monomethyl auristatin E. Nectin-4 is a cellular adhesion protein that is overexpressed in urothelial cancer. EV was approved in December 2019 for patients with locally advanced or metastatic urothelial cancer who previously received platinum-based chemotherapy and immune checkpoint inhibitors. Here, we reviewed the clinical efficacy and safety data that led to the accelerated approval of EV for treating patients with metastatic urothelial cancer. Emerging clinical data on EV-based combinational therapeutic trials for metastatic urothelial cancer were also reviewed.

Comprehensive literature review of randomized clinical trials examining novel treatment advances in patients with colon cancer.

The treatment of colon cancer has had numerous recent advances, in terms of surgical approach, adjuvant therapies, and more. In this review, the authors examine randomized clinical trials comparing open surgery to laparoscopic surgery (including total mesocolic excision), and also examine the role of robotic surgery. Novel surgical techniques including the no-touch technique, side-to-side anastomosis, suture technique, complete mesocolic excision (CME) with central vascular ligation (CVL), and natural orifice transluminal endoscopic surgery (NOTES) are outlined. The role of placing endoscopic self-expandable metal stents (SEMS) for colonic obstruction is compared and contrasted with the surgical approach, and the effect that the anti-VEGF inhibitor bevacizumab may have on this side effect profile is further explored. The role of the resection of the primary tumor in the setting of metastatic disease is examined with respect to survival benefit. Pathways of perioperative care which can accelerate post-surgical recovery, including enhanced recovery after surgery (ERAS) are examined. The role of adjuvant chemotherapy in patients with high-risk stage II and patients with stage III disease is examined, along with the role on circulating tumor DNA (ctDNA) as well as with the biologic targeted agents cetuximab and bevacizumab. Lastly, the authors detail the postoperative surveillance schedules after surgical resection with respect to survival outcomes.

Impact of DPP4 Inhibitors in Survival of Patients With Prostate, Pancreas, and Breast Cancer.

Background: Dipeptidyl peptidase-4 (DPP4), a cell surface protein, exhibits a crucial role in tumor biology and regulation of the immune system. We aim to study the impact of DPP4 inhibitors (DPP4i) in patients with prostate cancer (PRC), pancreatic cancer (PC) and breast cancer (BC). Methods: Using the SEER and Medicare linked database, we identified patients with PRC or PC or BC with coexisting type II diabetes mellitus between 2007 and 2015. Patients were classified into four groups: (1) not on either DPP4i or metformin (reference group), this group included patient that were on anti-diabetic agents other than metformin or DPP4i (2) metformin only, (3) DPP4i only, and (4) DPP4i along with metformin (combination group). Overall survival (OS) analyses were performed using SAS®, version 9.4. Results: We identified 15,330 patients with PRC, 5,359 patients with PC and 16,085 patients with BC. In PRC cohort, patients on DPP4i had significant survival advantage with HR 0.77 (95% CI: 0.64-0.93), P = 0.005 when compared to the reference group. Patients taking metformin also had significant OS benefit with HR 0.87 (95% CI: 0.81-0.93), P < 0.0001 when compared to the reference group. However, in BC cohort, OS did not favor the patients taking DPP4i with HR 1.07 (95% CI: 0.93-1.25, P = 0.33). Similarly, in PC cohort, OS was indifferent for the patients on DPP4i with HR 1.07 (95% CI: 0.93-1.24, P = 0.68). Upon subgroup analyses of PRC patients, the survival favored the group taking DPP4i, irrespective of stage, use of chemotherapy, androgen-deprivation therapy, and prostatectomy or radiation therapy. Conclusions: DPP4i seems to improve survival in PRC patients; however, not in PC or BC patients. While the exact mechanism involved remains to be elucidated, a prospective clinical trial would help to confirm these findings.

Dissecting Outcomes: Should Cytoreductive Nephrectomy Be Performed for Patients With Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation?

BACKGROUND: It is highly contested whether cytoreductive nephrectomy for treating advanced renal cell carcinoma (RCC) with sarcomatoid features (sRCC) benefits overall survival. Patients with sRCC are known to have a poor prognosis, and these tumors have a more aggressive biology than those without sarcomatoid features. METHODS: Patients with clear cell RCC or non-clear cell RCC underwent cytoreductive nephrectomy in efforts to improve overall survival (OS). Patients were stratified by presence or absence of histologic sarcomatoid features within tumor samples. RESULTS: Of 167 patients who underwent cytoreductive nephrectomy, 127 had clear cell RCC, of whom 14 had sarcomatoid features, and 40 had non-clear cell RCC, of whom 13 had sarcomatoid features. Median age of the cohort was 62 years (range, 56.5-69 years). The cohort included 119 male (71.3%) and 48 (28.7%) female patients. Among all patients with advanced RCC, having sRCC had a significantly worse OS after cytoreductive nephrectomy (30 vs 8 months; hazard ratio [HR], 2.88; P <0.0001). Additionally, favorable-risk patients had significantly longer OS compared to intermediate- or poor-risk patients (56 vs 30 vs 10 months; HR, 0.21; P =0.00016). For patients with clear cell RCC, having sRCC conferred a significantly poorer survival (30 vs 9 months; HR, 2.82; P=0.0035). Patients with non-clear cell sRCC also had significantly worse outcomes compared to patients whose tumors did not have sarcomatoid features (30 vs 6.5 months; HR, 3; P =0.009). When patients with sRCC were stratified by whether there was >10% or ≤10% sarcomatoid features present within the sample, there was no significant difference in OS (8 vs 8.5 months; P =0.32). CONCLUSIONS: Sarcomatoid features within tumor histology confer significantly poor prognosis. Patients with sRCC, regardless of clear cell vs non-clear cell histology, have significantly shorter OS. Even among patients with 10% or less sarcomatoid features, there was no OS benefit to cytoreductive nephrectomy. Based on our findings, there appears to be a limited to no role of cytoreductive nephrectomy if sRCC is identified on pretreatment biopsy. The role of radiomics and pre-operative biopsies may confer significant benefit in this patient population.

Case Report: Two Cases of Chemotherapy Refractory Metastatic Penile Squamous Cell Carcinoma With Extreme Durable Response to Pembrolizumab.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a rare malignancy, and those patients with metastatic disease have limited treatment options. Treatment is largely comprised of platinum-based chemotherapy; however, patients progressing after initial chemotherapy have a median overall survival (OS) of less than 6 months. Based on a high percentage of PD-L1 expression in patients with PSCC, and its biological similarities to other squamous cell carcinomas, we present two patient cases treated with pembrolizumab with extraordinary durable treatment response far beyond treatment with standard therapy. MAIN BODY: The first patient is a 64 year old male with PSCC who was treated with neoadjuvant chemotherapy, partial penectomy, and adjuvant radiation prior to developing metastatic disease. He had a high TMB (14 mutations/Mb) and was started on pembrolizumab with a complete response, which has been maintained for 38 months. The second patient is an 85 year old male with PSCC who was treated with partial penectomy and adjuvant chemotherapy and radiation prior to developing metastatic disease. He had positive PD-L1 expression CPS 130) and was started on pembrolizumab with a partial response, which has been maintained for 18 months after starting treatment. CONCLUSIONS: These two cases of extreme durable response with pembrolizumab (with molecular data including TMB and PD-L1 status) represent a significant clinical benefit in this patient population. With limited treatment options that result in a median OS of less than 6 months, along with the toxicity profile of chemotherapy which may not be tolerated in elderly patients with comorbidities, this survival benefit with pembrolizumab, along with advances in tumor sequencing and clinical trials shows that there is a potentially significant benefit with novel therapies in this patient population.

Investigation of Complications Following Port Insertion in a Cancer Patient Population: A Retrospective Analysis.

Central venous access devices, specifically implantable ports, play an essential role in the care of oncology patients; however, complications are prevalent. This retrospective single-institutional review was performed to identify rates of complications from port placement and potential factors associated with these events. A retrospective analysis of 539 cancer patients who underwent port insertion between March 2016 and March 2017 at our institution was conducted. Data examining 18 potentially predictive factors were collected, and multivariate analysis was conducted using logistic regression and odds ratios (ORs) with standard errors to determine predictive factors. Out of 539 patients, 100 patients (19%) experienced 1 complication, and 12 patients (2%) experienced 2 or more complications. An overall lower rate of complications was seen in patients on therapeutic anticoagulation (OR: 0.17, P < .001) or on antiplatelet agents (OR: 0.47, P = .02). No patients on therapeutic anticoagulation developed venous thromboembolism (VTE; 0%). Right-sided port insertion was associated with decreased rates of infection (OR: 0.44, P = .04). Insertion as inpatient was associated with an increased risk for mechanical failure (OR: 4.60, P < .01). This analysis identified multiple predictive factors that can potentially put patients at a higher risk of experiencing complications following port insertion. Our data show lower rates of VTE for patients on anticoagulation or antiplatelet therapy. Further analysis is also necessary to determine why port insertion as an inpatient places patients at a higher risk of complications. This study highlights the risks associated with port placement and prompts the clinician to have an informed discussion with the patient weighing the risks and benefits.

Immunotherapy for Colorectal Cancer: A Review of Current and Novel Therapeutic Approaches.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the United States. Although immunotherapy has dramatically changed the landscape of treatment for many advanced cancers, the benefit in CRC has thus far been limited to patients with microsatellite instability high (MSI-H):DNA mismatch repair-deficient (dMMR) tumors. Recent studies in the refractory CRC setting have led to US Food and Drug Administration approvals for pembrolizumab as well as nivolumab (with or without ipilimumab) for tumors harboring an MSI-H:dMMR molecular profile. Several randomized controlled trials are underway to move immunotherapy into the frontline for metastatic cancer (with or without chemotherapy) and the adjuvant setting. Awareness of these studies is critical given the relatively low incidence (approximately 3%-5%) of MSI-H:dMMR in advanced or metastatic CRC to support study completion, because the results could be potentially practice changing. The real challenge in this disease is related to demonstrating the benefit of immunotherapy for the vast majority of patients with CRC not harboring MSI-H:dMMR. Given the rapid pace of scientific changes, this article provides a narrative review regarding the current landscape of immunotherapy for CRC. Particular attention is paid to the currently available data that inform today's clinical practice along with upcoming randomized controlled trials that may soon dramatically change the treatment landscape for CRC.

A multi-center retrospective analysis of the effect of DPP4 inhibitors on progression-free survival in advanced airway and colorectal cancers.

Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase IV (DPP4), is a cell surface protein with exopeptidase activity and is expressed by most cell types. CD26/DPP4 is a multifunctional molecule with diverse biological effects, including regulatory effects on tumor growth, invasion and metastasis, and is a potential novel therapeutic target for selected cancers. In this study, we retrospectively analyzed diabetic patients with concurrent advanced airway or colorectal cancer to examine the effect of DPP4-inhibitors on progression-free survival (PFS). We performed a multi-center retrospective review of patients with advanced colorectal or airway (lung, head and neck) cancer and a concurrent diagnosis of diabetes. The control group included patients on metformin and a sulfonylurea, and the study group included patients on metformin and a DPP4 inhibitor. Ninety-six patients were eligible for the study. The cancers progressed in 23.7% of patients treated with DPP4 inhibitors compared to 50.9% of patients in the control group with an odds ratio of 0.303 [95% confidence interval (CI): 0.106-0.809] and P=0.010. There was a statistically significant improvement in PFS in the study group as compared to the control group, hazard ratio=0.42 (95% CI: 0.21-0.84) and P=0.014. There was a trend toward improvement in overall survival, although this effect was not statistically significant (P=0.11). Exposure to DPP4 inhibitors in the study group led to higher PFS in patients with advanced colorectal and airway cancers. Additional investigations with larger patient cohorts are needed to validate the relationship between DPP4 inhibition and the clinical outcome of selected malignancies.

Pericardial effusion as an atypical initial presentation of extra-gonadal nonseminomatous germ cell tumor: a case report and literature review.

Extra gonadal germ cell tumors have variable clinical presentations and locations. We report a case of an extra-gonadal germ cell tumor in a 26-year-old male who presented with chest pain. Imaging revealed a large pericardial effusion with underlying mass invading the pericardium. Pericardial effusion is an extremely rare initial site of diagnosis or site of metastasis for malignancy. This case illustrates the importance of a thorough history and physical examination, broad differential diagnosis, and to keep in mind serious complications from rare presentations of disease.

A review of racial disparities in transcatheter aortic valve replacement (TAVR): accessibility, referrals and implantation.

Racial disparities in transcatheter aortic valve replacement (TAVR) implantation results from several factors, including socioeconomic disparities, inherent biases in healthcare provision, fewer referrals to specialists and language barriers in some minority populations. In this review article, we discuss the current data on the racial disparities in TAVR, explore the prevalence of aortic stenosis in different demographics in the United States and we proffer practical solutions to these problems.

Permanent pacemaker insertion in patients with conduction abnormalities post transcatheter aortic valve replacement: a review and proposed guidelines.

Conduction abnormalities are a common and serious complication of transcatheter aortic valve replacement (TAVR) with well-established predictive factors. Current guidelines are not concrete, leaving several questions unanswered about indications, timing and risks of pacemaker implantation post-TAVR. In this review article, we discuss current guidelines, predictors of pacemaker implantation, clinical implications of this procedure and our recommendations for reducing the pacemaker implantation rate post-TAVR.

Incidence and predictors of acute coronary syndrome within a year following a negative stress test-a false sense of security: is routine screening any useful?

One of the major issues in management of the acute coronary syndrome (ACS) is classification of patients with atypical presentation who have low risk of having a coronary episode at presentation. There have been multiple studies on the stratification of high risk patients and medical management of such cases, however, there is a sub-class of patients who do not fit any category. In this paper, we have looked at the current literature on stratification of patients based on the study tools available and the risk of having a coronary episode during the following year. In our overview, we have found that the current methods in place namely, cardiac stress test and stress echocardiogram have a good prognostic factor in terms of mortality in the next one year and can safely stratify the patients at low risk when correlated with clinical presentation and laboratory studies. However, such data are limited for computerized tomography or magnetic resonant imaging and their application might be limited due to accessibility and cost of studies. Current guidelines for classification of high risk patient do an excellent job and we believe that proper application of stress tests together with other imaging modalities together with laboratory, clinical judgment, and proper use of medical management can help with safe discharge of patients from the emergency department (ED) and reduction of burden from healthcare.

Asian-Indians: a review of coronary artery disease in this understudied cohort in the United States.

Coronary artery disease (CAD) is a major cause of cardiovascular death worldwide. Prevalence of CAD is highly variable among different races. Asian Indians have been noted to have the highest CAD rates and the conventional risk factors fail to explain this difference completely. Asian Indians constitute a fifth of the global population, and the higher rates of CAD in this population constitute a major health challenge. There have been studies in the early 2000s that investigate the risk factors in this population; however, very few studies have been done since then that explore the higher CAD rates in Asian Indians. This is a comprehensive and current review of the known risk factors for CAD in Asian Indians and strategies physicians should consider relieving this burden.