Ankur Jain

Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for patients with relapsed or refractory multiple myeloma (RRMM) who failed ≥1 prior lines of therapy. We performed a systematic review of carfilzomib literature with meta-analysis to determine cumulative incidence of cardiotoxicity. After the literature search, we included a total of 29 eligible phase I/II, phase II and phase III clinical trials which used carfilzomib. The cumulative incidence and overall odds ratios (OR) were calculated with random effect model, using ‘R’ software with metaphor package. A total of 4164 patients with various malignancies were included. The overall estimated cumulative incidence of cardiotoxicity was 8.68% and 4.92%, respectively, for all-grade and high-grade (≥ grade 3) toxicity, which seems higher than other PIs. Compared to control group, the odds of developing cardiotoxicity due to carfilzomib was significantly higher with OR of 2.03 (95% CI: 1.19–3.46, p = .010) and 2.04 (95% CI: 1.31–3.17, p = .002) for all-grades and high grades, respectively. Concomitant immunomodulatory agents seem to increase the risk of cardiotoxicity (high-grade cardiotoxicity 6.45% and 4.34% with and without concomitant immunomodulatory agents, respectively (p = .033)). There was no variation in the incidence of cardiotoxicity among newly diagnosed versus RRMM (p = .38), and high versus standard dose carfilzomib (p = .86).

Background: Complete revascularization of patients with ST‐elevation myocardial infarction and multivessel coronary artery disease reduces adverse events compared to infarct‐related artery only revascularization. Whether complete revascularization should be done as multivessel intervention during index procedure or as a staged procedure remains controversial.Method: We performed a meta‐analysis of randomized controlled trials comparing outcomes of multivessel intervention in patients with ST‐elevation myocardial infarction and multivessel coronary artery disease as staged procedure versus at the time of index procedure. Composite of death or myocardial infarction was the primary outcome. Mantel‐Haenszel risk ratios were calculated using random effect model.Results: Six randomized studies with a total of 1126 patients met our selection criteria. At a mean follow‐up of 13 months, composite of myocardial infarction or death (7.2% vs 11.7%, RR: 1.66, 95%CI: 1.09‐2.52, P = 0.02), all cause mortality (RR: 2.55, 95%CI: 1.42‐4.58, P < 0.01), cardiovascular mortality (RR: 2.8, 95%CI: 1.33‐5.86, P = 0.01), and short‐term (P < 0.01) occurred less often in staged versus index procedure multivessel revascularization. There was no difference in major adverse cardiac events (RR: 1.14, 95%CI: 0.88‐1.49, P = 0.33), repeat myocardial infarction (RR: 1.14, 95%CI: 0.68‐1.92, P = 0.61), and repeat revascularization (RR: 0.92, 95%CI: 0.66‐1.28, P = 0.62).Conclusion: In patients with ST‐elevation myocardial infarction and multivessel coronary artery disease, a strategy of complete revascularization as a staged procedure compared to index procedure revascularization results in reduced mortality without an increase in repeat myocardial infarction or need for repeat revascularization.

E21622 Background: Carfilzomib (Carf) is a novel proteasome inhibitor that is approved for patients with relapsed multiple myeloma (RMM) who have failed ≥ 1 prior lines of therapy. The incidence and seriousness of Carf associated reno-vascular toxicities (RVT) is not well known. We performed systematic review of Carf literature with meta-analysis to determine its incidence and overall risk. Methods: Initial search of literature led to a total of 175 Carf related articles. However, we used a total of 29 publications; phase I/II, phase II and phase III clinical trials (n = 3) which used Carf as monotherapy or in combination. We excluded phase I studies. Incidence rates and odds ratios (OR) were calculated with either fixed effect or random effect model based on the heterogeneity of included studies. Toxicity such as hypertension (HTN), renal failure (RF) and venous thromboembolism (VTE) were reported according to CTCAE v4.0. Results: A total of 4560 patients with various hematological and solid malignancies were included. Incidences of toxicities were: 15.9% and 4.7 % for HTN, 11.2% and 3.44% for RF, 6.47% and 2.22% for VTE, respectively for all grades and high grades in each category. When compared to control group taken from phase III clinical trials, the risk of HTN and RF due to Carf was significantly higher [OR = 2.91 and 3.32 in HTN (P < 0.001)], [OR = 1.71 and 1.79 (P < 0.05) for RF], respectively for all grade and high grade in each category. Moreover, incidence of HTN with higher than standard dose of carf (27 mg/m2 twice weekly) was significantly higher (P < 0.001). RF and VTE did not have the dose effect. Concomitant use of immunomodulator (IMiD) significantly increased, as expected, the incidence of VTE (P < 0.001). There was no variation in the incidence of RVT among newly diagnosed versus RMM (P = 0.4). Conclusions: Overall incidence and risk of hypertension and renal toxicities seems to be high when using Carf. Higher doses of Carf seem to lead to higher incidence of HTN, while the risk of VTE is higher with concomitant IMiD use. The pathophysiology for these complications is poorly understood, however it could be secondary to endothelial effect of carf. Physician should be vigilant about these effects as it can lead to poor overall outcomes.

Introduction: Angina pectoris is the most prevalent symptomatic manifestation of ischemic heart disease, frequently leads to a poor quality of life, and is a major cause of medical resource consumption. Since the early descriptions of nitrite and nitrate in the 19^th century, there has been considerable advancement in the pharmacologic management of angina. Areas covered: Management of chronic angina is often challenging for clinicians. Despite introduction of several pharmacological agents in last few decades, a significant proportion of patients continue to experience symptoms (i.e., refractory angina) with subsequent disability. For the purpose of this review, we searched PubMed and Cochrane databases from inception to August 2016 for the most clinically relevant publications that guide current practice in angina therapy and its development. In this article, we briefly review the pathophysiology of angina and mechanism-based classification of current therapy. This is followed by evidence-based insight into the traditional and novel pharmacotherapeutic agents, highlighting their clinical usefulness. Expert opinion: Considering the wide array of available therapies with different mechanism efficacy and limiting factors, a personalized approach is essential, particularly for patients with refractory angina. Ongoing research with novel pharmacologic modalities is likely to provide new options for management of angina.