Targeted Cancer Therapies and QT Interval Prolongation: Unveiling the Mechanisms Underlying Arrhythmic Complications and the Need for Risk Stratification Strategies.

The care and treatment of cancer patients has significantly changed in the last decade with a remarkable shift towards novel targeted therapies. These promising new drugs may represent effective and potentially life-saving therapeutic options in cancer patients, but are also emerging in the cardiotoxicity scenario for their arrhythmogenic potential due to their QT-prolonging activity. In this article we review the mechanisms underlying drug-induced QT interval prolongation and the classes of anticancer-targeted therapies most frequently responsible for this adverse event, with a particular focus on tyrosine kinase-targeting molecules. Since up to 49 % of serious adverse drug reactions (ADRs) and 58 % of potentially fatal ADRs may not appear on initial drug safety labels, we also review and discuss data from the post-marketing VigiBase® safety reporting system, the World Health Organization's global database of ADRs. Finally, we discuss arrhythmic risk stratification and prevention strategies in the complex multiple-risk setting of cancer patients, paying particular attention to drug-drug interactions with common antimicrobial, psychotropic and antiemetic supportive care, and we also provide an electrocardiographic QT monitoring algorithm for patients who are candidates for targeted cancer therapies.

Randomized comparison of biolimus-eluting stents with biodegradable polymer versus everolimus-eluting stents with permanent polymer coatings assessed by optical coherence tomography.

We sought to compare the healing patterns of biolimus-eluting stents with biodegradable polymer (BP-BES, Nobori) versus everolimus-eluting stents with permanent polymer (PP-EES, Xience) using intravascular optical coherence tomography (OCT). A total of 34 patients undergoing treatment of de novo coronary lesions were randomly assigned to receive BP-BES (n = 15) or PP-EES (n = 19). Stent tissue coverage and apposition as well as the incidence of peri-strut low intensity area (PLIA) were assessed by OCT at 6-8 months. Generalized linear mixed models were used to account for clustered data. OCT imaging was available for 17 lesions with 2,805 struts in the BP-BES group and 22 lesions with 3,890 struts in the PP-EES group. BP-BES as compared to PP-EES showed similar rates of uncovered struts (479 vs. 588, odds ratio (OR) 1.54 (95 % CI 0.63-3.79), P = 0.34) and malapposed struts (46 vs. 32 struts, OR 1.64 [95 % CI 0.21-12.5], P = 0.64). Three lesions with BP-BES (17.6 %) versus 5 lesions with PP-EES (22.7 %) had >30 % uncovered struts (P = 0.78). The proportion of patients with PLIA was similar in both groups (BP-BES 41.2 % vs. PP-EES 36.4 %, OR 1.11 [95 % CI 0.43-2.87], P = 0.83). New generation BP-BES as compared to PP-EES showed similar stent coverage and apposition as assessed by OCT at 6-8 months. In addition, PLIA-possible markers of delayed arterial healing-were observed with similar frequency in both groups.

Early vascular healing with rapid breakdown biodegradable polymer sirolimus-eluting versus durable polymer everolimus-eluting stents assessed by optical coherence tomography.

BACKGROUND: Differences in early arterial healing patterns after stent implantation between biodegradable and durable polymer based new generation drug-eluting stents are not well understood. The aim of this study was to compare the healing patterns of a novel rapid breakdown (≤8 weeks) biodegradable polymer sirolimus-eluting stent (BP-SES) with a durable polymer everolimus-eluting stent (EES) using intravascular optical coherence tomography (OCT) at 4 months. METHODS: A total of 20 patients were randomly assigned to stenting with BP-SES (n=11) or EES (n=9). Overall intravascular imaging was available for 15 (75%) patients. The primary endpoint was the difference in rate of uncovered struts between BP-SES and EES. To account for strut-level clustering, the results in both treatment groups were compared using a generalized linear mixed model approach. RESULTS: Regarding the primary endpoint, BP-SES as compared to EES showed similar rates of uncovered struts (37 [6.8%] versus 167 [17.5%], odds ratio (OR) 0.45 (95% CI 0.09-2.24), p=0.33). There were no malapposed struts in BP-SES group and 14 malapposed struts in EES group (p=0.97). No difference in percent neointimal volume (14.1±8.2% vs. 11.4±6.4%, p=0.56) was observed. CONCLUSIONS: Although rapid-breakdown BP-SES as compared to EES showed signs of improved early tissue coverage, after adjustment for strut-level clustering these differences were not statistically significant. No differences in ability to suppress neointimal hyperplasia after stent implantation between 2 stents were observed.