RESUMEN
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.
Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Arritmias Cardíacas/inducido químicamente , Síndrome de QT Prolongado/inducido químicamente , Medición de Riesgo , Arritmias Cardíacas/fisiopatología , Sistemas de Liberación de Medicamentos , Humanos , Síndrome de QT Prolongado/fisiopatologíaRESUMEN
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.
Asunto(s)
Materiales Biocompatibles Revestidos , Stents Liberadores de Fármacos , Ensayo de Materiales , Polímeros , Sirolimus/análogos & derivados , Tomografía de Coherencia Óptica/métodos , Anciano , Reestenosis Coronaria/prevención & control , Vasos Coronarios/efectos de los fármacos , Everolimus , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Inmunosupresores/administración & dosificación , Masculino , Oportunidad Relativa , Estudios Prospectivos , Sirolimus/administración & dosificación , Resultado del TratamientoRESUMEN
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.