Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen.

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC)

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.(AU)

Dual antiplatelet therapy duration based on ischemic and bleeding risks after coronary stenting

Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)

Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials

Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods: A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk...

Vertebroplastia e cifoplastia: técnicas complementares para o tratamento da fratura vertebral osteoporótica dolorosa tipo compressão / Vertebroplastia y cifoplastia: técnicas complementarias para el tratamiento de la fractura vertebral osteoporótica dolorosa tipo compresión / Vertebroplasty and kyphoplasty: complementary tecniques for the treatment of painful osteoporotic vertebral compression fractures

In a prospective study, we aimed to evaluate the potential use of kyphoplasty (KP) and vertebroplasty (VP) as complementary techniques in the treatment of painful osteoporotic vertebral compression fractures (VCFs). METHODS: after one month of conservative treatment for VCFs, patients with intractable pain were offered treatment with KP or VP according to a treatment algorithm that considers time from fracture (Ãt) and amount of Vertebral Body Collapse (VBC). Bone biopsy was obtained intraoperatively to exclude patients affected by malignancy or osteomalacia. RESULTS: hundred and sixty-four patients were included according to the above criteria. Mean age was 67.6 years. Mean followup was 33 months. Ten patients (6.1 percent) were lost to follow-up and 154 reached the minimum two years follow-up. 118 (69.5 percent) underwent VP and 36 (30.5 percent) underwent KP. Complications affected five patients treated with VP, whose one suffered a transient intercostal neuropathy and four a subsequent VCF (two at adjacent level). Results in terms of VAS and Oswestry scores were not different among treatment groups. CONCLUSION: in conclusion, at an average follow-up of almost 3 years from surgical treatment of osteoporotic VCFs, VP and KP show similar good clinical outcomes and appear to be complementary techniques with specific different indications.

Estudo prospectivo para avaliar a utilização da cifoplastia e vertebroplastia como técnicas complementares para o tratamento das fraturas osteoporóticas tipo compressão. MÉTODOS: após um mês de tratamento conservador, os pacientes com fratura osteoporótica do tipo compressão e com dor intratável, foram submetidos à cifoplastia ou vertebroplastia de acordo com algoritmo que considera o tempo da fratura e a quantidade do colapso do corpo vertebral. Biópsia óssea foi obtida no intra-operatório para excluir os pacientes com tumor ou osteomalácia. RESULTADOS: cento e trinta e quatro pacientes foram incluídos de acordo com os critérios do estudo. A média de idade foi 67,7 anos. O seguimento médio foi 33 meses. Dez pacientes não foram seguidos e 154 atingiram um seguimento mínimo de dois; 118 pacientes (69,5 por cento) foram submetidos à vertebroplastia e 36 (30,5 por cento) à cifoplastia. Ocorreram complicações em cinco pacientse tratados por verebroplastia, sendo que um paciente apresentou neuropatia intercostal transitória e quatro pacientes fratura por compressão, tendo ocorrido na vértebra adjacente em dois pacientes. Não foi observada diferença nos escores da avaliação da dor e do questionário de Oswestry. CONCLUSÃO: após um seguimento médio de três anos foram observados resultados satisfatórios com a utilização da vertebroplastia ou cifoplastia para o tratamento das fraturas osteoporóticas por compressão. Ambas as técnicas mostraram bons resultados, de acordo com a sua indicação específica.

Estudio prospectivo para evaluar la utilización de la cifoplastia y vertebroplastia como técnicas complementarias para el tratamiento de las fracturas osteoporóticas tipo compresión. MÉTODOS: después de 1 mes de tratamiento conservador, los pacientes con fractura osteoporótica del tipo compresión y de haber presentado un dolor intratable, los pacientes fueron sometidos a la cifoplastia o vertebroplastia de acuerdo con el algoritmo que considera el tiempo de la fractura y la cantidad del colapso del cuerpo vertebral. Biopsia ósea fue obtenida en el intraoperatorio para excluir los pacientes con tumor u osteomalacia. RESULTADOS: ciento treinta y cuatro pacientes fueron incluidos de acuerdo con los criterios del estudio. El promedio de edad fue 67.7 años. El seguimiento promedio fue de 33 meses. Diez pacientes no fueron seguidos y 154 llegaron a un seguimiento mínimo de dos. 118 pacientes (69.5 por ciento) fueron sometidos a la vertebroplastia y 36 (30.5 por ciento) a la cifoplastia. Complicaciones ocurrieron en cinco pacientes tratados por vertebroplastia, siendo que un paciente presentó neuropatía intercostal transitoria y cuatro pacientes una fractura por compresión en la vértebra adyacente. No fue observada diferencia entre los índices de la evaluación del dolor y del cuestionario de Oswestry. CONCLUSIÓN: después del seguimiento promedio de tres años fueron observados resultados satisfactorios con la utilización de la vertebroplastia o cifoplastia para el tratamiento de las fracturas osteoporóticas por compresión. Ambas técnicas mostraron buenos resultados de acuerdo con su indicación específica.