RESUMEN
BACKGROUND: The Wellcome Trust, the World Health Organization, and cardiologists have advocated for the idea of a "polypill" containing multiple cardiovascular drugs to be co-formulated into a single pill for over a decade. Some cardiologists have asserted that the drugs commonly considered for inclusion into such a polypill are older and therefore free of patent protection. We tested this assertion. This project was requested by the World Heart Federation (WHF). METHODS, DATA AND MATERIALS: Two cardiologists from the WHF provided a list of 48 cardiovascular drugs for evaluation. We designated the United States and Canada as the base jurisdictions for this patent study. We linked patent data from these countries' national medicine patent registers to patent information in over 96 other countries using Derwent and INPADOC via Thomson Innovation. We expanded our study beyond the aforementioned data linkage through a systematic search of the World Intellectual Property Organization's PatentScope, which was based primarily upon the drugs' active ingredient names. RESULTS: In the United States and Canada, eight of the drugs were only available in the patent-protected, brand name formulation in one or both countries. Another 21 drugs had relevant patents, but generic equivalents were nevertheless available. Only 19 drugs (40 %) appeared entirely post-patent. Broadening the co-formulation searches globally, the overwhelming majority of drugs (40/48) were mentioned in patent applications for cardiovascular drug combinations. CONCLUSION: The assertion that most of these cardiovascular drugs are post-patent is accurate, but only in the sense that many of the original patents on these active ingredients have expired and that generic alternatives are usually available. The landscape of patents covering novel (co-) formulations is far more complex, however. Most research and development for cardiovascular combination medicines are likely to be undertaken by companies whose original patents on the active ingredient will soon expire or have recently expired. Cardiologists looking to accelerate polypill development may consider approaching such companies to partner.
Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Descubrimiento de Drogas , Patentes como Asunto , Polifarmacia , Canadá , Química Farmacéutica , Medicamentos Genéricos/uso terapéutico , Humanos , Internacionalidad , Estados UnidosRESUMEN
BACKGROUND: Post-transcatheter aortic valve implantation (TAVI) dual-antiplatelet therapy (DAPT) with acetylsalicylic acid and clopidogrel is common practice to reduce ischemic complications despite the lack of clinical trial evidence demonstrating superiority over mono-antiplatelet therapy (MAPT). METHODS: A systematic search was conducted to retrieve studies that investigated DAPT vs MAPT in patients who have undergone TAVI. Outcomes of interest included both ischemic and bleeding events at 30 days and 6 months. RESULTS: Four studies met inclusion criteria-2 randomized control trials and 2 observational studies, with 286 patients in the DAPT group and 354 patients in the MAPT group. For the primary outcome of a combined end point of 30-day major stroke, spontaneous myocardial infarction (MI), all-cause mortality, and combined lethal and major bleeding, there was a trend toward increased harm in the DAPT group (29%) compared with the MAPT group (16%), with an odds ratio (OR) of 1.88 (P = 0.05). Secondary outcome analysis revealed that there was no significant difference between groups regarding 30-day stroke, 30-day spontaneous MI, and 30-day all-cause mortality. Patients who received DAPT had a significant increase in combined 30-day lethal and major bleeding (OR, 2.62; P = 0.008). Further analysis revealed that increased adverse events were driven by observational studies, with no difference in outcomes between groups in randomized controlled trials. CONCLUSIONS: DAPT in patients who have undergone TAVI demonstrated no benefit over MAPT in reduction of ischemic events, with a trend toward increased harm because of bleeding. Future considerations should be given to MAPT with clopidogrel alone, as well as the omission of clopidogrel loading before the procedure.
Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Clopidogrel , Quimioterapia Combinada , Femenino , Humanos , Masculino , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Análisis de Supervivencia , Ticlopidina/uso terapéutico , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Resultado del Tratamiento , UltrasonografíaRESUMEN
BACKGROUND: The Variation in Revascularization Practice in Ontario (VRPO) project helped describe variations in revascularization across Ontario. Coronary anatomy was the most important predictor of revascularization strategy. We conducted a novel angiographic substudy of the VRPO cohort to: (1) validate "real-world" coronary angiographic reporting in the province of Ontario; and (2) understand the relationship between variability in revascularization and coronary anatomy complexity. METHODS: Seventeen hundred eighty-seven angiograms from 17 cardiac centres were randomly sampled from the VRPO cohort. The core lab assessment involved blinded interpretation of each angiographic film. A comparison of agreement in coronary anatomy and treatment strategy between abstracted chart data from the VRPO study and blinded film review was undertaken. Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) scores were calculated for all patients with multivessel disease. RESULTS: The weighted κ statistic for coronary anatomy was 0.75 (95% confidence interval, 0.72-0.77), suggesting substantial agreement between abstracted chart data and blinded film review. The weighted κ for revascularization strategy was 0.51 (95% confidence interval, 0.47-0.54) suggesting only moderate agreement. There were no significant differences in the mean/median SYNTAX scores across all 4 percutaneous coronary intervention: coronary artery bypass graft (CABG) groups. CONCLUSIONS: Abstracted chart data in the VRPO project provides a valid assessment of coronary anatomy and furthermore serves as validation of "real-world" coronary angiographic reporting in the province of Ontario. The uniform distribution of coronary complexity across centres in Ontario, with respect to the SYNTAX score, suggests the variation of percutaneous coronary intervention: CABG ratio is not related to a difference in coronary anatomy complexity across sites, but rather a difference in management strategies for the same anatomy.
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Enfermedad de la Arteria Coronaria/cirugía , Revascularización Miocárdica/métodos , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/estadística & datos numéricosAsunto(s)
Infarto del Miocardio/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , Inhibidores de Agregación Plaquetaria/uso terapéutico , Vigilancia de la Población/métodos , Pautas de la Práctica en Medicina , Trombosis/prevención & control , Warfarina/uso terapéutico , Adulto , Anticoagulantes/uso terapéutico , Canadá/epidemiología , Quimioterapia Combinada , Cardiopatías/epidemiología , Cardiopatías/etiología , Cardiopatías/prevención & control , Humanos , Incidencia , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Trombosis/epidemiología , Trombosis/etiologíaRESUMEN
BACKGROUND: In randomized trials, paclitaxel-eluting stents (PES) are superior to bare metal stents (BMS) in reducing target lesion revascularization (TLR). However, recent reports suggest there may be an increase in late stent thrombosis with long-term follow-up in PES-treated patients. METHODS: Prospectively collected data from a regional cardiac referral centre were analyzed to compare PES versus BMS in all consecutive patients undergoing percutaneous coronary intervention from April 2003 to March 2004. Outcomes included combined death, myocardial infarction and clinically driven TLR, as well as stent thrombosis at four years follow-up. RESULTS: A total of 512 patients were treated with PES and 722 patients with BMS. At four years, there was 92% follow-up in both groups. The composite outcome of death, myocardial infarction and TLR was 13.9% in the PES group compared with 20% in the BMS group (P=0.01). This difference was primarily driven by the reduction in TLR in the PES cohort (3.9% versus 8%, P<0.01). The rate of definite stent thrombosis was 1.6% in the PES group compared with 0.4% in the BMS group (P=0.03). CONCLUSION: While PES offers an absolute 4.1% reduction in clinically driven TLR at four years, there is an associated increased risk of stent thrombosis. Further long-term studies addressing clinical outcomes including stent thrombosis with PES versus BMS are required to clarify this risk/ benefit balance.
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Angioplastia Coronaria con Balón/métodos , Estenosis Coronaria/cirugía , Stents Liberadores de Fármacos , Paclitaxel/farmacología , Anciano , Antineoplásicos Fitogénicos/farmacología , Angiografía Coronaria , Reestenosis Coronaria/epidemiología , Reestenosis Coronaria/prevención & control , Estenosis Coronaria/diagnóstico , Electrocardiografía , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Ontario/epidemiología , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
UNLABELLED: In the current era of early revascularization and routine use of dual antiplatelet therapy, the incremental benefit of warfarin to reduce the incidence of left ventricular thrombus (LVT) in patients with impaired left ventricular ejection fraction post anterior ST-elevation myocardial infarction (aSTEMI), remains uncertain. The purpose of this study is to assess the feasibility of evaluating the added benefit and safety of triple therapy (TT-warfarin, ASA, and clopidogrel) versus dual therapy (DT-ASA and clopidogrel) in patients at risk of LVT post aSTEMI. DESIGN: Open-label randomized controlled trial. INCLUSION: aSTEMI, ejection fraction <40%, and no evidence of LVT. EXCLUSION: contraindication to, or alternate indication for anticoagulation. INTERVENTION: TT versus DT. FOLLOW-UP: pre-discharge and 3 month echocardiogram. OUTCOMES: composite of death, MI, stroke, systemic embolizarion, LVT or major bleeding at three months. 295 patients with aSTEMI were screened: 27% of patients with LVEF < 40% had an LVT; 20/52 eligible patients were randomized to receive TT (n = 10) or DT (n = 10). Baseline characteristics: mean age 60 years, male gender 65%, diabetics 20%, and in hospital PCI 95%. There was no significant difference in the composite endpoint at 3 months (TT-20% with 1 LVT and 1 major bleed versus DT-10% with 1 MI). The incidence of definite or probable LVT in the screened population of patients post aSTEMI with an LVEF < 40% was 26.6% despite 94% having early revascularization. STEMI patients have a high incidence of LVT despite the routine use of early revascularization and dual antiplatelet therapy. More effective antithrombotic strategies merit evaluation in adequately powered randomized trials.
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Anticoagulantes/uso terapéutico , Aspirina/uso terapéutico , Infarto del Miocardio/terapia , Revascularización Miocárdica , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis/prevención & control , Ticlopidina/análogos & derivados , Warfarina/uso terapéutico , Anciano , Anticoagulantes/efectos adversos , Aspirina/efectos adversos , Clopidogrel , Quimioterapia Combinada , Embolia/etiología , Estudios de Factibilidad , Femenino , Hemorragia/inducido químicamente , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/mortalidad , Revascularización Miocárdica/efectos adversos , Revascularización Miocárdica/mortalidad , Ontario , Inhibidores de Agregación Plaquetaria/efectos adversos , Recurrencia , Accidente Cerebrovascular/etiología , Trombosis/etiología , Trombosis/mortalidad , Ticlopidina/efectos adversos , Ticlopidina/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/terapia , Warfarina/efectos adversosRESUMEN
BACKGROUND: In randomized trials, paclitaxel-eluting stents (PES) have been shown to be superior to bare metal stents (BMS) in reducing restenosis. However, the effectiveness of PES in patients treated during routine practice has not been fully established. METHODS: A retrospective comparison of PES with BMS in consecutive patients undergoing percutaneous coronary intervention (PCI) from April 2003 to March 2004 was conducted. Outcomes included the composite of death, myocardial infarction and target lesion revascularization (TLR) at one year, as well as stent thrombosis. RESULTS: A total of 512 patients were treated with PES, and 722 patients were treated with BMS. Patients in the PES group were more likely to receive stents that were 20 mm in length or longer (52.2% versus 33.3%, P<0.0001), 2.5 mm in diameter or smaller (29.1% versus 12.5%, P<0.0001) and implanted in bifurcation positions (15.4% versus 11.6%, P=0.02). At one year, the composite outcome of death, myocardial infarction and TLR was 6.1% in the PES group compared with 10.8% in the BMS group (P=0.004). The one-year rate of stent thrombosis was 0.59% in the PES group compared with 0.28% in the BMS group (P=0.4). CONCLUSIONS: Despite being used in higher-risk lesions, there was a lower rate of major cardiac events at one year in patients treated with PES, primarily driven by the reduction in TLR. Thus, the experience with PES in contemporary practice applied to a broader population appears to be consistent with the results reported in randomized trials.