RESUMO
AIMS: Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment. METHODS AND RESULTS: The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL (P < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively; P < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80-0.96; 0.68, 0.49-0.94; and 0.65, 0.44-0.97, respectively; Pinteraction = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34-2.16; 3.16%, 0.38-5.94; 7.97%, 0.42-15.51; Pinteraction = 0.106). CONCLUSIONS: PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.
Assuntos
Síndrome Coronariana Aguda , Anticolesterolemiantes , Isquemia Encefálica , Inibidores de Hidroximetilglutaril-CoA Redutases , Acidente Vascular Cerebral , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Humanos , Pró-Proteína Convertase 9 , Resultado do TratamentoRESUMO
BACKGROUND: The Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX trial demonstrated superiority of cangrelor in reducing ischemic events at 48 hours in patients undergoing percutaneous coronary intervention compared with clopidogrel. METHODS AND RESULTS: We analyzed all patients included in the modified intention-to-treat analysis in US (n=4097; 37.4%) and non-US subgroups (n=6845; 62.6%). The US cohort was older, had a higher burden of cardiovascular risk factors, and had more frequently undergone prior cardiovascular procedures. US patients more frequently underwent percutaneous coronary intervention for stable angina (77.9% versus 46.2%). Almost all US patients (99.1%) received clopidogrel loading doses of 600 mg, whereas 40.5% of non-US patients received 300 mg. Bivalirudin was more frequently used in US patients (56.7% versus 2.9%). At 48 hours, rates of the primary composite end point were comparable in the US and non-US cohorts (5.5% versus 5.2%; P=0.53). Cangrelor reduced rates of the primary composite end point compared with clopidogrel in US (4.5% versus 6.4%; odds ratio 0.70 [95% confidence interval 0.53-0.92]) and in non-US patients (4.8% versus 5.6%; odds ratio 0.85 [95% confidence interval 0.69-1.05]; interaction P=0.26). Similarly, rates of the key secondary end point, stent thrombosis, were reduced by cangrelor in both regions. Rates of Global Use of Strategies to Open Occluded Arteries (GUSTO)-defined severe bleeding were low and not significantly increased by cangrelor in either region. CONCLUSIONS: Despite broad differences in clinical profiles and indications for percutaneous coronary intervention by region in a large global cardiovascular clinical trial, cangrelor consistently reduced rates of ischemic end points compared with clopidogrel without an excess in severe bleeding in both the US and non-US subgroups. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01156571.
Assuntos
Monofosfato de Adenosina/análogos & derivados , Trombose Coronária/prevenção & controle , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Idoso , Brasil , Distribuição de Qui-Quadrado , Clopidogrel , Trombose Coronária/sangue , Trombose Coronária/etiologia , Método Duplo-Cego , Europa (Continente) , Feminino , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Razão de Chances , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Estudos Prospectivos , Fatores de Risco , Tailândia , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
AIM: To determine the current prevalence and control of major cardiovascular risk factors in stable CAD outpatients worldwide. METHODS: We analysed variations in cardiovascular risk factors in stable CAD outpatients from CLARIFY, a 5-year observational longitudinal cohort study, in seven geographical zones (Western/Central Europe; Canada/South Africa/Australia/UK; Eastern Europe; Central/South America; Middle East; East Asia; and India). RESULTS: Patient presentation (N=32,954, mean age 64.2 years, 78% male) varied between zones, as did prevalence of risk factors (all p < 0.0001). Obesity ranged from 20% (East Asia) to 42% (Middle East), raised blood pressure from 28% (Central/South America and East Asia) to 48% (Eastern Europe), raised LDL cholesterol from 24% (Canada/South Africa/Australia/UK) to 65% (Eastern Europe), elevated heart rate (≥70 bpm) from 38% (Western/Central Europe) to 78% (India), diabetes from 17% (Eastern Europe) to 60% (Middle East), and smoking from 6% (Central/South America) to 19% (Eastern Europe). Aspirin and lipid-lowering drugs were widely used everywhere (≥84% and ≥88%, respectively). Rates of risk factor control varied geographically (all p < 0.0001). Rate of controlled blood pressure in hypertension varied from 47% (Eastern Europe) to 66% (Central/South America), glucose control in diabetes from 23% (India) to 51% (Western/Central Europe and East Asia), controlled LDL cholesterol and dyslipidaemia from 32% (Eastern Europe) to 75% (Canada/South Africa/Australia/UK), heart rate <70 bpm from 22% (India) to 62% (Western/Central Europe), and heart rate ≤60 bpm in angina patients from 2% (India) to 29% (Canada/South Africa/Australia/UK and Central/South America). CONCLUSION: Prevalence and control of major cardiovascular risk factors in stable CAD vary markedly worldwide. Many stable CAD outpatients are being treated suboptimally.