Dr.ssa Michela D AgosKno

Transcription

1 Scuola di Specializzazione in Mala/e dell Apparato Cardiovascolare Dire8ore Prof. Massimo Volpe Facoltà di Medicina e Psicologia, Università di Roma Sapienza Anno Accademico Dr.ssa Michela D AgosKno Proge8o Formazione Avanzata in Cardiologia nel Web 2014 Scuola di Specializzazione in Mala/e dell Apparato Cardiovascolare Dire8ore: Prof. Massimo Volpe E- mail: massimo.volpe@uniroma1.it Coordinatore: Dr. Giuliano Tocci E- mail: giuliano.tocci@uniroma1.it

2 Low- Dose Aspirin for Primary Preven4on of Cardiovascular Events in Japanase Pa4ents 60 Years or Older With Atherosclero4c Risk Factors: A Randomized Clinical Trial Ikeda Y, Shimada K, Teramoto T, Uchiyama S, Yamazaki T, Oikawa S, Sugawara M, Ando K, Murata M, Yokoyama K, Ishizuka N

3 Background (1/3) The World Health OrganizaKon (WHO) eskmates that annual global mortality due to cardiovascular diseases will approach 25 million by A recent study of secular trends in cardiovascular disease in Japan indicated that, from 1960 to 2000, the prevalence of smoking decreased and blood pressure control among hypertensive individuals improved significantly. Conversely, a steep increase in the prevalence of glucose intolerance, hypercholesterolemia and obesity was observed. By the year 2030, an eskmated 1 of every 4 persons in Japan will be aged > 60 years. Together with the aging of the polulakon, adopkon of Western diets and lifestyles has contributed to the rising prevalence of lifestyle- related diseases, including hypertension, dyslipidemia, and diabetes mellitus. As a result, the prevenkon of atherosclerokc disease has become one of the most important public health issues in Japan.

4 Background (2/3) Aspirin reduces the incidence of serious vascular events in high- risk pakets with acute or established atherosclerokc disease. The meta- analysis conducted by the AnKthromboKc Trialists ColaboraKon involving >30 countries (including Japan) showed that aspirin at daily doses of > 75 mg significantly reduced the risk of serious vascular events (non fatal MI or stroke, or death due to vascular cause) by 23% overall compared with no aspirin use in the secondary prevenkon se/ng. In 2009, AnKthromboKc Trialists CollaboraKon reviewed the benefit- risk profile of low- dose aspirin for the primary prevenkon of vascular desease in meta- analysis of the 6 large clinic studies in Europe and North America. Aspirin was associated with a significant 12% proporkonal reduckon in serious vascular events compared with no aspirin, mainly due to reduckon in non fatal MI of approximately 20%. Aspirin increased major gastrointesknal and extracranial bleeding compared with control, reduckon in ischemic stroke but an increase in hemorrhagic stroke.

5 Background (3/3) To date, no trials with aspirin for primary prevenkon of ischemic heart disease have been reported in a general populakon of Japanese pakents, and no epidemiological data for this populakon are available to allow seleckon of suitable candidates for aspirin therapy. In Japan, the use of aspirin for primary prevenkon of IHD has not been widespread in clinical prackce.

6 Objec4ves The Japanese Primary PrevenKon Project (JPPP) was designed to test the clinical hypothesis that the benefit of primary prevenkon with low- dose, enteric- coated aspirin in reducing total atherosclerokc events (IHD and stroke) will outweigh risks of gastrointesknal or cerebrovascular bleeding in elderly Japanese pakents with hypertension, hyperlipidemia, or diabetes.

7 Study Design MulKcenter, open- label, randomized, parallel- group clinical trial. PaKents were recruited consecukvely at each clinic by primary care physicians between March 2005 and June The last included pakent completed follow- up in May 2012.

8 Study Design: Inclusion Criteria Hypertension (SBP 140 mmhg or DBP 90 mmhg) Dyslipidemia (Total Cholesterol 220 mg/dl or LDL 140 mmhg or HDL < 40 mg/dl or Triglycerides 150 mg/dl) Diabetes Mellitus (FasKng morning blood glucose 126 mg/dl or any blood glucose 200 mg/dl or 2- hour blood glucose 200 mg/ dl in the 75- g glucose tolerance test or glycated hemoglobin 6,5%)

9 Study Design: Exclusion Criteria History of coronary artery disease or cerebrovascular disease (including TIA) AtheroscleroKc disease requiring surgery or intervenkon Atrial fibrillakon (confermed os suspected) PepKc ulcer or condikons associated with bleeding (eg. von Willebrand disease, clo/ng factor deficiencies) Aspirin- sensikve asthsma or history of hypersensikvity to aspirin or salicylic acid Use of ankplatelet agents, ankcoagulants or long- term treatment with nonsteroidal ank- infiammatory drugs.

10 Study Design

11 Study Design: Pa4ents Alloca4on

12 Study Endpoints

13 SAFETY ENDPOINTS GastrointesKnal adverse events GastrointesKnal hemorrhage Gastroduodenal ulcer Reflux esophagiks Erosive gastriks Stomach or abdominal discomfort, pain or pressure Heartburn Nausea

14 BASELINE CHARACTERISTICS FOR PATIENTS

15 RESULTS (1): Kaplan- Meier curves for the Primary Endpoint

16 RESULTS (2): PRIMARY ENDPOINTS

17 RESULTS (3): PRIMARY ENDPOINTS

18 RESULTS (4): SECONDARY ENDPOINTS

19 RESULTS (5): INCIDENCE OF PRESPECIFIED GASTROINTESTINAL EVENTS OF INTEREST

20 CONCLUSIONS This study indicates that primary prevenkon with daily low- dose aspirin does not reduce the risk of the composite outcome of CV death, nonfatal stroke and nonfatal MI in elderly Japanese pakents with atherosclerokc risk factors. However, the study was disconknued prematurely before the study reached stakskcal power. Aspirin significantly reduced the incidence of non- fatal MI and TIA, while it increased the risk of serious extracranial bleeding. It is possible that the low incidence of fatal and nonfatal cardiovascular events is due to the characteriskcs of Japanese pakents. Further analyses are planned.

21 Scuola di Specializzazione in Mala/e dell Apparato Cardiovascolare Dire8ore Prof. Massimo Volpe Facoltà di Medicina e Psicologia, Università di Roma Sapienza Anno Accademico Dr.ssa Michela D AgosKno Grazie per la Vostra Attenzione! Proge8o Formazione Avanzata in Cardiologia nel Web 2014 Scuola di Specializzazione in Mala/e dell Apparato Cardiovascolare Dire8ore: Prof. Massimo Volpe E- mail: massimo.volpe@uniroma1.it Coordinatore: Dr. Giuliano Tocci E- mail: giuliano.tocci@uniroma1.it