Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study

The composition and use of oral contraceptives (OCs) have changed since their cardiovascular side-effects were established 20 years ago. This report describes the risk of idiopathic venous thromboembolic (VTE) events (deep vein thrombosis [DVT] and/or pulmonary embolism [PEI]) in association with current use of combined OCs among 1143 cases aged 20-44 and 2998 age-matched controls, as evaluated in a hospital-based, case-control study in 21 centres in Africa, Asia, Europe, and Latin America.OC use was associated with an increased risk of VTE in Europe (odds ratio 4.15 [95% CI 3.09-5.57]) and in non-European (''developing'') countries (3.25 [2.59-4.08]). Risk estimates were generally higher for DVT than for PE but no consistent trend by certainty of diagnosis (definite, probable, possible) was found. Increased risk was apparent within 4 months of starting OCs, was unaffected by duration of current episode of OC use, and had disappeared within 3 months of stopping OCs. Relative risk estimates of VTE associated with OC use were unaffected by age of user, by history of hypertension (excluding hypertension in pregnancy), or in any consistent way by smoking. However, in both groups of countries increased body mass index (BMI) was an independent risk factor for VTE, and OC-associated odds ratios were higher among those with a BMI above 25 kg/m(2) than among those with smaller BMIs. OC-associated risk estimates were high among women in Europe with a history of hypertension in pregnancy.Odds ratios associated with the use of OCs containing a third-generation progestagen observed with progestagens type) and second (norgestrel group) generation. Odds ratios associated with first and second generation progestagens tended to be lower, though not significantly, when used in combination with low (<50 mu g oestrogen) rather than higher oestrogen doses. This study confirms an association between OC use and VTE in Europe and the developing countries, although overall risk estimates associated with use were lower than demonstrated in most previous studies of non-fatal idiopathic VTE.ESCOLA PAULISTA MED,SAO PAULO,BRAZILESCUELA MED,VALPARAISO,CHILESHANGHAI INST PLANNED PARENTHOOD RES,SHANGHAI,PEOPLES R CHINAUNIV VALLE,FAC SALUD,CALI,COLOMBIAUNIV OXFORD,OXFORD,ENGLANDZENTRUM EPIDEMIOL & GESUNDHEITFORSCH,BERLIN,GERMANYCHINESE UNIV HONG KONG,HONG KONG,HONG KONGALBERT SZENT GYORGYI MED UNIV,H-6701 SZEGED,HUNGARYUNIV INDONESIA,FAC MED,JAKARTA,INDONESIAUNIV W INDIES,TROP METAB RES UNIT,KINGSTON 7,JAMAICAKENYA GOVT MED RES CTR,NAIROBI,KENYAGRP INTERUNIV MEXICANO INVEST EPIDEMIOL SALUD REP,DURANGO,MEXICOUNIV LJUBLJANA,INST PUBL HLTH,LJUBLJANA,SLOVENIACHULALONGKORN HOSP,BANGKOK,THAILANDSIRIRAJ HOSP,SIRIRAJ FAMILY HLTH RES CTR,BANGKOK,THAILANDUNIV BELGRADE,SCH MED,BELGRADE,YUGOSLAVIAUNIV LUSAKA,TEACHING HOSP,LUSAKA,ZAMBIAUNIV ZIMBABWE,HARARE,ZIMBABWEESCOLA PAULISTA MED,SAO PAULO,BRAZILWeb of Scienc

Acute myocardial infarction and combined oral contraceptives: Results of an international multicentre case-control study

Background The association between oral contraceptive (OC) use and acute myocardial infarction (AMI) was established in studies from northern Europe and the USA, which took place during the 1960s and 1970s. Few data are available to quantify the risk worldwide of AMI associated with use of OCs introduced since those early studies. This hospital-based case-control study examined the association between a first AMI and current OC use in women from Africa, Asia, Europe, and Latin America (21 centres).Methods Cases were women aged 20-44 years who had definite or possible AMI (classified by history, electrocardiographic, and cardiac-enzyme criteria), who were admitted to hospital, and who survived for at least 24 h. Up to three hospital controls matched by 5-year age-band were recruited for each of the 368 cases (941 controls). All participants were interviewed while in hospital with the same questionnaire, which included information on medical and personal history, lifetime contraceptive use, and blood-pressure screening before the most recent episode of OC use. Odds ratios compared the risk of AMI in current OC users and in non-users (past users and never-users combined).Findings The overall odds ratio for AMI was 5.01 (95% CI 2.54-9.90) in Europe and 4.78 (2.52-9.07) in the non-European (developing) countries; however, these risk estimates reflect the frequent coexistence of other risk factors among OC users who have AMI. Very few AMIs were identified among women who had no cardiovascular risk factors and who reported that their blood pressure had been checked before OC use; odds ratios associated with OC use in such women were not increased in either Europe or the developing countries. Among OC users who smoked ten or more cigarettes per day, the odds ratios in Europe and in the developing countries were over 20. Similarly, among OC users with a history of hypertension (during pregnancy or at any other time), odds ratios were at least ten in both groups of countries, No consistent association between odds ratios for AMI and age of OC users or oestrogen dose was apparent in either group of countries, No significant increase in odds ratios was apparent with increasing duration of OC use among current users, and odds ratios were not significantly increased in women who had stopped using OCs, even after long exposure. The study had insufficient power to examine whether progestagen dose or type had any effect on AMI risk.Interpretation Current use of combined OCs is associated with an increased risk of AMI among women with known cardiovascular risk factors and among those who have not been effectively screened, particularly for blood pressure, AMI is extremely rare in younger (<35 years) non-smoking women who use OCs, and the estimated excess risk of AMI in such women in the European centres is about 3 per 10(6) woman-years. The risk is likely to be even lower if blood pressure is screened before, and presumably during, OC use. Only among older women who smoke is the degree of excess risk associated with OCs substantial (about 400 per 10(6) woman-years).ESCOLA PAULISTA MED,BR-04023 SAO PAULO,BRAZILUNIV CHILE,ESCUELA SALUD PUBL,SANTIAGO,CHILENATL RES INST FAMILY PLANNING,BEIJING,PEOPLES R CHINASICHUAN FAMILY PLANNING RES INST,CHENGDU,PEOPLES R CHINASHANGHAI INST PLANNED PARENTHOOD RES,SHANGHAI,PEOPLES R CHINAUNIV VALLE,FAC SALUD,CALI,COLOMBIAZENTRUM EPIDEMIOL & GESUNDHEITSFORSCH,BERLIN,GERMANYCHINESE UNIV HONG KONG,SHATIN 100083,HONG KONGALBERT SZENT GYORGYI MED UNIV,H-6701 SZEGED,HUNGARYUNIV INDONESIA,FAC MED,JAKARTA,INDONESIAKENYA GOVT MED RES CTR,NAIROBI,KENYAINTERUNIV MEXICANO INVEST EPIDEMIOL SALUD REPROD,DURANGO,MEXICOUNIV W INDIES,TROP METAB RES UNIT,KINGSTON 7,JAMAICAESCUELA MED,VALPARAISO,CHILEUNIV LJUBLJANA,INST PUBL HLTH,LJUBLJANA,SLOVENIACHULALONGKORN HOSP,BANGKOK,THAILANDSIRIRAJ HOSP,BANGKOK,THAILANDUNIV OXFORD,OXFORD,ENGLANDUNIV BELGRADE,SCH MED,YU-11001 BELGRADE,YUGOSLAVIAUNIV TEACHING HOSP,LUSAKA,ZAMBIAUNIV ZIMBABWE,HARARE,ZIMBABWEUNIV OXFORD,OXFORD OX1 2JD,ENGLANDKAISER PERMANENTE,PASADENA,CANICHHD,BETHESDA,MDAARHUS UNIV,DANISH EPIDMEIOL SCI CTR,DK-8000 AARHUS C,DENMARKLONDON SCH HYG & TROP MED,LONDON WC1,ENGLANDESCOLA PAULISTA MED,BR-04023 SAO PAULO,BRAZILWeb of Scienc