Heparin versus placebo for acute coronary syndromes

 

Abstract

Background

Acute coronary syndromes (ACS) represent a spectrum of disease including unstable angina (UA) and non-ST segment myocardial infarction (NSTEMI). Despite treatment with aspirin, beta-blockers and nitroglycerin, UA/NSTEMI is still associated with significant morbidity and mortality. Although emerging evidence suggests that low molecular weight heparin (LMWH) is more efficacious compared to unfractionated heparin (UFH), there is limited data to support the role of heparins as a drug class in the treatment of ACS.

Objectives

To determine the effect of heparins (UFH and LMWH) compared with placebo for the treatment of patients with ACS.

Search strategy

We searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (issue 4, 2002), MEDLINE (1966 to May 2002), EMBASE (1980 to May 2002) and CINAHL (1982 to May 2002). Authors of included studies and pharmaceutical industry representatives were contacted to determine if unpublished studies which met the inclusion criteria were available.

Selection criteria

Randomized controlled trials of parenteral UFH or LMWH versus placebo in people with ACS (UA or NSTEMI).

Data collection and analysis

Two reviewers independently assessed quality of studies. Data were extracted independently by two reviewers. Study authors were contacted to verify and clarify missing data.

Main results

Eight studies (3118 participants) were included in this review. We found no evidence for difference in overall mortality between the groups treated with heparin and placebo (RR = 0.84, 95% CI 0.36 to 1.98). Heparins reduced the occurrence of MI (RR = 0.40, 95% CI 0.25 to 0.63, NNT = 33). An increase in the incidence of minor bleeds (RR = 6.80, 95% CI 1.23 to 37.49, NNH = 17).

Authors' conclusions

Compared to placebo, patients treated with heparins had similar risk of mortality, revascularization, recurrent angina, major bleeding and thrombocytopenia. However, those treated with heparins had decreased risk of MI and a higher incidence of minor bleeding.

 

Plain language summary

Heparins reduce the number of heart attacks but caused more minor bleeding after acute coronary syndromes compared to placebo

Blood clots in the arteries leading to the heart can cause acute coronary syndromes: unstable angina (a feeling of tightness in the chest) or a type of heart attack (non-ST segment myocardial infarction - NSTEMI). Drugs that prevent clots from forming (such as aspirin) or thin the blood (such as heparin) can relieve the problem. Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are two types of heparin. This review of trials found that UFH and LMWH when given to patients with high-risk unstable angina or NSTEMI in the acute phase of treatment in addition to standard therapy with aspirin, prevent more heart attacks than placebo but do not reduce mortality, the need for revascularization procedures or recurrent angina. Although there was limited reporting of side effects, heparins caused more cases of minor bleeding.

 

Resumen

Antecedentes

Heparina versus placebo para los síndromes coronarios agudos

Los síndromes coronarios agudos (SCA) representan una variedad de enfermedades que incluye angina inestable (AI) e infarto de miocardio sin elevación del segmento ST (IMSEST). A pesar del tratamiento con aspirina, betabloqueantes y nitroglicerina, dichas enfermedades están aún asociadas a morbilidad y mortalidad significativas. Aunque nuevas pruebas indican que la heparina de bajo peso molecular (HBPM) es más eficaz en comparación con la heparina no fraccionada (HNF), las pruebas que apoyan la función de las heparinas como un fármaco para el tratamiento del SCA son limitadas.

Objetivos

Determinar el efecto de las heparinas (HNF y HBPM) en comparación con placebo para el tratamiento de los pacientes con SCA.

Estrategia de búsqueda

Se hicieron búsquedas en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) en The Cochrane Library (número 4, 2002), MEDLINE (1966 hasta mayo 2002), EMBASE (1980 hasta mayo 2002) y en CINAHL (1982 hasta mayo 2002). Se contactó a los autores de todos los estudios incluidos y a representantes de industrias farmacéuticas para saber si estaban disponibles los estudios no publicados que cumplieron los criterios de inclusión.

Criterios de selección

Ensayos controlados aleatorios sobre HNF o HBPM parenteral versus placebo en personas con SCA (AI o IMSEST).

Obtención y análisis de los datos

Dos revisores evaluaron la calidad de los ensayos y recogieron los datos de manera independiente. Dos revisores extrajeron independientemente los datos. Se contactó con los autores de los estudios para verificar y clarificar los datos faltantes.

Resultados principales

Se incluyeron ocho estudios (3118 participantes) en esta revisión. No se observaron diferencias en la mortalidad global entre los grupos tratados con heparina o con placebo (RR = 0,84; IC del 95%: 0,36 a 1,98). Las heparinas redujeron la aparición del IM (RR = 0,40; IC del 95%: 0,25 a 0,63; NNT = 33). Un aumento de la incidencia de hemorragias leves (RR = 6,80; IC del 95%: 1,23 a 37,49; NND = 17).

Conclusiones de los autores

En comparación con el placebo, en los pacientes tratados con heparinas, el riesgo de mortalidad, revascularización, angina recurrente, hemorragia y trombocitopenia grave fue similar. Sin embargo, los pacientes tratados con heparinas habían reducido el riesgo de IM y la alta incidencia de hemorragia leve.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano