Original

Analysis and Characterization of the Pharmacotherapy of Low Molecular Weight Heparins Prescribed in Hospitalized Patients at the Hospital Clinica Biblica (Costa Rica) from March to August 2010

Gustavo Céspedes-Orozco¹, José Miguel Chaverri-Fernández^2,3, Jeime López-González¹, Esteban Zavaleta-Monestel.³

Clínica Bíblica Hospital, San José, Costa Rica

Abbreviations: ACCP, American College of Chest Physicians; LMWH, low molecular weight heparin; CBH, Clínica Bíblica Hospital; ISHM, Integrated System for Hospital Management; PTE, pulmonary thromboembolism; VTE, venous thromboembolism; DVT,  deep venous thrombosis.

¹ Pharmacy interns, University of Ibero-America, Costa Rica.

² Department of Pharmacology, Toxicology and Pharmacodependence, Faculty of Pharmacy, University of Costa Rica.
³ Pharmacy, Clínica Bíblica Hospital, Costa Rica. 

Correspondence:

jose.chaverri@ucr.ac.cr

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Abstract

Aim: To analyze the prescription of low molecular weight heparins in hospitalized patients at the Clinica Biblica Hospital (private hospital in Costa Rica) based on the guidelines established by the American College of Chest Physicians (ACCP;2008).

Material and methods: This study included 1651 hospitalized patients in the period from March to August 2010 who were treated with low molecular weight heparins, 250 patients were analyzed and randomly selected. A compilation of documents and information required for each patient for the analysis was made.

Results: A total of 43% of the hospitalized patients used low molecular weight heparins (707 patients). In 91% of cases low molecular weight heparins were used with a prophylactic purpose. 2% of patients did not need to use prophylactic heparin therapy. In 90% of cases the dose was correct. 18% of cases required dose adjustments. In 80% of the patients had clinically relevant drug interactions, 4% of patients had some form of bleeding, where 2% of cases this effect was linked to the use of low molecular weight heparins. In 9% of cases in which LMWH were used as treatment were addressed in accordance with established guidelines.

Keywords: Low molecular weight heparins, Drug utilization study, Deep vein thrombosis, thromboprophylaxis, side effects, bleeding.

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The type of thrombogenic substrate determines the use of LMWH for antithrombotic treatment. The main conditions where LMWH is preferred are: pulmonary thromboembolism (PTE), stroke, myocardial infarction, transient ischemic seizures and treatment or prophylaxis for deep venous thrombosis (DVT).^4,7

Routine assays have demonstrated that pharmacologic prophylaxis for DVT must be the treatment of choice in most patients hospitalized for more than one or two days, after risk stratification (main indication for LMWH)⁷. A single daily dose of LMWH is effective and safe, and it halves the risk of DVT without and increase on hemorrhagic complications.⁷

LMWH is widely used in the aforementioned indications, and, therefore, it is important to be able both to evaluate the efficacy or safety of the prescription and the way it is issued and its compliance with the accepted guideline (ACCP 2008 in our case). The latter variables are quantifiable by means of medication use evaluation studies.⁸

Medication use evaluation studies can provide plenty of information and multiple useful answers for the improvement of the management of drugs in a hospital, in order to accomplish a more rational use of them, to reduce the cost of treatments or to improve the way health conditions are treated.^8-12

The American College of Chest Physicians (ACCP) guidelines have been developed in order to assure the rational and correct use of anticoagulant therapy (including LMWH among others), by means of therapeutic proposals based on the best available scientific evidence.⁸

The aim of this study was to characterize and analyze the indications for LMWH prescribed to patients hospitalized in the Clínica Bíblica Hospital (CBH) and to provide an analysis of the anticoagulant pharmacotherapy (with LMWH) that those patients received in order to validate the pertinence, efficacy and safety of these drugs, their use in view of the international guidelines (ACCP 2008) and their safety through time.

Materials and Methods

This research was a retrospective, observational medication use evaluation study. The study was carried out on hospitalized patients at CBH from March to August 2010.

All patients over 18 that received LMWH were included except those who were not hospitalized for at least 24 h. The sample size was determined by a simple random probabilistic system. Daniel Wayne's 1998 9,10 formula for a known population with 95% confidence, 5% precision and an expected proportion of 50%, which maximizes the sample size, was employed, and random selection was achieved by the use of Microsoft Excel, Microsoft Office 2010.

All documents and necessary information for the study (clinical data for every patient, discharge report, nursing administration sheets, hospital's admission databases, epicrisis, clinical laboratory tests, medical notes, pharmacologic profile, among others) were gathered by means of the medical records and two in-house softwares at CBH: the Integrated System for Hospital Management (ISHM) and RECETARIO.

The information was centralized using a data collection sheet on which the most relevant aspects of each patient were recorded.

A comparison between the data obtained in the study and those reported in the literature¹¹ was carried out. A multivariate analysis including patient, disease and prescribed medicine-related factors was performed. The requirements for dose adjustment for each patient were evaluated by means of their clinical laboratory test data and the use of the creatinin clearance (Cockroft-Gault) adjusted at 72 kg.^12,13

The need for thrombo-prophylaxis was analyzed individually using an adaptation of the system used by the ACCP and stratifying patients in one of the four VTE risk levels according to the type of adequate surgical procedure, age and the presence of other additional risk factors the patient may have had.

The dosing for each indication was evaluated according to the literature review and what has been published by the ACCP. In order to determine clinically significant interactions we used two softwares: Micromedex ® 1.0 (Healthcare Series) by Thompson Reuters and Lexi-ComInteract ®, analyzing the validity and significance of the information they generated. For the processing of the data we used statistical analysis tools and programs such as Excel Microsoft Office 2010 and SPSS V18 (Statistical Program for the Social Sciences).

Results

Fifty-eight percent of the selected patients were women and 43% were men. The mean age of the patients was 62 ± 15 years. 

LMWH types that were used were enoxaparin (87% of the cases), bemiparin (8% of the cases), and fondaparinux (5% of the cases). Sixty-five different initial diagnoses were found, the most relevant of which are presented in Table 1.

 

In this hospital, the main condition where LMWH was used was DVT prophylaxis (91% of the cases). In a small group of patients (remaining 9%) LMWH was used for medical treatment of PTE, DVT, acute coronary syndrome and/or stroke. Patients who were treated under these conditions were given LMWH following the established guidelines, with correct doses and in combination with other necessary anticoagulant or antiplatelet agents.

In order to be able to stratify the patients to assess the need for thromboprophylaxis as recommended by the ACCP, an analysis of individual risk factors was carried out and the most relevant are presented in Table 2.

 

 

According to the risk stratification, 52.4% of the population had a medium risk of suffering a thromboembolic event. Fortytwo point seven percent had a high risk and 3.9% a low risk. Only 0.9% of the cases did not present any risk (Figure 1). Ninety-eight percent of the population included in the study and that received LMWH did require it. The LMWH treatment was changed in 4% of the patients without a clinically valid justification.

 

 

 

 

Regarding the laboratory tests performed on the selected patients, we found that 32% of the patients had prothrombin time (PT), 29% had activated thromboplastin time (aTPT), 33% had an INR, 9% had D dimer, and 79% had serum creatinin.

Discussion

The results from this study show that an important percentage of hospitalized patients (43%) received some type of LMWH, a proportion which is higher than that reported for a hospital in Madrid (36%), but similar to another report from the ENDORSE study (39%).^14,15 A higher proportion of female patients receiving this medication was also identified by this study and others.^14-18

Among the anticoagulant drugs analyzed in this study, enoxaparin was much more commonly used (86%), a fact also reported by Villar in 2004.¹⁷ Even though the ACCP guidelines do not specify any LMWH type, we believe that the preference towards this particular one is mainly due the higher amount indications and of clinical trial data available for it, something that may generate more confidence among prescribing clinicians.^{3,4,6,7,19-23}

As was expected according to previous reviews, in this hospital the main condition for which LMWH was used was DVT prophylaxis (91%). Most patients had either a medium or a high risk of developing thromboembolic complications, making a high proportion of potential LMWH users. In this study, in 98% of the cases where LMWH were used as prophylaxis the treatment was correctly selected, which means that, even though there is not a current institutional protocol on this, clinicians at CBH perform an adequate risk stratification.

Either because of the presence of a secondary effect or because of a deterioration of renal function, especially among elderly patients, some cases required an adjustment of the dosage. The guidelines recommend making adjustments when the creatinin clearance is lower than 30 mL/min, and this is something that must be considered and corrected where needed. Nineteen percent of the patients required a dose adjustment, and this was performed in 86% of the cases but 22% of these adjustments were incorrect possibly because of lack of clinical data. The Department of Pharmacy must be obliged to help the clinician with the necessary dosage adjustments by means of constant pharmacotherapeutic surveillance.

Eighty percent of the patients presented some clinically relevant pharmacologic interaction during their treatment. Adverse effects because of the concomitant use of different kinds of drugs were not observed, but this must not imply that one should not be aware of the possibility of these complications and of the clinical relevance of the data generated by these softwares and the correct use of this information prior to any intervention. It must be stressed that the information should be available before and not after a problem arises, in order to help the clinician decide following a correct risk-benefit analysis.

International guidelines underscore the fact that different types of LMWH should not be exchanged^25,26 and that each one must be tested individually in clinical trials for each indication.²⁶ Despite this, 4% of the patients had a change in the LMWH they were receiving, and in none of these cases was there a clinical or pharmacologic justification. This could be due to a personal preference from the prescribing clinician since in most cases this happened in parallel to a change of the treating clinician.

Even though one of the advantages of LMWH is that it does not require periodic laboratory test monitoring, the ACCP guidelines and much of the literature recommend that this control must be undertaken in cases where there is a concomitant use of other drugs that can increase the risk of bleeding.

In some cases, LMWH were used in (prophylactic) indications not yet approved by any international guideline. None of the studies on the safety and efficacy of the treatments for chronic cerebrospinal venous insufficiency, such as those where the patients undergo the insertion of stents or the dilation of jugular veins with balloons, has provided detailed data on this respect.^29,30 Both procedures imply risks associated with elastic retraction, rupture of the vein, and development of blood clots. This does not mean that the prophylactic treatments from these surgeries will not be considered in the future, but that there is a lack of research that demonstrates that LMWH is safe and effective in cases such as palliative care of multiple sclerosis.³¹

Additionally, we recommend that the hospital improve the controls for the correct recording of the clinically relevant data such as weight and height of each patient and to encourage the inclusion of all necessary information on the medical records among staff, in order for it to be available for future studies. Also, once established at the institution, it should be advisable to keep an up-to-date protocol for the therapeutic management of LMWH (as defined by the ACCP) and to allow the Department of Pharmacy to fully engage in the process of pharmacologic monitoring.

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References