Aspirin: benefit and risk in thromboprophylaxis

Aspirin is often perceived either as a harmless panacea or as a useless poison which causes endless, needless trouble. We have carefully reviewed the literature on all aspects of aspirin and find that neither view is justified. Regular use of even low-dose aspirin (150 mg/day or less) may lead to clinically-important adverse events, particularly haemorrhage. The risk of such an event is considerably outweighed by the benefit for patients with a significant risk of a thromboembolic event. For individuals without a clear risk of thrombosis or thromboembolism, the balance is more even: indiscriminate aspirin- taking is to be discouraged.      

Comparing therapeutic benefit and risk

Theoretically, the merit of a medical drug can be quantitatively determined by calculating benefit and risks as the drug-attributed gain or loss, respectively, of quality-adjusted life years. This calculation is based on comprehensive data concerning large numbers of patients. For most drugs, however, the data available are more or less incomplete. Therefore, large-scale intensive and continuous data collection needs to become routine in medical and pharmaceutical practice. In addition, important scientific, ethical, logistic and financial obstacles need to be overcome. Preliminary evidence suggests that the 'Principle of Threes' is a useful tool for categorizing the merit of drugs and for comparing drugs of a given therapeutic class. The safety of a drug is a dynamic rather than a constant feature. The merit of a drug is not an absolute quality, but is meaningful only in a given context. It is still uncertain whether merit assessment can present the dilemma that 'a drug causes benefit in many at the cost of serious injury in some' in a way the individual user can understand. Quantitative merit assessment will be welcome but should not be expected to replace individual therapeutic decision making. It remains to be seen whether merit assessment is to result in a gold standard for the acceptability or unacceptability of drugs.     

Assessment of gas exchange in lung disease: balancing accuracy against feasibility

While the principles underlying alveolar gas exchange have been well-known for over 50 years, we still struggle to assess gas exchange in hypoxemic patients. Unfortunately, simple measurements lack discrimination while complex measurements are infeasible in clinical care. The paper by Karbing et al. in this issue seeks a middle ground based on the arterial PO₂ (PaO₂)/inspired O₂ fraction (FIO₂) ratio measured at different FIO₂s with the outcomes fed into proprietary software to account for both shunting and ventilation/perfusion inequality. Whether this is the optimal compromise between measurement difficulty and information available will have to be answered by those willing to test the approach in their own patients.     

Paracetamol poisoning

Paracetamol is a common cause of fatal self-poisoning in the UK every year. Despite this, it continues to be sold freely without medical supervision and can be found in quantity in most household medicine cabinets.     

Interpretation of drug risk and benefit: individual and population perspectives

OBJECTIVE: To provide pharmacists with the necessary nomenclature and tools to interpret the medical literature on drug risks and benefits. DATA SOURCES: Primary articles were identified by MEDLINE search (1990-December 2003) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated, and all information from secondary sources deemed relevant was included. DATA SYNTHESIS: Articles in the primary and secondary literature were reviewed. The articles show that measurement of drug risks and benefits is consistently reported with similar terminology. However, the interpretation and subsequent balancing of risks and benefits can be difficult. CONCLUSIONS: All drugs have concomitant risks and benefits. The medical literature documents those risks and benefits and it is this medical evidence that is typically used to make drug therapy decisions. Pharmacists who either manage individual patients or populations of patients (pharmacy benefit managers) may interpret this medical evidence more clearly by understanding the implications of various statistical methods used in studies.     

Antithrombotic drugs in coronary artery disease: risk benefit ratio and bleeding

Summary. The antithrombotic treatment of coronary artery disease is becoming increasingly complex. Aspirin is often combined with more potent antiplatelet agents such as thienopyridines and glycoprotein IIb/IIIa inhibitors. The classic anticoagulant unfractionated heparin is giving way to low‐molecular‐weight heparin, the pentasaccharide fondaparinux and the direct thrombin inhibitor bivalirudin. Warfarin (or another vitamin K antagonist) and antiplatelet agents are often required in combination for several months. Patients and physicians who have experienced major bleeding complications sometimes question the benefit of these treatment strategies. It is therefore crucial to try and weigh the impact on efficacy against safety. In this review the net benefit is discussed both numerically, comparing absolute reductions vs. increases in risks, and also by addressing the qualitative importance of each component in reaching the net benefit. Except for primary prophylaxis in patients at low‐moderate risk for coronary events, there is a net benefit of antithrombotic therapy. With increasing severity of the coronary condition the net benefit generally prevails even with an increasing number of antithrombotic drugs combined. However, as the patient slowly stabilizes after appropriate interventions, it is necessary to de‐escalate the treatment in accordance with decreasing net benefit of prolonged combination therapy.