Are all angiotensin-converting enzyme inhibitors interchangeable?

In the treatment of most medical conditions, there are many choices. A critical question for practicing clinicians is: "Are all drugs within a class interchangeable?" In the past decade, the market has seen a proliferation of drugs within popular drug classes. The original drugs within a class typically have better scientific documentation than the newer ones, which are often referred to as "me-too" drugs. Due to a lesser financial investment, the latter may be available at a lower cost. Good reasons exist for grouping drugs, however, there is no accepted definition of the term "class effect." Although members of a drug class share main actions, they may have clinically important differences in terms of efficacy and safety. There are many such examples in the literature. This article reviews the class effect concept as it applies to the angiotensin-converting enzyme (ACE) inhibitors. Only half of the 10 ACE inhibitors available in the U.S. have been shown to improve survival and reduce morbidity in patients with heart failure or myocardial infarction. It is unknown whether the other five have the same safety and efficacy profiles or what their optimal doses are. Thus, we do not know whether all ACE inhibitors are fully interchangeable. The practice of medicine ought to be based on solid scientific evidence, not on assumptions or extrapolations. For our patients, such practice is a legitimate expectation. Therefore, it seems prudent to recommend that patients requiring ACE inhibitor therapy be prescribed one that has been proven effective and safe.     

Are the novel anticoagulants better than warfarin for patients with atrial fibrillation?

Atrial fibrillation (AF) is associated with significant morbidity and mortality related to stroke due to thromboembolism. Several novel oral anticoagulants (NOACs) have been developed that dose-dependently inhibit thrombin or activated factor X (factor Xa). These new agents offer potential advantages over vitamin K antagonists, however, several limitations exist. We will review the four large randomized trials comparing the efficacy and safety of new oral anticoagulants with warfarin for stroke prevention in patients with AF as well as assess “real world” data and discuss the limitations of the new agents.     

Are multisource levothyroxine sodium tablets marketed in Egypt interchangeable?

A clinical study was initiated in response to patients’ complaints, supported by the treating physicians, of suspected differences in efficacy among multisource levothyroxine sodium tablets marketed in Egypt. The study design was a multiple dose (100 μg levothyroxine sodium tablet once daily for 6 months) and involved 50 primary hypothyroidism female patients (5 equal groups). Tablets administered included five tablet batches (two brands, three origin locations) purchased from local pharmacies in Alexandria. Assessment parameters (measured on consecutive visits) included the thyroid stimulating hormone, total and free levothyroxine. Tablet dissolution rate was determined (BP/EP 2014 & USP 2014). In vitro vs in vivovs correlations were developed. Clinical and pharmaceutical data confirmed inter-brand and inter-source differences in efficacy. Correlations examined indicated potential usefulness of in vitro dissolution test in detecting poor performing levothyroxine sodium tablets during shelf life.     

Knowledge of proprietary and generic drug names among hospital prescribers: time to mandate generic prescribing?

Although medical students are taught clinical pharmacology using generic drug names, prescribing in hospitals often uses brand names. As a result, junior doctors may be prescribing drugs without knowing their nature or mode of action. We carried out a knowledge survey of 81 medical students and doctors at a 650‐bed Australian teaching hospital to assess their knowledge of common drugs when given the brand name. We identified 20 commonly prescribed drugs and their brand names based on current hospital inpatients. No participant was able to provide the generic name, class or mode of action for all 20 drugs, with an average of 8.3 of 20 and 6.3 of the 10 most common drug names correctly identified. These data support calls to mandate prescribing using generic rather than brand names of drugs in hospitals.     

Antiarrhythmic drug therapy for atrial fibrillation: Are the guidelines guiding clinical practice?

The AFFIRM study showed no clear survival advantage for a rhythm versus rate control strategy in patients with atrial fibrillation (AF). However, rhythm control with antiarrhythmic drugs (AADs) is appropriate in a large number of patients with AF. The American College of Cardiology/ American Heart Association/European Society of Cardiology AF management guidelines include a safety-based algorithm for selection of AAD therapy. Class 1C agents are recommended as first-line therapy in patients without or with minimal structural heart disease. However, market research and clinical study data indicate a growing use of class III agents (mainly amiodarone) despite long-term safety and tolerability concerns, suggesting that clinical practice does not adhere to current guidelines.     

Are erlotinib and gefitinib interchangeable,opposite or complementary for non-small cell lung cancer treatment? Biological,pharmacological and clinical aspects

Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of ‘oncogene addiction’, with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comparison and to improve their sequential use. In particular, toxicity profile resulted partially different, and these observations may be explained by several molecular and pharmacokinetic features. Therefore, this review integrates preclinical data with clinical evidences of TKIs to guide the optimization of currently available treatments in advanced NSCLC patients.     

Are the elderly different?

Background

The aim of this study was to investigate factors influencing mortality after percutaneous coronary intervention (PCI) in patients aged ≥?75 years compared to younger patients.

Patients and methods

A total of 1,809 coronary heart disease (CHD) patients after PCI with stent implantation in our hospital were assessed. Kaplan–Meier analyses with log-rank test and Cox regression analyses were performed on three predefined models concerning primary endpoint of all-cause mortality. Model 1 was a univariate analysis of the influence of age dichotomized by age 75 years on the primary endpoint. Model 2 included age and classical cardiovascular risk factors (CVRFs, e.g., body mass index (BMI), smoking, diabetes, and hypertension). Model 3 consisted of age, classical CVRFs, and additional factors (e.g., medication; hemoglobin, peripheral arterial disease (PAD), low-density lipoprotein cholesterol (LDL-C) and creatinine levels, and left ventricular ejection fraction (LVEF)).

Results

In the mean follow-up of 137?±?61 weeks 375 patients died. Age ≥?75 years was significantly related to mortality in all models. In model 3, previous stroke, PAD, diabetes, elevated levels of serum creatinine, and increased LDL-C were related to elevated mortality, higher hemoglobin levels, and LVEF >?50% were associated with decreased mortality in all patients and in patients <?75 years. In patients ≥?75 years arterial hypertension was associated with poor outcome (hazard ratio (HR) 7.989, p =?0.040), previous antiplatelet therapy showed reduced mortality (HR 0.098, p =?0.039).

Conclusion

Although risk factors such as previous stroke, PAD, diabetes, renal insufficiency, and anemia were predictors for death in all patients and patients <?75 years, in the elderly only arterial hypertension increased, whereas treatment with platelet inhibitors decreased mortality.