Drugs
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The clinical relevance and high social costs of atrial fibrillation have boosted interest in rate control as a cost-effective alternative to long-term maintenance of sinus rhythm (i.e. rhythm control). Prospective studies show that rate control (coupled with thromboembolic prophylaxis) is a valuable treatment option for all forms of atrial fibrillation. The rationale for rate control is that high ventricular rates, frequently found in atrial fibrillation, lead to haemodynamic impairment, consisting of a variable combination of loss of atrial kick, irregularity in ventricular response and inappropriately rapid ventricular rate, depending on the type of underlying heart disease. ⋯ Definite guidelines are required for each different subset of patients. Rate control is particularly tricky in patients with heart failure, for whom non-pharmacological options can also be considered. The preferred pharmacological options are beta-blockers for stabilised heart failure and digoxin for unstabilised forms.
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Review Randomized Controlled Trial Clinical Trial
Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia.
Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukaemia (CLL). While the optimal use of the drug in many clinical settings has yet to be clarified, two pivotal trials have established rituximab as a viable treatment option in patients with relapsed or refractory indolent NHL, and as a standard first-line treatment option when combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (the most common type of aggressive NHL). The former was a noncomparative trial in relapsed indolent NHL (follicular and small lymphocytic subtypes) with clinical responses achieved in about half of patients treated with rituximab 375 mg/m(2) intravenously once weekly for 4 weeks, which was similar to some of the most encouraging results reported with traditional chemotherapeutic agents. The latter was a randomised comparison of eight cycles of CHOP plus rituximab 375 mg/m(2) intravenously (one dose per cycle) versus CHOP alone in previously untreated elderly patients (60 to 80 years of age) with diffuse large B-cell lymphoma. In this pivotal trial, 2-year event-free and overall survival were significantly higher with rituximab plus CHOP, and there was no increase in clinically significant adverse effects compared with CHOP alone. Treatment with rituximab is generally well tolerated, particularly in terms of adverse haematological effects and serious or opportunistic infections relative to standard chemotherapy. Infusion-related reactions occur in the majority of patients treated with rituximab; these are usually mild to moderate flu-like symptoms that decrease in frequency with subsequent infusions. In approximately 10% of patients, however, severe infusion-related reactions develop (e.g. bronchospasm, hypotension). These reactions are usually reversible with appropriate interventions and supportive care but there have been rare reports of fatalities. ⋯ A number of studies have demonstrated efficacy of intravenous rituximab in patients with various lymphoid malignancies of B-cell origin, including indolent (e.g. follicular lymphoma) and aggressive (e.g. diffuse large B-cell lymphoma) forms of NHL, and CLL, but the drug has not yet been approved for use in CLL, and approved indications in NHL vary between countries. In the US, for example, rituximab is available for the treatment of patients with low-grade or follicular, relapsed or refractory, CD20-positive B-cell NHL. In Europe, the drug has similar approval for relapsed or refractory follicular NHL as in the US, but has also been approved for use in combination with CHOP chemotherapy for the most common aggressive form of NHL (CD20-positive, diffuse large B-cell lymphoma). Rituximab was approved for these indications primarily on the basis of results from two pivotal trials. In Japan, rituximab has been approved for indolent B-cell NHL and mantle cell lymphoma (an aggressive form of B-cell NHL), primarily on the basis of results of a Japanese phase II trial. Indolent NHL: Results of several studies evaluating rituximab 375 mg/m(2) once weekly for 4 weeks in patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic lymphomas) showed objective response (OR) rates ranging from approximately 40-60% in those receiving the drug for relapsed or refractory indolent B-cell NHL, and slightly higher (50-70%) for those receiving rituximab as first-line therapy. In a pivotal trial in 166 patients with relapsed or refractory low-grade or follicular B-cell NHL, intent-to-treat (ITT) analysis showed an OR rate of 48%, and a projected median time to progression of 13 months. Encouraging data are also emerging on the use of rituximab in combination with chemotherapeutic agents (e.g. CHOP, fludarabine-containing regimens) or other drugs (e.g. interferon-alpha2a) in previously untreated patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic subtypes). Rates for OR were consistently around 95%, with the majority being complete responses (CRs). Follow-up data from a study in 40 patients with low-grade or follicular B-cell NHL treated with rituximab plus CHOP as first-line therapy showed that responses were durable with a progression-free survival and median duration of response >5 years.Bcl-2 gene rearrangement (t14;18) occurs in malignant cells in up to 85% of patients with follicular lymphoma, and minimal residual disease in peripheral blood and bone marrow can be monitored using polymerase chain reaction (PCR). In several studies assessing blood and/or bone marrow, rituximab has achieved molecular response (conversion from PCR-positive to PCR-negative bcl-2 status) in at least half of the patients. Aggressive NHL: Studies with rituximab as monotherapy in aggressive B-cell NHL, a potentially curable disorder, have generally been restricted to patients with relapsed or recurrent disease, since CHOP has traditionally been the standard first-line treatment regimen. However, promising results from phase II monotherapy studies prompted further clinical investigation of rituximab in conjunction with chemotherapy. Thus, most studies with rituximab in patients with aggressive forms of B-cell NHL have involved combination therapy, including a pivotal randomised trial comparing eight cycles of standard CHOP therapy plus rituximab 375 mg/m(2) (one dose per cycle) versus CHOP alone in 399 previously untreated elderly patients (60-80 years of age) with diffuse large B-cell lymphoma. Results of the pivotal trial showed a clear advantage for rituximab plus CHOP versus CHOP in terms of event-free survival (primary endpoint) at 2 years (57% vs 38%, p < 0.001). Overall survival at 2 years (70% vs 57%, p < 0.01) and CR rate (76% vs 63%, p < 0.01) were also higher with the rituximab-CHOP combination. Other, smaller trials with rituximab in combination with CHOP or other chemotherapeutic regimens, either as first-line therapy or for patients with relapsed or refractory aggressive B-cell NHL, have also shown promising results in terms of clinical response rates.CLL: In relatively small trials (n < 40) conducted primarily in patients with relapsed or refractory B-cell CLL, rituximab monotherapy (various regimens) achieved OR rates of 23-45%, with median duration of response ranging from approximately 3-10 months. (ABSTRACT TRUNCATED)
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Review Multicenter Study
Treatment options for initial maintenance therapy of persistent asthma: a review of inhaled corticosteroids and leukotriene receptor antagonists.
Inhaled corticosteroids (ICSs) are recognized as the cornerstone of asthma therapy. They are considered to be the most effective anti-inflammatory medication currently available for the treatment of persistent asthma, regardless of its severity. Leukotriene receptor antagonists (LTRAs) are also used as initial maintenance therapy in patients whose asthma is uncontrolled by bronchodilators alone. ⋯ Studies that assessed the effectiveness, cost-effectiveness, and quality of life achieved with a salmeterol fluticasone propionate combination as initial maintenance therapy also showed it to be superior to LTRAs. In conclusion, in terms of efficacy and quality of life, fluticasone propionate is more effective than LTRAs as initial maintenance therapy and is associated with significantly lower healthcare costs and less frequent use of healthcare resources than LTRAs. There is also evidence to suggest that initial maintenance therapy with the combination of an inhaled steroid plus a long-acting beta-agonist bronchodilator may be a more effective option for the management of persistent asthma than treatment with a single-controller agent alone (ICS or LTRA).
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NSAIDs inhibit the cyclo-oxygenase enzymes, and decrease peripheral and central prostaglandin production. In addition to reducing the inflammation that accompanies tissue injury, decreasing prostaglandin production attenuates the response of the peripheral and central components of the nervous system to noxious stimuli. Such a reduction in the response to pain can reduce the peripheral and central sensitisation induced by noxious stimuli, and reduce the pain experienced in response to subsequent noxious stimuli. ⋯ However, the available perioperative trials of pre-emptive NSAID use have yielded modest or equivocal results, and these may be due, in part, to controversy associated with the definition of pre-emptive analgesia and how to conduct the corresponding clinical trials. Although NSAIDs may have a limited ability by themselves to induce a pre-emptive analgesic effect, the available trials suggest how the perioperative use of these drugs may be made more effective. It is expected that NSAIDs will play an increasing role in multimodal analgesia and pain relief in general.
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The rationale for an arginine vasopressin (argipressin) infusion was put forward after it was discovered that patients in shock states might have an endogenous arginine vasopressin deficiency. Subsequently, several investigations impressively demonstrated that arginine vasopressin can successfully stabilise haemodynamics even in advanced vasodilatory shock. We report on physiological and pharmacological aspects of arginine vasopressin, and summarise current clinical knowledge on employing a continuous arginine vasopressin infusion in critically ill patients with catecholamine-resistant vasodilatory shock of different aetiologies. ⋯ Because data on adverse effects are still limited, arginine vasopressin should be reserved for patients in whom adequate haemodynamic stabilisation cannot be achieved with conventional vasopressor therapy or who have obvious adverse effects of catecholamines that result in further significant haemodynamic deterioration. For the same reasons, arginine vasopressin should not be used as a single, alternative vasopressor agent instead of catecholamine vasopressors. Future prospective studies will be necessary to define the exact role of arginine vasopressin in the therapy of vasodilatory shock.