Background In the latter of 20th century, a global growth in allergic diseases has been witnessed, accompanying with spring-out of therapeutic drugs. However, trials did not clarify the comparative effectiveness and pharmaceutical economics of these agents. Severe adverse drug effects have been reported increasingly in the last few years. These made it difficult for clinical practice and selection of national essential drugs. Objective To assess astemizole, loratadine, cetirizine and tefenadine for allergic rhinitis (AR) and urticaria in terms of effectiveness, heart-related drug adverse effects and pharmaceutical economics. Search strategy Cochrane Library, Medline, Embase and Chinese Biomedical Database will be searched. Additional database should be searched for safety and economic studies. Selection Criteria The publication languages are restrained to English and Chinese. 1) Effectiveness: high-quality randomized controlled trials (RCTs) and systematic Reviews (SRs)/ meta-analysis for AR and uritcaria are included, with comparisons restrained to among these four drugs; 2) Safety: a hierarchy of evidences of these four drugs for allergic diseases are included. 3) Economical evaluation: cost-effectiveness and cost-utility assessment of these four drugs for AR and urticaria should be included. Methods of review data extraction sheet and quality appraisal table are separately designed. QUOROM STATEMENT and Jadad Scale are applied, respectively, to SRs and RCTs. Two reviewers independently select the studies, appraise the quality and extract the data. Any disagreement is solved by discussion. Data analysis Fixed effect model is first applied. Sensitivity analysis is employed to study the heterogeneity between trials. Randomized effect model is alternatively used when compromised.
Objective This review compared clinical effectiveness, cardiac safety and economics of astemizole, loratadine, cetirizine and terfenadine to provide evidence for adjustment of Essential Drug List in China. Search strategy We searched Medline, Cochrane Library, Embase and Chinese Biomedical Database. Fourteen databases for drug safety and pharmaceutical economics were additionally searched. Selection Criteria Randomized controlled trials and systematic reviews, published in English and Chinese and comparing two or more of these four antihistamines for allergic rhinitis and urticaria were included for study of effectiveness. Non-randomized clinical trials were additionally included for economic evaluation. Cardiac safety studies of antihistamines for allergic diseases of any type were included. Quality Appraisal Jadad scale was primarily applied to randomized controlled trials. Allocation concealment and intention-to-treat analysis were also appraised. The QUOROM statement was applied to systematic reviews and meta-analysis. Data extraction and analyses For the study of effectiveness, composite data were primarily extracted and analyzed by fixed effect model. Sensitivity analysis was done to explore the heterogeneity. For the study of cardiac safety, cases of adverse drug reactions and death were summarized. Difference of occurrence rate in sex and age were analyzed if possible.Electrocardiography and clinical symptoms were summarized. Results No studies on economic evaluation were identified. 27 and 6 randomized controlled trials, including 3 227 participants, for allergic rhinitis and urticaria were identified. Cetirizine was superior to loratadine (n=709) in symptom score and onset of action, superior to terfenadine (n=645) in Quality of Life and superior to astemizole (n=498) in patient satisfaction and onset of action. 73 h-ADR cases were identified in astemizole, 27 cases in terfenadine, 1 case in loratadine and none in cetirizine. No deaths were identified. Combination of terfenadine plus grapefruit juice (n=l8), itraconazole (n=6), nefazodone (n=67), and loratadine administration concomitant with cemitidine (n=30) significantly prolonged QTc interval. Conclusions Cetirizine was superior to other three antihistamines in terms of clinical effectiveness and drug safety. Astemizole and terfenadine could cause significantly more cardiac-related adverse reactions than cetirizine and loratadine.
Objective To evaluate the clinical effectiveness, safety, cost-effectiveness of eight angiotensin converting enzyme inhibitors (ACEIs) in order to provide evidence for adjustment of Essential Drug List in China. Method Collecting all clinical trials by searching Medline, Cochrane Library, Embase and Chinese Biomedical Database and conducting critical appraisal. High quality randomized controlled trials and systematic reviews were included to assess the effectiveness of ACEIs. Non-randomized controlled trials were also included to evaluate the safety and cost-effectiveness. Results New generation of ACEIs are better than enalapril and captopril in antihypertension and endurance. Meta-analysis showed that T/P ratio was less than 50% in prindopril, benazepril and captopril. Enalapril and captopril had the most adequate evidence in the treatment of chronic heart failure. The effects of lisinopril, prindopril, benazepril and cilazapril positive influence on heart failure were assessed by surrogates. Captopril, lisinopril could reduce the total death rate of acute period (during 36 hours of AMI). Enalapril, captopril, ramipril and prindopril had the effect of heart protection in late period of AMI (3 days after AMI). Only ramipril, lisinopril and prindopril had evidence to support the protective effect on cerebral vessels. The available evidence, though not adequate, showed all the ACEIs except benazepril could diminish proteinuria and delay the renal failure. The new generations of ACEIs were similar in adverse reactions to enalapril and captopril, while incidences were lower than enalapril and captopril. Few evidence on cost-effectiveness of ACEIs were identified. The available evidence showed enalapril was cost-effective in treating heart failure. However, it compromised to lisinopril. The studies on ethics were not available. Conclusions It was difficult to generally rank the eight ACEIs according to available evidence. Not all eight ACEIs had adequate evidence in organs protection. It was suggested that clinicians should select ACEIs with adequate evidence to treat patients on states.
Objective To assess the effectiveness and safety of nine lipid-lowing agents in the national essential drug list (2000) and provide evidence for the adjustment and selection of essential drugs. Methods Based on principles of health technology assessment (HTA) and evidence-based medicine, we searched for all published clinical studies about these drugs from the following databases: MEDLINE (1966-2002.8), The Cochrane Library, EMBASE (1974-2002), CBMdisk (1979-2002.8) and VIP (1989-2002.8), the database of National Center for Adverse Drug Reaction(ADR) Monitoring of China and the database of WHO Uppsala drug monitoring center. Included studies were appraised, analyzed and compared for the reduction of triglyceride (TC) or low density lipoprotein (LDL-C), the prevention for the coronary events and the incidence of ADR. Results The results from comparative trials for lipid-lowing agents showed that the equivalent dose of statins for 25% reduction of LDL-C was atorvastatin 10 mg/d, simvastatin 20 mg/d, pravastatin 40mg/d, lovastatin 40 mg/d, cerivastatin 0.3 mg/d and fluvastatin 80 mg/d. It was difficult to compare fenofibrate with gemfibrozil, acipimox with statins or fibrates based on available data. The study on the primary and secondary prevention of cardiovascular events showed that pravastatin and lovastatin were effective in primary prevention, and long-term use could reduce the incidence of cardiovascular disease.Gemfibrozil could reduce the mortality from coronary heart disease (CHD) but the overall mortality was not changed. Pravastatin, simvastatin, atorvastatin, fluvastatin, gemfibrozil and fenofibrate had a confirmed effect in secondary prevention. Data from large-scale clinical trials and the reports from ADR monitoring center of England, America, Canada and Australia suggested that the statins which had rare ADR were safe and tolerated. Rhabdomyolysis was rare but had a serious adverse reaction associated with statins. The rate of fatal rhabdomyolysis related to cerivastatin was the highest among 6 statins. The safety of simvastatin, lovastatin and atorvastatin was lower than cerivastatin but higher than simvastatin and atorvastatin. The number of ADR reports of fenofibrate was fewer than that of gemfibrozil. Conclusions At present, the best evidence focused on pravastatin, simvastatin and lovastatin are widely used and have a confirmed safety and efficacy. Atorvastatin, fluvastatin and fenofibrate still need more data to confirm their effects on coronary heart disease prevention. The drugs which were shown to be inferior or insufficient evidence are cerivastatin, gemfibrozil and acipimox.