Q&A

BACKGROUND: Options for removing cerumen include the use of a ceruminolytic, a curette, irrigation, or a combination. Irrigation and mechanical extraction carry the risk of patient discomfort, ossicle disruption, trauma, and infection. Ceruminolytics used in practice include water, sodium bicarbonate, hydrogen or carbamide peroxide, mineral or olive oil, glycerin, triethanolamine oleate, and propylene glycol. Although docusate has been used empirically, only in vitro data are available to support its use. The authors of this study evaluated the comparative efficacy of docusate and triethanolamine polypeptide for acute earwax removal.

POPULATION STUDIED: Fifty adult and pediatric patients from a university-based emergency department were enrolled on a convenience basis. The participants were older than 1 year, had a medical condition requiring tympanic membrane visualization, and had partially or totally obscured tympanic membranes. The sample subjects were 35% female and 26% very young (<5 years). Patients were excluded for known or suspected perforation, overt ear infection, or lack of cooperation.

STUDY DESIGN AND VALIDITY: The study was a randomized double-blind trial. A physician determined tympanic membrane obstruction. The authors reported an interobserver reliability of 79%, but the method of determination was not discussed. A 1-mL dose of either triethanolamine or docusate was placed in the affected ear canal and allowed to remain for 10 to 15 minutes. In an attempt to mask the treatments, doses were placed in opaque syringes to obscure the color difference. If the wax was not removed, the ear was irrigated once or twice with 50 mL normal saline. Overall the study has few faults. One concern is that a convenience sample of patients was used, and allocation may not have been concealed. As a result, the researchers could have chosen either particularly difficult or minor cerumen obstructions when enrolling patients in the study. The wide age range probably would not affect study results, because age does not affect cerumen quantity or quality.

OUTCOMES MEASURED: The main outcome measure was the percentage of tympanic membranes totally visualized with or without saline irrigation. The adverse events subjectively reported by patients were also recorded.

RESULTS: Immediately after ceruminolytic instillation there was no difference between the 2 treatments. However, after 2 irrigations with normal saline, complete clearing was achieved in 82% of the docusate-treated patients and 35% of the triethanolamine-treated patients (difference=47%; 95% confidence interval [CI], 22%-71%). In other words, every other patient treated with docusate instead of triethanolamine would have benefited (number needed to treat=2.13). Although this difference was markedly greater in children younger than 5 years (difference=90; 95% CI, 51%-100%), there were only 4 very young children who received triethanolamine. No adverse events were reported.

BACKGROUND: Options for removing cerumen include the use of a ceruminolytic, a curette, irrigation, or a combination. Irrigation and mechanical extraction carry the risk of patient discomfort, ossicle disruption, trauma, and infection. Ceruminolytics used in practice include water, sodium bicarbonate, hydrogen or carbamide peroxide, mineral or olive oil, glycerin, triethanolamine oleate, and propylene glycol. Although docusate has been used empirically, only in vitro data are available to support its use. The authors of this study evaluated the comparative efficacy of docusate and triethanolamine polypeptide for acute earwax removal.

POPULATION STUDIED: Fifty adult and pediatric patients from a university-based emergency department were enrolled on a convenience basis. The participants were older than 1 year, had a medical condition requiring tympanic membrane visualization, and had partially or totally obscured tympanic membranes. The sample subjects were 35% female and 26% very young (<5 years). Patients were excluded for known or suspected perforation, overt ear infection, or lack of cooperation.

STUDY DESIGN AND VALIDITY: The study was a randomized double-blind trial. A physician determined tympanic membrane obstruction. The authors reported an interobserver reliability of 79%, but the method of determination was not discussed. A 1-mL dose of either triethanolamine or docusate was placed in the affected ear canal and allowed to remain for 10 to 15 minutes. In an attempt to mask the treatments, doses were placed in opaque syringes to obscure the color difference. If the wax was not removed, the ear was irrigated once or twice with 50 mL normal saline. Overall the study has few faults. One concern is that a convenience sample of patients was used, and allocation may not have been concealed. As a result, the researchers could have chosen either particularly difficult or minor cerumen obstructions when enrolling patients in the study. The wide age range probably would not affect study results, because age does not affect cerumen quantity or quality.

OUTCOMES MEASURED: The main outcome measure was the percentage of tympanic membranes totally visualized with or without saline irrigation. The adverse events subjectively reported by patients were also recorded.

RESULTS: Immediately after ceruminolytic instillation there was no difference between the 2 treatments. However, after 2 irrigations with normal saline, complete clearing was achieved in 82% of the docusate-treated patients and 35% of the triethanolamine-treated patients (difference=47%; 95% confidence interval [CI], 22%-71%). In other words, every other patient treated with docusate instead of triethanolamine would have benefited (number needed to treat=2.13). Although this difference was markedly greater in children younger than 5 years (difference=90; 95% CI, 51%-100%), there were only 4 very young children who received triethanolamine. No adverse events were reported.

BACKGROUND: Options for removing cerumen include the use of a ceruminolytic, a curette, irrigation, or a combination. Irrigation and mechanical extraction carry the risk of patient discomfort, ossicle disruption, trauma, and infection. Ceruminolytics used in practice include water, sodium bicarbonate, hydrogen or carbamide peroxide, mineral or olive oil, glycerin, triethanolamine oleate, and propylene glycol. Although docusate has been used empirically, only in vitro data are available to support its use. The authors of this study evaluated the comparative efficacy of docusate and triethanolamine polypeptide for acute earwax removal.

POPULATION STUDIED: Fifty adult and pediatric patients from a university-based emergency department were enrolled on a convenience basis. The participants were older than 1 year, had a medical condition requiring tympanic membrane visualization, and had partially or totally obscured tympanic membranes. The sample subjects were 35% female and 26% very young (<5 years). Patients were excluded for known or suspected perforation, overt ear infection, or lack of cooperation.

STUDY DESIGN AND VALIDITY: The study was a randomized double-blind trial. A physician determined tympanic membrane obstruction. The authors reported an interobserver reliability of 79%, but the method of determination was not discussed. A 1-mL dose of either triethanolamine or docusate was placed in the affected ear canal and allowed to remain for 10 to 15 minutes. In an attempt to mask the treatments, doses were placed in opaque syringes to obscure the color difference. If the wax was not removed, the ear was irrigated once or twice with 50 mL normal saline. Overall the study has few faults. One concern is that a convenience sample of patients was used, and allocation may not have been concealed. As a result, the researchers could have chosen either particularly difficult or minor cerumen obstructions when enrolling patients in the study. The wide age range probably would not affect study results, because age does not affect cerumen quantity or quality.

OUTCOMES MEASURED: The main outcome measure was the percentage of tympanic membranes totally visualized with or without saline irrigation. The adverse events subjectively reported by patients were also recorded.

RESULTS: Immediately after ceruminolytic instillation there was no difference between the 2 treatments. However, after 2 irrigations with normal saline, complete clearing was achieved in 82% of the docusate-treated patients and 35% of the triethanolamine-treated patients (difference=47%; 95% confidence interval [CI], 22%-71%). In other words, every other patient treated with docusate instead of triethanolamine would have benefited (number needed to treat=2.13). Although this difference was markedly greater in children younger than 5 years (difference=90; 95% CI, 51%-100%), there were only 4 very young children who received triethanolamine. No adverse events were reported.

BACKGROUND: AOM is a frequent complication of viral URIs. Theoretically, intranasal steroids may reduce eustachian tube dysfunction and thus reduce AOM secondary to viral URIs. The authors designed a study to test this hypothesis.

POPULATION STUDIED: A total of 210 Finnish children 6 months to 4 years old (average=2.1 years) with less than 48 hours of symptoms of a URI were studied. Children were excluded from the study protocol for current AOM, antibiotic or steroid use within 2 weeks, history of adenoidectomy, or typanostomy tubes. Patients were recruited from outpatient clinics and through media advertisements and thus did not make up a tertiary referral population.

STUDY DESIGN AND VALIDITY: Children were randomly assigned in double-blind fashion to intranasal fluticasone (100 mg twice daily) for 7 days or matching placebo. Nasopharyngeal aspirates for viral cultures were also obtained. Children were reexamined at 7 days or earlier if desired by parents because of symptoms of AOM. Authors defined AOM as a middle ear effusion with signs or symptoms of acute infection. Treatment allocation assignment appears to have been concealed, although this was not explicitly stated. Follow-up was excellent, with 208 of 210 children (99%) being analyzed. Two children were not included in the analysis, because one did not use the medication and the other used it incorrectly. These 2 were not included in the final analysis (intention-to-treat analysis was not performed), but adding them to the results would not have affected the outcome. The control and treatment groups differed only by parental smoking status (47% in treatment group vs 30% in the control group). Since this was a negative trial (showing no difference between the treatment and control groups), it is important that the study was adequately powered to not miss a true difference. The study recruited enough patients to have an 80% power to detect a 60% reduction in AOM.

OUTCOMES MEASURED: Incidence of AOM was the primary outcome measured. Resolution of URI symptoms and viral pathogens identified were also measured.

RESULTS: There was a nonsignificant trend toward increased AOM in the steroid-treated group versus the control group (38% vs 28%; P=.13). There were significantly more cases of AOM identified in the treatment subgroup of children with URIs documented to be caused by rhinovirus infection (46.7% vs 14.7; P=.005; number needed to harm=3.2). There was no difference in symptom resolution between the 2 groups.

BACKGROUND: AOM is a frequent complication of viral URIs. Theoretically, intranasal steroids may reduce eustachian tube dysfunction and thus reduce AOM secondary to viral URIs. The authors designed a study to test this hypothesis.

POPULATION STUDIED: A total of 210 Finnish children 6 months to 4 years old (average=2.1 years) with less than 48 hours of symptoms of a URI were studied. Children were excluded from the study protocol for current AOM, antibiotic or steroid use within 2 weeks, history of adenoidectomy, or typanostomy tubes. Patients were recruited from outpatient clinics and through media advertisements and thus did not make up a tertiary referral population.

STUDY DESIGN AND VALIDITY: Children were randomly assigned in double-blind fashion to intranasal fluticasone (100 mg twice daily) for 7 days or matching placebo. Nasopharyngeal aspirates for viral cultures were also obtained. Children were reexamined at 7 days or earlier if desired by parents because of symptoms of AOM. Authors defined AOM as a middle ear effusion with signs or symptoms of acute infection. Treatment allocation assignment appears to have been concealed, although this was not explicitly stated. Follow-up was excellent, with 208 of 210 children (99%) being analyzed. Two children were not included in the analysis, because one did not use the medication and the other used it incorrectly. These 2 were not included in the final analysis (intention-to-treat analysis was not performed), but adding them to the results would not have affected the outcome. The control and treatment groups differed only by parental smoking status (47% in treatment group vs 30% in the control group). Since this was a negative trial (showing no difference between the treatment and control groups), it is important that the study was adequately powered to not miss a true difference. The study recruited enough patients to have an 80% power to detect a 60% reduction in AOM.

OUTCOMES MEASURED: Incidence of AOM was the primary outcome measured. Resolution of URI symptoms and viral pathogens identified were also measured.

RESULTS: There was a nonsignificant trend toward increased AOM in the steroid-treated group versus the control group (38% vs 28%; P=.13). There were significantly more cases of AOM identified in the treatment subgroup of children with URIs documented to be caused by rhinovirus infection (46.7% vs 14.7; P=.005; number needed to harm=3.2). There was no difference in symptom resolution between the 2 groups.

BACKGROUND: AOM is a frequent complication of viral URIs. Theoretically, intranasal steroids may reduce eustachian tube dysfunction and thus reduce AOM secondary to viral URIs. The authors designed a study to test this hypothesis.

POPULATION STUDIED: A total of 210 Finnish children 6 months to 4 years old (average=2.1 years) with less than 48 hours of symptoms of a URI were studied. Children were excluded from the study protocol for current AOM, antibiotic or steroid use within 2 weeks, history of adenoidectomy, or typanostomy tubes. Patients were recruited from outpatient clinics and through media advertisements and thus did not make up a tertiary referral population.

STUDY DESIGN AND VALIDITY: Children were randomly assigned in double-blind fashion to intranasal fluticasone (100 mg twice daily) for 7 days or matching placebo. Nasopharyngeal aspirates for viral cultures were also obtained. Children were reexamined at 7 days or earlier if desired by parents because of symptoms of AOM. Authors defined AOM as a middle ear effusion with signs or symptoms of acute infection. Treatment allocation assignment appears to have been concealed, although this was not explicitly stated. Follow-up was excellent, with 208 of 210 children (99%) being analyzed. Two children were not included in the analysis, because one did not use the medication and the other used it incorrectly. These 2 were not included in the final analysis (intention-to-treat analysis was not performed), but adding them to the results would not have affected the outcome. The control and treatment groups differed only by parental smoking status (47% in treatment group vs 30% in the control group). Since this was a negative trial (showing no difference between the treatment and control groups), it is important that the study was adequately powered to not miss a true difference. The study recruited enough patients to have an 80% power to detect a 60% reduction in AOM.

OUTCOMES MEASURED: Incidence of AOM was the primary outcome measured. Resolution of URI symptoms and viral pathogens identified were also measured.

RESULTS: There was a nonsignificant trend toward increased AOM in the steroid-treated group versus the control group (38% vs 28%; P=.13). There were significantly more cases of AOM identified in the treatment subgroup of children with URIs documented to be caused by rhinovirus infection (46.7% vs 14.7; P=.005; number needed to harm=3.2). There was no difference in symptom resolution between the 2 groups.

BACKGROUND: Asthma is the most common chronic disease of childhood in the United States and has increased dramatically in incidence and prevalence over the last 30 years. One hypothesis invokes the inverse relationship between the frequency of some allergic disorders and both childhood infections and the number of siblings. Children attending day-care have more infections, and this may have a similar protective effect.

POPULATION STUDIED: A total of 1246 newborns were enrolled in the Tucson Children’s Respiratory Study between 1980 and 1984. All newborns were healthy and were cared for by pediatricians of a large health maintenance organization in Tucson.

STUDY DESIGN AND VALIDITY: The parents of 1035 newborns completed at least¹ questionnaire and were included in a cross-sectional analysis. The parents of 875 children (83%) completed at least 1 questionnaire and provided information on day-care attendance, and these were included in a longitudinal study. Information was obtained from parents of enrolled children on the number of siblings at home, day-care attendance in the first 3 years of life, the diagnosis of asthma, and frequent wheezing at the ages of 6, 8, 11, or 13 years. Children were categorized as having asthma if they had a diagnosis of asthma in the previous year. Children with scores of 2 or higher on a wheezing frequency scale from 1 to 5 at 2 or 3 years were defined as having frequent wheezing. Skin test reactivity to common allergens in the Tucson area and serum immunoglobulin E were measured at 6 and 11 years as a biological marker of allergic disease. The analysis accounted for potential confounding variables including sex, a history of asthma in either parent, race of parents, mother’s level of education, mother’s smoking status during the prenatal period, and breastfeeding status. Study participants were more likely to have 1 or no siblings, a mother with a high level of education, and white parents than those who were excluded or refused to participate. The retrospective nature of the questionnaires may have led to some misclassification. Although follow-up was very good, the study may not be generalizable to other ethnic groups or practices in different geographic locations.

OUTCOMES MEASURED: The primary outcome was the development of asthma and frequent wheezing in childhood as related to day-care attendance and exposure to siblings.

RESULTS: The incidence of asthma among children with 2 or more older siblings or who attended day-care before 6 months was significantly lower than that among children who had one or no older siblings and no day-care (relative risk [RR]=0.6; 95% confidence interval [CI], 0.4-0.8; P=.002). In multivariate analysis, there was an inverse association of each additional sibling (adjusted RR=0.8; 95% confidence interval, 0.7-1.0; P=.04) and attendance at day-care at younger than 6 months of age (adjusted RR=0.4; 95% CI, 0.2-1.0; P=.04) with the development of asthma. Frequent wheezing at the age of 2 years was more likely in children with exposure to more siblings or to day-care (adjusted RR=1.4; 95% CI, 1.1-1.8; P=.01). Those children with greater exposure were less likely to have frequent wheezing from the age of 6 years (adjusted RR=0.8; 95% CI, 0.6-1.0; P=.03) through the age of 13 years (adjusted RR=0.3; 95% CI, 0.2-0.5; P <.001). Male sex (adjusted RR=1.5; 95% CI, 1.1-2.0; P=.02) and a history of asthma in the mother (adjusted RR=2.3; 95% CI, 1.6-3.3; P <.001) or father (adjusted RR=1.6; 95% CI, 1.1-2.4; P=.02) were positively associated with development of asthma in the child.

BACKGROUND: Asthma is the most common chronic disease of childhood in the United States and has increased dramatically in incidence and prevalence over the last 30 years. One hypothesis invokes the inverse relationship between the frequency of some allergic disorders and both childhood infections and the number of siblings. Children attending day-care have more infections, and this may have a similar protective effect.

POPULATION STUDIED: A total of 1246 newborns were enrolled in the Tucson Children’s Respiratory Study between 1980 and 1984. All newborns were healthy and were cared for by pediatricians of a large health maintenance organization in Tucson.

STUDY DESIGN AND VALIDITY: The parents of 1035 newborns completed at least¹ questionnaire and were included in a cross-sectional analysis. The parents of 875 children (83%) completed at least 1 questionnaire and provided information on day-care attendance, and these were included in a longitudinal study. Information was obtained from parents of enrolled children on the number of siblings at home, day-care attendance in the first 3 years of life, the diagnosis of asthma, and frequent wheezing at the ages of 6, 8, 11, or 13 years. Children were categorized as having asthma if they had a diagnosis of asthma in the previous year. Children with scores of 2 or higher on a wheezing frequency scale from 1 to 5 at 2 or 3 years were defined as having frequent wheezing. Skin test reactivity to common allergens in the Tucson area and serum immunoglobulin E were measured at 6 and 11 years as a biological marker of allergic disease. The analysis accounted for potential confounding variables including sex, a history of asthma in either parent, race of parents, mother’s level of education, mother’s smoking status during the prenatal period, and breastfeeding status. Study participants were more likely to have 1 or no siblings, a mother with a high level of education, and white parents than those who were excluded or refused to participate. The retrospective nature of the questionnaires may have led to some misclassification. Although follow-up was very good, the study may not be generalizable to other ethnic groups or practices in different geographic locations.

OUTCOMES MEASURED: The primary outcome was the development of asthma and frequent wheezing in childhood as related to day-care attendance and exposure to siblings.

RESULTS: The incidence of asthma among children with 2 or more older siblings or who attended day-care before 6 months was significantly lower than that among children who had one or no older siblings and no day-care (relative risk [RR]=0.6; 95% confidence interval [CI], 0.4-0.8; P=.002). In multivariate analysis, there was an inverse association of each additional sibling (adjusted RR=0.8; 95% confidence interval, 0.7-1.0; P=.04) and attendance at day-care at younger than 6 months of age (adjusted RR=0.4; 95% CI, 0.2-1.0; P=.04) with the development of asthma. Frequent wheezing at the age of 2 years was more likely in children with exposure to more siblings or to day-care (adjusted RR=1.4; 95% CI, 1.1-1.8; P=.01). Those children with greater exposure were less likely to have frequent wheezing from the age of 6 years (adjusted RR=0.8; 95% CI, 0.6-1.0; P=.03) through the age of 13 years (adjusted RR=0.3; 95% CI, 0.2-0.5; P <.001). Male sex (adjusted RR=1.5; 95% CI, 1.1-2.0; P=.02) and a history of asthma in the mother (adjusted RR=2.3; 95% CI, 1.6-3.3; P <.001) or father (adjusted RR=1.6; 95% CI, 1.1-2.4; P=.02) were positively associated with development of asthma in the child.

BACKGROUND: Asthma is the most common chronic disease of childhood in the United States and has increased dramatically in incidence and prevalence over the last 30 years. One hypothesis invokes the inverse relationship between the frequency of some allergic disorders and both childhood infections and the number of siblings. Children attending day-care have more infections, and this may have a similar protective effect.

POPULATION STUDIED: A total of 1246 newborns were enrolled in the Tucson Children’s Respiratory Study between 1980 and 1984. All newborns were healthy and were cared for by pediatricians of a large health maintenance organization in Tucson.

STUDY DESIGN AND VALIDITY: The parents of 1035 newborns completed at least¹ questionnaire and were included in a cross-sectional analysis. The parents of 875 children (83%) completed at least 1 questionnaire and provided information on day-care attendance, and these were included in a longitudinal study. Information was obtained from parents of enrolled children on the number of siblings at home, day-care attendance in the first 3 years of life, the diagnosis of asthma, and frequent wheezing at the ages of 6, 8, 11, or 13 years. Children were categorized as having asthma if they had a diagnosis of asthma in the previous year. Children with scores of 2 or higher on a wheezing frequency scale from 1 to 5 at 2 or 3 years were defined as having frequent wheezing. Skin test reactivity to common allergens in the Tucson area and serum immunoglobulin E were measured at 6 and 11 years as a biological marker of allergic disease. The analysis accounted for potential confounding variables including sex, a history of asthma in either parent, race of parents, mother’s level of education, mother’s smoking status during the prenatal period, and breastfeeding status. Study participants were more likely to have 1 or no siblings, a mother with a high level of education, and white parents than those who were excluded or refused to participate. The retrospective nature of the questionnaires may have led to some misclassification. Although follow-up was very good, the study may not be generalizable to other ethnic groups or practices in different geographic locations.

OUTCOMES MEASURED: The primary outcome was the development of asthma and frequent wheezing in childhood as related to day-care attendance and exposure to siblings.

RESULTS: The incidence of asthma among children with 2 or more older siblings or who attended day-care before 6 months was significantly lower than that among children who had one or no older siblings and no day-care (relative risk [RR]=0.6; 95% confidence interval [CI], 0.4-0.8; P=.002). In multivariate analysis, there was an inverse association of each additional sibling (adjusted RR=0.8; 95% confidence interval, 0.7-1.0; P=.04) and attendance at day-care at younger than 6 months of age (adjusted RR=0.4; 95% CI, 0.2-1.0; P=.04) with the development of asthma. Frequent wheezing at the age of 2 years was more likely in children with exposure to more siblings or to day-care (adjusted RR=1.4; 95% CI, 1.1-1.8; P=.01). Those children with greater exposure were less likely to have frequent wheezing from the age of 6 years (adjusted RR=0.8; 95% CI, 0.6-1.0; P=.03) through the age of 13 years (adjusted RR=0.3; 95% CI, 0.2-0.5; P <.001). Male sex (adjusted RR=1.5; 95% CI, 1.1-2.0; P=.02) and a history of asthma in the mother (adjusted RR=2.3; 95% CI, 1.6-3.3; P <.001) or father (adjusted RR=1.6; 95% CI, 1.1-2.4; P=.02) were positively associated with development of asthma in the child.

BACKGROUND: Although the effectiveness of older antihypertensives (eg, diuretics and b-blockers) in preventing complications from hypertension has long been established, the effectiveness of newer agents such as calcium-channel blockers has not been demonstrated. As demonstrated by the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial study,¹ the ability of a medication to lower blood pressure may not translate into fewer complications. Although calcium-channel blockers lower blood pressure, questions remain regarding their safety and ability to prevent complications. Since calcium-channel blockers are also more expensive, it is fair to ask if the added expense to patients is worth it.

POPULATION STUDIED: Patients aged between 50 and 74 years were recruited from primary health care centers in Norway and Sweden. Inclusion criteria included 2 or more diastolic blood pressures of Ž100 mm Hg on 2 or more occasions. If patients were on treatment, the medications were stopped and the 2 elevated diastolic blood pressure readings had to be at least 1 week apart.

STUDY DESIGN AND VALIDITY: his was an open label comparison of antihypertensives. Randomization was conducted using a central randomization center where treatment was assigned. There was no mention of allocation concealment. The groups were similar at baseline. Almost 11,000 patients were initially assigned to receive either diltiazem (180-360 mg/day) or a diuretic or b-blocker. Additional drugs were added in a stepwise fashion to control the blood pressure. An intention-to-treat analysis was used. Mean follow-up was 4.5 years. Only 52 (0.5%) of the patients were lost to follow-up, but there was complete information on fatal events for 31 of the 52. This was a large well-designed study. The relatively short follow-up of patients coupled with the low frequency of outcomes makes it more difficult to find a difference between diltiazem and the other agents, should one actually exist. However, because of the large number of patients the study had sufficient power to find such a difference, allowing us to feel confident in the equivalence of the different approaches.

OUTCOMES MEASURED: A committee using preset criteria and whose members were blinded to the treatment assessed the end points. The primary outcome was the combined rates of fatal and nonfatal stroke, fatal and nonfatal myocardial infarction, and other cardiovascular death. Secondary outcomes were the individual rates of fatal and nonfatal stroke and fatal and nonfatal myocardial infarction, and overall mortality.

RESULTS: Overall, the combined outcome of stroke, myocardial infarction, or cardiovascular death was the same in both groups (relative risk [RR]=1.0; 95% confidence interval [CI], 0.87-1.15). Overall mortality was also the identical for both groups. Taken individually, there was no difference in the incidence of myocardial infarction, though there were fewer strokes in the diltiazem-treated patients (RR=0.80; 95% CI, 0.65-0.99). However, the rate of events was relatively low in both groups (yes=0.64% per patient year in the diltiazem group vs 0.79% per patient year in the diuretic/b-blocker group). Subgroup analysis in patients with type 2 diabetes revealed no difference in end points. There were 4 adverse effects that differed significantly between the 2 groups: the diltiazem group experienced more headaches but less fatigue, dyspnea, and impotence.

BACKGROUND: Although the effectiveness of older antihypertensives (eg, diuretics and b-blockers) in preventing complications from hypertension has long been established, the effectiveness of newer agents such as calcium-channel blockers has not been demonstrated. As demonstrated by the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial study,¹ the ability of a medication to lower blood pressure may not translate into fewer complications. Although calcium-channel blockers lower blood pressure, questions remain regarding their safety and ability to prevent complications. Since calcium-channel blockers are also more expensive, it is fair to ask if the added expense to patients is worth it.

POPULATION STUDIED: Patients aged between 50 and 74 years were recruited from primary health care centers in Norway and Sweden. Inclusion criteria included 2 or more diastolic blood pressures of Ž100 mm Hg on 2 or more occasions. If patients were on treatment, the medications were stopped and the 2 elevated diastolic blood pressure readings had to be at least 1 week apart.

STUDY DESIGN AND VALIDITY: his was an open label comparison of antihypertensives. Randomization was conducted using a central randomization center where treatment was assigned. There was no mention of allocation concealment. The groups were similar at baseline. Almost 11,000 patients were initially assigned to receive either diltiazem (180-360 mg/day) or a diuretic or b-blocker. Additional drugs were added in a stepwise fashion to control the blood pressure. An intention-to-treat analysis was used. Mean follow-up was 4.5 years. Only 52 (0.5%) of the patients were lost to follow-up, but there was complete information on fatal events for 31 of the 52. This was a large well-designed study. The relatively short follow-up of patients coupled with the low frequency of outcomes makes it more difficult to find a difference between diltiazem and the other agents, should one actually exist. However, because of the large number of patients the study had sufficient power to find such a difference, allowing us to feel confident in the equivalence of the different approaches.

OUTCOMES MEASURED: A committee using preset criteria and whose members were blinded to the treatment assessed the end points. The primary outcome was the combined rates of fatal and nonfatal stroke, fatal and nonfatal myocardial infarction, and other cardiovascular death. Secondary outcomes were the individual rates of fatal and nonfatal stroke and fatal and nonfatal myocardial infarction, and overall mortality.

RESULTS: Overall, the combined outcome of stroke, myocardial infarction, or cardiovascular death was the same in both groups (relative risk [RR]=1.0; 95% confidence interval [CI], 0.87-1.15). Overall mortality was also the identical for both groups. Taken individually, there was no difference in the incidence of myocardial infarction, though there were fewer strokes in the diltiazem-treated patients (RR=0.80; 95% CI, 0.65-0.99). However, the rate of events was relatively low in both groups (yes=0.64% per patient year in the diltiazem group vs 0.79% per patient year in the diuretic/b-blocker group). Subgroup analysis in patients with type 2 diabetes revealed no difference in end points. There were 4 adverse effects that differed significantly between the 2 groups: the diltiazem group experienced more headaches but less fatigue, dyspnea, and impotence.

BACKGROUND: Although the effectiveness of older antihypertensives (eg, diuretics and b-blockers) in preventing complications from hypertension has long been established, the effectiveness of newer agents such as calcium-channel blockers has not been demonstrated. As demonstrated by the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial study,¹ the ability of a medication to lower blood pressure may not translate into fewer complications. Although calcium-channel blockers lower blood pressure, questions remain regarding their safety and ability to prevent complications. Since calcium-channel blockers are also more expensive, it is fair to ask if the added expense to patients is worth it.

POPULATION STUDIED: Patients aged between 50 and 74 years were recruited from primary health care centers in Norway and Sweden. Inclusion criteria included 2 or more diastolic blood pressures of Ž100 mm Hg on 2 or more occasions. If patients were on treatment, the medications were stopped and the 2 elevated diastolic blood pressure readings had to be at least 1 week apart.

STUDY DESIGN AND VALIDITY: his was an open label comparison of antihypertensives. Randomization was conducted using a central randomization center where treatment was assigned. There was no mention of allocation concealment. The groups were similar at baseline. Almost 11,000 patients were initially assigned to receive either diltiazem (180-360 mg/day) or a diuretic or b-blocker. Additional drugs were added in a stepwise fashion to control the blood pressure. An intention-to-treat analysis was used. Mean follow-up was 4.5 years. Only 52 (0.5%) of the patients were lost to follow-up, but there was complete information on fatal events for 31 of the 52. This was a large well-designed study. The relatively short follow-up of patients coupled with the low frequency of outcomes makes it more difficult to find a difference between diltiazem and the other agents, should one actually exist. However, because of the large number of patients the study had sufficient power to find such a difference, allowing us to feel confident in the equivalence of the different approaches.

OUTCOMES MEASURED: A committee using preset criteria and whose members were blinded to the treatment assessed the end points. The primary outcome was the combined rates of fatal and nonfatal stroke, fatal and nonfatal myocardial infarction, and other cardiovascular death. Secondary outcomes were the individual rates of fatal and nonfatal stroke and fatal and nonfatal myocardial infarction, and overall mortality.

RESULTS: Overall, the combined outcome of stroke, myocardial infarction, or cardiovascular death was the same in both groups (relative risk [RR]=1.0; 95% confidence interval [CI], 0.87-1.15). Overall mortality was also the identical for both groups. Taken individually, there was no difference in the incidence of myocardial infarction, though there were fewer strokes in the diltiazem-treated patients (RR=0.80; 95% CI, 0.65-0.99). However, the rate of events was relatively low in both groups (yes=0.64% per patient year in the diltiazem group vs 0.79% per patient year in the diuretic/b-blocker group). Subgroup analysis in patients with type 2 diabetes revealed no difference in end points. There were 4 adverse effects that differed significantly between the 2 groups: the diltiazem group experienced more headaches but less fatigue, dyspnea, and impotence.

BACKGROUND: A recent Cochrane review found that early endoscopy was not more effective than initial acid suppressive therapy, but the 3 available studies lacked statistical power to confirm a clear difference. No eligible trials of treatment guided by the results of H pylori testing versus treatment guided by initial endoscopy were found.¹

POPULATION STUDIED: A total of 576 dyspeptic patients with a median age of approximately 45 years were recruited from Danish general practitioners. After exclusion for significant comorbidities or complicating factors, such as such as upper gastrointestinal bleeding, 500 patients were randomized, and 447 completed 1 year follow-up.

STUDY DESIGN AND VALIDITY: This was a randomized controlled trial of prompt endoscopy versus a test-and-eradicate strategy. Randomization using random number tables was accomplished using sealed numbered envelopes. Groups were similar at the beginning of the study, although patients in the prompt endoscopy group had a longer history of dyspepsia. Patients were interviewed at follow-up intervals of 1 month and 1 year and completed a diary for 1 week out of each month during the study year. Patients randomized to the test-and-eradicate strategy had C-urea breath testing for H pylori. Those with a positive test were treated with a 2-week course of lansoprazole 30 mg twice daily (a proton pump inhibitor [PPI]), metronidazole 500 mg 3 times daily, and amoxicillin 1000 mg twice daily. H pylori negative patients with primarily reflux symptoms were treated with a PPI for 1 month and continued on demand. Patients who did not improve or relapsed during follow-up were offered endoscopy. Patients randomized to prompt endoscopy were treated according to endoscopic findings. Those with duodenal ulcers received eradication therapy followed by 2 weeks of PPI. Patients with gastric ulcerations were treated according to H pylori status. Gastric ulcers were biopsied every 6 weeks until healed. Patients with reflux esophagitis were given PPI therapy, for 8 weeks of PPI. Those diagnosed with functional dyspepsia were reassured, given lifestyle modification advice, and prescribed PPIs if they had previously used them successfully. The strengths of this study include its randomized design, high follow-up rate, recruitment from primary care practices, and focus on patient-oriented outcomes. The authors do not mention if attempts were made to blind interviewers or assessors to patient group status. The results are likely applicable to primary care populations, but referral to a teaching hospital may have created expectation biases on the part of patients. Although analysis was not by intention to treat, the number of dropouts was the same between groups and was only 10% overall. The sample size was adequate to detect a difference of 10% in the number of days of symptoms.

OUTCOMES MEASURED: The main outcome was the percentage of days without dyspeptic symptoms. Secondary outcomes included the number of sick leave days, quality of life measured with a visual analog scale, and the gastrointestinal symptoms rating scale, visits to general practitioners, hospital admissions, satisfaction, use of endoscopy, and use of PPIs.

RESULTS: No differences were found in the proportion of days without dyspeptic symptoms, scores on quality of life measures, outpatient visits, hospital admissions, or sick leave days. Significantly more patients in the prompt endoscopy group (20% vs 28%) reported improved symptoms at 1 month, but there were no differences at 1 year. The patients assigned to the test-and-eradicate strategy were more likely to be dissatisfied at 1 year (12% vs 4%). As expected, the use of encoscopy (0.5 vs 1.25 per person, P <.001) was significantly lower in the test-and-eradicate group.

BACKGROUND: A recent Cochrane review found that early endoscopy was not more effective than initial acid suppressive therapy, but the 3 available studies lacked statistical power to confirm a clear difference. No eligible trials of treatment guided by the results of H pylori testing versus treatment guided by initial endoscopy were found.¹

POPULATION STUDIED: A total of 576 dyspeptic patients with a median age of approximately 45 years were recruited from Danish general practitioners. After exclusion for significant comorbidities or complicating factors, such as such as upper gastrointestinal bleeding, 500 patients were randomized, and 447 completed 1 year follow-up.

STUDY DESIGN AND VALIDITY: This was a randomized controlled trial of prompt endoscopy versus a test-and-eradicate strategy. Randomization using random number tables was accomplished using sealed numbered envelopes. Groups were similar at the beginning of the study, although patients in the prompt endoscopy group had a longer history of dyspepsia. Patients were interviewed at follow-up intervals of 1 month and 1 year and completed a diary for 1 week out of each month during the study year. Patients randomized to the test-and-eradicate strategy had C-urea breath testing for H pylori. Those with a positive test were treated with a 2-week course of lansoprazole 30 mg twice daily (a proton pump inhibitor [PPI]), metronidazole 500 mg 3 times daily, and amoxicillin 1000 mg twice daily. H pylori negative patients with primarily reflux symptoms were treated with a PPI for 1 month and continued on demand. Patients who did not improve or relapsed during follow-up were offered endoscopy. Patients randomized to prompt endoscopy were treated according to endoscopic findings. Those with duodenal ulcers received eradication therapy followed by 2 weeks of PPI. Patients with gastric ulcerations were treated according to H pylori status. Gastric ulcers were biopsied every 6 weeks until healed. Patients with reflux esophagitis were given PPI therapy, for 8 weeks of PPI. Those diagnosed with functional dyspepsia were reassured, given lifestyle modification advice, and prescribed PPIs if they had previously used them successfully. The strengths of this study include its randomized design, high follow-up rate, recruitment from primary care practices, and focus on patient-oriented outcomes. The authors do not mention if attempts were made to blind interviewers or assessors to patient group status. The results are likely applicable to primary care populations, but referral to a teaching hospital may have created expectation biases on the part of patients. Although analysis was not by intention to treat, the number of dropouts was the same between groups and was only 10% overall. The sample size was adequate to detect a difference of 10% in the number of days of symptoms.

OUTCOMES MEASURED: The main outcome was the percentage of days without dyspeptic symptoms. Secondary outcomes included the number of sick leave days, quality of life measured with a visual analog scale, and the gastrointestinal symptoms rating scale, visits to general practitioners, hospital admissions, satisfaction, use of endoscopy, and use of PPIs.

RESULTS: No differences were found in the proportion of days without dyspeptic symptoms, scores on quality of life measures, outpatient visits, hospital admissions, or sick leave days. Significantly more patients in the prompt endoscopy group (20% vs 28%) reported improved symptoms at 1 month, but there were no differences at 1 year. The patients assigned to the test-and-eradicate strategy were more likely to be dissatisfied at 1 year (12% vs 4%). As expected, the use of encoscopy (0.5 vs 1.25 per person, P <.001) was significantly lower in the test-and-eradicate group.

BACKGROUND: A recent Cochrane review found that early endoscopy was not more effective than initial acid suppressive therapy, but the 3 available studies lacked statistical power to confirm a clear difference. No eligible trials of treatment guided by the results of H pylori testing versus treatment guided by initial endoscopy were found.¹

POPULATION STUDIED: A total of 576 dyspeptic patients with a median age of approximately 45 years were recruited from Danish general practitioners. After exclusion for significant comorbidities or complicating factors, such as such as upper gastrointestinal bleeding, 500 patients were randomized, and 447 completed 1 year follow-up.

STUDY DESIGN AND VALIDITY: This was a randomized controlled trial of prompt endoscopy versus a test-and-eradicate strategy. Randomization using random number tables was accomplished using sealed numbered envelopes. Groups were similar at the beginning of the study, although patients in the prompt endoscopy group had a longer history of dyspepsia. Patients were interviewed at follow-up intervals of 1 month and 1 year and completed a diary for 1 week out of each month during the study year. Patients randomized to the test-and-eradicate strategy had C-urea breath testing for H pylori. Those with a positive test were treated with a 2-week course of lansoprazole 30 mg twice daily (a proton pump inhibitor [PPI]), metronidazole 500 mg 3 times daily, and amoxicillin 1000 mg twice daily. H pylori negative patients with primarily reflux symptoms were treated with a PPI for 1 month and continued on demand. Patients who did not improve or relapsed during follow-up were offered endoscopy. Patients randomized to prompt endoscopy were treated according to endoscopic findings. Those with duodenal ulcers received eradication therapy followed by 2 weeks of PPI. Patients with gastric ulcerations were treated according to H pylori status. Gastric ulcers were biopsied every 6 weeks until healed. Patients with reflux esophagitis were given PPI therapy, for 8 weeks of PPI. Those diagnosed with functional dyspepsia were reassured, given lifestyle modification advice, and prescribed PPIs if they had previously used them successfully. The strengths of this study include its randomized design, high follow-up rate, recruitment from primary care practices, and focus on patient-oriented outcomes. The authors do not mention if attempts were made to blind interviewers or assessors to patient group status. The results are likely applicable to primary care populations, but referral to a teaching hospital may have created expectation biases on the part of patients. Although analysis was not by intention to treat, the number of dropouts was the same between groups and was only 10% overall. The sample size was adequate to detect a difference of 10% in the number of days of symptoms.

OUTCOMES MEASURED: The main outcome was the percentage of days without dyspeptic symptoms. Secondary outcomes included the number of sick leave days, quality of life measured with a visual analog scale, and the gastrointestinal symptoms rating scale, visits to general practitioners, hospital admissions, satisfaction, use of endoscopy, and use of PPIs.

RESULTS: No differences were found in the proportion of days without dyspeptic symptoms, scores on quality of life measures, outpatient visits, hospital admissions, or sick leave days. Significantly more patients in the prompt endoscopy group (20% vs 28%) reported improved symptoms at 1 month, but there were no differences at 1 year. The patients assigned to the test-and-eradicate strategy were more likely to be dissatisfied at 1 year (12% vs 4%). As expected, the use of encoscopy (0.5 vs 1.25 per person, P <.001) was significantly lower in the test-and-eradicate group.

BACKGROUND: In some settings, “diastolic dysfunction” has become a diagnosis of exclusion used to define any patient with symptoms suggestive of CHF but with normal left ventricular (LV) systolic function on echocardiography. This descriptive case series identifies potential diagnoses other than diastolic dysfunction in such patients.

POPULATION STUDIED: The investigators identified 159 consecutive patients with suspected heart failure referred for an outpatient echocardiogram in Scotland. No information was given regarding the previous work-up of these patients or criteria for referral. Fifty (31%) were found to have LV systolic dysfunction, atrial fibrillation, or valvular heart disease and were excluded from further study. Of the remaining 109, most were elderly; 73% were women; and all are presumed to be white. It is likely that the patients are similar to many seen by family physicians in the United States, but clinicians should be cautious about extending the findings to younger persons, men, and people of color.

STUDY DESIGN AND VALIDITY: This study was a case series of patients with preserved LV systolic function but suspected CHF. They obtained a full standardized clinical history for every patient and objective measures including body mass index (BMI), pulmonary function testing, electrocardiograms, and transthoracic echocardiography. The study was purely descriptive in design and provides only prevalence rates of specific abnormalities. The methodology of this study was limited. Although the case series establishes many potential explanations for patients’ symptoms of dyspnea, lower extremity edema, and other findings suggestive of CHF, it cannot establish which diagnosis is causing the symptoms without follow-up, comparison groups, or trials of treatment. This study also has other minor weaknesses: (1) lack of reporting of reasons for initial referral, or possible selection bias; (2) lack of attention to inter-rater reliability and quality of the echocardiography; and (3) lack of attention to confounding factors such as the variability of other cardiac evaluation and of the use of medications and other health interventions that might alter symptoms.

OUTCOMES MEASURED: Prevalence rates were reported for subjective symptoms, past medical problems, and objective measures of abnormal BMI, forced expiratory volume in 1 second (FEV1), electrocardiography, and echocardiography. The overlap of certain findings (obesity, respiratory disease, and cardiac abnormalities) were also assessed. The investigators made no attempts to measure costs, prognosis, response to therapy, functional status, quality of life, or patient satisfaction, all of which are important to assessing the value of this information in daily practice.

RESULTS: Most patients reported ankle swelling (68%) and dyspnea on exertion (92%). Fewer reported paroxysmal nocturnal dyspnea (23%) or dyspnea at rest (25%). Many had some previous medical condition (47% hypertension, 11% myocardial infarction, 28% angina, 6% coronary artery bypass graft, 23% pulmonary disease), and 81% were overweight or obese by BMI. Half of the patients had FEV1 measures less than 70% of predicted. After considering clinical history and electrocardiographic findings, 38% had evidence of coronary disease. Echocardiography detected signs of poor ventricular filling in 67% and left ventricular hypertrophy in 26% of all patients. Many patients had more than one abnormal finding. Only 7% of the patients had no abnormalities of BMI, respiratory, or coronary function.

BACKGROUND: In some settings, “diastolic dysfunction” has become a diagnosis of exclusion used to define any patient with symptoms suggestive of CHF but with normal left ventricular (LV) systolic function on echocardiography. This descriptive case series identifies potential diagnoses other than diastolic dysfunction in such patients.

POPULATION STUDIED: The investigators identified 159 consecutive patients with suspected heart failure referred for an outpatient echocardiogram in Scotland. No information was given regarding the previous work-up of these patients or criteria for referral. Fifty (31%) were found to have LV systolic dysfunction, atrial fibrillation, or valvular heart disease and were excluded from further study. Of the remaining 109, most were elderly; 73% were women; and all are presumed to be white. It is likely that the patients are similar to many seen by family physicians in the United States, but clinicians should be cautious about extending the findings to younger persons, men, and people of color.

STUDY DESIGN AND VALIDITY: This study was a case series of patients with preserved LV systolic function but suspected CHF. They obtained a full standardized clinical history for every patient and objective measures including body mass index (BMI), pulmonary function testing, electrocardiograms, and transthoracic echocardiography. The study was purely descriptive in design and provides only prevalence rates of specific abnormalities. The methodology of this study was limited. Although the case series establishes many potential explanations for patients’ symptoms of dyspnea, lower extremity edema, and other findings suggestive of CHF, it cannot establish which diagnosis is causing the symptoms without follow-up, comparison groups, or trials of treatment. This study also has other minor weaknesses: (1) lack of reporting of reasons for initial referral, or possible selection bias; (2) lack of attention to inter-rater reliability and quality of the echocardiography; and (3) lack of attention to confounding factors such as the variability of other cardiac evaluation and of the use of medications and other health interventions that might alter symptoms.

OUTCOMES MEASURED: Prevalence rates were reported for subjective symptoms, past medical problems, and objective measures of abnormal BMI, forced expiratory volume in 1 second (FEV1), electrocardiography, and echocardiography. The overlap of certain findings (obesity, respiratory disease, and cardiac abnormalities) were also assessed. The investigators made no attempts to measure costs, prognosis, response to therapy, functional status, quality of life, or patient satisfaction, all of which are important to assessing the value of this information in daily practice.

RESULTS: Most patients reported ankle swelling (68%) and dyspnea on exertion (92%). Fewer reported paroxysmal nocturnal dyspnea (23%) or dyspnea at rest (25%). Many had some previous medical condition (47% hypertension, 11% myocardial infarction, 28% angina, 6% coronary artery bypass graft, 23% pulmonary disease), and 81% were overweight or obese by BMI. Half of the patients had FEV1 measures less than 70% of predicted. After considering clinical history and electrocardiographic findings, 38% had evidence of coronary disease. Echocardiography detected signs of poor ventricular filling in 67% and left ventricular hypertrophy in 26% of all patients. Many patients had more than one abnormal finding. Only 7% of the patients had no abnormalities of BMI, respiratory, or coronary function.

BACKGROUND: In some settings, “diastolic dysfunction” has become a diagnosis of exclusion used to define any patient with symptoms suggestive of CHF but with normal left ventricular (LV) systolic function on echocardiography. This descriptive case series identifies potential diagnoses other than diastolic dysfunction in such patients.

POPULATION STUDIED: The investigators identified 159 consecutive patients with suspected heart failure referred for an outpatient echocardiogram in Scotland. No information was given regarding the previous work-up of these patients or criteria for referral. Fifty (31%) were found to have LV systolic dysfunction, atrial fibrillation, or valvular heart disease and were excluded from further study. Of the remaining 109, most were elderly; 73% were women; and all are presumed to be white. It is likely that the patients are similar to many seen by family physicians in the United States, but clinicians should be cautious about extending the findings to younger persons, men, and people of color.

STUDY DESIGN AND VALIDITY: This study was a case series of patients with preserved LV systolic function but suspected CHF. They obtained a full standardized clinical history for every patient and objective measures including body mass index (BMI), pulmonary function testing, electrocardiograms, and transthoracic echocardiography. The study was purely descriptive in design and provides only prevalence rates of specific abnormalities. The methodology of this study was limited. Although the case series establishes many potential explanations for patients’ symptoms of dyspnea, lower extremity edema, and other findings suggestive of CHF, it cannot establish which diagnosis is causing the symptoms without follow-up, comparison groups, or trials of treatment. This study also has other minor weaknesses: (1) lack of reporting of reasons for initial referral, or possible selection bias; (2) lack of attention to inter-rater reliability and quality of the echocardiography; and (3) lack of attention to confounding factors such as the variability of other cardiac evaluation and of the use of medications and other health interventions that might alter symptoms.

OUTCOMES MEASURED: Prevalence rates were reported for subjective symptoms, past medical problems, and objective measures of abnormal BMI, forced expiratory volume in 1 second (FEV1), electrocardiography, and echocardiography. The overlap of certain findings (obesity, respiratory disease, and cardiac abnormalities) were also assessed. The investigators made no attempts to measure costs, prognosis, response to therapy, functional status, quality of life, or patient satisfaction, all of which are important to assessing the value of this information in daily practice.

RESULTS: Most patients reported ankle swelling (68%) and dyspnea on exertion (92%). Fewer reported paroxysmal nocturnal dyspnea (23%) or dyspnea at rest (25%). Many had some previous medical condition (47% hypertension, 11% myocardial infarction, 28% angina, 6% coronary artery bypass graft, 23% pulmonary disease), and 81% were overweight or obese by BMI. Half of the patients had FEV1 measures less than 70% of predicted. After considering clinical history and electrocardiographic findings, 38% had evidence of coronary disease. Echocardiography detected signs of poor ventricular filling in 67% and left ventricular hypertrophy in 26% of all patients. Many patients had more than one abnormal finding. Only 7% of the patients had no abnormalities of BMI, respiratory, or coronary function.

BACKGROUND: With the high morbidity and mortality associated with AF, it is important to define safe effective treatments to convert AF to sinus rhythm. Although patients with underlying cardiac disease are at higher risk for developing serious arrhythmias and hypotension from Class III antiarrhythmics, comparable risks have not been shown in a low-risk population with new-onset AF. The authors of this study evaluated the risks and benefits of using the Class III antiarrhythmics sotalol and amiodarone versus digoxin in conversion of new-onset AF to sinus rhythm at 48 hours.

POPULATION STUDIED: The authors of this study enrolled 115 patients with new-onset (<24 hours) AF. Patients with significant left ventricular dysfunction (ejection fraction <30% or requiring >40 mg of furosemide daily) or wide complex tachycardia were excluded. Patients who had used any of the study drugs within a defined period of time or who were prescribed a b-blocker were also excluded.

STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Concealed allocation did not occur for the majority of patients enrolled in the study. Patients were randomized to receive amiodarone, sotalol, or digoxin; all 3 groups had similar baseline characteristics. The trial medication was discontinued before 48 hours of treatment in 5 patients because of stroke, hypotension, or bradyarrhythmia, but these patients were still included in the analysis. At 24 hours those patients still in AF were started on heparin. Cardioversion was attempted in 20 of 29 patients who remained in AF after 48 hours of the study drug. The 9 patients excluded from cardioversion had significant left ventricular dysfunction, stroke, inadequate anticoagulation, or hypotension. Adverse events from all medications were recorded and analyzed. This study lacked long-term follow-up for monitoring of subsequent spontaneous reversion to AF, which may be a major factor in the drug to choose for sinus rhythm conversion. In addition, this study excluded those patients who had left ventricular dysfunction, a group that is at particular risk for developing complications from new-onset AF.

OUTCOMES MEASURED: The primary outcome measured was successful conversion to sinus rhythm within 48 hours of antiarrhythmic treatment or cardioversion. Secondary outcomes considered were time to conversion; ventricular rate if in AF at 4, 24, and 48 hours; and adverse events.

RESULTS: The number of patients in sinus rhythm after 48 hours of medication was greater in both the amiodarone (77%) and sotalol (88%; number needed to treat=3) groups compared with the digoxin group (58%) This was statistically significant (P <.01) for the sotalol group and the combined sotalol and aminodarone groups. There was also a nonsignificant trend toward more successful cardioversion in those receiving either study drug. The average time to reversion was greater for digoxin-treated patients (27 hours) than amiodarone-treated (18 hours; P <.05) or sotalol-treated (13 hours; P <.01) patients. Major adverse events included left ventricular failure, bradyarrhythmia, hypotension, and stroke. Digoxin treatment was associated with a significantly higher risk of major complications compared with either other drug (22% vs 7.7% and 5%).

BACKGROUND: With the high morbidity and mortality associated with AF, it is important to define safe effective treatments to convert AF to sinus rhythm. Although patients with underlying cardiac disease are at higher risk for developing serious arrhythmias and hypotension from Class III antiarrhythmics, comparable risks have not been shown in a low-risk population with new-onset AF. The authors of this study evaluated the risks and benefits of using the Class III antiarrhythmics sotalol and amiodarone versus digoxin in conversion of new-onset AF to sinus rhythm at 48 hours.

POPULATION STUDIED: The authors of this study enrolled 115 patients with new-onset (<24 hours) AF. Patients with significant left ventricular dysfunction (ejection fraction <30% or requiring >40 mg of furosemide daily) or wide complex tachycardia were excluded. Patients who had used any of the study drugs within a defined period of time or who were prescribed a b-blocker were also excluded.

STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Concealed allocation did not occur for the majority of patients enrolled in the study. Patients were randomized to receive amiodarone, sotalol, or digoxin; all 3 groups had similar baseline characteristics. The trial medication was discontinued before 48 hours of treatment in 5 patients because of stroke, hypotension, or bradyarrhythmia, but these patients were still included in the analysis. At 24 hours those patients still in AF were started on heparin. Cardioversion was attempted in 20 of 29 patients who remained in AF after 48 hours of the study drug. The 9 patients excluded from cardioversion had significant left ventricular dysfunction, stroke, inadequate anticoagulation, or hypotension. Adverse events from all medications were recorded and analyzed. This study lacked long-term follow-up for monitoring of subsequent spontaneous reversion to AF, which may be a major factor in the drug to choose for sinus rhythm conversion. In addition, this study excluded those patients who had left ventricular dysfunction, a group that is at particular risk for developing complications from new-onset AF.

OUTCOMES MEASURED: The primary outcome measured was successful conversion to sinus rhythm within 48 hours of antiarrhythmic treatment or cardioversion. Secondary outcomes considered were time to conversion; ventricular rate if in AF at 4, 24, and 48 hours; and adverse events.

RESULTS: The number of patients in sinus rhythm after 48 hours of medication was greater in both the amiodarone (77%) and sotalol (88%; number needed to treat=3) groups compared with the digoxin group (58%) This was statistically significant (P <.01) for the sotalol group and the combined sotalol and aminodarone groups. There was also a nonsignificant trend toward more successful cardioversion in those receiving either study drug. The average time to reversion was greater for digoxin-treated patients (27 hours) than amiodarone-treated (18 hours; P <.05) or sotalol-treated (13 hours; P <.01) patients. Major adverse events included left ventricular failure, bradyarrhythmia, hypotension, and stroke. Digoxin treatment was associated with a significantly higher risk of major complications compared with either other drug (22% vs 7.7% and 5%).

BACKGROUND: With the high morbidity and mortality associated with AF, it is important to define safe effective treatments to convert AF to sinus rhythm. Although patients with underlying cardiac disease are at higher risk for developing serious arrhythmias and hypotension from Class III antiarrhythmics, comparable risks have not been shown in a low-risk population with new-onset AF. The authors of this study evaluated the risks and benefits of using the Class III antiarrhythmics sotalol and amiodarone versus digoxin in conversion of new-onset AF to sinus rhythm at 48 hours.

POPULATION STUDIED: The authors of this study enrolled 115 patients with new-onset (<24 hours) AF. Patients with significant left ventricular dysfunction (ejection fraction <30% or requiring >40 mg of furosemide daily) or wide complex tachycardia were excluded. Patients who had used any of the study drugs within a defined period of time or who were prescribed a b-blocker were also excluded.

STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Concealed allocation did not occur for the majority of patients enrolled in the study. Patients were randomized to receive amiodarone, sotalol, or digoxin; all 3 groups had similar baseline characteristics. The trial medication was discontinued before 48 hours of treatment in 5 patients because of stroke, hypotension, or bradyarrhythmia, but these patients were still included in the analysis. At 24 hours those patients still in AF were started on heparin. Cardioversion was attempted in 20 of 29 patients who remained in AF after 48 hours of the study drug. The 9 patients excluded from cardioversion had significant left ventricular dysfunction, stroke, inadequate anticoagulation, or hypotension. Adverse events from all medications were recorded and analyzed. This study lacked long-term follow-up for monitoring of subsequent spontaneous reversion to AF, which may be a major factor in the drug to choose for sinus rhythm conversion. In addition, this study excluded those patients who had left ventricular dysfunction, a group that is at particular risk for developing complications from new-onset AF.

OUTCOMES MEASURED: The primary outcome measured was successful conversion to sinus rhythm within 48 hours of antiarrhythmic treatment or cardioversion. Secondary outcomes considered were time to conversion; ventricular rate if in AF at 4, 24, and 48 hours; and adverse events.

RESULTS: The number of patients in sinus rhythm after 48 hours of medication was greater in both the amiodarone (77%) and sotalol (88%; number needed to treat=3) groups compared with the digoxin group (58%) This was statistically significant (P <.01) for the sotalol group and the combined sotalol and aminodarone groups. There was also a nonsignificant trend toward more successful cardioversion in those receiving either study drug. The average time to reversion was greater for digoxin-treated patients (27 hours) than amiodarone-treated (18 hours; P <.05) or sotalol-treated (13 hours; P <.01) patients. Major adverse events included left ventricular failure, bradyarrhythmia, hypotension, and stroke. Digoxin treatment was associated with a significantly higher risk of major complications compared with either other drug (22% vs 7.7% and 5%).

BACKGROUND: Acute mountain sickness results in symptoms such as headache, loss of appetite, nausea, fatigue, insomnia, and increased mortality in the first few days of exertion at high altitudes. Acetazolamide and dexamethasone have been recommended as treatments to prevent acute mountain sickness, although their efficacy and tolerability have not been well established.

DATA SOURCE: Thirty-three clinical trials comparing any pharmacologic treatment with placebo for the prevention of acute mountain sickness were identified through a comprehensive search of MEDLINE, EMBASE, the Cochrane Library, a high altitude bibliography Web site, and the bibliographies of retrieved reports and review articles. Of these trials, 18 reported complete prevention of acute mountain sickness as an outcome and as related to ascents to 4050 to 5890 meters (13300 to 19300 feet). These were included in a qualitative analysis of efficacy for any pharmacologic treatment (all 18 trials) and statistical meta-analyses for dexamethasone (8 trials representing 161 subjects) and acetazolamide (9 trials representing 295 subjects).

STUDY DESIGN AND VALIDITY: Only one author determined whether studies met inclusion criteria. All 3 authors read the included articles for validity, applying the 3-item 5-point Oxford score. The mean quality score was 3 (range=2-5). A total of 17 of the 33 trials used an adequate method of blinding. Validity was not a criteria for inclusion in the review. Following the qualitative analysis of efficacy, relative benefit (relative risk [RR] of prevention of mountain sickness) and numbers needed to treat (NNTs) were calculated for 2 interventions, dexamethasone and acetazolamide. Although the studies were rated for validity using previously tested criteria, no information on study limitations is given with which to judge the direction of effect. Using more than one author to determine eligibility would have minimized investigator bias. Although included studies varied in their definitions of acute mountain sickness, the results were homogenous. The investigators limited the outcome to complete prevention of symptoms. This conservative approach would underestimate the efficacy of the treatments making any significant benefit more likely to be real. Unfortunately, no information is provided on the subjects in the trials, including information such as age, sex, training, smoking status, and other risk factors for acute mountain sickness. This information would have helped generalize the study results.

OUTCOMES MEASURED: The primary outcome measured was complete prevention of acute mountain sickness according to the definition used in each of the original studies. Although reported for some of the studies, the reduction in symptom severity was not considered a criterion for efficacy in this study. Secondary outcomes included prevention of headache, nausea, insomnia, and dizziness, and the development of adverse drug reactions.

RESULTS: In 8 trials of dexamethasone (n=161) and 9 of acetazolamide (n=295), all with exposure above 4000 meters, single daily doses of dexamethasone 8 mg, 12 mg, and 16 mg or acetazolamide 750 mg were all more efficacious than placebo (NNT=3 for both). Smaller doses (dexamethasone 0.5 and 2 mg in one trial, acetazolamide 500 mg in 3 trials) did not prevent mountain sickness over placebo. Five trials of acetazolamide reported symptom end points including insomnia, headache, nausea, and dizziness; all results favored acetazolamide (NNT=3-6). Both dexamethasone and acetazolamide demonstrated a trend toward greater efficacy (lower NNT) with faster ascent rates. There was no relative benefit (RR for prophylaxis=1) for trials with ascent rates below approximately 500 meters per day; but there was a five- to six-fold relative benefit for prophylaxis at the highest ascent rates. Regarding adverse effects, subjects in 2 of 5 studies were more likely to experience depression on weaning of dexamethasone (overall RR=4.5). Acetazolamide was associated with polyuria (RR=4.2) and paraesthesia (RR=4.0).

BACKGROUND: Acute mountain sickness results in symptoms such as headache, loss of appetite, nausea, fatigue, insomnia, and increased mortality in the first few days of exertion at high altitudes. Acetazolamide and dexamethasone have been recommended as treatments to prevent acute mountain sickness, although their efficacy and tolerability have not been well established.

DATA SOURCE: Thirty-three clinical trials comparing any pharmacologic treatment with placebo for the prevention of acute mountain sickness were identified through a comprehensive search of MEDLINE, EMBASE, the Cochrane Library, a high altitude bibliography Web site, and the bibliographies of retrieved reports and review articles. Of these trials, 18 reported complete prevention of acute mountain sickness as an outcome and as related to ascents to 4050 to 5890 meters (13300 to 19300 feet). These were included in a qualitative analysis of efficacy for any pharmacologic treatment (all 18 trials) and statistical meta-analyses for dexamethasone (8 trials representing 161 subjects) and acetazolamide (9 trials representing 295 subjects).

STUDY DESIGN AND VALIDITY: Only one author determined whether studies met inclusion criteria. All 3 authors read the included articles for validity, applying the 3-item 5-point Oxford score. The mean quality score was 3 (range=2-5). A total of 17 of the 33 trials used an adequate method of blinding. Validity was not a criteria for inclusion in the review. Following the qualitative analysis of efficacy, relative benefit (relative risk [RR] of prevention of mountain sickness) and numbers needed to treat (NNTs) were calculated for 2 interventions, dexamethasone and acetazolamide. Although the studies were rated for validity using previously tested criteria, no information on study limitations is given with which to judge the direction of effect. Using more than one author to determine eligibility would have minimized investigator bias. Although included studies varied in their definitions of acute mountain sickness, the results were homogenous. The investigators limited the outcome to complete prevention of symptoms. This conservative approach would underestimate the efficacy of the treatments making any significant benefit more likely to be real. Unfortunately, no information is provided on the subjects in the trials, including information such as age, sex, training, smoking status, and other risk factors for acute mountain sickness. This information would have helped generalize the study results.

OUTCOMES MEASURED: The primary outcome measured was complete prevention of acute mountain sickness according to the definition used in each of the original studies. Although reported for some of the studies, the reduction in symptom severity was not considered a criterion for efficacy in this study. Secondary outcomes included prevention of headache, nausea, insomnia, and dizziness, and the development of adverse drug reactions.

RESULTS: In 8 trials of dexamethasone (n=161) and 9 of acetazolamide (n=295), all with exposure above 4000 meters, single daily doses of dexamethasone 8 mg, 12 mg, and 16 mg or acetazolamide 750 mg were all more efficacious than placebo (NNT=3 for both). Smaller doses (dexamethasone 0.5 and 2 mg in one trial, acetazolamide 500 mg in 3 trials) did not prevent mountain sickness over placebo. Five trials of acetazolamide reported symptom end points including insomnia, headache, nausea, and dizziness; all results favored acetazolamide (NNT=3-6). Both dexamethasone and acetazolamide demonstrated a trend toward greater efficacy (lower NNT) with faster ascent rates. There was no relative benefit (RR for prophylaxis=1) for trials with ascent rates below approximately 500 meters per day; but there was a five- to six-fold relative benefit for prophylaxis at the highest ascent rates. Regarding adverse effects, subjects in 2 of 5 studies were more likely to experience depression on weaning of dexamethasone (overall RR=4.5). Acetazolamide was associated with polyuria (RR=4.2) and paraesthesia (RR=4.0).

BACKGROUND: Acute mountain sickness results in symptoms such as headache, loss of appetite, nausea, fatigue, insomnia, and increased mortality in the first few days of exertion at high altitudes. Acetazolamide and dexamethasone have been recommended as treatments to prevent acute mountain sickness, although their efficacy and tolerability have not been well established.

DATA SOURCE: Thirty-three clinical trials comparing any pharmacologic treatment with placebo for the prevention of acute mountain sickness were identified through a comprehensive search of MEDLINE, EMBASE, the Cochrane Library, a high altitude bibliography Web site, and the bibliographies of retrieved reports and review articles. Of these trials, 18 reported complete prevention of acute mountain sickness as an outcome and as related to ascents to 4050 to 5890 meters (13300 to 19300 feet). These were included in a qualitative analysis of efficacy for any pharmacologic treatment (all 18 trials) and statistical meta-analyses for dexamethasone (8 trials representing 161 subjects) and acetazolamide (9 trials representing 295 subjects).

STUDY DESIGN AND VALIDITY: Only one author determined whether studies met inclusion criteria. All 3 authors read the included articles for validity, applying the 3-item 5-point Oxford score. The mean quality score was 3 (range=2-5). A total of 17 of the 33 trials used an adequate method of blinding. Validity was not a criteria for inclusion in the review. Following the qualitative analysis of efficacy, relative benefit (relative risk [RR] of prevention of mountain sickness) and numbers needed to treat (NNTs) were calculated for 2 interventions, dexamethasone and acetazolamide. Although the studies were rated for validity using previously tested criteria, no information on study limitations is given with which to judge the direction of effect. Using more than one author to determine eligibility would have minimized investigator bias. Although included studies varied in their definitions of acute mountain sickness, the results were homogenous. The investigators limited the outcome to complete prevention of symptoms. This conservative approach would underestimate the efficacy of the treatments making any significant benefit more likely to be real. Unfortunately, no information is provided on the subjects in the trials, including information such as age, sex, training, smoking status, and other risk factors for acute mountain sickness. This information would have helped generalize the study results.

OUTCOMES MEASURED: The primary outcome measured was complete prevention of acute mountain sickness according to the definition used in each of the original studies. Although reported for some of the studies, the reduction in symptom severity was not considered a criterion for efficacy in this study. Secondary outcomes included prevention of headache, nausea, insomnia, and dizziness, and the development of adverse drug reactions.

RESULTS: In 8 trials of dexamethasone (n=161) and 9 of acetazolamide (n=295), all with exposure above 4000 meters, single daily doses of dexamethasone 8 mg, 12 mg, and 16 mg or acetazolamide 750 mg were all more efficacious than placebo (NNT=3 for both). Smaller doses (dexamethasone 0.5 and 2 mg in one trial, acetazolamide 500 mg in 3 trials) did not prevent mountain sickness over placebo. Five trials of acetazolamide reported symptom end points including insomnia, headache, nausea, and dizziness; all results favored acetazolamide (NNT=3-6). Both dexamethasone and acetazolamide demonstrated a trend toward greater efficacy (lower NNT) with faster ascent rates. There was no relative benefit (RR for prophylaxis=1) for trials with ascent rates below approximately 500 meters per day; but there was a five- to six-fold relative benefit for prophylaxis at the highest ascent rates. Regarding adverse effects, subjects in 2 of 5 studies were more likely to experience depression on weaning of dexamethasone (overall RR=4.5). Acetazolamide was associated with polyuria (RR=4.2) and paraesthesia (RR=4.0).

BACKGROUND: Strong evidence exists that the greater the blood pressure reduction in patients with type 2 diabetes, the greater the clinical benefit in reducing significant cardiovascular events and death.1 It is not known whether these benefits are actually due to the lowering of blood pressure or if there is a drug class effect, particularly among ACEIs.

POPULATION STUDIED: The average age of participants in the 4 studies was 58 years, and 60% were men. The study settings (primary care or referral) were not reported. Baseline blood pressures ranged from 155 to 170 systolic and 93 to 98 diastolic. The duration of diabetes was 8.5 to 10.7 years in 2 studies, 2.7 years in 1 study, and was not reported in 1 study.

STUDY DESIGN AND VALIDITY: This was a meta-analysis. The authors performed a MEDLINE search for studies pertaining to ACEIs, diabetes, and hypertension but did not search any other databases such as the Cochrane Controlled Trials Register. Studies were included if they were randomized controlled trials of patients with type 2 diabetes that evaluated an ACEI versus another antihypertensive medication with a minimum follow-up of 2 years. There was no indication whether retrieved studies were reviewed independently by 2 or more authors for inclusion. Tests for heterogeneity were appropriately applied to assure that only data from similar studies were combined. A fixed effects model, which assumes homogeneity, was used to combine data.

OUTCOMES MEASURED: The outcomes measured were acute myocardial infarction (AMI), stroke, combined cardiovascular events, and all-cause mortality. The combined cardiovascular events varied depending on the particular trial and could include cardiovascular death, fatal and nonfatal MI, fatal and nonfatal stroke, angina, congestive heart failure, and pulmonary infarction.

RESULTS: The initial search identified 195 articles of which 4 studies with a total of 2180 patients met the inclusion criteria. After applying tests for heterogeneity, only data from 3 trials (which studied enalopril vs nisoldipine, captopril vs diuretic/b-blocker, and fosinopril vs amlodipine) were used in the meta-analysis. In one of these trials (captopril vs diuretic/b-blocker), the number of events in persons with diabetes was not reported; it was therefore estimated by the authors of this review. This is a limitation of this meta-analysis. The relative risk calculations for these 3 studies showed that using ACEIs versus other antihypertensives lowered the number of AMIs (summary risk ratio [RR]=0.37; 95% confidence interval [CI], 0.24-0.57), had no affect on the incidence of stroke (RR=0.76; 95% CI, 0.48-1.22), lowered the number of combined cardiovascular events (RR=0.49; 95% CI, 0.36-0.67), and lowered overall cardiovascular mortality (RR=0.57; 95% CI, 0.38-0.87). On the basis of these data, to prevent an additional AMI, cardiovascular event, or death one would have to treat 17, 13, and 40 patients respectively with an ACEI instead of another agent for approximately 4.5 years. The study excluded from the meta-analysis compared outcomes in patients taking an ACEI versus atenolol and found no statistically significant differences between the groups for the 4 clinical outcomes.¹

BACKGROUND: Strong evidence exists that the greater the blood pressure reduction in patients with type 2 diabetes, the greater the clinical benefit in reducing significant cardiovascular events and death.1 It is not known whether these benefits are actually due to the lowering of blood pressure or if there is a drug class effect, particularly among ACEIs.

POPULATION STUDIED: The average age of participants in the 4 studies was 58 years, and 60% were men. The study settings (primary care or referral) were not reported. Baseline blood pressures ranged from 155 to 170 systolic and 93 to 98 diastolic. The duration of diabetes was 8.5 to 10.7 years in 2 studies, 2.7 years in 1 study, and was not reported in 1 study.

STUDY DESIGN AND VALIDITY: This was a meta-analysis. The authors performed a MEDLINE search for studies pertaining to ACEIs, diabetes, and hypertension but did not search any other databases such as the Cochrane Controlled Trials Register. Studies were included if they were randomized controlled trials of patients with type 2 diabetes that evaluated an ACEI versus another antihypertensive medication with a minimum follow-up of 2 years. There was no indication whether retrieved studies were reviewed independently by 2 or more authors for inclusion. Tests for heterogeneity were appropriately applied to assure that only data from similar studies were combined. A fixed effects model, which assumes homogeneity, was used to combine data.

OUTCOMES MEASURED: The outcomes measured were acute myocardial infarction (AMI), stroke, combined cardiovascular events, and all-cause mortality. The combined cardiovascular events varied depending on the particular trial and could include cardiovascular death, fatal and nonfatal MI, fatal and nonfatal stroke, angina, congestive heart failure, and pulmonary infarction.

RESULTS: The initial search identified 195 articles of which 4 studies with a total of 2180 patients met the inclusion criteria. After applying tests for heterogeneity, only data from 3 trials (which studied enalopril vs nisoldipine, captopril vs diuretic/b-blocker, and fosinopril vs amlodipine) were used in the meta-analysis. In one of these trials (captopril vs diuretic/b-blocker), the number of events in persons with diabetes was not reported; it was therefore estimated by the authors of this review. This is a limitation of this meta-analysis. The relative risk calculations for these 3 studies showed that using ACEIs versus other antihypertensives lowered the number of AMIs (summary risk ratio [RR]=0.37; 95% confidence interval [CI], 0.24-0.57), had no affect on the incidence of stroke (RR=0.76; 95% CI, 0.48-1.22), lowered the number of combined cardiovascular events (RR=0.49; 95% CI, 0.36-0.67), and lowered overall cardiovascular mortality (RR=0.57; 95% CI, 0.38-0.87). On the basis of these data, to prevent an additional AMI, cardiovascular event, or death one would have to treat 17, 13, and 40 patients respectively with an ACEI instead of another agent for approximately 4.5 years. The study excluded from the meta-analysis compared outcomes in patients taking an ACEI versus atenolol and found no statistically significant differences between the groups for the 4 clinical outcomes.¹

BACKGROUND: Strong evidence exists that the greater the blood pressure reduction in patients with type 2 diabetes, the greater the clinical benefit in reducing significant cardiovascular events and death.1 It is not known whether these benefits are actually due to the lowering of blood pressure or if there is a drug class effect, particularly among ACEIs.

POPULATION STUDIED: The average age of participants in the 4 studies was 58 years, and 60% were men. The study settings (primary care or referral) were not reported. Baseline blood pressures ranged from 155 to 170 systolic and 93 to 98 diastolic. The duration of diabetes was 8.5 to 10.7 years in 2 studies, 2.7 years in 1 study, and was not reported in 1 study.

STUDY DESIGN AND VALIDITY: This was a meta-analysis. The authors performed a MEDLINE search for studies pertaining to ACEIs, diabetes, and hypertension but did not search any other databases such as the Cochrane Controlled Trials Register. Studies were included if they were randomized controlled trials of patients with type 2 diabetes that evaluated an ACEI versus another antihypertensive medication with a minimum follow-up of 2 years. There was no indication whether retrieved studies were reviewed independently by 2 or more authors for inclusion. Tests for heterogeneity were appropriately applied to assure that only data from similar studies were combined. A fixed effects model, which assumes homogeneity, was used to combine data.

OUTCOMES MEASURED: The outcomes measured were acute myocardial infarction (AMI), stroke, combined cardiovascular events, and all-cause mortality. The combined cardiovascular events varied depending on the particular trial and could include cardiovascular death, fatal and nonfatal MI, fatal and nonfatal stroke, angina, congestive heart failure, and pulmonary infarction.

RESULTS: The initial search identified 195 articles of which 4 studies with a total of 2180 patients met the inclusion criteria. After applying tests for heterogeneity, only data from 3 trials (which studied enalopril vs nisoldipine, captopril vs diuretic/b-blocker, and fosinopril vs amlodipine) were used in the meta-analysis. In one of these trials (captopril vs diuretic/b-blocker), the number of events in persons with diabetes was not reported; it was therefore estimated by the authors of this review. This is a limitation of this meta-analysis. The relative risk calculations for these 3 studies showed that using ACEIs versus other antihypertensives lowered the number of AMIs (summary risk ratio [RR]=0.37; 95% confidence interval [CI], 0.24-0.57), had no affect on the incidence of stroke (RR=0.76; 95% CI, 0.48-1.22), lowered the number of combined cardiovascular events (RR=0.49; 95% CI, 0.36-0.67), and lowered overall cardiovascular mortality (RR=0.57; 95% CI, 0.38-0.87). On the basis of these data, to prevent an additional AMI, cardiovascular event, or death one would have to treat 17, 13, and 40 patients respectively with an ACEI instead of another agent for approximately 4.5 years. The study excluded from the meta-analysis compared outcomes in patients taking an ACEI versus atenolol and found no statistically significant differences between the groups for the 4 clinical outcomes.¹