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In patients with heart disease, is the benefit of lipid-lowering therapy with statins similar in older patients to that in younger patients?
BACKGROUND: Some physicians seem reluctant to treat older patients with statins to lower lipids; they think statins are more effective in high-risk younger patients. This study used existing data from a large study of both older and younger patients to compare the level of benefit in these 2 types of patients.
POPULATION STUDIED: The authors enrolled 9014 patients from 87 centers in Australia and New Zealand who were between the ages of 31 and 75 years. Patients had a history of a myocardial infarction or had been hospitalized for unstable angina. Their baseline total cholesterol was between 155 and 271 mg per dL.
STUDY DESIGN AND VALIDITY: This subgroup analysis of the previously published Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study1 compared the outcomes of the 3514 patients between the ages of 65 and 75 years with the remaining population younger than 65 years. This double-blind placebo-controlled clinical trial randomized patients to receive either placebo or pravastatin (Pravachol) 40 mg per day for an average of 6.1 years. Other lipid-lowering therapy could be used at the discretion of the patients’ usual physician. Both groups received education on a low cholesterol diet. The randomization method and allocation concealment were not specifically addressed.2 The groups were similar at the outset of the trial. Data were analyzed on an intention-to-treat basis. An outcomes assessment committee blinded to treatment group assignment reviewed all deaths, myocardial infarctions, and strokes. Although no difference in the relative risk of outcomes was found between age groups, the study was not powered to detect such differences in outcomes by age.
OUTCOMES MEASURED: The main outcome measure was death resulting from coronary heart disease. Secondary end points included nonfatal myocardial infarction (MI), stroke, coronary revascularization, death of any cause including cardiovascular, and duration of hospital stay.
RESULTS: As would be expected, the death rate was higher during the 6 years of study in the group 65 years and older (20.6%) than in the group aged 34 to 64 (9.8%). The risk of MI, unstable angina, and stroke was also significantly higher, though not as marked. In patients older than 65 years, pravastatin decreased overall mortality 21% (95% confidence interval [CI], 7%-32%) and heart disease-related death by 24% (95% CI, 7%-38%), as well as decreasing the rate of MI or stroke. Although the relative risk reduction was similar in older and younger groups, the absolute risk reduction and number needed to treat (NNT) were approximately twice that seen in younger patients. Among older patients, 22 patients would have to be treated for 6 years to prevent 1 of them from dying during this period (NNT=22; 95% CI, 17-36), and 35 to prevent 1 heart disease–related death (NNT=35; 95% CI, 24-67). This benefit was due to the fact that the rate of adverse outcomes (eg, heart disease–related death) was greater in the older age group. There were no differences in the relative risk of the secondary end points by age. The rates of adverse events were not significantly different by age groups.
Lowering average cholesterol levels is beneficial in patients with preexisting heart disease regardless of age. Older patients (between ages 65 and 75 years) are actually more likely to receive benefit than are younger patients, because older patients are at greater risk for heart disease–related events. Whether this benefit extends to people older than 75 years is not known.
BACKGROUND: Some physicians seem reluctant to treat older patients with statins to lower lipids; they think statins are more effective in high-risk younger patients. This study used existing data from a large study of both older and younger patients to compare the level of benefit in these 2 types of patients.
POPULATION STUDIED: The authors enrolled 9014 patients from 87 centers in Australia and New Zealand who were between the ages of 31 and 75 years. Patients had a history of a myocardial infarction or had been hospitalized for unstable angina. Their baseline total cholesterol was between 155 and 271 mg per dL.
STUDY DESIGN AND VALIDITY: This subgroup analysis of the previously published Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study1 compared the outcomes of the 3514 patients between the ages of 65 and 75 years with the remaining population younger than 65 years. This double-blind placebo-controlled clinical trial randomized patients to receive either placebo or pravastatin (Pravachol) 40 mg per day for an average of 6.1 years. Other lipid-lowering therapy could be used at the discretion of the patients’ usual physician. Both groups received education on a low cholesterol diet. The randomization method and allocation concealment were not specifically addressed.2 The groups were similar at the outset of the trial. Data were analyzed on an intention-to-treat basis. An outcomes assessment committee blinded to treatment group assignment reviewed all deaths, myocardial infarctions, and strokes. Although no difference in the relative risk of outcomes was found between age groups, the study was not powered to detect such differences in outcomes by age.
OUTCOMES MEASURED: The main outcome measure was death resulting from coronary heart disease. Secondary end points included nonfatal myocardial infarction (MI), stroke, coronary revascularization, death of any cause including cardiovascular, and duration of hospital stay.
RESULTS: As would be expected, the death rate was higher during the 6 years of study in the group 65 years and older (20.6%) than in the group aged 34 to 64 (9.8%). The risk of MI, unstable angina, and stroke was also significantly higher, though not as marked. In patients older than 65 years, pravastatin decreased overall mortality 21% (95% confidence interval [CI], 7%-32%) and heart disease-related death by 24% (95% CI, 7%-38%), as well as decreasing the rate of MI or stroke. Although the relative risk reduction was similar in older and younger groups, the absolute risk reduction and number needed to treat (NNT) were approximately twice that seen in younger patients. Among older patients, 22 patients would have to be treated for 6 years to prevent 1 of them from dying during this period (NNT=22; 95% CI, 17-36), and 35 to prevent 1 heart disease–related death (NNT=35; 95% CI, 24-67). This benefit was due to the fact that the rate of adverse outcomes (eg, heart disease–related death) was greater in the older age group. There were no differences in the relative risk of the secondary end points by age. The rates of adverse events were not significantly different by age groups.
Lowering average cholesterol levels is beneficial in patients with preexisting heart disease regardless of age. Older patients (between ages 65 and 75 years) are actually more likely to receive benefit than are younger patients, because older patients are at greater risk for heart disease–related events. Whether this benefit extends to people older than 75 years is not known.
BACKGROUND: Some physicians seem reluctant to treat older patients with statins to lower lipids; they think statins are more effective in high-risk younger patients. This study used existing data from a large study of both older and younger patients to compare the level of benefit in these 2 types of patients.
POPULATION STUDIED: The authors enrolled 9014 patients from 87 centers in Australia and New Zealand who were between the ages of 31 and 75 years. Patients had a history of a myocardial infarction or had been hospitalized for unstable angina. Their baseline total cholesterol was between 155 and 271 mg per dL.
STUDY DESIGN AND VALIDITY: This subgroup analysis of the previously published Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study1 compared the outcomes of the 3514 patients between the ages of 65 and 75 years with the remaining population younger than 65 years. This double-blind placebo-controlled clinical trial randomized patients to receive either placebo or pravastatin (Pravachol) 40 mg per day for an average of 6.1 years. Other lipid-lowering therapy could be used at the discretion of the patients’ usual physician. Both groups received education on a low cholesterol diet. The randomization method and allocation concealment were not specifically addressed.2 The groups were similar at the outset of the trial. Data were analyzed on an intention-to-treat basis. An outcomes assessment committee blinded to treatment group assignment reviewed all deaths, myocardial infarctions, and strokes. Although no difference in the relative risk of outcomes was found between age groups, the study was not powered to detect such differences in outcomes by age.
OUTCOMES MEASURED: The main outcome measure was death resulting from coronary heart disease. Secondary end points included nonfatal myocardial infarction (MI), stroke, coronary revascularization, death of any cause including cardiovascular, and duration of hospital stay.
RESULTS: As would be expected, the death rate was higher during the 6 years of study in the group 65 years and older (20.6%) than in the group aged 34 to 64 (9.8%). The risk of MI, unstable angina, and stroke was also significantly higher, though not as marked. In patients older than 65 years, pravastatin decreased overall mortality 21% (95% confidence interval [CI], 7%-32%) and heart disease-related death by 24% (95% CI, 7%-38%), as well as decreasing the rate of MI or stroke. Although the relative risk reduction was similar in older and younger groups, the absolute risk reduction and number needed to treat (NNT) were approximately twice that seen in younger patients. Among older patients, 22 patients would have to be treated for 6 years to prevent 1 of them from dying during this period (NNT=22; 95% CI, 17-36), and 35 to prevent 1 heart disease–related death (NNT=35; 95% CI, 24-67). This benefit was due to the fact that the rate of adverse outcomes (eg, heart disease–related death) was greater in the older age group. There were no differences in the relative risk of the secondary end points by age. The rates of adverse events were not significantly different by age groups.
Lowering average cholesterol levels is beneficial in patients with preexisting heart disease regardless of age. Older patients (between ages 65 and 75 years) are actually more likely to receive benefit than are younger patients, because older patients are at greater risk for heart disease–related events. Whether this benefit extends to people older than 75 years is not known.
Are antibiotics appropriate for the treatment of acute sinusitis in adults?
BACKGROUND: Antibiotic use is an important factor in the recent dramatic increase in antibiotic-resistant Streptococcus pneumoniae. Although most outpatient antibiotic prescriptions are for upper respiratory tract infections (URIs), systematic reviews have shown that these drugs have either a very modest benefit or no benefit in the treatment of common URIs. Because of the high rate of antibiotic use and growing resistance, the Centers for Disease Control and Prevention began a program to educate patients and physicians about the dangers of overuse. They first turned their attention to pediatric infections and then sponsored the development of guidelines for appropriate antibiotic use for URIs in adults. Numerous organizations, including the American Academy of Family Physicians (AAFP) and the American College of Physicians–American Society of Internal Medicine have endorsed these guidelines. This review will only cover the recommendations for acute sinusitis.
POPULATION STUDIED: These guidelines apply to nonhospitalized patients with acute sinusitis of a known or unknown etiology.
STUDY DESIGN AND VALIDITY: These are well-developed evidence-based practice guidelines for the appropriate use of antibiotics for acute sinusitis. When appropriate, the authors graded the evidence for the principles,1 using a modification of the method proposed by Sackett and colleagues.2 The authors addressed 3 specific questions (How is the diagnosis established? What is the likelihood that the symptoms are bacterial in origin? Is antibiotic therapy indicated?).2 Although the specific search criteria are not given, the evidence for the reviews is based on Cochrane Collaboration and Agency for Healthcare Research and Quality systematic reviews. The authors updated the literature search for these reviews through March 2000. The recommendations were reviewed by experts in the field and several national organizations including the AAFP. The guidelines have not been subjected to testing.
OUTCOMES MEASURED: Patient-oriented outcomes for acute sinusitits (eg, resolution of symptoms at 14 days) were examined.
RESULTS: Sinus radiographs are not recommended for uncomplicated sinusitis (grade B evidence of no benefit). For patients with acute bacterial sinusitis (<2% of patients with a URI have a bacterial cause) and mild or moderate symptoms, antibiotics are not required (grade A evidence of no benefit). On the basis of the results of 3 meta-analyses, broader spectrum antibiotics offer no additional benefit. In patients with severe or persistent moderate symptoms, narrow spectrum antibiotics, such as amoxicillin, should be used.
These guidelines emphasize that physicians overuse antibiotics for acute sinusitis. The guidelines for the other URIs are similar. We need to use fewer antibiotics and engage in more patient education.
BACKGROUND: Antibiotic use is an important factor in the recent dramatic increase in antibiotic-resistant Streptococcus pneumoniae. Although most outpatient antibiotic prescriptions are for upper respiratory tract infections (URIs), systematic reviews have shown that these drugs have either a very modest benefit or no benefit in the treatment of common URIs. Because of the high rate of antibiotic use and growing resistance, the Centers for Disease Control and Prevention began a program to educate patients and physicians about the dangers of overuse. They first turned their attention to pediatric infections and then sponsored the development of guidelines for appropriate antibiotic use for URIs in adults. Numerous organizations, including the American Academy of Family Physicians (AAFP) and the American College of Physicians–American Society of Internal Medicine have endorsed these guidelines. This review will only cover the recommendations for acute sinusitis.
POPULATION STUDIED: These guidelines apply to nonhospitalized patients with acute sinusitis of a known or unknown etiology.
STUDY DESIGN AND VALIDITY: These are well-developed evidence-based practice guidelines for the appropriate use of antibiotics for acute sinusitis. When appropriate, the authors graded the evidence for the principles,1 using a modification of the method proposed by Sackett and colleagues.2 The authors addressed 3 specific questions (How is the diagnosis established? What is the likelihood that the symptoms are bacterial in origin? Is antibiotic therapy indicated?).2 Although the specific search criteria are not given, the evidence for the reviews is based on Cochrane Collaboration and Agency for Healthcare Research and Quality systematic reviews. The authors updated the literature search for these reviews through March 2000. The recommendations were reviewed by experts in the field and several national organizations including the AAFP. The guidelines have not been subjected to testing.
OUTCOMES MEASURED: Patient-oriented outcomes for acute sinusitits (eg, resolution of symptoms at 14 days) were examined.
RESULTS: Sinus radiographs are not recommended for uncomplicated sinusitis (grade B evidence of no benefit). For patients with acute bacterial sinusitis (<2% of patients with a URI have a bacterial cause) and mild or moderate symptoms, antibiotics are not required (grade A evidence of no benefit). On the basis of the results of 3 meta-analyses, broader spectrum antibiotics offer no additional benefit. In patients with severe or persistent moderate symptoms, narrow spectrum antibiotics, such as amoxicillin, should be used.
These guidelines emphasize that physicians overuse antibiotics for acute sinusitis. The guidelines for the other URIs are similar. We need to use fewer antibiotics and engage in more patient education.
BACKGROUND: Antibiotic use is an important factor in the recent dramatic increase in antibiotic-resistant Streptococcus pneumoniae. Although most outpatient antibiotic prescriptions are for upper respiratory tract infections (URIs), systematic reviews have shown that these drugs have either a very modest benefit or no benefit in the treatment of common URIs. Because of the high rate of antibiotic use and growing resistance, the Centers for Disease Control and Prevention began a program to educate patients and physicians about the dangers of overuse. They first turned their attention to pediatric infections and then sponsored the development of guidelines for appropriate antibiotic use for URIs in adults. Numerous organizations, including the American Academy of Family Physicians (AAFP) and the American College of Physicians–American Society of Internal Medicine have endorsed these guidelines. This review will only cover the recommendations for acute sinusitis.
POPULATION STUDIED: These guidelines apply to nonhospitalized patients with acute sinusitis of a known or unknown etiology.
STUDY DESIGN AND VALIDITY: These are well-developed evidence-based practice guidelines for the appropriate use of antibiotics for acute sinusitis. When appropriate, the authors graded the evidence for the principles,1 using a modification of the method proposed by Sackett and colleagues.2 The authors addressed 3 specific questions (How is the diagnosis established? What is the likelihood that the symptoms are bacterial in origin? Is antibiotic therapy indicated?).2 Although the specific search criteria are not given, the evidence for the reviews is based on Cochrane Collaboration and Agency for Healthcare Research and Quality systematic reviews. The authors updated the literature search for these reviews through March 2000. The recommendations were reviewed by experts in the field and several national organizations including the AAFP. The guidelines have not been subjected to testing.
OUTCOMES MEASURED: Patient-oriented outcomes for acute sinusitits (eg, resolution of symptoms at 14 days) were examined.
RESULTS: Sinus radiographs are not recommended for uncomplicated sinusitis (grade B evidence of no benefit). For patients with acute bacterial sinusitis (<2% of patients with a URI have a bacterial cause) and mild or moderate symptoms, antibiotics are not required (grade A evidence of no benefit). On the basis of the results of 3 meta-analyses, broader spectrum antibiotics offer no additional benefit. In patients with severe or persistent moderate symptoms, narrow spectrum antibiotics, such as amoxicillin, should be used.
These guidelines emphasize that physicians overuse antibiotics for acute sinusitis. The guidelines for the other URIs are similar. We need to use fewer antibiotics and engage in more patient education.
Is rofecoxib safer than naproxen?
BACKGROUND: The adverse gastrointestinal effects of older nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are well documented. These effects are attributed to the drugs’ inhibition of cyclooxygenase-1 (COX-1), which is found in the gastrointestinal tract. The newer NSAIDs that selectively inhibit cyclooxygenase-2 (COX-2) have been shown to cause fewer endoscopically proven gastrointestinal erosions/ulcerations than nonselective NSAIDs that inhibit both COX-1 and COX-2. This disease-oriented evidence leads to concern about whether selective NSAIDs are really safer in the clinical setting than nonselective NSAIDs. This study attempts to answer the following question: Does rofecoxib, a selective COX-2 NSAID, lead to fewer clinically significant gastrointestinal events than naproxen, a nonselective NSAID?
POPULATION STUDIED: Patients were aged 50 years or older with rheumatoid arthritis (or 40 years or older with rheumatoid arthritis and taking long-term glucocorticoids) and were expected to be taking an NSAID for at least 1 year. Patients were recruited from 301 centers in 22 countries.
STUDY DESIGN AND VALIDITY: This was a randomized double-blinded controlled trial. In general it was a well-designed study with no major flaws. The randomization process and the steps taken to conceal the treatment assignment were not described in detail. A total of 8076 patients were initially assigned to either 50 mg of rofecoxib once daily or 500 mg of naproxen twice daily. Patients were not allowed to take other NSAIDs but could take antacids and H2-receptor antagonists. Median follow-up was 9.0 months. Patients were followed until the study ended even if they stopped taking the study medications. Only 71.1% of the patients continued to take their assigned medication until the end of the study. Rates of discontinuation (29.3% for rofecoxib, 28.5% for naproxen), discontinuation for adverse events (16.4% and 16.1%, respectively), and discontinuation for lack of efficacy (6.3% and 6.5%, respectively) were similar between the groups. A committee using preset criteria and blinded to the treatment assessed the end points.
OUTCOMES MEASURED: Two outcomes were measured: the total number of gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcer) and the number of complicated events (perforation, obstruction, and severe upper gastrointestinal bleeding). Also, the effectiveness of medication in reducing disease activity was measured using the Global Assessment of Disease Activity questionnaire. Finally, all episodes of confirmed and unconfirmed gastrointestinal bleeding were analyzed.
RESULTS: The risk of a gastrointestinal event was lower for patients receiving rofecoxib for the year of the study period (2.1 vs 4.5 events per 100 patient years, number needed to treat [NNT]=42). The risk of a complicated event was also lower for patients receiving rofecoxib (0.6 vs 1.6 events per 100 patient years, NNT=100). Overall mortality between the 2 groups was similar. Both drugs were equally effective in relieving the symptoms of rheumatoid arthritis. Of note, the rate of myocardial infarction was lower in the rofecoxib groups (0.1%) than in the naproxen group (0.4%); however, the mortality rates from cardiovascular causes were similar between the 2 groups. The difference in the rate of myocardial infarctions has been attributed to the antiplatelet effect (related to COX-1) of traditional NSAIDs, which the selective NSAIDs do not possess.
The risk of gastrointestinal events is lower with rofecoxib than with naproxen in patients treated continuously for 1 year with standard doses. The absolute difference between these 2 agents is small and should be weighed against the increased cost of rofecoxib. A recent study comparing celecoxib with ibuprofen and diclofenac showed similar results.1 Of note in the previous study was that patients taking aspirin for cardiovascular prophylaxis and celecoxib had the same rate of adverse gastrointestinal events as those taking ibuprofen or diclofenac. Even a small amount of aspirin seems to negate the advantage of the selective NSAID. A selective NSAID may be a better choice for patients at high risk for adverse gastrointestinal events and who need long-term treatment, while a nonselective NSAID is probably the better choice for patients who are at low risk and require short-term therapy.
BACKGROUND: The adverse gastrointestinal effects of older nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are well documented. These effects are attributed to the drugs’ inhibition of cyclooxygenase-1 (COX-1), which is found in the gastrointestinal tract. The newer NSAIDs that selectively inhibit cyclooxygenase-2 (COX-2) have been shown to cause fewer endoscopically proven gastrointestinal erosions/ulcerations than nonselective NSAIDs that inhibit both COX-1 and COX-2. This disease-oriented evidence leads to concern about whether selective NSAIDs are really safer in the clinical setting than nonselective NSAIDs. This study attempts to answer the following question: Does rofecoxib, a selective COX-2 NSAID, lead to fewer clinically significant gastrointestinal events than naproxen, a nonselective NSAID?
POPULATION STUDIED: Patients were aged 50 years or older with rheumatoid arthritis (or 40 years or older with rheumatoid arthritis and taking long-term glucocorticoids) and were expected to be taking an NSAID for at least 1 year. Patients were recruited from 301 centers in 22 countries.
STUDY DESIGN AND VALIDITY: This was a randomized double-blinded controlled trial. In general it was a well-designed study with no major flaws. The randomization process and the steps taken to conceal the treatment assignment were not described in detail. A total of 8076 patients were initially assigned to either 50 mg of rofecoxib once daily or 500 mg of naproxen twice daily. Patients were not allowed to take other NSAIDs but could take antacids and H2-receptor antagonists. Median follow-up was 9.0 months. Patients were followed until the study ended even if they stopped taking the study medications. Only 71.1% of the patients continued to take their assigned medication until the end of the study. Rates of discontinuation (29.3% for rofecoxib, 28.5% for naproxen), discontinuation for adverse events (16.4% and 16.1%, respectively), and discontinuation for lack of efficacy (6.3% and 6.5%, respectively) were similar between the groups. A committee using preset criteria and blinded to the treatment assessed the end points.
OUTCOMES MEASURED: Two outcomes were measured: the total number of gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcer) and the number of complicated events (perforation, obstruction, and severe upper gastrointestinal bleeding). Also, the effectiveness of medication in reducing disease activity was measured using the Global Assessment of Disease Activity questionnaire. Finally, all episodes of confirmed and unconfirmed gastrointestinal bleeding were analyzed.
RESULTS: The risk of a gastrointestinal event was lower for patients receiving rofecoxib for the year of the study period (2.1 vs 4.5 events per 100 patient years, number needed to treat [NNT]=42). The risk of a complicated event was also lower for patients receiving rofecoxib (0.6 vs 1.6 events per 100 patient years, NNT=100). Overall mortality between the 2 groups was similar. Both drugs were equally effective in relieving the symptoms of rheumatoid arthritis. Of note, the rate of myocardial infarction was lower in the rofecoxib groups (0.1%) than in the naproxen group (0.4%); however, the mortality rates from cardiovascular causes were similar between the 2 groups. The difference in the rate of myocardial infarctions has been attributed to the antiplatelet effect (related to COX-1) of traditional NSAIDs, which the selective NSAIDs do not possess.
The risk of gastrointestinal events is lower with rofecoxib than with naproxen in patients treated continuously for 1 year with standard doses. The absolute difference between these 2 agents is small and should be weighed against the increased cost of rofecoxib. A recent study comparing celecoxib with ibuprofen and diclofenac showed similar results.1 Of note in the previous study was that patients taking aspirin for cardiovascular prophylaxis and celecoxib had the same rate of adverse gastrointestinal events as those taking ibuprofen or diclofenac. Even a small amount of aspirin seems to negate the advantage of the selective NSAID. A selective NSAID may be a better choice for patients at high risk for adverse gastrointestinal events and who need long-term treatment, while a nonselective NSAID is probably the better choice for patients who are at low risk and require short-term therapy.
BACKGROUND: The adverse gastrointestinal effects of older nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are well documented. These effects are attributed to the drugs’ inhibition of cyclooxygenase-1 (COX-1), which is found in the gastrointestinal tract. The newer NSAIDs that selectively inhibit cyclooxygenase-2 (COX-2) have been shown to cause fewer endoscopically proven gastrointestinal erosions/ulcerations than nonselective NSAIDs that inhibit both COX-1 and COX-2. This disease-oriented evidence leads to concern about whether selective NSAIDs are really safer in the clinical setting than nonselective NSAIDs. This study attempts to answer the following question: Does rofecoxib, a selective COX-2 NSAID, lead to fewer clinically significant gastrointestinal events than naproxen, a nonselective NSAID?
POPULATION STUDIED: Patients were aged 50 years or older with rheumatoid arthritis (or 40 years or older with rheumatoid arthritis and taking long-term glucocorticoids) and were expected to be taking an NSAID for at least 1 year. Patients were recruited from 301 centers in 22 countries.
STUDY DESIGN AND VALIDITY: This was a randomized double-blinded controlled trial. In general it was a well-designed study with no major flaws. The randomization process and the steps taken to conceal the treatment assignment were not described in detail. A total of 8076 patients were initially assigned to either 50 mg of rofecoxib once daily or 500 mg of naproxen twice daily. Patients were not allowed to take other NSAIDs but could take antacids and H2-receptor antagonists. Median follow-up was 9.0 months. Patients were followed until the study ended even if they stopped taking the study medications. Only 71.1% of the patients continued to take their assigned medication until the end of the study. Rates of discontinuation (29.3% for rofecoxib, 28.5% for naproxen), discontinuation for adverse events (16.4% and 16.1%, respectively), and discontinuation for lack of efficacy (6.3% and 6.5%, respectively) were similar between the groups. A committee using preset criteria and blinded to the treatment assessed the end points.
OUTCOMES MEASURED: Two outcomes were measured: the total number of gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcer) and the number of complicated events (perforation, obstruction, and severe upper gastrointestinal bleeding). Also, the effectiveness of medication in reducing disease activity was measured using the Global Assessment of Disease Activity questionnaire. Finally, all episodes of confirmed and unconfirmed gastrointestinal bleeding were analyzed.
RESULTS: The risk of a gastrointestinal event was lower for patients receiving rofecoxib for the year of the study period (2.1 vs 4.5 events per 100 patient years, number needed to treat [NNT]=42). The risk of a complicated event was also lower for patients receiving rofecoxib (0.6 vs 1.6 events per 100 patient years, NNT=100). Overall mortality between the 2 groups was similar. Both drugs were equally effective in relieving the symptoms of rheumatoid arthritis. Of note, the rate of myocardial infarction was lower in the rofecoxib groups (0.1%) than in the naproxen group (0.4%); however, the mortality rates from cardiovascular causes were similar between the 2 groups. The difference in the rate of myocardial infarctions has been attributed to the antiplatelet effect (related to COX-1) of traditional NSAIDs, which the selective NSAIDs do not possess.
The risk of gastrointestinal events is lower with rofecoxib than with naproxen in patients treated continuously for 1 year with standard doses. The absolute difference between these 2 agents is small and should be weighed against the increased cost of rofecoxib. A recent study comparing celecoxib with ibuprofen and diclofenac showed similar results.1 Of note in the previous study was that patients taking aspirin for cardiovascular prophylaxis and celecoxib had the same rate of adverse gastrointestinal events as those taking ibuprofen or diclofenac. Even a small amount of aspirin seems to negate the advantage of the selective NSAID. A selective NSAID may be a better choice for patients at high risk for adverse gastrointestinal events and who need long-term treatment, while a nonselective NSAID is probably the better choice for patients who are at low risk and require short-term therapy.
Is diltiazem as effective as diuretics and b-blockers in preventing complications from hypertension?
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.
Another study published in the same issue of Lancet2 also showed no difference between sustained-release nifedipine and diuretics/b-blockers. These 2 studies found no difference in the effectiveness of these agents. However, an unpublished meta-analysis is purported to show a higher risk of heart failure, heart attack, and major cardiovascular events with calcium-channel blockers compared with diuretics, b-blockers, clonidine, or ACE inhibitors.3 Until this question is resolved, the effective less expensive agents remain the best choice for most patients with hypertension.
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.
Another study published in the same issue of Lancet2 also showed no difference between sustained-release nifedipine and diuretics/b-blockers. These 2 studies found no difference in the effectiveness of these agents. However, an unpublished meta-analysis is purported to show a higher risk of heart failure, heart attack, and major cardiovascular events with calcium-channel blockers compared with diuretics, b-blockers, clonidine, or ACE inhibitors.3 Until this question is resolved, the effective less expensive agents remain the best choice for most patients with hypertension.
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.
Another study published in the same issue of Lancet2 also showed no difference between sustained-release nifedipine and diuretics/b-blockers. These 2 studies found no difference in the effectiveness of these agents. However, an unpublished meta-analysis is purported to show a higher risk of heart failure, heart attack, and major cardiovascular events with calcium-channel blockers compared with diuretics, b-blockers, clonidine, or ACE inhibitors.3 Until this question is resolved, the effective less expensive agents remain the best choice for most patients with hypertension.