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BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin.

METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause.

RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.28% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P < 0.001 for noninferiority; P = 0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P < 0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P = 0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < 0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42).

CONCLUSIONS: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.

From the abstract above, what is the number needed to treat with apixiban compared to warfarin to prevent one incidence of the primary outcome?
Abstract

BACKGROUND:
Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure.

METHODS:
A total of 9,297 high-risk patients who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes.

RESULTS:
A total of 4,645 patients were assigned to receive ramipril 10 mg daily and 4,652 were assigned to receive placebo. Of the patients taking ramipril, 650 patients reached the primary endpoint as compared with 826 patients who were assigned to receive placebo (p < 0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1% vs. 8.1% in the placebo group, p < 0.001), myocardial infarction (9.9% vs. 12.3%, p < 0.001), stroke (3.4% vs. 4.9%, p < 0.001) and death from any cause (10.4% vs. 12.2%, p = 0.005).

CONCLUSION:
Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.

Question:
From the abstract above, what is the number needed to treat to prevent the composite endpoint of myocardial infarction, stroke, or death from cardiovascular causes? Round up to the nearest WHOLE number.
Strongheart Study for Patients with NYHA Functional Class II-IV

BACKGROUND: Strongheart is a new drug being investigated for chronic heart failure patients.

METHODS: We enrolled 3,991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with an ejection fraction of 0.40 or less, stabilized on optimal standard therapy, in a double-blind, randomized controlled study. Randomization was preceded by a 2-week single-blind placebo run-in period. Of the 3,991 patients, 1,990 patients were randomly assigned to Strongheart 12.5 mg daily and 2,001 patients were assigned to placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analyzed by intention to treat.

RESULTS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the Strongheart group than in the placebo group (146 patient-deaths versus 219 patient-deaths; p = 0.00009, [95% CI 0.53-0.81]). There were fewer sudden deaths in the Strongheart group than in the placebo group (79 vs. 132; p = 0.0002) and deaths from worsening heart failure (30 vs 58; p = 0.0023).

CONCLUSIONS: Strongheart once daily in addition to optimal standard therapy improved survival.

From the abstract above, what is the absolute risk reduction of the primary endpoint of all-cause mortality in patients randomized to the Strongheart group? (Round to the nearest TENTH. Put your answer in percentage form. Do not include the percentage sign when you type in the number.)
Abstract

BACKGROUND:
Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure.

METHODS:
A total of 9,297 high-risk patients who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes.

RESULTS:
A total of 4,645 patients were assigned to receive ramipril 10 mg daily and 4,652 were assigned to receive placebo. Of the patients taking ramipril, 650 patients reached the primary endpoint as compared with 826 patients who were assigned to receive placebo (p value < 0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1% vs. 8.1% in the placebo group, p < 0.001), myocardial infarction (9.9% vs. 12.3%, < 0.001), stroke (3.4% vs. 4.9%, p < 0.001) and death from any cause (10.4% vs. 12.2%, p = 0.005).

CONCLUSION:
Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a road range of high-risk patients who are not known to have a low ejection fraction or heart failure.

Question:
From the abstract above, what is the relative risk reduction of the primary endpoint of myocardial infarction, stroke, or death from cardiovascular causes?
Strongheart Study for Patients with NYHA Functional Class II-IV

BACKGROUND: Strongheart is a new drug being investigated for chronic heart failure patients.

METHODS: We enrolled 3,991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with an ejection fraction of 0.40 or less, stabilized on optimal standard therapy, in a double-blind, randomized controlled study. Randomization was preceded by a two-week single-blind placebo run-in period. Of the 3,991 patients, 1,990 patients were randomly assigned to Strongheart 12.5 mg daily and 2,001 patients were assigned to placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analyzed by intention to treat.

RESULTS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in Strongheart group than in the placebo group (146 patient-deaths versus 219 patient-deaths; p = 0.00009, [95% CI 0.53-0.81]). There were fewer sudden deaths in the Strongheart group than in the placebo group (79 vs. 132; p = 0.0002) and deaths from worsening heart failure (30 vs 58; p = 0.0023).

CONCLUSIONS: Strongheart once daily in addition to optimal standard therapy improved survival.

From the abstract above, what is the relative risk of the primary endpoint in the Strongheart group versus the placebo group? (Round to the nearest HUNDREDTH. Enter the relative risk as a decimal, not a percentage).
BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin.

METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause.

RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.28% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P < 0.001 for noninferiority; P = 0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P < 0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P = 0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < 0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42).

CONCLUSIONS: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.

From the abstract above, what is the relative risk reduction of the primary outcome in patients receiving apixaban compared to warfarin? Round to the nearest WHOLE number. (Enter your answer as a percentage but do not enter the percentage sign.)
Abstract

BACKGROUND:
Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure.

METHODS:
A total of 9,297 high-risk patients who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes.

RESULTS:
A total of 4,645 patients were assigned to receive ramipril 10 mg daily and 4,652 were assigned to receive placebo. Of the patients taking ramipril, 650 patients reached the primary endpoint as compared with 826 patients who were assigned to receive placebo (p < 0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1% vs. 8.1% in the placebo group, < 0.001), myocardial infarction (9.9% vs. 12.3%, p < 0.001), stroke (3.4% vs. 4.9%, p < 0.001) and death from any cause (10.4% vs. 12.2%, p = 0.005).

CONCLUSION:
Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.

Question:
From the abstract above, calculate the absolute risk reduction of the composite primary endpoint of myocardial infarction, stroke, or death from cardiovascular causes. (Round to the nearest TENTH. Put your answer in percentage form. Do not include the percentage sign when you type in the number.)
Strongheart Study for Patients with NYHA Functional Class II-IV

BACKGROUND: Strongheart is a new drug being investigated for chronic heart failure patients.

METHODS: We enrolled 3,991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with an ejection fraction of 0.40 or less, stabilized on optimal standard therapy, in a double-blind, randomized controlled study. Randomization was preceded by a 2-week single-blind placebo run-in period. Of the 3,991 patients, 1,990 patients were randomly assigned to Strongheart 12.5 mg daily and 2,001 patients were assigned to placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analyzed by intention to treat.

RESULTS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the Strongheart group than in the placebo group (146 patient-deaths versus 219 patient-deaths; p = 0.00009, [95% CI 0.53-0.81]). There were fewer sudden deaths in the Strongheart group than in the placebo group (79 vs. 132; p = 0.0002) and deaths from worsening heart failure (30 vs 58; p = 0.0023).

CONCLUSIONS: Strongheart once daily in addition to optimal standard therapy improved survival.

From the abstract above, what is the relative risk reduction of the primary endpoint of all-cause mortality in patients randomized to the Strongheart group? (Round to the nearest WHOLE number. Put your answer in percentage form. Do not include the percentage sign when you type in the number.)
Abstract

BACKGROUND:
Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure.

METHODS:
A total of 9,297 high-risk patients who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes.

RESULTS:
A total of 4,645 patients were assigned to receive ramipril 10 mg daily and 4,652 were assigned to receive placebo. Of the patients taking ramipril, 650 patients reached the primary endpoint as compared with 826 patients who were assigned to receive placebo (p < 0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1% vs. 8.1% in the placebo group, p < 0.001), myocardial infarction (9.9% vs. 12.3%, p < 0.001), stroke (3.4% vs. 4.9%, p < 0.001) and death from any cause (10.4% vs. 12.2%, p = 0.005).

CONCLUSION:
Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.

Question:
From the abstract above, calculate the relative risk of the primary endpoint in the ramipril group compared to the placebo group.
Answer
BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin.

METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause.

RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.28% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P < 0.001 for noninferiority; P = 0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P < 0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P = 0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < 0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42).

CONCLUSIONS: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.

From the abstract above, what is the absolute risk reduction of the primary outcome in patients receiving apixaban compared to warfarin? (Enter your answer as a percentage but do not enter the percentage sign.)
Abstract

BACKGROUND:
Although low-density lipoprotein (LDL) lowering has been the mainstay of therapy for primary and secondary cardiovascular (CV) prevention, the data have been primarily for statins. Other nonstatin agents such as fibrates, niacin, and high-density lipoprotein (HDL)-raising agents have failed to show a clinical benefit when added to statins. The current trial sought to study the safety and efficacy of ezetimibe/simvastatin compared with simvastatin alone in reducing CV events in patients at high risk.

METHODS:
Patients with recent ACS were randomized in a 1:1 fashion to either ezetimibe 10 mg/simvastatin 40 mg or simvastatin 40 mg in this placebo-controlled, randomized, double-blinded parallel study.

RESULTS:
A total of 18,144 patients were randomized at 1,158 sites in 39 countries, 9,067 to ezetimibe/simvastatin and 9,077 to simvastatin alone as part of the intention-to-treat group. Baseline characteristics were fairly similar between the two arms. Presentation was ST-segment elevation MI (STEMI) in 29%, NSTEMI in 47%, and unstable angina (UA) in 24%. Nearly 88% underwent diagnostic angiography and 70% underwent percutaneous coronary intervention. Premature discontinuation was observed in 42% of patients in both arms.

Baseline LDL cholesterol (LDL-C) levels were 95 mg/dL in both arms; the median follow-up average was 53.7 mg/dL versus 69.5 mg/dL in the ezetimibe/simvastatin and simvastatin arms, respectively. LDL lowering was observed as early as 1 month, and appeared sustained over the duration of follow-up. At 1 year, triglycerides were also lowered by 16.7 mg/dL in the combination arm, while HDL was increased by 0.6 mg/dL. The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.89-0.99).

Other endpoints including MI (13.1% vs. 14.8%, p = 0.002), stroke (4.2% vs. 4.8%, p = 0.05), ischemic stroke (3.4% vs. 4.1%, p = 0.008), and CV death/MI/stroke (20.4% vs. 22.2%, p = 0.003) were all lower in the ezetimibe/simvastatin arm; no differences were noted for all-cause mortality (15.4% vs. 15.3%, p = 0.78), CV mortality (6.9% vs. 6.8%, p = 0.99) and need for coronary revascularization (21.8% vs. 23.4%, p = 0.11). Per protocol analysis confirmed and further embellished the primary intention-to-treat analyses; the primary endpoint was significantly reduced in the ezetimibe/simvastatin arm compared with placebo (29.8% vs. 32.4%, HR 0.92, 95% CI 0.87-0.98, p = 0.012).

Question:
What does "intention-to-treat" mean in this trial?
Answer

A
Chi-squared testing can be performed on the trial results.
B
All patients randomized in the trial were included in the analysis of the results.
C
Patients who took all doses of the medication were included in the analysis of the results.
D
Wilcoxon rank sum testing can be performed on the trial results.
E
The informed consent form was not signed by the study participant.
Abstract

BACKGROUND:
In patients with established cardiovascular disease, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL) cholesterol is superior to simvastatin alone in reducing such residual risk.

METHODS:
We randomly assigned eligible patients to receive extended-release niacin, 1500 to 2000 mg per day, or matching placebo. All patients received simvastatin, 40 to 80 mg per day, plus ezetimibe, 10 mg per day, if needed, to maintain an LDL cholesterol level of 40 to 80 mg per deciliter (1.03 to 2.07 mmol per liter). The primary end point was the first event of the composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.

RESULTS:
A total of 3414 patients were randomly assigned to receive niacin (1718) or placebo (1696). The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy. At 2 years, niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter (0.91 mmol per liter) to 42 mg per deciliter (1.08 mmol per liter), lowered the triglyceride level from 164 mg per deciliter (1.85 mmol per liter) to 122 mg per deciliter (1.38 mmol per liter), and lowered the LDL cholesterol level from 74 mg per deciliter (1.91 mmol per liter) to 62 mg per deciliter (1.60 mmol per liter). The primary end point occurred in 282 patients in the niacin group and in 275 patients in the placebo group (p = 0.79).

Question:
In the trial above, what is the number needed to harm?
Abstract

BACKGROUND:
In patients with established cardiovascular disease, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL) cholesterol is superior to simvastatin alone in reducing such residual risk.

METHODS:
We randomly assigned eligible patients to receive extended-release niacin, 1500 to 2000 mg per day, or matching placebo. All patients received simvastatin, 40 to 80 mg per day, plus ezetimibe, 10 mg per day, if needed, to maintain an LDL cholesterol level of 40 to 80 mg per deciliter (1.03 to 2.07 mmol per liter). The primary end point was the first event of the composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.

RESULTS:
A total of 3414 patients were randomly assigned to receive niacin (1718) or placebo (1696). The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy. At 2 years, niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter (0.91 mmol per liter) to 42 mg per deciliter (1.08 mmol per liter), lowered the triglyceride level from 164 mg per deciliter (1.85 mmol per liter) to 122 mg per deciliter (1.38 mmol per liter), and lowered the LDL cholesterol level from 74 mg per deciliter (1.91 mmol per liter) to 62 mg per deciliter (1.60 mmol per liter). The primary end point occurred in 282 patients in the niacin group and in 275 patients in the placebo group (p = 0.79).

Question:
In the trial above, what is the hazard ratio of the primary endpoint?
Abstract

BACKGROUND:
A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period.

METHODS:
In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes.

RESULTS:
Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P < 0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P < 0.001).

CONCLUSIONS:
A once-yearly infusion of zoledronic acid during a 3-year period reduced the risk of vertebral, hip, and other fractures.

Question:
In the trial above, what is the absolute risk reduction of morphometric vertebral fractures?
Abstract

BACKGROUND:
A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period.

METHODS:
In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes.

RESULTS:
Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P < 0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P < 0.001).

CONCLUSIONS:
A once-yearly infusion of zoledronic acid during a 3-year period reduced the risk of vertebral, hip, and other fractures.

Question:
In the trial above, what is/are the independent variable/s? (Select ALL that apply.)
Abstract

BACKGROUND:
Although low-density lipoprotein (LDL) lowering has been the mainstay of therapy for primary and secondary cardiovascular (CV) prevention, the data have been primarily for statins. Other nonstatin agents such as fibrates, niacin, and high-density lipoprotein (HDL)-raising agents have failed to show a clinical benefit when added to statins. The current trial sought to study the safety and efficacy of ezetimibe/simvastatin compared with simvastatin alone in reducing CV events in patients at high risk.

METHODS:
Patients with recent ACS were randomized in a 1:1 fashion to either ezetimibe 10 mg/simvastatin 40 mg or simvastatin 40 mg in this randomized, controlled, double-blinded parallel study.

RESULTS:
A total of 18,144 patients were randomized at 1,158 sites in 39 countries, 9,067 to ezetimibe/simvastatin and 9,077 to simvastatin alone as part of the intention-to-treat group. Baseline characteristics were fairly similar between the two arms. Presentation was ST-segment elevation MI (STEMI) in 29%, NSTEMI in 47%, and unstable angina (UA) in 24%. Nearly 88% underwent diagnostic angiography and 70% underwent percutaneous coronary intervention. Premature discontinuation was observed in 42% of patients in both arms.

Baseline LDL cholesterol (LDL-C) levels were 95 mg/dL in both arms; the median follow-up average was 53.7 mg/dL versus 69.5 mg/dL in the ezetimibe/simvastatin and simvastatin arms, respectively. LDL lowering was observed as early as 1 month, and appeared sustained over the duration of follow-up. At 1 year, triglycerides were also lowered by 16.7 mg/dL in the combination arm, while HDL was increased by 0.6 mg/dL. The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%; p = 0.016).

Other endpoints including MI (13.1% vs. 14.8%, p = 0.002), stroke (4.2% vs. 4.8%, p = 0.05), ischemic stroke (3.4% vs. 4.1%, p = 0.008), and CV death/MI/stroke (20.4% vs. 22.2%, p = 0.003) were all lower in the ezetimibe/simvastatin arm; no differences were noted for all-cause mortality (15.4% vs. 15.3%, p = 0.78), CV mortality (6.9% vs. 6.8%, p = 0.99) and need for coronary revascularization (21.8% vs. 23.4%, p = 0.11). Per protocol analysis confirmed and further embellished the primary intention-to-treat analyses; the primary endpoint was significantly reduced in the ezetimibe/simvastatin arm compared with simvastatin (29.8% vs. 32.4%, HR 0.92, 95% CI 0.87-0.98, p = 0.012).

Question:
In the trial above, what is the number of people needed to treat to prevent 1 primary endpoint event in the per protocol population?
Abstract

BACKGROUND:
Although low-density lipoprotein (LDL) lowering has been the mainstay of therapy for primary and secondary cardiovascular (CV) prevention, the data have been primarily for statins. Other nonstatin agents such as fibrates, niacin, and high-density lipoprotein (HDL)-raising agents have failed to show a clinical benefit when added to statins. The current trial sought to study the safety and efficacy of ezetimibe/simvastatin compared with simvastatin alone in reducing CV events in patients at high risk.

METHODS:
Patients with recent ACS were randomized in a 1:1 fashion to either ezetimibe 10 mg/simvastatin 40 mg or simvastatin 40 mg in this randomized, controlled, double-blinded parallel study.

RESULTS:
A total of 18,144 patients were randomized at 1,158 sites in 39 countries, 9,067 to ezetimibe/simvastatin and 9,077 to simvastatin alone as part of the intention-to-treat group. Baseline characteristics were fairly similar between the two arms. Presentation was ST-segment elevation MI (STEMI) in 29%, NSTEMI in 47%, and unstable angina (UA) in 24%. Nearly 88% underwent diagnostic angiography and 70% underwent percutaneous coronary intervention. Premature discontinuation was observed in 42% of patients in both arms.

Baseline LDL cholesterol (LDL-C) levels were 95 mg/dL in both arms; the median follow-up average was 53.7 mg/dL versus 69.5 mg/dL in the ezetimibe/simvastatin and simvastatin arms, respectively. LDL lowering was observed as early as 1 month, and appeared sustained over the duration of follow-up. At 1 year, triglycerides were also lowered by 16.7 mg/dL in the combination arm, while HDL was increased by 0.6 mg/dL. The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.89-0.99).

Other endpoints including MI (13.1% vs. 14.8%, p = 0.002), stroke (4.2% vs. 4.8%, p = 0.05), ischemic stroke (3.4% vs. 4.1%, p = 0.008), and CV death/MI/stroke (20.4% vs. 22.2%, p = 0.003) were all lower in the ezetimibe/simvastatin arm; no differences were noted for all-cause mortality (15.4% vs. 15.3%, p = 0.78), CV mortality (6.9% vs. 6.8%, p = 0.99) and need for coronary revascularization (21.8% vs. 23.4%, p = 0.11). Per protocol analysis confirmed and further embellished the primary intention-to-treat analyses; the primary endpoint was significantly reduced in the ezetimibe/simvastatin arm compared with simvastatin (29.8% vs. 32.4%, HR 0.92, 95% CI 0.87-0.98, p = 0.012).

Question:
In the trial above, what is the number of people needed to treat to prevent 1 primary endpoint event in the intention-to-treat population?
Abstract

BACKGROUND:
In patients with established cardiovascular disease, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL) cholesterol is superior to simvastatin alone in reducing such residual risk.

METHODS:
We randomly assigned eligible patients to receive extended-release niacin, 1500 to 2000 mg per day, or matching placebo. All patients received simvastatin, 40 to 80 mg per day, plus ezetimibe, 10 mg per day, if needed, to maintain an LDL cholesterol level of 40 to 80 mg per deciliter (1.03 to 2.07 mmol per liter). The primary end point was the first event of the composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.

RESULTS:
A total of 3414 patients were randomly assigned to receive niacin (1718) or placebo (1696). The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy. At 2 years, niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter (0.91 mmol per liter) to 42 mg per deciliter (1.08 mmol per liter), lowered the triglyceride level from 164 mg per deciliter (1.85 mmol per liter) to 122 mg per deciliter (1.38 mmol per liter), and lowered the LDL cholesterol level from 74 mg per deciliter (1.91 mmol per liter) to 62 mg per deciliter (1.60 mmol per liter). The primary end point occurred in 282 patients in the niacin group and in 275 patients in the placebo group (p = 0.79).

Question:
Looking at the results of the trial above, which of the following statements are correct? (Select ALL that apply.)
Answer

A
The addition of niacin to statin therapy did not lead to a clinically significant reduction in death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.
B
The addition of niacin to statin therapy led to a statistically significant reduction in death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.
C
The addition of niacin to statin therapy led to a clinically significant reduction in death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.
D
The addition a statin to niacin therapy led to a statistically significant reduction in death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.
E
The addition of a statin to niacin therapy did not lead to a clinically significant reduction in death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.
Abstract

BACKGROUND:
Although low-density lipoprotein (LDL) lowering has been the mainstay of therapy for primary and secondary cardiovascular (CV) prevention, the data have been primarily for statins. Other nonstatin agents such as fibrates, niacin, and high-density lipoprotein (HDL)-raising agents have failed to show a clinical benefit when added to statins. The current trial sought to study the safety and efficacy of ezetimibe/simvastatin compared with simvastatin alone in reducing CV events in patients at high risk.

METHODS:
Patients with recent ACS were randomized in a 1:1 fashion to either ezetimibe 10 mg/simvastatin 40 mg or simvastatin 40 mg in this placebo-controlled, randomized, double-blinded parallel study.

RESULTS:
A total of 18,144 patients were randomized at 1,158 sites in 39 countries, 9,067 to ezetimibe/simvastatin and 9,077 to simvastatin alone as part of the intention-to-treat group. Baseline characteristics were fairly similar between the two arms. Presentation was ST-segment elevation MI (STEMI) in 29%, NSTEMI in 47%, and unstable angina (UA) in 24%. Nearly 88% underwent diagnostic angiography and 70% underwent percutaneous coronary intervention. Premature discontinuation was observed in 42% of patients in both arms.

Baseline LDL cholesterol (LDL-C) levels were 95 mg/dL in both arms; the median follow-up average was 53.7 mg/dL versus 69.5 mg/dL in the ezetimibe/simvastatin and simvastatin arms, respectively. LDL lowering was observed as early as 1 month, and appeared sustained over the duration of follow-up. At 1 year, triglycerides were also lowered by 16.7 mg/dL in the combination arm, while HDL was increased by 0.6 mg/dL. The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.89-0.99).

Other endpoints including MI (13.1% vs. 14.8%, p = 0.002), stroke (4.2% vs. 4.8%, p = 0.05), ischemic stroke (3.4% vs. 4.1%, p = 0.008), and CV death/MI/stroke (20.4% vs. 22.2%, p = 0.003) were all lower in the ezetimibe/simvastatin arm; no differences were noted for all-cause mortality (15.4% vs. 15.3%, p = 0.78), CV mortality (6.9% vs. 6.8%, p = 0.99) and need for coronary revascularization (21.8% vs. 23.4%, p = 0.11). Per protocol analysis confirmed and further embellished the primary intention-to-treat analyses; the primary endpoint was significantly reduced in the ezetimibe/simvastatin arm compared with simvastatin (29.8% vs. 32.4%, HR 0.92, 95% CI 0.87-0.98, p = 0.012).

Question:
Looking at the results of the trial above, what is the absolute risk reduction of the primary endpoint in the intention-to-treat population?
Abstract

BACKGROUND:
Although low-density lipoprotein (LDL) lowering has been the mainstay of therapy for primary and secondary cardiovascular (CV) prevention, the data have been primarily for statins. Other nonstatin agents such as fibrates, niacin, and high-density lipoprotein (HDL)-raising agents have failed to show a clinical benefit when added to statins. The current trial sought to study the safety and efficacy of ezetimibe/simvastatin compared with simvastatin alone in reducing CV events in patients at high risk.

METHODS:
Patients with recent ACS were randomized in a 1:1 fashion to either ezetimibe 10 mg/simvastatin 40 mg or simvastatin 40 mg in this randomized, controlled, double-blinded parallel study.

RESULTS:
A total of 18,144 patients were randomized at 1,158 sites in 39 countries, 9,067 to ezetimibe/simvastatin and 9,077 to simvastatin alone as part of the intention-to-treat group. Baseline characteristics were fairly similar between the two arms. Presentation was ST-segment elevation MI (STEMI) in 29%, NSTEMI in 47%, and unstable angina (UA) in 24%. Nearly 88% underwent diagnostic angiography and 70% underwent percutaneous coronary intervention. Premature discontinuation was observed in 42% of patients in both arms.

Baseline LDL cholesterol (LDL-C) levels were 95 mg/dL in both arms; the median follow-up average was 53.7 mg/dL versus 69.5 mg/dL in the ezetimibe/simvastatin and simvastatin arms, respectively. LDL lowering was observed as early as 1 month, and appeared sustained over the duration of follow-up. At 1 year, triglycerides were also lowered by 16.7 mg/dL in the combination arm, while HDL was increased by 0.6 mg/dL. The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.89-0.99).

Other endpoints including MI (13.1% vs. 14.8%, p = 0.002), stroke (4.2% vs. 4.8%, p = 0.05), ischemic stroke (3.4% vs. 4.1%, p = 0.008), and CV death/MI/stroke (20.4% vs. 22.2%, p = 0.003) were all lower in the ezetimibe/simvastatin arm; no differences were noted for all-cause mortality (15.4% vs. 15.3%, p = 0.78), CV mortality (6.9% vs. 6.8%, p = 0.99) and need for coronary revascularization (21.8% vs. 23.4%, p = 0.11). Per protocol analysis confirmed and further embellished the primary intention-to-treat analyses; the primary endpoint was significantly reduced in the ezetimibe/simvastatin arm compared with placebo (29.8% vs. 32.4%, HR 0.92, 95% CI 0.87-0.98).

Question:
Looking at the results of the trial above, which of the following statements is correct?
Answer

A
Ezetimibe 10 mg/simvastatin 40 mg is not superior to simvastatin 40 mg alone in reducing CV events in post high-risk ACS patients.
B
Ezetimibe 10 mg/simvastatin 40 mg is superior to simvastatin 40 mg alone in reducing CV events in post high-risk ACS patients.
C
Ezetimibe 10 mg/simvastatin 40 mg is inferior to simvastatin 40 mg alone in reducing CV events in post high-risk ACS patients.
D
Ezetimibe 10 mg/simvastatin 40 mg is similar to simvastatin 40 mg alone in reducing CV events in post high-risk ACS patients.
E
There is no statistical difference between ezetimibe 10 mg/simvastatin 40 mg and simvastatin 40 mg alone in reducing CV events in post high-risk ACS patients.
Abstract

BACKGROUND:
Although low-density lipoprotein (LDL) lowering has been the mainstay of therapy for primary and secondary cardiovascular (CV) prevention, the data have been primarily for statins. Other nonstatin agents such as fibrates, niacin, and high-density lipoprotein (HDL)-raising agents have failed to show a clinical benefit when added to statins. The current trial sought to study the safety and efficacy of ezetimibe/simvastatin compared with simvastatin alone in reducing CV events in patients at high risk.

METHODS:
Patients with recent ACS were randomized in a 1:1 fashion to either ezetimibe 10 mg/simvastatin 40 mg or simvastatin 40 mg in this randomized, controlled, double-blinded parallel study.

RESULTS:
A total of 18,144 patients were randomized at 1,158 sites in 39 countries, 9,067 to ezetimibe/simvastatin and 9,077 to simvastatin alone as part of the intention-to-treat group. Baseline characteristics were fairly similar between the two arms. Presentation was ST-segment elevation MI (STEMI) in 29%, NSTEMI in 47%, and unstable angina (UA) in 24%. Nearly 88% underwent diagnostic angiography and 70% underwent percutaneous coronary intervention. Premature discontinuation was observed in 42% of patients in both arms.

Baseline LDL cholesterol (LDL-C) levels were 95 mg/dL in both arms; the median follow-up average was 53.7 mg/dL versus 69.5 mg/dL in the ezetimibe/simvastatin and simvastatin arms, respectively. LDL lowering was observed as early as 1 month, and appeared sustained over the duration of follow-up. At 1 year, triglycerides were also lowered by 16.7 mg/dL in the combination arm, while HDL was increased by 0.6 mg/dL. The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%, p = 0.016).

Other endpoints including MI (13.1% vs. 14.8%, p = 0.002), stroke (4.2% vs. 4.8%, p = 0.05), ischemic stroke (3.4% vs. 4.1%, p = 0.008), and CV death/MI/stroke (20.4% vs. 22.2%, p = 0.003) were all lower in the ezetimibe/simvastatin arm; no differences were noted for all-cause mortality (15.4% vs. 15.3%, p = 0.78), CV mortality (6.9% vs. 6.8%, p = 0.99) and need for coronary revascularization (21.8% vs. 23.4%, p = 0.11). Per protocol analysis confirmed and further embellished the primary intention-to-treat analyses; the primary endpoint was significantly reduced in the ezetimibe/simvastatin arm compared with simvastatin (29.8% vs. 32.4%, p = 0.012).

Question:
In the trial above, what is the hazard ratio of the primary endpoint in the intention-to-treat population?
Abstract

BACKGROUND:
Although low-density lipoprotein (LDL) lowering has been the mainstay of therapy for primary and secondary cardiovascular (CV) prevention, the data have been primarily for statins. Other nonstatin agents such as fibrates, niacin, and high-density lipoprotein (HDL)-raising agents have failed to show a clinical benefit when added to statins. The current trial sought to study the safety and efficacy of ezetimibe/simvastatin compared with simvastatin alone in reducing CV events in patients at high risk.

METHODS:
Patients with recent ACS were randomized in a 1:1 fashion to either ezetimibe 10 mg/simvastatin 40 mg or simvastatin 40 mg in this randomized, controlled, double-blinded parallel study.

RESULTS:
A total of 18,144 patients were randomized at 1,158 sites in 39 countries, 9,067 to ezetimibe/simvastatin and 9,077 to simvastatin alone as part of the intention-to-treat group. Baseline characteristics were fairly similar between the two arms. Presentation was ST-segment elevation MI (STEMI) in 29%, NSTEMI in 47%, and unstable angina (UA) in 24%. Nearly 88% underwent diagnostic angiography and 70% underwent percutaneous coronary intervention. Premature discontinuation was observed in 42% of patients in both arms.

Baseline LDL cholesterol (LDL-C) levels were 95 mg/dL in both arms; the median follow-up average was 53.7 mg/dL versus 69.5 mg/dL in the ezetimibe/simvastatin and simvastatin arms, respectively. LDL lowering was observed as early as 1 month, and appeared sustained over the duration of follow-up. At 1 year, triglycerides were also lowered by 16.7 mg/dL in the combination arm, while HDL was increased by 0.6 mg/dL. The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%; p = 0.016).

Other endpoints including MI (13.1% vs. 14.8%, p = 0.002), stroke (4.2% vs. 4.8%, p = 0.05), ischemic stroke (3.4% vs. 4.1%, p = 0.008), and CV death/MI/stroke (20.4% vs. 22.2%, p = 0.003) were all lower in the ezetimibe/simvastatin arm; no differences were noted for all-cause mortality (15.4% vs. 15.3%, p = 0.78), CV mortality (6.9% vs. 6.8%, p = 0.99) and need for coronary revascularization (21.8% vs. 23.4%, p = 0.11). Per protocol analysis confirmed and further embellished the primary intention-to-treat analyses; the primary endpoint was significantly reduced in the ezetimibe/simvastatin arm compared with simvastatin (29.8% vs. 32.4%, HR 0.92, 95% CI 0.87-0.98, p = 0.012).

Question:
Which of the following statements is correct when referring to the primary endpoint's absolute risk reduction?
Answer

A
There is a 2% reduction in risk in all patients taking simvastatin.
B
There will be two less primary endpoint events for every 100 patients taking ezetimibe/simvastatin.
C
One hundred patients need to be treated with simvastatin for two patients to benefit.
D
There is a 98% reduction in risk in all patients taking ezetimibe/simvastatin.
E
There will be two less primary endpoint events for every 100 patients taking simvastatin.
Abstract

BACKGROUND:
A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period.

METHODS:
In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes.

RESULTS:
Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P < 0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P < 0.001).

CONCLUSIONS:
A once-yearly infusion of zoledronic acid during a 3-year period reduced the risk of vertebral, hip, and other fractures.

Question:
In the trial above, which statement is accurate regarding the relative risk of morphometric vertebral fractures?
Answer

A
Patients taking zoledronic acid were 30% less likely to experience morphometric vertebral fractures than patients taking placebo.
B
Patients taking placebo were 30% less likely to experience morphometric vertebral fractures than patients taking zoledronic acid.
C
Patients taking zoledronic acid were 30% as likely to experience morphometric vertebral fractures than patients taking placebo.
D
Patients taking placebo were 30% as likely to experience morphometric vertebral fractures than patients taking zoledronic acid.
E
Patients taking zoledronic acid were 30% more likely to experience morphometric vertebral fractures than patients taking placebo.
Abstract

BACKGROUND:
A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period.

METHODS:
In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes.

RESULTS:
Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P < 0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P < 0.001).

CONCLUSIONS:
A once-yearly infusion of zoledronic acid during a 3-year period reduced the risk of vertebral, hip, and other fractures.

Question:
In reading the trial above, which of the following statements regarding the null hypothesis is true?
Answer

A
The null hypothesis should be accepted.
B
The null hypothesis should fail to be accepted.
C
The null hypothesis does not exist for this trial.
D
A decision regarding the null hypothesis cannot be made from the information provided.
E
None of the above statements are true.
Abstract

BACKGROUND:
A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period.

METHODS:
In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes.

RESULTS:
Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P < 0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P < 0.001).

CONCLUSIONS:
A once-yearly infusion of zoledronic acid during a 3-year period reduced the risk of vertebral, hip, and other fractures.

Question:
In the trial above, what is/are the dependent variable/s? (Select ALL that apply.)
Answer

A
Vertebral fractures
B
Zoledronic acid
C
Placebo
D
Hip fractures
E
Cost of the medication
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