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Donepezil minimally effective for patients with vascular dementia
Donepezil (Aricept—a potent acetylcholin-esterase inhibitor) had small effects on mentation for patients with mild to moderate vascular dementia as measured by validated instruments of cognition.
Donepezil’s side effects are similar to placebo at 5 mg but double at 10 mg, with no improvement in the patient’s cognition. Even though this medication was minimally effective, there are no other highly effective medical treatments for vascular dementia. Therefore, if a patient chooses a trial of donepezil, the lower, 5-mg dose should be offered.
The medication’s effect is likely a class effect and not an individual drug effect; therefore, rivastigmine (Exelon) and galantamine(Reminyl) are 2 other acetylcholinesterase inhibitors that should also be considered. Cost is similar for all 3 drugs at about $130.00 per month.
Donepezil (Aricept—a potent acetylcholin-esterase inhibitor) had small effects on mentation for patients with mild to moderate vascular dementia as measured by validated instruments of cognition.
Donepezil’s side effects are similar to placebo at 5 mg but double at 10 mg, with no improvement in the patient’s cognition. Even though this medication was minimally effective, there are no other highly effective medical treatments for vascular dementia. Therefore, if a patient chooses a trial of donepezil, the lower, 5-mg dose should be offered.
The medication’s effect is likely a class effect and not an individual drug effect; therefore, rivastigmine (Exelon) and galantamine(Reminyl) are 2 other acetylcholinesterase inhibitors that should also be considered. Cost is similar for all 3 drugs at about $130.00 per month.
Donepezil (Aricept—a potent acetylcholin-esterase inhibitor) had small effects on mentation for patients with mild to moderate vascular dementia as measured by validated instruments of cognition.
Donepezil’s side effects are similar to placebo at 5 mg but double at 10 mg, with no improvement in the patient’s cognition. Even though this medication was minimally effective, there are no other highly effective medical treatments for vascular dementia. Therefore, if a patient chooses a trial of donepezil, the lower, 5-mg dose should be offered.
The medication’s effect is likely a class effect and not an individual drug effect; therefore, rivastigmine (Exelon) and galantamine(Reminyl) are 2 other acetylcholinesterase inhibitors that should also be considered. Cost is similar for all 3 drugs at about $130.00 per month.
Heliox of minimal benefit in acute asthma
This meta-analysis showed that heliox, a mixture of helium and oxygen, offers minimal benefit during the first hour of treatment, and this benefit is not sustained. More importantly, it was not demonstrated that there was a difference in important clinical outcomes. Patients on a traditional air-oxygen mixture do just as well in the medium to long term.
Hypoxemic patients are not suitable for heliox therapy. Therefore, heliox should not be used in place of traditional oxygen or oxygen-air mixtures in acute exacerbations of asthma.
This meta-analysis showed that heliox, a mixture of helium and oxygen, offers minimal benefit during the first hour of treatment, and this benefit is not sustained. More importantly, it was not demonstrated that there was a difference in important clinical outcomes. Patients on a traditional air-oxygen mixture do just as well in the medium to long term.
Hypoxemic patients are not suitable for heliox therapy. Therefore, heliox should not be used in place of traditional oxygen or oxygen-air mixtures in acute exacerbations of asthma.
This meta-analysis showed that heliox, a mixture of helium and oxygen, offers minimal benefit during the first hour of treatment, and this benefit is not sustained. More importantly, it was not demonstrated that there was a difference in important clinical outcomes. Patients on a traditional air-oxygen mixture do just as well in the medium to long term.
Hypoxemic patients are not suitable for heliox therapy. Therefore, heliox should not be used in place of traditional oxygen or oxygen-air mixtures in acute exacerbations of asthma.
Antioxidants do not prevent heart disease in high-risk individuals
ABSTRACT
BACKGROUND: Several nonrandomized, observational studies have suggested that antioxidant vitamins decrease vascular disease, cancer, and mortality. However, large randomized trials are needed to counter biases such as the “healthy user effect” often seen in observational studies.
POPULATION STUDIED: The investigators studied 20,536 adults (mostly men from the United Kingdom) aged 40 to 80 years with diabetes, peripheral artery disease, or coronary artery disease. Patients were included if their total cholesterol concentration was above 3.5 mmol/L (135 mg/dL) and they were at a “substantial risk” for more than 5 years of death from coronary disease due to the presence of known cardiovascular disease (coronary artery disease, peripheral artery disease, cerebrovascular disease), diabetes, or hypertension. Patients were excluded if they had other life-threatening illnesses, diagnosed cancer, or were already taking high-dose vitamin E supplements.
STUDY DESIGN AND VALIDITY: Patients in this impressive placebo-controlled, double-blind randomized (masked allocation via central telephone system) trial received antioxidant supplementation (vitamin E 600 mg, vitamin C 250 mg, and beta-carotene 20 mg daily) or matching placebo. This study was part of the MRC/BHF study on simvastatin. All patients in the vitamin treatment group also received simvastatin. In an 8- to 10-week “prerandomization run-in” phase eligibility and compliance with the 5-year study protocol was assessed. Patients were seen at 4, 8, and 12 months, and then every 6 months during a 5-year period.
OUTCOMES MEASURED: The primary outcomes measured were “major coronary events” (nonfatal myocardial infarction or death from coronary disease) and fatal coronary heart disease. Secondary outcomes measured were effects on major coronary events and major vascular events and nonfatal or fatal stroke. Other outcomes included site-specific cancer, cerebral hemorrhage, vascular procedures, and hospitalization for various causes.
RESULTS: Patients taking vitamins had significantly higher levels of these vitamins in their blood. Despite this increase no difference was noted in all-cause mortality or deaths due to vascular or nonvascular causes. There were no differences in nonfatal myocardial infarctions, coronary death, nonfatal or fatal stroke, or coronary or noncoronary revascularization. No differences were noted in cancer incidence or hospitalization for any other nonvascular cause.
This impressive placebo-controlled, double-blind randomized trial clearly shows that antioxidants, specifically vitamin E and C and beta-carotene, should not be recommended for secondary prevention of heart disease in high-risk patients. Site-specific cancers were not affected in this study. However, the study was too short (5 years) to be able to conclusively comment about the antioxidants’ effects on cancer.
ABSTRACT
BACKGROUND: Several nonrandomized, observational studies have suggested that antioxidant vitamins decrease vascular disease, cancer, and mortality. However, large randomized trials are needed to counter biases such as the “healthy user effect” often seen in observational studies.
POPULATION STUDIED: The investigators studied 20,536 adults (mostly men from the United Kingdom) aged 40 to 80 years with diabetes, peripheral artery disease, or coronary artery disease. Patients were included if their total cholesterol concentration was above 3.5 mmol/L (135 mg/dL) and they were at a “substantial risk” for more than 5 years of death from coronary disease due to the presence of known cardiovascular disease (coronary artery disease, peripheral artery disease, cerebrovascular disease), diabetes, or hypertension. Patients were excluded if they had other life-threatening illnesses, diagnosed cancer, or were already taking high-dose vitamin E supplements.
STUDY DESIGN AND VALIDITY: Patients in this impressive placebo-controlled, double-blind randomized (masked allocation via central telephone system) trial received antioxidant supplementation (vitamin E 600 mg, vitamin C 250 mg, and beta-carotene 20 mg daily) or matching placebo. This study was part of the MRC/BHF study on simvastatin. All patients in the vitamin treatment group also received simvastatin. In an 8- to 10-week “prerandomization run-in” phase eligibility and compliance with the 5-year study protocol was assessed. Patients were seen at 4, 8, and 12 months, and then every 6 months during a 5-year period.
OUTCOMES MEASURED: The primary outcomes measured were “major coronary events” (nonfatal myocardial infarction or death from coronary disease) and fatal coronary heart disease. Secondary outcomes measured were effects on major coronary events and major vascular events and nonfatal or fatal stroke. Other outcomes included site-specific cancer, cerebral hemorrhage, vascular procedures, and hospitalization for various causes.
RESULTS: Patients taking vitamins had significantly higher levels of these vitamins in their blood. Despite this increase no difference was noted in all-cause mortality or deaths due to vascular or nonvascular causes. There were no differences in nonfatal myocardial infarctions, coronary death, nonfatal or fatal stroke, or coronary or noncoronary revascularization. No differences were noted in cancer incidence or hospitalization for any other nonvascular cause.
This impressive placebo-controlled, double-blind randomized trial clearly shows that antioxidants, specifically vitamin E and C and beta-carotene, should not be recommended for secondary prevention of heart disease in high-risk patients. Site-specific cancers were not affected in this study. However, the study was too short (5 years) to be able to conclusively comment about the antioxidants’ effects on cancer.
ABSTRACT
BACKGROUND: Several nonrandomized, observational studies have suggested that antioxidant vitamins decrease vascular disease, cancer, and mortality. However, large randomized trials are needed to counter biases such as the “healthy user effect” often seen in observational studies.
POPULATION STUDIED: The investigators studied 20,536 adults (mostly men from the United Kingdom) aged 40 to 80 years with diabetes, peripheral artery disease, or coronary artery disease. Patients were included if their total cholesterol concentration was above 3.5 mmol/L (135 mg/dL) and they were at a “substantial risk” for more than 5 years of death from coronary disease due to the presence of known cardiovascular disease (coronary artery disease, peripheral artery disease, cerebrovascular disease), diabetes, or hypertension. Patients were excluded if they had other life-threatening illnesses, diagnosed cancer, or were already taking high-dose vitamin E supplements.
STUDY DESIGN AND VALIDITY: Patients in this impressive placebo-controlled, double-blind randomized (masked allocation via central telephone system) trial received antioxidant supplementation (vitamin E 600 mg, vitamin C 250 mg, and beta-carotene 20 mg daily) or matching placebo. This study was part of the MRC/BHF study on simvastatin. All patients in the vitamin treatment group also received simvastatin. In an 8- to 10-week “prerandomization run-in” phase eligibility and compliance with the 5-year study protocol was assessed. Patients were seen at 4, 8, and 12 months, and then every 6 months during a 5-year period.
OUTCOMES MEASURED: The primary outcomes measured were “major coronary events” (nonfatal myocardial infarction or death from coronary disease) and fatal coronary heart disease. Secondary outcomes measured were effects on major coronary events and major vascular events and nonfatal or fatal stroke. Other outcomes included site-specific cancer, cerebral hemorrhage, vascular procedures, and hospitalization for various causes.
RESULTS: Patients taking vitamins had significantly higher levels of these vitamins in their blood. Despite this increase no difference was noted in all-cause mortality or deaths due to vascular or nonvascular causes. There were no differences in nonfatal myocardial infarctions, coronary death, nonfatal or fatal stroke, or coronary or noncoronary revascularization. No differences were noted in cancer incidence or hospitalization for any other nonvascular cause.
This impressive placebo-controlled, double-blind randomized trial clearly shows that antioxidants, specifically vitamin E and C and beta-carotene, should not be recommended for secondary prevention of heart disease in high-risk patients. Site-specific cancers were not affected in this study. However, the study was too short (5 years) to be able to conclusively comment about the antioxidants’ effects on cancer.
Are oral contraceptives (OCPs) with anti-androgenic progestins preferred over other OCPs in patients with acne?
ABSTRACT
BACKGROUND: Some women with acne may suffer from a hypersensitivity of the sebaceous glands to androgens. The use of OCPs with anti-androgenic properties may therefore be a useful approach to treating these patients.
POPULATION STUDIED: The population studied included 199 women 18 to 40 years of age (smokers up to age 30 years), with mild to moderate papulo pustular acne of the face and acne-related disorders. Patients were recruited from 32 office-based gynecology centers in Germany.
STUDY DESIGN AND VALIDITY: Patients were randomized in an investigator blinded-only fashion (nonconcealed allocation assignment) to 12 treatment cycles with one of 2 OCPs—either Belara, a monophasic OCP containing 0.3 mg of ethinylestradiol and 2 mg of chlormadinone acetate (EE/CMA), a progestogen derivative with anti-androgenic properties or Microgynon, an OCP containing an equal dose of estrogen and a more commonly used progestin, levonorgestrel (EE/LNG). Blinded observers performed regular skin exams after cycles 4, 7, 10 and 12. Women were not allowed to use any other treatments for acne.
OUTCOMES MEASURED: The primary endpoint was the number of papules/pustules per half of the face decreasing by 50% in the 12th medication cycle. Secondary endpoints were the assessment of comedomal acne of the face, acne of the décolleté and back, further signs of adrogenization, such as seborrhea, alopecia, and hirsuitism. Blood levels of androgens, SHBG, cycle stability and incidence of adverse events were also examined.
RESULTS: A total of 59% of patients on EE/CMA compared with 46% on EE/LNG showed a 50% reduction in the number of papules/pustules after 12 treatment cycles (P=.02; number needed to treat=8). The number of women with complete resolution reached 16.5% by cycle 12 in those taking EE/CMA compared with 4.3% by cycle 12 in the EE/LNG group (difference nonsignificant). Similar nonsignificant trends were seen for a reduction in comedonal acne favoring the EE/CMA group. Equal improvements were seen in each group for seborrhea, alopecia, and hirsuitism. There was no difference in the incidence and intensity of break-through bleeding or amenorrhea between the 2 groups. Adverse events were similar between the 2 groups.
OCPs with an anti-androgenic progestin derivative may be slightly more effective than other OCPs in improving mild to moderate acne. However, nearly half of the women in this study treated with either OCP had a significant reduction in their acne after 12 cycles of treatment. The progestin in this phase III trial (chlormadinone) is currently not used in any OCP available in the United States. Other combination pills have been shown in randomized controlled trials to be effective for treating acne.1-3 For now it makes sense to prescribe cheaper OCPs in women with acne and switch to more expensive “designer” brands only in the case of a nonresponse.
ABSTRACT
BACKGROUND: Some women with acne may suffer from a hypersensitivity of the sebaceous glands to androgens. The use of OCPs with anti-androgenic properties may therefore be a useful approach to treating these patients.
POPULATION STUDIED: The population studied included 199 women 18 to 40 years of age (smokers up to age 30 years), with mild to moderate papulo pustular acne of the face and acne-related disorders. Patients were recruited from 32 office-based gynecology centers in Germany.
STUDY DESIGN AND VALIDITY: Patients were randomized in an investigator blinded-only fashion (nonconcealed allocation assignment) to 12 treatment cycles with one of 2 OCPs—either Belara, a monophasic OCP containing 0.3 mg of ethinylestradiol and 2 mg of chlormadinone acetate (EE/CMA), a progestogen derivative with anti-androgenic properties or Microgynon, an OCP containing an equal dose of estrogen and a more commonly used progestin, levonorgestrel (EE/LNG). Blinded observers performed regular skin exams after cycles 4, 7, 10 and 12. Women were not allowed to use any other treatments for acne.
OUTCOMES MEASURED: The primary endpoint was the number of papules/pustules per half of the face decreasing by 50% in the 12th medication cycle. Secondary endpoints were the assessment of comedomal acne of the face, acne of the décolleté and back, further signs of adrogenization, such as seborrhea, alopecia, and hirsuitism. Blood levels of androgens, SHBG, cycle stability and incidence of adverse events were also examined.
RESULTS: A total of 59% of patients on EE/CMA compared with 46% on EE/LNG showed a 50% reduction in the number of papules/pustules after 12 treatment cycles (P=.02; number needed to treat=8). The number of women with complete resolution reached 16.5% by cycle 12 in those taking EE/CMA compared with 4.3% by cycle 12 in the EE/LNG group (difference nonsignificant). Similar nonsignificant trends were seen for a reduction in comedonal acne favoring the EE/CMA group. Equal improvements were seen in each group for seborrhea, alopecia, and hirsuitism. There was no difference in the incidence and intensity of break-through bleeding or amenorrhea between the 2 groups. Adverse events were similar between the 2 groups.
OCPs with an anti-androgenic progestin derivative may be slightly more effective than other OCPs in improving mild to moderate acne. However, nearly half of the women in this study treated with either OCP had a significant reduction in their acne after 12 cycles of treatment. The progestin in this phase III trial (chlormadinone) is currently not used in any OCP available in the United States. Other combination pills have been shown in randomized controlled trials to be effective for treating acne.1-3 For now it makes sense to prescribe cheaper OCPs in women with acne and switch to more expensive “designer” brands only in the case of a nonresponse.
ABSTRACT
BACKGROUND: Some women with acne may suffer from a hypersensitivity of the sebaceous glands to androgens. The use of OCPs with anti-androgenic properties may therefore be a useful approach to treating these patients.
POPULATION STUDIED: The population studied included 199 women 18 to 40 years of age (smokers up to age 30 years), with mild to moderate papulo pustular acne of the face and acne-related disorders. Patients were recruited from 32 office-based gynecology centers in Germany.
STUDY DESIGN AND VALIDITY: Patients were randomized in an investigator blinded-only fashion (nonconcealed allocation assignment) to 12 treatment cycles with one of 2 OCPs—either Belara, a monophasic OCP containing 0.3 mg of ethinylestradiol and 2 mg of chlormadinone acetate (EE/CMA), a progestogen derivative with anti-androgenic properties or Microgynon, an OCP containing an equal dose of estrogen and a more commonly used progestin, levonorgestrel (EE/LNG). Blinded observers performed regular skin exams after cycles 4, 7, 10 and 12. Women were not allowed to use any other treatments for acne.
OUTCOMES MEASURED: The primary endpoint was the number of papules/pustules per half of the face decreasing by 50% in the 12th medication cycle. Secondary endpoints were the assessment of comedomal acne of the face, acne of the décolleté and back, further signs of adrogenization, such as seborrhea, alopecia, and hirsuitism. Blood levels of androgens, SHBG, cycle stability and incidence of adverse events were also examined.
RESULTS: A total of 59% of patients on EE/CMA compared with 46% on EE/LNG showed a 50% reduction in the number of papules/pustules after 12 treatment cycles (P=.02; number needed to treat=8). The number of women with complete resolution reached 16.5% by cycle 12 in those taking EE/CMA compared with 4.3% by cycle 12 in the EE/LNG group (difference nonsignificant). Similar nonsignificant trends were seen for a reduction in comedonal acne favoring the EE/CMA group. Equal improvements were seen in each group for seborrhea, alopecia, and hirsuitism. There was no difference in the incidence and intensity of break-through bleeding or amenorrhea between the 2 groups. Adverse events were similar between the 2 groups.
OCPs with an anti-androgenic progestin derivative may be slightly more effective than other OCPs in improving mild to moderate acne. However, nearly half of the women in this study treated with either OCP had a significant reduction in their acne after 12 cycles of treatment. The progestin in this phase III trial (chlormadinone) is currently not used in any OCP available in the United States. Other combination pills have been shown in randomized controlled trials to be effective for treating acne.1-3 For now it makes sense to prescribe cheaper OCPs in women with acne and switch to more expensive “designer” brands only in the case of a nonresponse.
Outcomes for New Anti-hypertensives in the Elderly
CLINICAL QUESTION: Is there a difference in efficacy between older and newer antihypertensive medications in preventing cardiovascular morbidity and mortality?
BACKGROUND: It is well known that b-blockers and diuretics decrease cardiovascular morbidity and mortality.1 However, the efficacy of newer classes of antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists, has not been established.
POPULATION STUDIED: Subjects included 6628 hypertensive men and women aged 70 to 84 years from 312 health centers in Sweden. Hypertension was defined as a reading of >179 mm Hg systolic, >104 mm Hg diastolic, or both.
STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Patients were assigned treatment to 1 of 3 categories of medications: conventional antihypertensive drugs, ACE inhibitors, or calcium antagonists. Conventional drugs used were oral atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg, all given once daily. The ACE inhibitors were enalapril 10 mg or lisinopril 10 mg given once daily, and the calcium antagonists were felodipine 2.5 mg or isradipine 2.5 mg given once daily. If the target blood pressure of 160/95 mm Hg had not been reached by 2 months, combination therapy was instituted. Patients on b-blockers or ACE inhibitors were given a diuretic, while those on diuretics or calcium antagonists were given a b-blocker. After the initial dose-titration periods, patients were seen twice each year. At each visit heart rate and blood pressure were measured. Adverse events were evaluated from the patient’s history. Laboratory tests and electrocardiograms were done annually and on an as-needed basis.
OUTCOMES MEASURED: The primary end point was the rate of cardiovascular mortality. Secondary outcomes included the rates of fatal and nonfatal stroke, fatal and nonfatal myocardial infarction, atrial fibrillation, congestive heart failure, diabetes mellitus, and all-cause mortality. Subgroup analysis was performed on people with diabetes.
RESULTS: Most patients in this study had Stage 3 hypertension > 180 mm Hg systolic or 110 mm Hg diastolic). The rates of the primary and secondary end points were similar among the 3 treatment arms. The only difference was fewer fatal and nonfatal myocardial infarctions and less congestive heart failure among patients taking ACE inhibitors than those taking calcium antagonists. Although 46% of patients required more than one drug to control their hypertension, 61% to 66% of the patients in each group were on their original regimen at the end of the trial. Adverse events were common in all 3 groups: 25.5% of patients taking calcium antagonists had ankle edema, 30% on an ACE inhibitor had cough, and 25% to 28% in each group had dizziness.
The risk of cardiovascular morbidity and mortality was similar in all groups of elderly patients taking either conventional hypertensives, ACE inhibitors, or calcium antagonists. It is reassuring that there was no increase in stroke using ACE inhibitors as suggested in the Captopril Prevention Project study.2 Side effects were very common in all groups. Diuretics and b-blockers should still be recommended as first-line treatment on the basis of cost and efficacy. In general, ACE inihibitors are preferred to calcium antagonists because the former are more effective at preventing myocardial infarction and congestive heart failure.
CLINICAL QUESTION: Is there a difference in efficacy between older and newer antihypertensive medications in preventing cardiovascular morbidity and mortality?
BACKGROUND: It is well known that b-blockers and diuretics decrease cardiovascular morbidity and mortality.1 However, the efficacy of newer classes of antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists, has not been established.
POPULATION STUDIED: Subjects included 6628 hypertensive men and women aged 70 to 84 years from 312 health centers in Sweden. Hypertension was defined as a reading of >179 mm Hg systolic, >104 mm Hg diastolic, or both.
STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Patients were assigned treatment to 1 of 3 categories of medications: conventional antihypertensive drugs, ACE inhibitors, or calcium antagonists. Conventional drugs used were oral atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg, all given once daily. The ACE inhibitors were enalapril 10 mg or lisinopril 10 mg given once daily, and the calcium antagonists were felodipine 2.5 mg or isradipine 2.5 mg given once daily. If the target blood pressure of 160/95 mm Hg had not been reached by 2 months, combination therapy was instituted. Patients on b-blockers or ACE inhibitors were given a diuretic, while those on diuretics or calcium antagonists were given a b-blocker. After the initial dose-titration periods, patients were seen twice each year. At each visit heart rate and blood pressure were measured. Adverse events were evaluated from the patient’s history. Laboratory tests and electrocardiograms were done annually and on an as-needed basis.
OUTCOMES MEASURED: The primary end point was the rate of cardiovascular mortality. Secondary outcomes included the rates of fatal and nonfatal stroke, fatal and nonfatal myocardial infarction, atrial fibrillation, congestive heart failure, diabetes mellitus, and all-cause mortality. Subgroup analysis was performed on people with diabetes.
RESULTS: Most patients in this study had Stage 3 hypertension > 180 mm Hg systolic or 110 mm Hg diastolic). The rates of the primary and secondary end points were similar among the 3 treatment arms. The only difference was fewer fatal and nonfatal myocardial infarctions and less congestive heart failure among patients taking ACE inhibitors than those taking calcium antagonists. Although 46% of patients required more than one drug to control their hypertension, 61% to 66% of the patients in each group were on their original regimen at the end of the trial. Adverse events were common in all 3 groups: 25.5% of patients taking calcium antagonists had ankle edema, 30% on an ACE inhibitor had cough, and 25% to 28% in each group had dizziness.
The risk of cardiovascular morbidity and mortality was similar in all groups of elderly patients taking either conventional hypertensives, ACE inhibitors, or calcium antagonists. It is reassuring that there was no increase in stroke using ACE inhibitors as suggested in the Captopril Prevention Project study.2 Side effects were very common in all groups. Diuretics and b-blockers should still be recommended as first-line treatment on the basis of cost and efficacy. In general, ACE inihibitors are preferred to calcium antagonists because the former are more effective at preventing myocardial infarction and congestive heart failure.
CLINICAL QUESTION: Is there a difference in efficacy between older and newer antihypertensive medications in preventing cardiovascular morbidity and mortality?
BACKGROUND: It is well known that b-blockers and diuretics decrease cardiovascular morbidity and mortality.1 However, the efficacy of newer classes of antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists, has not been established.
POPULATION STUDIED: Subjects included 6628 hypertensive men and women aged 70 to 84 years from 312 health centers in Sweden. Hypertension was defined as a reading of >179 mm Hg systolic, >104 mm Hg diastolic, or both.
STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Patients were assigned treatment to 1 of 3 categories of medications: conventional antihypertensive drugs, ACE inhibitors, or calcium antagonists. Conventional drugs used were oral atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg, all given once daily. The ACE inhibitors were enalapril 10 mg or lisinopril 10 mg given once daily, and the calcium antagonists were felodipine 2.5 mg or isradipine 2.5 mg given once daily. If the target blood pressure of 160/95 mm Hg had not been reached by 2 months, combination therapy was instituted. Patients on b-blockers or ACE inhibitors were given a diuretic, while those on diuretics or calcium antagonists were given a b-blocker. After the initial dose-titration periods, patients were seen twice each year. At each visit heart rate and blood pressure were measured. Adverse events were evaluated from the patient’s history. Laboratory tests and electrocardiograms were done annually and on an as-needed basis.
OUTCOMES MEASURED: The primary end point was the rate of cardiovascular mortality. Secondary outcomes included the rates of fatal and nonfatal stroke, fatal and nonfatal myocardial infarction, atrial fibrillation, congestive heart failure, diabetes mellitus, and all-cause mortality. Subgroup analysis was performed on people with diabetes.
RESULTS: Most patients in this study had Stage 3 hypertension > 180 mm Hg systolic or 110 mm Hg diastolic). The rates of the primary and secondary end points were similar among the 3 treatment arms. The only difference was fewer fatal and nonfatal myocardial infarctions and less congestive heart failure among patients taking ACE inhibitors than those taking calcium antagonists. Although 46% of patients required more than one drug to control their hypertension, 61% to 66% of the patients in each group were on their original regimen at the end of the trial. Adverse events were common in all 3 groups: 25.5% of patients taking calcium antagonists had ankle edema, 30% on an ACE inhibitor had cough, and 25% to 28% in each group had dizziness.
The risk of cardiovascular morbidity and mortality was similar in all groups of elderly patients taking either conventional hypertensives, ACE inhibitors, or calcium antagonists. It is reassuring that there was no increase in stroke using ACE inhibitors as suggested in the Captopril Prevention Project study.2 Side effects were very common in all groups. Diuretics and b-blockers should still be recommended as first-line treatment on the basis of cost and efficacy. In general, ACE inihibitors are preferred to calcium antagonists because the former are more effective at preventing myocardial infarction and congestive heart failure.