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Antihypertensive drug therapies and the risk of ischemic stroke
ing or long-acting calcium antagonists or other antihypertensive drugs and were followed for at least 2 years. Results: The nine trials reviewed included 27,743 subjects. All therapies achieved comparable systolic and diastolic pressure control. Compared to patients assigned to diuretics, beta-blockers, ACE inhibitors (ACEi) or clonidine (total of 15,044), those assigned to calcium antagonists (12,699) had a significantly higher risk of acute myocardial infarction (hazard ratio [HR] ⫽ 1.26) and congestive heart failure (HR ⫽ 1.25) but no difference in risk of stroke or all-cause mortality. Conclusions: A summary of randomised trials in hypertension suggests calcium antagonists are inferior to other antihypertensive therapies for reducing cardiovascular risk. On the basis of these data, the longer acting calcium antagonists cannot be recommended as first-line therapy for hypertension. Perspective: Until the results of ALLHAT (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) are available, it would be prudent to follow the JCN-VI guidelines: calcium channel blockers and alpha receptor blocking drugs (based on the results of doxazosin in ALLHAT) should be reserved primarily for those patients unable to take or perhaps are refractory to diuretics, betablockers and ACEi. There is increasing evidence that nonblood pressure effects of the antihypertensive drugs (i.e., ACEi) may have a significant impact on outcome in hypertension and CHD. MR
duration of treatment, number of antihypertensive drugs, and percentage with diabetes (31 vs. 11%) and CVD (60 vs. 38%). Among those without CVD, compared to those regimens that used a thiazide, the relative risk of an ischemic stroke was 2.4 in single drug and 1.4 in two-drug regimens, an 85% increase overall. The association persisted after adjustment for confounding factors including age and blood pressure and clinical subsets but was less pronounced in those with CVD. Conclusions: Antihypertensive drug regimens that did not include a thiazide diuretic were associated with an increased risk of ischemic stroke compared to regimens that did include a thiazide. These results support the use of thiazide diuretics as first-line antihypertensive agents, particularly in the elderly. Perspective: The findings from randomized controlled trials (RCT) of antihypertensive agents are not uniform, but several are in agreement with this case-controlled study. It is heartening that in older non-CVD patients, the cheapest antihypertensive drug for preventing strokes may also be the best. Because the benefit of each agent in the prevention of coronary events and cardiovascular and total mortality in men and women of all ages cannot be gleaned from this study, the results should be used with some caution. MR
Effects of ACE Inhibitors, Calcium Antagonists, and Other Blood Pressure Lowering Drugs: Results of Prospectively Designed Overviews of Randomised Trials
Antihypertensive Drug Therapies and the Risk of Ischemic Stroke
Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000;355:1955– 64.
Klungel OH, Heckbert SR, Longstreth WT, et al. Arch Int Med 2001;161:37-43.
Study Question: To determine whether the choice of antihypertensive drug or intensity of blood pressure lowering strategy influences the risk of subsequent cardiovascular events in hypertension and coronary disease (CHD). Methods: A combined analysis of major trials using antihypertensive agents, regardless of indication for the trial, was performed by a consortium of major hypertension trialists. Dominant drug classes were ACE inhibitors (ACEi), calcium channel blockers (CCBs), beta-blockers (BBs) and diuretics. Specified outcomes were stroke (CVA), myocardial infarction (MI), heart failure (CHF), all cardiovascular events (CVE), deaths from any CVE and total mortality. Results: Outcome data were available from 15 studies that included 74,696 subjects with an average age of 62 years, and 53% were male. Five placebo-controlled trials (ACEi and CCBs) were conducted in non-hypertension (e.g., HOPE and PREVENT), three trials examined intensity of pressure lowering (e.g., HOT and ABCD) and the remaining compared two or more antihypertensive agents. In both CAD and hypertension trials, ACEi reduced rates of stroke, MI, CHF, CVE, CV and total deaths. When compared to
Study Question: There is accumulating evidence that when treating hypertension, drug class may influence event rates independent of blood pressure targets. This study sought to determine the association between stroke and use of antihypertensive drugs. Methods: This population case-controlled study used data from a staff model HMO in Western Washington to compare antihypertensive therapies pre stroke in 380 patients hospitalized with a first ischemic stroke with 2790 controls. Two hundred and thirty-one cases and 715 controls had been excluded because of congestive heart failure, drug non-compliance or drug inconsistency. Among the covariables assessed were smoking, medical history, history of cardiovascular disease (CVD) and individual combinations of antihypertensive drug classes, including diuretics (thiazide and non-thiazide), beta-blockers, angiotensin converting enzyme inhibitors and calcium-channel blockers. Results: Compared to the controls, the patients were older (70 vs. 66 years), more were women (54% vs. 33%) and systolic pressure was higher, as was sedentary life style,
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duration of treatment, number of antihypertensive drugs, and percentage with diabetes (31 vs. 11%) and CVD (60 vs. 38%). Among those without CVD, compared to those regimens that used a thiazide, the relative risk of an ischemic stroke was 2.4 in single drug and 1.4 in two-drug regimens, an 85% increase overall. The association persisted after adjustment for confounding factors including age and blood pressure and clinical subsets but was less pronounced in those with CVD. Conclusions: Antihypertensive drug regimens that did not include a thiazide diuretic were associated with an increased risk of ischemic stroke compared to regimens that did include a thiazide. These results support the use of thiazide diuretics as first-line antihypertensive agents, particularly in the elderly. Perspective: The findings from randomized controlled trials (RCT) of antihypertensive agents are not uniform, but several are in agreement with this case-controlled study. It is heartening that in older non-CVD patients, the cheapest antihypertensive drug for preventing strokes may also be the best. Because the benefit of each agent in the prevention of coronary events and cardiovascular and total mortality in men and women of all ages cannot be gleaned from this study, the results should be used with some caution. MR
Effects of ACE Inhibitors, Calcium Antagonists, and Other Blood Pressure Lowering Drugs: Results of Prospectively Designed Overviews of Randomised Trials
Antihypertensive Drug Therapies and the Risk of Ischemic Stroke
Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000;355:1955– 64.
Klungel OH, Heckbert SR, Longstreth WT, et al. Arch Int Med 2001;161:37-43.
Study Question: To determine whether the choice of antihypertensive drug or intensity of blood pressure lowering strategy influences the risk of subsequent cardiovascular events in hypertension and coronary disease (CHD). Methods: A combined analysis of major trials using antihypertensive agents, regardless of indication for the trial, was performed by a consortium of major hypertension trialists. Dominant drug classes were ACE inhibitors (ACEi), calcium channel blockers (CCBs), beta-blockers (BBs) and diuretics. Specified outcomes were stroke (CVA), myocardial infarction (MI), heart failure (CHF), all cardiovascular events (CVE), deaths from any CVE and total mortality. Results: Outcome data were available from 15 studies that included 74,696 subjects with an average age of 62 years, and 53% were male. Five placebo-controlled trials (ACEi and CCBs) were conducted in non-hypertension (e.g., HOPE and PREVENT), three trials examined intensity of pressure lowering (e.g., HOT and ABCD) and the remaining compared two or more antihypertensive agents. In both CAD and hypertension trials, ACEi reduced rates of stroke, MI, CHF, CVE, CV and total deaths. When compared to
Study Question: There is accumulating evidence that when treating hypertension, drug class may influence event rates independent of blood pressure targets. This study sought to determine the association between stroke and use of antihypertensive drugs. Methods: This population case-controlled study used data from a staff model HMO in Western Washington to compare antihypertensive therapies pre stroke in 380 patients hospitalized with a first ischemic stroke with 2790 controls. Two hundred and thirty-one cases and 715 controls had been excluded because of congestive heart failure, drug non-compliance or drug inconsistency. Among the covariables assessed were smoking, medical history, history of cardiovascular disease (CVD) and individual combinations of antihypertensive drug classes, including diuretics (thiazide and non-thiazide), beta-blockers, angiotensin converting enzyme inhibitors and calcium-channel blockers. Results: Compared to the controls, the patients were older (70 vs. 66 years), more were women (54% vs. 33%) and systolic pressure was higher, as was sedentary life style,
ACC CURRENT JOURNAL REVIEW May/Jun 2001
28