Biomedical subjects

T Ekbom

Publications and source records attributed to T Ekbom.

At least 19 recordsLinked to original sources

PubMed2000

Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials.

BACKGROUND: Previous meta-analysis of outcome trials in hypertension have not specifically focused on isolated systolic hypertension or they have explained treatment benefit mainly in function of the achieved diastolic blood pressure reduction. We therefore undertook a quantitative overview of the trials to further evaluate the risks associated with systolic blood pressure in treated and untreated older patients with isolated systolic hypertension METHODS: Patients were 60 years old or more. Systolic blood pressure was 160 mm Hg or greater and diastolic blood pressure was less than 95 mm Hg. We used non-parametric methods and Cox regression to model the risks associated with blood pressure and to correct for regression dilution bias. We calculated pooled effects of treatment from stratified 2 x 2 contingency tables after application of Zelen's test of heterogeneity. FINDINGS: In eight trials 15 693 patients with isolated systolic hypertension were followed up for 3.8 years (median). After correction for regression dilution bias, sex, age, and diastolic blood pressure, the relative hazard rates associated with a 10 mm Hg higher initial systolic blood pressure were 1.26 (p=0.0001) for total mortality, 1.22 (p=0.02) for stroke, but only 1.07 (p=0.37) for coronary events. Independent of systolic blood pressure, diastolic blood pressure was inversely correlated with total mortality, highlighting the role of pulse pressure as risk factor. Active treatment reduced total mortality by 13% (95% CI 2-22, p=0.02), cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%. The number of patients to treat for 5 years to prevent one major cardiovascular event was lower in men (18 vs 38), at or above age 70 (19 vs 39), and in patients with previous cardiovascular complications (16 vs 37). INTERPRETATION: Drug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mm Hg or higher. Absolute benefit is larger in men, in patients aged 70 or more and in those with previous cardiovascular complications or wider pulse pressure. Treatment prevented stroke more effectively than coronary events. However, the absence of a relation between coronary events and systolic blood pressure in untreated patients suggests that the coronary protection may have been underestimated.

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PubMed2000

Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension-2. STOP Hypertension-2 Study Group.

BACKGROUND: The benefits of treating hypertension in elderly diabetic patients, in terms of achieving reductions in cardiovascular morbidity and mortality, have been documented in several recent prospective trials. There has, however, been some controversy regarding the effect of different antihypertensive drugs on the frequency of myocardial infarction in this group of patients. DESIGN: STOP Hypertension-2 was a prospective, randomized, open trial with blinded endpoint evaluation. METHODS: We studied 6614 elderly patients aged 70-84 years; 719 of them had diabetes mellitus at the start of the study (mean age 75.8 years). Patients were randomly assigned to one of three treatment strategies: conventional antihypertensive drugs (diuretics or beta-blockers), calcium antagonists, or angiotensin converting enzyme (ACE) inhibitors. RESULTS: Reduction in blood pressure was similar in the three treatment groups of diabetics. The prevention of cardiovascular mortality was also similar; the frequency of this primary endpoint did not differ significantly between the three groups. There were, however, significantly fewer (P = 0.025) myocardial infarctions during ACE inhibitor treatment (n = 17) than during calcium antagonist treatment (n = 32; relative risk 0.51, 95% confidence interval 0.28-0.92); but a (non-significant) tendency to more strokes during ACE inhibitor treatment (n = 34 compared with n = 29; relative risk 1.16, 95% confidence interval 0.71-1.91). CONCLUSION: Treatment of hypertensive diabetic patients with conventional antihypertensive drugs (diuretics, beta-blockers, or both) seemed to be as effective as treatment with newer drugs such as calcium antagonists or ACE inhibitors.

Adrenergic beta-Antagonists↗

PubMed2000

Efficacy of diuretics and beta-blockers in diabetic hypertensive patients. Results from a meta-analysis. The INDANA Steering Committee.

OBJECTIVE: To review the effectiveness of diuretic or beta-blocker-based treatment of hypertension in diabetic patients. RESEARCH DESIGN AND METHODS: A meta-analysis on individual patient data was performed on four trials of the treatment of hypertension in which diabetic patients were included and treated with first-line diuretics or beta-blockers. The main outcomes were the relative risk of death, fatal or nonfatal stroke, fatal or nonfatal coronary events, and major cardiovascular events. RESULTS: There were 92 diabetic patients who received first-line beta-blockers and 1,008 who received diuretics. In the control groups, diabetic patients had nearly twice the risk of any outcome when compared with nondiabetic patients. The same blood pressure reduction was achieved under treatment in the diabetic and nondiabetic patients, except for systolic pressure, which decreased more in the nondiabetic patients at 1 year. In the 15,843 nondiabetic patients, the risk of all four outcomes was reduced significantly in the treated group. In the 2,254 diabetic patients, the risk reduction was significant only for fatal and nonfatal stroke (36%, P = 0.011) and major cardiovascular events (20%, P = 0.032), but not for death (5%, P = 0.65) and fatal or nonfatal coronary events (15%, P = 0.23). However, no heterogeneity was detected between diabetic patients and nondiabetic patients for any outcome. The numbers of outcomes avoided for 1,000 patients treated for 5 years were higher in diabetic patients (e.g., 38 major cardiovascular events) than with nondiabetic patients (e.g., 28 major cardiovascular events). CONCLUSIONS: These results show that hypertensive diabetic patients benefit from first-line treatment with diuretics. No conclusion can be drawn for beta-blockers, owing to the small sample size.

Adrenergic beta-Antagonists↗

PubMed1999

Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study.

BACKGROUND: The efficacy of new antihypertensive drugs has been questioned. We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients. METHODS: We did a prospective, randomised trial in 6614 patients aged 70-84 years with hypertension (blood pressure > or = 180 mm Hg systolic, > or = 105 mm Hg diastolic, or both). Patients were randomly assigned conventional antihypertensive drugs (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily) or newer drugs (enalapril 10 mg or lisinopril 10 mg, or felodipine 2.5 mg or isradipine 2-5 mg daily). We assessed fatal stroke, fatal myocardial infarction, and other fatal cardiovascular disease. Analysis was by intention to treat. FINDINGS: Blood pressure was decreased similarly in all treatment groups. The primary combined endpoint of fatal stroke, fatal myocardial infarction, and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group (19.8 events per 1000 patient-years) and in 438 of 4401 in the newer drugs group (19.8 per 1000; relative risk 0.99 [95% CI 0.84-1.16], p=0.89). The combined endpoint of fatal and non-fatal stroke, fatal and non-fatal myocardial infarction, and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs (0.96 [0.86-1.08], p=0.49). INTERPRETATION: Old and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events. Decrease in blood pressure was of major importance for the prevention of cardiovascular events.

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PubMed1999

Identification of risk factors in hypertensive patients: contribution of randomized controlled trials through an individual patient database.

BACKGROUND: Predicting individual risk is needed to target preventive interventions toward people with the highest probability of benefit over a given time period. We assessed which prognostic factors should be used in predicting risk for hypertensive patients and in searching for treatment modifiers. METHODS AND RESULTS: Data from 24 390 hypertensive participants who constituted the control groups from 8 controlled trials (1726 deaths over 5 years) were analyzed in multivariate survival models. Outcomes were coronary heart disease death, stroke death, and cardiovascular death. We explored systematically the heterogeneity of results between trials. Left ventricular hypertrophy was electrocardiographically confirmed to be a powerful risk factor and should be included in risk scoring. Height, glomerular filtration rate, and serum uric acid deserve further exploration. Body mass index and heart rate were not confirmed as independent cardiovascular risk factors in this population. The association between male sex and coronary heart disease death was significantly stronger in British cohorts. The lack of prognostic value of diastolic blood pressure was explained by an interaction with age, with a positive association before 65 years and a negative association thereafter. Previous antihypertensive treatment was a significant risk factor. CONCLUSIONS: Clinical trials provide valuable information for risk prediction. Carefully exploring the heterogeneity among trials is a way to assess the generalizability of findings. This approach, if systematically performed, should increase the ability to identify risk modifiers and to predict individual therapeutic benefit.

Age Factors↗

PubMed1999

Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group.

BACKGROUND: Beneficial clinical effects of treatment with antihypertensive drugs have been shown in middle-aged patients and in those hypertensive patients over 60 years old, but whether treatment is beneficial in patients over 80 years old is not known. METHODS: We collected data from all participants aged 80 years and over in randomised controlled trials of antihypertensive drugs through direct contact with study investigators. Our primary outcome was fatal and non-fatal stroke. Secondary outcomes were death from all causes, cardiovascular death, fatal and non-fatal major coronary and cardiovascular events, and heart failure. FINDINGS: There were 57 strokes and 34 deaths among 874 actively treated patients, compared with 77 strokes and 28 stroke deaths among 796 controls, representing 1 non-fatal stroke prevented for about 100 patients treated each year. The meta-analysis of data from 1670 participants aged 80 years or older suggested that treatment prevented 34% (95% CI 8-52) of strokes. Rates of major cardiovascular events and heart failure were significantly decreased, by 22% and 39%, respectively. However, there was no treatment benefit for cardiovascular death, and a non-significant 6% (-5 to 18) relative excess of death from all causes. INTERPRETATIONS: The inconclusive findings for mortality contrast with the benefit of treatment for non-fatal events. Results of a large-scale specific trial are needed for definite conclusion that antihypertensive treatment is beneficial in very elderly hypertensive patients. Meanwhile, an age threshold beyond which hypertension should not be treated cannot be justified.

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PubMed1997

Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men. A meta-analysis of individual patient data from randomized, controlled trials. The INDANA Investigators.

BACKGROUND: Trials of drug therapy for hypertension have shown that such therapy has a clear overall benefit in preventing cardiovascular disease. Although these trials have included slightly more women than men, it is still not clear whether treatment benefit is similar for both sexes. OBJECTIVE: To quantify the average treatment effect in both sexes and to determine whether available data show significant differences in treatment effect between women and men. DESIGN: Subgroup meta-analysis of individual patient data according to sex. Analysis was based on seven trials from the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) database and was adjusted for possible confounders. PATIENTS: 20,802 women and 19,975 men recruited between 1972 and 1990. INTERVENTIONS: Primarily beta-blockers and thiazide diuretics. RESULTS: In women, treatment effect was statistically significant for stroke (fatal strokes and all strokes) and for major cardiovascular events. In men, it was statistically significant for all categories of events (total and specific mortality, all coronary events, all strokes, and major cardiovascular events). The odds ratios for any category of event did not differ significantly between men and women. In absolute terms, the benefit in women was seen primarily for strokes; in men, treatment prevented as many coronary events as strokes. Graphical analyses suggest that these results could be completely explained by the difference in untreated risk. CONCLUSIONS: In terms of relative risk, treatment benefit did not differ between women and men. The absolute risk reduction attributable to treatment seemed to depend on untreated risk. These findings underline the need to predict accurately the untreated cardiovascular risk of an individual person in order to rationalize and individualize antihypertensive treatment.

Adrenergic beta-Antagonists↗

PubMed1997

Effect of antihypertensive treatment in patients having already suffered from stroke. Gathering the evidence. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators.

BACKGROUND AND PURPOSE: Drug treatment of high blood pressure has been shown to reduce the associated cardiovascular risk. Stroke represents the type of event more strongly linked with high blood pressure, responsible for a high rate of death or invalidity, and with the highest proportion of events that can be avoided by treatment. Hypertensive patients with a history of cerebrovascular accident are at particularly high risk of recurrence. Specific trials of blood pressure lowering drugs in stroke survivors showed inconclusive results in the past. METHODS: We performed a meta-analysis using all available randomized controlled clinical trials assessing the effect of blood pressure lowering drugs on clinical outcomes (recurrence of stroke, coronary events, cause-specific, and overall mortality) in patients with prior stroke or transient ischemic attack. RESULTS: We identified 9 trials, including a total of 6752 patients: 2 trials included 551 hypertensive stroke survivors; 6 trials of hypertensive patients included a small proportion of stroke survivors (536 patients); 1 trial included stroke survivors, whether hypertensive or not (5665 patients). The recurrence of stroke, fatal and nonfatal, was significantly reduced in active groups compared with control groups consistently across the different sources of data (relative risk of 0.72, 95% confidence interval: 0.61 to 0.85). There was no evidence that this intervention induced serious adverse effect. CONCLUSIONS: Blood pressure lowering drug interventions reduced the risk of stroke recurrence in stroke survivors. Available data did not allow to verify whether such benefit depends on initial blood pressure level. More data are needed before considering antihypertensive therapy in normotensive patients at high cerebrovascular risk.

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PubMed1996

Changes in cardiovascular risk factors by combined pharmacological and nonpharmacological strategies: the main results of the CELL Study.

OBJECTIVE: The objectives of the Cost Effectiveness of Lipid Lowering (CELL) study were twofold: (i) to evaluate the effect on overall cardiovascular risk of two types of health care advice ("usual' and "intensive') given in primary care, with or without pharmacological medication, with the target being to attain a moderate decrease in cholesterol; (ii) to evaluate the ritual of daily medication on compliance with the health care advice. DESIGN: A prospective, double-blind, randomized, controlled trial of 18 months' duration. SETTING: The study was carried out in 32 health centres (out of a total of approximately 850) in Sweden. SUBJECTS: In all, 681 subjects, aged 30-59 years, were randomized. They had at least two cardiovascular risk factors in addition to moderate primary hyperlipidaemia (total cholesterol of at least 6.50 mmol L-1 on three occasions measured by Reflotron triglycerides less than 4.0 mmol L-1 and an LDL:HDL cholesterol ratio of more than 4.0). Most (87%) of the subjects were males; 626 subjects (92%) completed the 18-month follow-up. INTERVENTION: Half the subjects were randomized to 'intensive advice' given in group sessions led by doctors and nurses in primary care. The other half received 'usual advice'. In each of the two advice groups, one-third received an active lipid-lowering drug (pravastatin), one-third placebo, and one-third no drug at all. The tablets were titrated to achieve a 15% reduction in cholesterol. MAIN OUTCOME MEASURES: Changes in the overall Framingham risk score, and the development of adverse events in each group. RESULTS: The change in Framingham risk score was significantly reduced only in subjects taking lipid-lowering medication (together with intensive advice -0.13; 95% CI-0.20, -0.06, and together with usual advice -0.16; 95% CI -0.23, -0.09). The other subjects receiving intensive advice tended to fare better than those on usual advice. Lifestyle was not influenced significantly over the study period. The ritual of daily medication did not affect the outcome. CONCLUSION: As expected, lipid-lowering medication reduced serum cholesterol as well as overall cardiovascular risk in subjects with several risk factors for cardiovascular disease. There was no additive effect of intensive advice to these subjects. However, there was a meagre but significant effect of intensive advice in subjects not receiving active lipid-lowering drugs. One explanation for this difference may be that those on active lipid-lowering medication who had substantial drops in cholesterol might have felt less inclined to change their lifestyle compared with those on other treatment regimens who had less successful drops in cholesterol. There was no benefit from the ritual of taking daily medication.

Adult↗

PubMed1996

Decrease in high density lipoprotein cholesterol during prolonged storage. CELL Study Group.

Different studies on the stability of high density lipoprotein cholesterol (HDL) in frozen serum or plasma have yielded conflicting results, namely increase, decrease, or no change at all during prolonged storage under freezing conditions. As part of a major trial on lipid-lowering strategies we statistically demonstrated a time-related decrease in HDL cholesterol during storage up to 46 months at -20 degrees C. We therefore re-analysed 85 frozen samples that had been analysed fresh and then stored from 26 to 46 months, using the dextran sulphate 500/Mg2+ method. A linear regression analysis of change in HDL cholesterol on time was performed. The slope was significantly negative (p < 0.0005). The regression equation was (decrease in HDL) = 0.05 - 0.008 x (time in months), i.e. after 6 months' storage at -20 degrees C there was almost a 1% decrease in the HDL cholesterol concentration per month of storage.

Cholesterol, HDL↗

PubMed1996

The Swedish Trial in old patients with hypertension-2 (STOP-hypertension-2): a progress report.

OBJECTIVE: The Swedish Trial in Old Patients with Hypertension-2 (STOP-Hypertension-2) was designed by a project group of the Swedish Hypertension Society to test whether the "newer" treatment alternatives (ACE inhibitors and calcium antagonists) are as good as, better or less good than, the "older" ones (beta-blockers and diuretics) in terms of preventing cardiovascular morbidity and mortality in elderly hypertensives. The aim of the present paper is to report on the progress of the study. DESIGN: Prospective, open trial with blinded end-point committee and centralized randomization (PROBE design). STOP-Hypertension-2 may be regarded as a scientific follow-up of the previously published Swedish Trial in Old Patients with Hypertension (STOP-Hypertensioon-1) (6) using the same study organization. SUBJECTS: By the end of 1994 when recruitment was stopped, 6628 hypertensive men (34%) and women (66%) aged 70-84 (mean age 76) had been included at 312 Swedish health centres (out of approximately 850). In the whole cohort 11% are diabetics and 9% smokers. The mean total cholesterol value is 6.5 mmol/L. RESULTS: In the whole study cohort, blood pressure was lowered from 194/98 mmHg to 167/85 mmHg after one year. At the end of 1995, 319 fatal events (all-cause mortality) had been reported, corresponding to a mortality rate of 21.3 per 1000 person-years. CONCLUSION: In STOP-Hypertension-2, 6628 elderly hypertensive have been randomized to three different treatment regimes: beta-blocker+diuretics (the active treatment arm in STOP-Hypertension-1), ACE inhibitors, or calcium antagonists. Their average lowering of blood pressure was 27/13 mmHg and end-points have occurred at the expected rate. Thus, it should be possible to terminate STOP-Hypertension-2 within two to three years.

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PubMed1995

The impact of health care advice given in primary care on cardiovascular risk. CELL Study Group.

OBJECTIVE: To evaluate the additional benefit of "intensive" health care advice through six group sessions, compared with the advice usually offered to subjects with multiple risk factors for cardiovascular disease. DESIGN: Prospective, randomised controlled clinical study lasting 18 months. SETTING: 681 subjects aged 30-59 years, with at least two cardiovascular risk factors in addition to moderately high lipid concentrations: total cholesterol > or = 6.5 mmol/l on three occasions, triglycerides < 4.0 mmol/l, and ratio of low density lipoprotein cholesterol to high density lipoprotein cholesterol > 4.0. Most (577) of the subjects were men. MAIN OUTCOME MEASURE: Percentage reduction in total cholesterol concentration (target 15%); quantification of the differences between the two types of health care advice (intensive v usual) for the Framingham cardiovascular risk and for individual risk factors. RESULTS: In the group receiving intensive health care advice total cholesterol concentration decreased by 0.15 mmol/l more (95% confidence interval 0.04 to 0.26) than in the group receiving usual advice. The overall Framingham risk dropped by 0.068 more (0.014 to 0.095) in the group receiving intensive advice, and most of the risk factors showed a greater change in a favourable direction in this group than in the group receiving usual advice, but the differences were seldom significant. The results from questionnaires completed at the group sessions showed that the subjects improved their lifestyle and diet. CONCLUSION: Limited additional benefit was gained from being in the group receiving the intensive health care advice. It is difficult to make an important impact on cardiovascular risk in primary care by using only the practice staff. Better methods of communicating the messages need to be devised.

Adult↗

PubMed1994

A 5-year prospective, observational study of the withdrawal of antihypertensive treatment in elderly people.

OBJECTIVES: To observe blood pressure, cardiovascular events, and total mortality after withdrawing antihypertensive treatment for elderly patients. DESIGN: Multicentre observational study. SETTING: Sweden. A 5-year follow-up of 333 elderly hypertensive patients, aged 70-84 years (mean age 75.2 +/- SD 3.8 years, 68% females). In all, 74 out of the 333 patients (22%) died during the study period. METHOD: After withdrawal of the antihypertensive therapy, all patients started in the untreated state and during the 5-year follow-up they could then either remain in the untreated state, or be reverted to blood-pressure-lowering drug treatment because of hypertension or other diseases, e.g. angina pectoris, oedema, congestive heart failure, etc. RESULTS: The probability of remaining without treatment for 5 years was estimated to be 20%. During the state of no treatment the patients had a lower total mortality risk than that of the general Swedish population, matched for age and sex. They also had a lower risk of cardiovascular events than those in the treated states. Markers indicating a successful withdrawal were monotherapy in low doses and relatively low blood pressure before withdrawal. CONCLUSION: These results suggest that with frequent check-ups, withdrawal of antihypertensive therapy in the elderly can be tried without increased risk of cardiovascular events.

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PubMed1993

The cost-effectiveness of treating hypertension in elderly people--an analysis of the Swedish Trial in Old Patients with Hypertension (STOP Hypertension).

OBJECTIVES: The aim of this study was to estimate the cost-effectiveness of antihypertensive treatment in elderly people based on the results of the Swedish Trial in Old Patients with Hypertension (STOP Hypertension). DESIGN: The STOP Hypertension study was a randomized trial comparing active antihypertensive treatment with a placebo. The risk of stroke, cardiovascular disease and total mortality was significantly reduced in the actively treated group compared to placebo. SETTING: One hundred and sixteen primary health care centres in Sweden. SUBJECTS: A total of 1627 hypertensive patients aged 70-84. No patient was lost to follow-up. INTERVENTIONS: Antihypertensive treatment with beta blockers and diuretics for a mean follow-up of 25 months. MAIN OUTCOME MEASURE: The cost-effectiveness ratio estimated as the net cost (the treatment cost minus saved costs of reduced cardiovascular morbidity) divided by the number of life-years gained (the increase in life expectancy from treatment). RESULTS: The cost per life-year gained was estimated as SEK 5000 for men and SEK 15,000 for women ($1 = SEK 6; 1 pound = SEK 10). The cost per life-year gained did not exceed SEK 100,000 in any of the sensitivity analyses. CONCLUSIONS: It is concluded that treatment of elderly hypertensive patients with beta blockers and/or diuretics is cost-effective according to the results of the STOP Hypertension study.

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PubMed1993

The cost of screening for hypercholesterolaemia--results from a clinical trial in Swedish primary health care.

The cost of screening for hypercholesterolaemia in a clinical trial was investigated at a primary health care centre. A convenience sample of the population was screened for inclusion in a study of the effectiveness of a lipid lowering programme. Included in the study were adults 30-59 years of age with a S-Cholesterol of 6.50-7.79 mmol l-1 at randomization, plus two previous values > or = 6.50 mmol l-1 at screening and selection, with at least two other cardiovascular risk factors. In total 447 persons were screened and 37 were randomized into the lipid lowering programme. The mean cost per randomized person was estimated at about SEK 7500 (Swedish Crowns). An analysis of different inclusion criteria for treatment was also carried out. The cost of finding a patient to treat in the clinical trial was estimated to be more than three times as high with a total cholesterol cut-off point of 7.80 mmol l-1 compared with a cut-off point of 5.20 mmol l-1.

Adult↗

PubMed1993

STOP-Hypertension 2: a prospective intervention trial of "newer" versus "older" treatment alternatives in old patients with hypertension. Swedish Trial in Old Patients with Hypertension.

It is well established that hypertensive patients benefit from drug treatment of their disorder. In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits, i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity. In all these studies beta-blockers and/or diuretics were used in comparison with placebo. Newer therapeutic alternatives have, however, at least theoretically, many advantages which could result in further improvements in prognosis. The initial Swedish Trial in Old Patients with Hypertension (STOP-Hypertension 1) was conducted in men and women aged 70-84 years. STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors (enalapril and lisinopril) or on calcium antagonists (isradipine and felodipine), using the PROBE design (Prospective, Randomised, Open, Blinded Endpoint evaluation). The primary aim will be to assess the effect on cardiovascular mortality. Statistical calculations indicate that 6,600 patients, followed for four years will be needed (2p < 0.05, power 90%) to obtain significance if there is a 25% difference between the new and the established therapy. Patients in primary health care (300 centres) will be included if their supine blood pressure is > or = 180/105 mmHg (and/or). Recruitment of patients started in September 1992 and so far more than 100 patients/week have been included.

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PubMed1993

Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) analyses performed up to 1992.

Hypertension is increasingly common with advancing age and a risk factor for all kinds of cardiovascular complications. Moreover, cardiovascular disease is a major cause of morbidity and mortality in the elderly. The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was set up by the Swedish Hypertension Society to investigate the value of antihypertensive treatment in the elderly. In this placebo controlled randomised prospective study 1,627 men and women aged 70-84 years with a supine blood pressure > or = 180/105 mmHg (and/or) but not isolated systolic hypertension participated. Three beta-blockers and one diuretic were used as blood pressure lowering agents and the average follow-up in the study was 25 months (3,390 patient-years). Administration of active antihypertensive therapy, reduced supine blood pressure from 195/102 mmHg to 167/87 mmHg at longest follow-up in comparison with placebo. A majority of the patients needed combined treatment to reach the goal blood pressure (160/95 mmHg). Associated with a fall in blood pressure were significant reductions in all cardiovascular primary endpoints (-40%, p = 0.0031), in fatal and non-fatal stroke (-47%, p = 0.0081) and in total mortality (-43%, p = 0.0079). In addition to the substantial effects on primary endpoints active treatment also showed clinically relevant effects on secondary endpoints (e.g. heart failure). The impact on cardiovascular morbidity and mortality with antihypertensive treatment in this elderly cohort was greater than previously seen in middle-aged hypertensive patients, with maintained tolerability and a favourable cost-effectiveness ratio. Finally, women benefited from treatment at least as much as men.

Adrenergic beta-Antagonists↗

PubMed1993

Hypertension in the elderly.

Several studies have demonstrated an increased risk of cardiovascular disease (CVD) in relation to high blood pressure in elderly patients aged below 70-75, whereas the risk seemed to decline with age in the older elderly. Early studies on the effect of treatment of mild to moderate hypertension in the elderly indicated (but did not convincingly show) a reduction of CVD. In the 1980s, both the EWPHE trial (European Working Party on High Blood Pressure in the Elderly) and the HEP study (The Randomised Trial of the Treatment of Hypertension in Elderly Patients in Primary Care) provided evidence of the benefit of treating high blood pressure in the elderly, at least up to the age of 70-74. These results have lately been confirmed by three major trials SHEP (Systolic Hypertension in the Elderly Program), STOP (Swedish Trial in Old Patients with Hypertension) and MRC (Medical Research Council), also including older patients (STOP) and those with isolated systolic hypertension (SHEP). This satisfactory effect was not impaired by a low tolerability of the drugs used (beta-blockers and diuretics). In conclusion, drug treatment with beta-blockers and diuretics in hypertensive men and women aged 70 and above confers highly significant and clinically relevant reductions in cardiovascular (especially stroke) morbidity and mortality. The clinical implication of this is that blood pressure lowering therapy should be considered in elderly hypertensives, at least up until they are 80. It should also be remembered that elderly hypertensives often have other diseases as well and that the drug treatment should be adjusted accordingly.

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