Tord Ekbom

Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension–2

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 β-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, β-blockers, or both) seemed to be as effective as treatment with newer drugs such as calcium antagonists or ACE inhibitors.

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.

The impact of health care advice given in primary care on cardiovascular risk

Abstract 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 >/=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. Key messages Key messages This multicentre study examined the effects of “usual” or “intensive” health care advice on 681 subjects aged 30-59 years with a moderately high cholesterol concentration and two or more other cardiovascular risk factors The intensive advice programme was based mainly on group sessions led by doctors and nurses from health centres The study found that after 18 months of intervention limited additional benefit was derived from the intensive health care advice Messages and the means of delivering them to individuals in need should be customised for each person

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

Abstract. 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).

Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP-Hypertension-2.

Objective: To perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension. Design and methods: The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs (diuretics, beta‐blockers) with that of newer ones [angiotensin‐converting enzyme (ACE) inhibitors, calcium antagonists]. In all, 6614 elderly patients with hypertension (mean age 76.0 years, range 70–84 years at baseline) were included in STOP‐Hypertension‐2. In the present subgroup analysis of STOP‐Hypertension‐2, isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg, in accordance with the Syst‐Eur and Syst‐China study criteria. In total, 2280 patients in STOP‐Hypertension‐2 met these criteria. In the study, patients were randomized to one of three treatment groups: “conventional” antihypertensive therapy with beta‐blockers or diuretics (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily); ACE inhibitors (enalapril 10 mg or lisinopril 10 mg daily); or calcium antagonists (felodipine 2.5 mg or isradipine 2.5 mg daily). Analysis was by intention to treat. Results: The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens: 35/13 mmHg in the conventional group (n = 717), 34/12 mmHg in the ACE inhibitor group (n = 724), and 35/13 mmHg in the calcium antagonist group (n = 708). Prevention of cardiovascular mortality, the primary endpoint of the study, did not differ between the three treatment groups. All stroke events, i.e. fatal and non‐fatal stroke together, were significantly reduced by 25% in the newer‐drugs group compared with the conventional group (95% CI 0.58–0.97; p = 0.027). This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups. New cases of atrial fibrillation were significantly increased by 43% (95% CI 1.02–1.99; p = 0.037) on “newer” drugs compared with “conventional” therapy, mainly attributable to the calcium antagonists. There were no significant differences between the three treatment groups with respect to the risks of myocardial infarction, sudden death or congestive heart failure. Conclusions: The analysis demonstrated that “newer” therapy (ACE inhibitors/calcium antagonists) was significantly better (25%) than “conventional” (diuretics/beta‐blockers) in preventing all stroke in elderly patients with isolated systolic hypertension.

Incidence of femoral and tibial shaft fractures. Epidemiology 1950-1983 in Malmö, Sweden.

We studied 362 fractures of the femur that had occurred during the years 1950-57 and 1973-83, and 849 fractures of the tibia that occurred during the the years 1950-55 and 1980-83. There was an increase in age-specific incidence over aged 60 years. The risk of low-energy femoral shaft fractures also had increased in elderly women. Both fracture types shifted their age- and sex-specific incidence in the direction of a fragility pattern. There was no increase in the incidence of tibial shaft fractures. Fracture type, site, and degree of displacement of the tibial fractures remained unchanged during the 30 years, i.e, they were predominantly distal, longitudinal fractures with moderate displacement.

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

Abstract. Objectives. To observe blood pressure, cardiovascular events, and total mortality after withdrawing antihypertensive treatment for elderly patients.

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.

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.

The Stroke Preventive Effect in Elderly Hypertensives Cannot Fully be Explained by the Reduction in Office Blood Pressure–Insights from the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension)

OBJECTIVE To study whether the cardiovascular preventive effect of antihypertensive therapy can be explained solely by the reduction in office blood pressure, and to what extent the risk of stroke and cardiac events is associated with in-study diastolic blood pressure (DBP) and systolic blood pressure (SBP). DESIGN The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. The study group comprised 1,627 elderly patients (mean blood pressure 195/102 mm Hg; mean age 75.7, SD 3.7; 63% females). The average follow-up was 25 months (range 6-65 months). No patient was lost to follow-up. METHOD We applied a Poisson model taking current age, sex, treatment, DBP and SBP into account for all patients in the study. The constants of the model were estimated by the maximum likelihood method. RESULTS The risk of stroke was significantly lower (42%, p = 0.0402) for a patient on active therapy than for a patient on placebo having the same blood pressure level, age, and sex. There was a corresponding, non-significant, reduction in cardiac events of 21%. In the whole study group the risk of stroke increased by 3% per mmHg (p = 0.0247) with increasing diastolic blood pressure for a given systolic pressure. The corresponding value for cardiac events was 2% per mmHg (p = 0.0376). CONCLUSION In STOP-Hypertension we found a substantial risk reduction in stroke in actively treated patients, which was not solely explained by the blood pressure reduction obtained by treatment with beta-blockers and a potassium-sparing diuretic combination.