Dihydropyridine calciumchannel blockers for antihypertensive treatment in older patients evidence from the systolic hypertension in Europe trial

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Dihydropyridine calcium channel blockers for antihypertensive treatment in older patients – evidence from the systolic hypertension in, Europe trial

Objective, The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension.Design.Randomised,place~ontrolled,doubl~blind outcome trial.Setting. Hypertension clinics or general practitioners' surgeries in 198 centres in 23 Western and Eastern European countries.Subjects. Patients aged ~ 60 years with sitting systolic blood pressure (BP) 160 - 219 mmHg and sitting diastolic BP < 95 mmHg during run-in phase.Methods and Results. Four thousand, six hundred and ninety-five patients were randomly assigned to active treatment (N = 2 398), Le. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or to matching placebos (N = 2 297). In the intention-to-treat analysis, the between-group difference in blood pressure (BP) amounted to 10.1 /4.5 mmHg (P < 0.(01). Active treatment reduced the incidence of fatal and non-fatal stroke (primary endpoint) by 42% (P = 0.(03). On active treatment all cardiac endpoints decreased by 26% (P =0.03) and all cardiovascular endpoints by 31% (P < O.OOl). Cardiovascular mortality was slightly lower on active treatment (-27%, P = 0.07), but all-cause mortality was not influenced (-14%, P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age, and for total mortality it decreased with lower systolic BP at entry (P =0.05). The benefits of active treatment were not independently related to sex or to the presence of cardiovascular complications at entry. The antihypertensive regimen was more effective in patients with diabetes than in those without diabetes at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. Active treatment reduced all strokes by 44% (P = 0.004), all cardiac endpoints by 26% (P = 0.05) and all cardiovascular endpoints by 32% (P < 0.(01). Total mortality was reduced by 26% (P = 0.05), but a similar reduction in cardiovascular mortality did not reach statistical significance in this analysis. Compared with placebo, active treatment also reduced the incidence of dementia by 50%.Conclusion. Stepwise antihypertensive drug treatment, starting with the dihydropiridine calcium-channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension

How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2)

BACKGROUND: The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2). It describes BP control and adherence to study medications. METHODS: After the end of Syst-Eur 1 all patients, treated either actively or with placebo, were invited either to continue or to start antihypertensive treatment with the same drugs as previously used in the active treatment arm. In order to reach the target BP (sitting SBP <150 mmHg), the first line agent, nitrendipine, could be associated with enalapril and/or hydrochlorothiazide. RESULTS: Of the 3787 eligible patients, 3516 (93%) entered Syst-Eur 2. At the last available visit, 72% of the patients were taking nitrendipine. SBP/DBP at entry in Syst-Eur 2 averaged 160/83 mmHg in the former placebo group and 151/80 mmHg in the former active-treatment group. At the last follow-up visit SBP/DBP in the patients previously randomised to placebo or active treatment had decreased by 16/5 mmHg and 7/5 mmHg, respectively. The target BP was reached by 74% of the patients. CONCLUSION: Substantial reductions in systolic BP may be achieved in older patients with isolated systolic hypertension with a treatment strategy starting with the dihydropyridine calcium-channel blocker, nitrendipine, with the possible addition of enalapril and/or hydrochlorothiazide

Self-measurement of blood pressure at home in the management of hypertension

To be suitable for the management of hypertension, self-measurement of blood pressure (BP) at home should follow international recommendations.The use of accurate and validated measuring devices is an important prerequisite. Upper arm BP monitors are the first choice, while wrist and finger devices cannot be recommended. Measurements should, preferentially, be downloaded from the memory of a device or printed. Reference values have been proposed, but were mostly based on cross-sectional observations and have not yet been widely validated by prospective outcome studies. Currently, levels of home BP of <135 mm Hg systolic and 85 mm Hg diastolic are usually considered normal. Home BP measurement is sometimes recommended as an alternative to ambulatory BP monitoring to diagnose white-coat hypertension.However, home BP measurement cannot replace ambulatory BP monitoring in the diagnosis of hypertension (white-coat), but both techniques have complementary roles. The appropriateness of home BP measurement to guide antihypertensive treatment has only been tested in one large-scale randomized trial: the THOP (Treatment of Hypertension Based on Home or Office Blood Pressure) trial. The THOP trial showed that antihypertensive treatment based on home instead of office BP led to less intensive drug treatment, but also to less BP control with no differences in general wellbeing and left ventricular mass. Home BP monitoring also contributed to the identification of patients with white-coat hypertension. On balance, most evidence supports the view that office BP measurement remains the key in the diagnosis and treatment of hypertension. Treatment can be started without confirmation of elevated office BP in patients with high office BP and target organ damage, or a high cardiovascular risk profile. In patients with raised office BP but without target organ damage (white-coat hypertension), or with normal office BP but unexplained target organ damage (masked hypertension), ambulatory or home BP monitoring or both must be used to confirm the diagnosis. Few longitudinal studies have addressed the long-term prognostic meaning of home BP measurement. Until more prospective data become available, management of hypertension exclusively based on self-measurement of BP at home cannot be recommended.status: publishe

Risk and benefit of treatment of isolated systolic hypertension in the elderly: evidence from the Systolic Hypertension in Europe Trial

The Syst-Eur trial investigated whether active treatment starting with the dihydropyridine calcium channel blocker (CCB) nitrendipine, could reduce the cardiovascular complications of isolated systolic hypertension (ISH) in the elderly. The intention-to-treat analysis showed that active treatment improved outcome. The per-protocol analysis largely confirmed these results. The effect of treatment on total and cardiovascular mortality might be attenuated in very old patients. Further analysis also suggested benefit in those patients who remained on nitrendipine monotherapy. Active treatment was more beneficial in patients with diabetes as compared with those without diabetes at entry and reduced the incidence of dementia by 50%. Analyses of data from the Ambulatory Blood Pressure Monitoring (ABPM) Side Project suggested that most of the benefit of treatment was seen in patients with a daytime systolic BP > or = 160 mm Hg. Finally, a meta-analysis partly based on Syst-Eur data showed that in older hypertensive patients pulse pressure and not mean pressure is the major determinant of cardiovascular risk.status: publishe

Determinants of white-coat syndrome assessed by ambulatory blood pressure or self-measured home blood pressure

BACKGROUND: Gender, age, smoking, race, and body mass index have been reported to determine the ambulatory white-coat effect (WCE) and white-coat hypertension (WCH). METHODS: Baseline conventional, day-time ambulatory and self-measured home blood pressure measurements from the THOP trial were used to study the effect of gender, age, body mass index, smoking habits and treatment status on the white-coat syndrome as assessed by ambulatory monitoring or self-measurement. RESULTS: The mean systolic/diastolic WCE was 9.1/6.7 mmHg if based on ambulatory blood pressure and 12.2/8.7 mmHg if based on self-measured blood pressure. The ambulatory WCE was significantly higher in women, in older subjects (65+), in obese subjects, in non-smokers and in patients on antihypertensive drug treatment. The self-measured WCE was significantly higher in women and in non-smokers. Ambulatory WCH was present in 6.6% of the untreated patients and 14.2% had self-measured WCH. The proportion of ambulatory WCH was significantly higher in obese subjects; the proportion of self-measured WCH did not differ by gender, age, body mass index, or smoking habits. CONCLUSIONS: The ambulatory white-coat syndrome was determined by gender, age, body mass index, smoking habits, and treatment status. The self-measured white-coat syndrome was greater than the ambulatory white-coat syndrome but depended less on the determinants under study.status: publishe

Antihypertensive treatment based on home or office blood pressure--the THOP trial

OBJECTIVE AND METHODS: In this randomized clinical trial, conducted in 400 hypertensive patients [sitting diastolic blood pressure (DBP) >95 mmHg], blood pressure-lowering therapy was adjusted in a stepwise manner, either on the basis of the self-measured DBP at home or on the basis of conventional DBP measured at the doctor's office. RESULTS: Therapy guided by home blood pressure instead of office blood pressure led to less intensive drug treatment and marginally lower costs, but also to less blood pressure control with no differences in left ventricular mass. Self-measurement helped to identify patients with white-coat hypertension. CONCLUSIONS: The present findings support a stepwise strategy for the evaluation of blood pressure, in which self-measurement and ambulatory monitoring are complementary to conventional office blood pressure measurement.status: publishe