Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study.

BACKGROUND: Drugs that inhibit the renin-angiotensin-aldosterone system benefit patients at risk for or with existing cardiovascular disease. However, evidence for this effect in Asian populations is scarce. We aimed to investigate whether addition of an angiotensin receptor blocker, valsartan, to conventional cardiovascular treatment was effective in Japanese patients with cardiovascular disease. METHODS: We initiated a multicentre, prospective, randomised controlled trial of 3081 Japanese patients, aged 20-79 years, (mean 65 [SD 10] years) who were undergoing conventional treatment for hypertension, coronary heart disease, heart failure, or a combination of these disorders. In addition to conventional treatment, patients were assigned either to valsartan (40-160 mg per day) or to other treatment without angiotensin receptor blockers. Our primary endpoint was a composite of cardiovascular morbidity and mortality. Analysis was by intention to treat. The study was registered at clintrials.gov with the identifier NCT00133328. FINDINGS: After a median follow-up of 3.1 years (range 1-3.9) the primary endpoint was recorded in fewer individuals given valsartan than in controls (92 vs 149; absolute risk 21.3 vs 34.5 per 1000 patient years; hazard ratio 0.61, 95% CI 0.47-0.79, p=0.0002). This difference was mainly attributable to fewer incidences of stroke and transient ischaemic attack (29 vs 48; 0.60, 0.38-0.95, p=0.028), angina pectoris (19 vs 53; 0.35, 0.20-0.58, p<0.0001), and heart failure (19 vs 36; 0.53, 0.31-0.94, p=0.029) in those given valsartan than in the control group. Mortality or tolerability did not differ between groups. INTERPRETATION: The addition of valsartan to conventional treatment prevented more cardiovascular events than supplementary conventional treatment. These benefits cannot be entirely explained by a difference in blood pressure control.

Chronobiological analysis by ambulatory blood pressure monitoring of the hyperbaric and hypobaric indexes for evaluation of the antihypertensive effect of long-acting nifedipine.

BACKGROUND: It has been suggested that chronobiology can provide new insights into the evaluation and treatment of cardiovascular disease. In the present study the hyperbaric index (hyperBI) and hypobaric index (hypoBI) were compared with the mean blood pressure (BP) over 24 h to evaluate the antihypertensive effect of long-acting nifedipine on essential hypertension. METHODS AND RESULTS: Fourteen patients were treated with nifedipine CR (20-40 mg/day) for 6 months. Ambulatory BP monitoring was performed before and after treatment. The hyperBI (mmHg . h/day) was calculated as the integrated BP area above the conventional upper limit (140/90 mmHg for the daytime and 120/80 mmHg at night), and the hypoBI was calculated as the integrated BP area below the conventional lower limit (110/60 mmHg for the daytime and 100/50 mmHg at night). At baseline, both the systolic and diastolic 24-h hyperBI values closely correlated with the 24-h mean BP (r=0.994 and 0.935, p<0.0001). Treatment with nifedipine significantly lowered both the 24-h mean systolic and diastolic BP (143+/-14/89 +/-12 to 124+/-16/80+/-8 mmHg, p<0.001/p=0.001), as well as the casual BP (167+/-11/101 +/-8 to 140+/-13/86+/-10 mmHg, p<0.001/p<0.01). Reduction of both the systolic and diastolic hyperBI values was statistically significant over the 24-h period (274+/-266 to 90+/-155, p=0.009; 145+/-187 to 41+/-63, p=0.024), as well as during the daytime (200+/-181 to 66+/-116, p=0.014; 105+/-120 to 24+/-38, p=0.017) and at night (systolic, 74+/-106 to 24+/-52, p=0.021). The 24-h mean BP was normalized, but a small excess BP load persisted despite treatment. There was no significant increase of systolic hypoBI during the 24-h period (1+/-2 to 25+/-30, p=0.065), the daytime (0+/-0 to 14+/-38, p=0.20), or at night (1+/-3 to 11+/-19, p=0,052). Similar findings were obtained for diastolic hypoBI. CONCLUSIONS: Nifedipine CR improved the 24-h hyperBI and mean BP without causing excessive hypotension. These 2 parameters have a close relationship when assessment is done by 24-h BP monitoring. The hyperBI and hypoBI may assist in providing adequate antihypertensive therapy for individual patients by detecting an excessive BP load or hypotension, respectively.

JIKEI HEART Study--a morbi-mortality and remodeling study with valsartan in Japanese patients with hypertension and cardiovascular disease.

BACKGROUND: Several recent clinical trials have demonstrated that angiotensin II receptor blockers (ARBs) have cardiovascular as well as renal protective effects. Asian patients including Japanese were under-represented in these trials, however, and no large-scale clinical trials of ARBs have yet been performed in Japan. It is therefore important to verify that the results of these studies are also valid for Japanese patients. The JIKEI HEART Study has been designed to investigate whether concomitant treatment with valsartan, an angiotensin II receptor blocker, in addition to conventional treatment, will improve the prognosis of Japanese patients with cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure). METHOD AND EVALUATION OF RESULTS: Around 3,000 patients with hypertension, ischemic heart disease and/or congestive heart failure will be randomized to receive either additional treatment with valsartan (80 mg/day) or conventional therapy. The follow-up period will be three years. The primary endpoint will be the onset of any cardiovascular event. Secondary endpoints will include death from any cause, changes in left ventricular size and function, renal function, changes in neuro-hormonal levels and quality-of-life assessments. Sub-studies will explore the effect in patients with diabetes mellitus, hyperlipidemia and the effects of combination of drugs. CONCLUSION: Improved prognosis would confirm the role of angiotensin II receptor blockers in the treatment of the cardiovascular disease in Japanese patients.

Effect of low-dose isoproterenol infusion on left atrial appendage function soon after cardioversion of chronic atrial tachyarrhythmias.

BACKGROUND: Cardioversion of chronic atrial fibrillation or atrial flutter to sinus rhythm is often associated with transient atrial mechanical dysfunction, i.e. 'atrial stunning', which may increase the risk of subsequent thromboembolic events. We hypothesized that, because of its positive inotropic action, a low-dose isoproterenol infusion might improve postcardioversion atrial mechanical function. METHOD: Eighteen patients (15 male, three female; 12 atrial fibrillation, six atrial flutter; mean age 65+/-10 years) exhibiting atrial postcardioversion stunning were included in the study. Isoproterenol was infused for 10 min at a dose sufficient to increase the heart rate by about 10%. Using transesophageal echocardiography, both the left atrial appendage emptying/filling flow velocity and function (fractional area change) were examined at baseline, before isoproterenol (immediately after cardioversion) and after isoproterenol. RESULTS: With infusion of 0.005-0.008 microg/kg/min isoproterenol, heart rate increased by 11.1+/-2.9%, and left atrial appendage emptying velocity, which was diminished following cardioversion, increased significantly (P<0.001) (baseline, before and after isoproterenol: 41.1+/-18.0, 20.3+/-8.5 and 27.3+/-9.6 cm/s, respectively). No major complications were associated with isoproterenol infusion. CONCLUSIONS: Short-term infusion of low-dose isoproterenol improved atrial function after cardioversion of chronic atrial fibrillation and atrial flutter.