Home blood pressure and cardiovascular outcomes in very elderly patients receiving antihypertensive drug therapy: a subgroup analysis of Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study.

The appropriate target blood pressure (BP) in elderly patients with hypertension remains uncertain. We investigated the relationship between morning home systolic blood pressure (MHSBP) during follow-up and cardiovascular (CV) risk in outpatients receiving olmesartan-based treatment aged <75 years (n = 16799) and ≥75 years (n = 4792) in the HONEST study. In the follow-up period (mean 2.02 years), the risk for major CV events was significantly higher in patients with MHSBP ≥155 mmHg compared with <125 mmHg in both age groups in Cox proportional hazards model adjusted for other risk factors and there was no significant difference in trend between the two groups (interaction P = 0.9917 for MHSBP). Hazard ratios for CV events for 1-mmHg increase in MHSBP were similar in patients aged <75 years and in patients aged ≥75 years. The incidence of adverse drug reactions related to excessive BP lowering was lower in patients <75 years than in patients ≥75 years (0.73 vs 1.02%, P = 0.0461). In conclusion, the study suggests even in patients ≥75 years antihypertensive treatment targeting the same MHSBP levels in patients <75 years may be beneficial in reducing CV risk when treatment is tolerated.

Prognostic significance of on-treatment home and clinic blood pressure for predicting cardiovascular events in hypertensive patients in the HONEST study.

OBJECTIVE: We investigated the prognostic significance of morning home SBP (MHSBP) and clinic SBP (CSBP) at baseline and during follow-up in on-treatment hypertensive patients. METHODS: In the Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure study, more than 20 000 Japanese hypertensive patients who started treatment with olmesartan were followed for cardiovascular events for 2 years. MHSBP and CSBP measured at baseline and during follow-up were compared in terms of the prognostic significance in predicting cardiovascular events. RESULTS: The analysis included 21 591 patients (50.6% female; average age 64.9 years; mean follow-up 2.02 years; and 280 cardiovascular events). The mean MHSBP and CSBP were 151.2 and 153.6 mmHg at baseline and 135.2 and 135.2 mmHg during follow-up. Hazard ratios per 1 mmHg increase were 1.011 (95% confidence interval 1.004-1.019) and 1.006 (1.000-1.012) at baseline, and 1.039 (1.029-1.049) and 1.026 (1.016-1.036) during follow-up. When MHSBP and CSBP at baseline and during follow-up were included in the same model, only MHSBP during follow-up was identified as a significant predictive factor. The concordance index of all blood pressure variables showed reasonable discrimination abilities, and that of mean during follow-up were higher than that of SBP at baseline. The results of net reclassification improvement analyses showed that follow-up MHSBP had better reclassification ability than follow-up CSBP. CONCLUSION: SBP during follow-up (as compared with SBP at baseline), particularly MHSBP (as compared with CSBP), had better prognostic significance in predicting cardiovascular events in Japanese hypertensive patients during a 2-year clinical study.

Rationale, study design, baseline characteristics and blood pressure at 16 weeks in the HONEST Study.

On the basis of the studies that investigated the relationship between baseline clinic blood pressure (CBP) or home blood pressure (HBP) values and cardiovascular (CV) events, HBP has been reported to have a stronger prognostic ability. However, few studies have compared the prognostic ability of on-treatment CBP and HBP. The relationship between on-treatment HBP, measured twice in the morning and twice at bedtime, and CV events was investigated in over 20 000 patients in the HONEST (Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure) Study, a prospective, 2-year observational study of treatment with an angiotensin receptor blocker, olmesartan (OLM), in OLM-naive hypertensive patients. This report summarizes the study protocol, the baseline characteristics of the patients and CBP and HBP at 16 weeks. A total of 22 373 patients were registered across Japan; baseline data from 22 162 patients were collected. Baseline HBP (mean±s.d.) in the morning (the first measurement) was 151.6±16.4/87.1±11.8 mm Hg and at bedtime was 144.3±16.8/82.8±11.9 mm Hg, whereas CBP was 153.6±19.0/87.1±13.4 mm Hg. At 16 weeks, morning HBP was 135.0±13.7/78.8±9.9 mm Hg and bedtime HBP was 129.7±13.8/74.7±10.1 mm Hg, whereas CBP was 135.6±15.4/77.6±10.9 mm Hg. The follow-up period for each patient ends on 30 September 2012. The HONEST Study is expected to provide evidence showing the relationship between baseline and on-treatment CBP and HBP levels (both first and second measurements) and CV events.

Olmesartan medoxomil and azelnidipine therapy in patients with hypertension and chronic kidney disease in Japan.

BACKGROUND: In the present investigation we extracted data on hypertensive patients with chronic kidney disease (CKD) who were enrolled in 3 studies - 2 studies of the angiotensin receptor blocker (ARB) olmesartan medoxomil (OLM), lasting 12 weeks and 2 years, respectively, and one of the calcium channel blocker (CCB) azelnidipine (AZ) lasting 12 weeks - to assess the effects of OLM and AZ on blood pressure (BP), estimated glomerular filtration rate (eGFR) and proteinuria in hypertensive patients with CKD in the setting of daily clinical practice. METHODS: The 3 studies followed open prospective cohort designs that represented daily clinical practice in Japan. Patients with CKD at baseline were selected. Change of BP, eGFR and proteinuria on OLM therapy or AZ therapy were analyzed. RESULTS: At 12 weeks, OLM (n=1,317) and AZ (n=952) therapies exhibited similar BP-lowering effects. AZ led to a significantly (p=0.0069) greater increase of eGFR compared with OLM, while OLM tended to improve proteinuria to a greater extent than AZ. Treatment with OLM for 2 years (n=109) significantly improved proteinuria but did not alter eGFR. CONCLUSION: This study shows that OLM and AZ reduced BP and proteinuria without decreasing eGFR in Japanese hypertensive patients with CKD in the setting of daily clinical practice.

Artist® tablets (carvedilol) for hypertensive patients in Japan: results of a long-term special survey.

BACKGROUND: In Japan, when pharmaceutical companies launch a new drug, they are obligated to conduct a post-marketing survey to evaluate the safety and efficacy of the drug in accordance with Good Post-Marketing Surveillance Practice under Article 14-4 (re-examination) of the Pharmaceutical Affairs Law at contracted medical institutions. We report the results of a long-term special survey that we conducted as a post-marketing survey. OBJECTIVE: The results of a prospective post-marketing survey that was conducted to assess the safety and efficacy of the ß-adrenergic receptor antagonist (ß-blocker) Artist® tablets 10 mg, 20 mg (carvedilol) in patients with hypertension in Japan, were investigated in order to examine the safety and efficacy of the drug during long-term treatment (18 months). PATIENTS: Patients were carvedilol-naive and had essential hypertension or renal parenchymal hypertension. METHODS: We performed this survey as a prospective cohort study (special survey) utilizing a centralized registration method over 3 years (starting from April 1994), for an observation period of 18 months of carvedilol treatment. RESULTS: Sixty-one medical institutions across Japan collected 380 case report forms of patients who received long-term administration of carvedilol, with 363 and 341 cases evaluated for safety and efficacy, respectively. The discontinuation rate was 7.2% and the incidence of adverse drug reactions was 5.23% (19 of 363) in the safety population. There was no significant change in fasting plasma glucose levels from baseline (118.1 ± 46.5 mg/dL) to after carvedilol treatment (114.6 ± 43.3 mg/dL).[n = 141; p = 0.310]. In 341 evaluable patients in the efficacy population, decreases in both blood pressure and pulse rate were statistically significant at all assessment points in comparison with baseline data (p < 0.001). Similarly, in hypertensive patients with diabetes mellitus, decreases in blood pressure were statistically significant at all assessment points in comparison with baseline data (p < 0.001). CONCLUSIONS: The results of this study show that carvedilol exerted stable antihypertensive effects leading to favorable blood pressure control throughout long-term treatment, without showing any safety concerns. It was concluded that there were no clinically significant issues in terms of safety or efficacy with the long-term treatment of carvedilol in patients with hypertension.

Artist® tablets (carvedilol) for hypertensive patients in Japan: results of a drug use survey.

BACKGROUND: In Japan, when pharmaceutical companies launch a new drug, they are obligated to conduct a post-marketing survey to evaluate the safety and efficacy of the drug in accordance with Good Post-Marketing Surveillance Practice under Article 14.4 (re-examination) of the Pharmaceutical Affairs Law at contracted medical institutions. We report the results of a drug use survey, which we conducted as a post-marketing survey. OBJECTIVE: This prospective post-marketing drug use survey was conducted to assess the safety and efficacy of the ß-adrenergic receptor antagonist (ß-blocker) Artist® Tablets (carvedilol) in patients with hypertension in Japan. PATIENTS: Patients were carvedilol-naive and had essential hypertension or renal parenchymal hypertension. METHODS: This was a prospective survey conducted over 3 years from October 1993 to September 1996. The standard observation period for the patients was defined as 12 weeks of treatment with carvedilol. RESULTS: We collected data on 4961 patients at 561 medical institutions who had not been previously treated with carvedilol; 4574 patients were included in the safety analysis and 4422 in the efficacy analysis. The incidence of adverse drug reactions (the proportion of patients with adverse drug reactions) was 4.31% (197 of 4574 patients), which is less than that shown in the pre-approval clinical trial of carvedilol (6.85% [68 of 993]). The most common adverse drug reactions were bradycardia, dizziness, hypotension, headache, and feeling light-headed. After 12 weeks' treatment with carvedilol, systolic/diastolic blood pressure (SBP/DBP) was reduced from 168.2 ± 18.6/95.7 ± 11.3 mmHg at baseline to 144.3 ± 17.3/83.4 ± 10.8 mmHg. Patients were classified according to which antihypertensive drug they had been using when carvedilol treatment was initiated. Coadministered agents were calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), diuretics, and α-adrenergic receptor antagonists (α-blockers). At 12 weeks, the change in SBP/DBP in the monotherapy group was -22.7/-12.2 mmHg and that of each combination therapy subgroup, CCB, ACEI, diuretic, and ß-blocker, was -26.1/-12.7 mmHg, -25.4/-11.9 mmHg, -26.3/-13.0 mmHg, and -24.4/-11.5 mmHg, respectively. The achievement rates for target BP (<140/90 mmHg) were 29.5% in the monotherapy group, 34.8% in the CCB group, 31.3% in the ACEI group, 31.8% in the diuretic group, and 32.4% in the ß-blocker group. There was no significant difference in the achievement of target BP among the four combination therapy subgroups (p = 0.475). These results indicate that carvedilol exerts reasonable BP reduction regardless of whether it is used as monotherapy or in combination therapy, and that the effect is not influenced by the coadministered drug. Moreover, carvedilol was also effective in reducing BP levels in elderly patients (≥65 years) and in patients with diabetes mellitus or renal diseases. CONCLUSIONS: The results of this study reflect the results of clinical trials up to the time of approval and it was confirmed that carvedilol is a highly useful drug in the treatment of hypertension.