Abstract
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 β-adrenergic receptor antagonist (β-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 β-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 β-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.