title: Artist® tablets (carvedilol) for hypertensive patients in Japan: results of a drug use survey.
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.
  
  
  METHODS
  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.
authors.affiliation: Post Marketing Study Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mori
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Iizuka
authors.forename: Natsuko
authors.initials: N
authors.lastname: Zenimura
authors.forename: Takuyuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Hiramatsu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Komiya
mesh_terms: D000293:Adolescent; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001769:Blood / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000097:blood; D048909:Diabetes Complications / Q000097:blood / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006331:Heart Diseases / Q000150:complications / Q000453:epidemiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D007564:Japan; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology; D008107:Liver Diseases / Q000150:complications / Q000453:epidemiology; D008297:Male; D011358:Product Surveillance, Postmarketing; D011412:Propanolamines / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D013607:Tablets; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001786:Blood Glucose; D002121:Calcium Channel Blockers; D002227:Carbazoles; D004232:Diuretics; D007004:Hypoglycemic Agents; D011412:Propanolamines; D013607:Tablets; D000077261:Carvedilol; D003404:Creatinine