Diovan Incident


November 28, 2021

The Diovan case (Diovan Jiken) is a conflict of interest problem in which an employee of Novartis Pharma, a Japanese subsidiary of Novartis, was involved as a statistical analyst in a doctor-led clinical study of Diovan (generic name: valsartan), a drug for the treatment of hypertension. COI: Conflict of Interest), and the case where a series of papers were withdrawn because there was a problem with the data of the papers that published the results of clinical research. Five universities (Kyoto Prefectural University of Medicine, Jikei University School of Medicine, Shiga University of Medical Science, Chiba University, Nagoya University) are involved in Diovan's clinical research in Japan, respectively, Kyoto Heart Study, Jikei Heart Study, and SMART ( The Shiga Microalbuminuria Reduction Trial), VART (The Valsartan Amlodipine Randomized Trial), and Nagoya Heart Study were conducted and the papers were published. However, in August 2018, the Nagoya Heart Study paper was withdrawn, and all of the above five papers were retracted.

Outline of the paper

Jikei Heart Research (JHS, Jikei University School of Medicine)

Current treatment + valsartan group (group V. Increasing dose. Non-ARB drug can be added after 12 to 16 weeks) and antihypertensive drug other than ARB for 3,081 Japanese patients with hypertension / heart failure (21 institutions) The patients were divided into treatment groups (Group S. The dose of antihypertensive drug could be increased, and standard antihypertensive drug could be added), and the follow-up was conducted for 3.1 years (median) by the PROBE method. The primary endpoints are cardiovascular death + cardiovascular complications (hospitalization for stroke / transient ischemic attack [TIA]; myocardial infarction [MI]; hospitalization for congestive heart failure; hospitalization for angina; aortic aneurysm dissection; It was doubling of serum creatinine levels; transition to dialysis). The change in blood pressure (at baseline → at the end of the test) was as follows: V group: 139.2 / 81.4 → 132.0 / 76.7 mmHg, S group: 138.8 / 81.4 → 132.0 / 76.6 mmHg. The evaluation items were V group: 92 cases (6.0%); 21.3 cases / 1000 persons / year, S group: 149 cases (9.7%); 34.5 cases / 1000 persons / year, hazard ratio [HR] 0.61; 95%. Confidence interval [CI] 0.47 to 0.79, p 0.0002, significantly decreased in group V. Of the primary endpoints, the items with significant differences between the two groups were stroke, angina, heart failure, and dissecting aortic aneurysm, and there were significant differences in total mortality, cardiovascular death, myocardial infarction, and exacerbation of renal disease. I was not able to admit. Of these, new onset of angina was reduced by 65%, but the reason was unknown.

Kyoto Heart Research (KHS, Kyoto Prefectural University of Medicine)

Current treatment + valsartan group (V group. Increasing dose. ARB) for 3,031 patients (31 institutions) with Japanese coronary artery disease, cerebrovascular disorder, peripheral arterial obstructive disease, or one or more cardiovascular risk factors. / Divided into antihypertensive therapy excluding ACE inhibitors) and non-ARB group (S group. Antihypertensive drug can be increased, antihypertensive therapy excluding ARB / ACE inhibitors can be added), and 3.27 years (median value) by PROBE method ) Follow-up. The primary endpoint was new onset or worsening of cardiovascular events, cerebrovascular events, and other vascular events. The change in blood pressure (at baseline → at the end of the study) was not different between the V group: 157/88 → 133/76 mmHg and the S group: 157/88 mmHg → 133/76 mmHg, but the primary endpoint was V group: 83 cases (5.5%), S group: 155 cases (10.2%): HR 0.55; 95% CI 0.42 to 0.72, p 0.00001, which decreased significantly in the V group. Of the primary endpoints, those with significant differences between the two groups were stroke / transient ischemic attack (25 vs 46: HR 0.55; 95% CI 0.34 to 0.89, p 0.01488), angina. (22 vs 44: HR 0.51; 95% CI 0.31-0.86, p 0.01058), acute myocardial infarction, heart failure, dissecting aortic aneurysm, lower limb artery occlusion, transition to dialysis or doubling of plasma Cr concentration. In addition, there is a difference between all deaths and cardiovascular deaths.

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