Clinical Outcomes of Patients With Diabetic Nephropathy Randomized to Clopidogrel Plus Aspirin Versus Aspirin Alone (A post hoc Analysis of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA] Trial)

• Published in: The American journal of cardiology 2009-05, Vol.103 (10), p.1359-1363
• Main Authors: Dasgupta, Arijit, MD, Steinhubl, Steven R., MD, Bhatt, Deepak L., MD, MPH, Berger, Peter B., MD, Shao, Mingyuan, MSc, Mak, Koon-Hou, MD, Fox, Keith A.A., MB, ChB, Montalescot, Gilles, MD, PhD, Weber, Michael A., MD, Haffner, Steven M., MD, Dimas, Alexios P., MD, Steg, P. Gabriel, MD, Topol, Eric J., MD
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Aspirin; Aspirin - adverse effects; Aspirin - therapeutic use; Associated diseases and complications; Biological and medical sciences; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Cardiovascular Diseases - mortality; Cardiovascular Diseases - prevention & control; Chi-Square Distribution; Clinical trials; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - mortality; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Kidney diseases; Kidneys; Male; Medical sciences; Middle Aged; Mortality; Nephrology. Urinary tract diseases; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - therapeutic use; Proportional Hazards Models; Risk factors; Studies; Survival Analysis; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives; Ticlopidine - therapeutic use; Treatment Outcome; Urinary system involvement in other diseases. Miscellaneous
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2009.01.342

No prospective randomized trial has specifically examined the long-term outcomes of clopidogrel use in patients with chronic kidney disease. This study aimed to determine the risks and benefits of long-term clopidogrel administration in patients with diabetic nephropathy, the most common form of chronic kidney disease. We performed a post hoc analysis of the CHARISMA trial, which randomly assigned patients without active acute coronary syndrome, but with established atherosclerotic disease (symptomatic) or multiple risk factors for atherosclerotic disease (asymptomatic), to clopidogrel plus aspirin versus placebo plus aspirin. All CHARISMA patients (n = 15,603) were separated into the 3 groups: nondiabetic patients, diabetic patients without nephropathy, and diabetic patients with nephropathy. Within each group, outcomes of patients randomly assigned to clopidogrel were compared with those of patients randomly assigned to placebo. Outcomes in the prespecified CHARISMA subgroups of asymptomatic and symptomatic patients were also compared with respect to study drug assignment and nephropathy status. Patients with nephropathy who received clopidogrel had no difference in bleeding, but experienced significantly increased cardiovascular (CV) and overall mortality compared with those randomly assigned to placebo. There were no differences in bleeding, overall mortality, or CV mortality for nondiabetic or diabetic patients without nephropathy who received clopidogrel versus placebo. In the asymptomatic cohort, patients with nephropathy randomly assigned to clopidogrel had significantly increased overall and CV mortality compared with placebo, whereas asymptomatic patients without nephropathy randomly assigned to clopidogrel had no significant mortality difference compared with placebo. In conclusion, this post hoc analysis suggested that clopidogrel may be harmful in patients with diabetic nephropathy. Additional studies are needed to investigate this possible interaction.