The association between purine and pyrimidine inhibitors and the risk of hypertension: systematic review and meta-analysis

Objective: To compare the effects of various purine and pyrimidine inhibitors in drug format on the risk of hypertension. Design and method: Various meta-analyses and systematic reviews of randomised-control trials (RCTs) were identified using a selection of relevant electronic databases, including MEDLINE Ovid, EMBASE Ovid and CENTRAL. These documents were then all assessed to extrapolate current approaches towards analysis of the effects of purine and pyrimidine inhibitors in adult patients with respect to hypertension. Results: The search as described yielded data for 27 trials, featuring a total of 8,907 participants, across three relevant medications: Azathioprine, Mycophenolate Mofetil (MMF), and Leflunomide. Purine and pyrimidine inhibitors were compared to placebos in five studies, which included 1,748 patients, and to other active drugs in 22 studies, which thus included 7,159 patients. A total of 50 (4.1%) and 16 (3%) events occurred for purine and pyrimidine inhibitors and the placebo groups, respectively. The risk of hypertension was higher among the purine and pyrimidine inhibitor groups than the placebo groups, although the resulting risk ratio was not statistically significant (RR = 1.37, 95% CI 0.78; 2.44, P = 0.28). A total of 696 and 971 events occurred in purine and pyrimidine inhibitor and the active drug groups, respectively. The risk of hypertension was significantly lower in the purine and pyrimidine inhibitor groups than in those featuring other active drugs (RR = 0.8, 95% CI 0.65; 0.99, P = 0.04), thus favouring the use of purine and pyrimidine inhibitors. Studies by Gheith and Becker contributed to 10.7% and 10.8% of the meta-analysis weight, respectively. Substantial heterogeneity was thus observed between studies (I2 = 77%, P < 0.00001). Conclusions: The final outcomes indicated that the initial hypothesis of this meta-analysis, that purine and pyrimidine meta-analysis do not cause any additional risk of hypertension as compared to the placebo group could not be rejected. Additionally, a reduction in levels of risk as compared to other active drugs emerged that may require further analysis.