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Cardiovascular disease is a prevalent and prognostically important comorbidity among patients with kidney disease, and individuals with kidney disease make up a sizeable proportion (30%–60%) of patients with cardiovascular disease. However, several systematic reviews of cardiovascular trials have observed that patients with kidney disease, particularly those with advanced kidney disease, are often excluded from trial participation. Thus, currently available trial data for cardiovascular interventions in patients with kidney disease may be insufficient to make recommendations on the optimal approach for many therapies. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration, convened a multidisciplinary, international work group and hosted a stakeholder workshop intended to understand and develop strategies for overcoming the challenges with involving patients with kidney disease in cardiovascular clinical trials, with a particular focus on those with advanced disease. These efforts considered perspectives from stakeholders, including academia, industry, contract research organizations, regulatory agencies, patients, and care partners. This article outlines the key challenges and potential solutions discussed during the workshop centered on the following areas for improvement: building the business case, re-examining study design and implementation, and changing the clinical trial culture in nephrology. Regulatory and financial incentives could serve to mitigate financial concerns with involving patients with kidney disease in cardiovascular trials. Concerns that their inclusion could affect efficacy or safety results could be addressed through thoughtful approaches to study design and risk mitigation strategies. Finally, there is a need for closer collaboration between nephrologists and cardiologists and systemic change within the nephrology community such that participation of patients with kidney disease in clinical trials is prioritized. Ultimately, greater participation of patients with kidney disease in cardiovascular trials will help build the evidence base to guide optimal management of cardiovascular disease for this population.

Hot flashes are the most prominent side effect of tamoxifen, the most frequently prescribed antitumor agent in the world. Little detailed information is available to predict who will develop hot flashes on tamoxifen, to describe the natural history of these hot flashes, and/or to predict who will request therapy for such a side effect. This current trial was developed to address these items. Women who were about to begin adjuvant tamoxifen for locally treated breast cancer were approached for this trial. Before initiating tamoxifen, patients completed a short questionnaire designed to inquire about potential prognostic factors. Upon starting tamoxifen, women were asked to complete a hot flash diary daily for 3 months, and then daily for 1 week of each of the subsequent 9 months. Fifty patients, aged 51-83 years, provided data for this report. Approximately half of the women reported that they did not have any substantial hot flashes while the other half reported hot flashes of variable intensity. On average, these hot flashes gradually increased over 3 months and then plateaued. Baseline factors that appeared to predict for subsequent hot flash problems included a prior history of moderate to severe hot flashes with menopause and a history of prior estrogen therapy use. Overall, 16% of the women reported the desire for therapy for their hot flashes. Thirty-seven and one-half percent of the women (6/16) had a history of both prior estrogen use and moderate to severe hot flashes with menopause as compared to none (0/14) of the women without either of these factors. The data from this study can be utilized to better identify and educate women as to their probability of developing hot flashes after starting tamoxifen, to describe the average time frame for these hot flashes, and to predict the likelihood of whether resultant hot flashes will be substantial enough to have a woman request therapy for them.

Hot flashes may be a significant clinical problem in men undergoing androgen deprivation therapy with gonadotropin releasing hormone analogues, oral antiandrogens and/or surgical bilateral orchiectomy. Anecdotal information suggests that a low dose of the relatively new antidepressant venlafaxine may abrogate this clinical problem. We developed the current pilot trial to investigate further whether venlafaxine alleviates hot flashes in such men.

To determine the efficacy of transdermal clonidine for alleviating post-orchiectomy hot flashes, a randomized, double-blind, crossover clinical trial was designed including 70 men with a history of prostate cancer who had undergone a medical or surgical orchiectomy and were suffering from hot flashes. The results of this study demonstrated that clonidine did not significantly decrease hot flash frequency or severity. Future research is necessary to find effective means of alleviating hot flashes in post-orchiectomy patients.