Cardiovascular safety of drugs not intended for cardiovascular use: need for a new conceptual basis for assessment and approval

Recently, several drugs for non-cardiovascular diseases have ceased marketing because of cardiovascular risk, highlighting the importance of evaluating the cardiovascular safety of new drugs even if not intended for cardiovascular diseases. Assessing and ensuring acceptable cardiovascular safety of non-cardiovascular drugs is difficult; nonetheless, governmental regulatory agencies are likely to change the requirements for drug safety information. This article explores our recommendations for rethinking current regulatory policies, emphasizing the need for mandatory post-marketing surveillance registries and highlighting the exposures necessary to subserve the need for greater assessment of safety issue

Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure

Aims Surveys on heart failure management suggest under-utilization of life-saving evidence-based treatment. Evidence-based medicine and clinical guidelines are based on the results of randomized controlled trials. Therefore, we investigated how patients who fulfilled the enrolment criteria of randomized trials were treated in real life. Methods and results We selected three large placebo-controlled trials of patients with chronic heart failure, in which ACE-inhibitors (ACE-Is), β-blockers, and spironolactone proved to be safe and effective. The major enrolment criteria of trials were identified and applied to patients enrolled in the Euro Heart Survey on Heart Failure to identify the proportion of patients eligible for treatment and also treated appropriately. Of the 10 701 patients who were enrolled in the Euro Heart Survey on Heart Failure, only a small percentage (13%) would have qualified for participation in at least one of the selected trials. Patients who fulfilled enrolment criteria of the identified trials were more likely to be treated with ACE-Is (83% of SOLVD-eligible patients), β-blockers (54% of MERIT-HF-eligible patients), and aldosterone antagonists (43% of RALES-eligible patients) than trial-ineligible patients. Almost half of SOLVD-eligible patients who were treated with ACE-Is received the target dose as recommended in the guidelines, but only <10% of MERIT-HF eligible patients who were treated with β-blockers received the target dose. Conclusion ACE-Is are widely utilized but given in lower doses than proven effective in clinical trials. β-Blockers are underused and given in lower doses to patients who fulfil the enrolment criteria of relevant landmark trial

Cardiovascular safety of drugs not intended for cardiovascular use: need for a new conceptual basis for assessment and approval

Recently, several drugs for non-cardiovascular diseases have ceased marketing because of cardiovascular risk, highlighting the importance of evaluating the cardiovascular safety of new drugs even if not intended for cardiovascular diseases. Assessing and ensuring acceptable cardiovascular safety of non-cardiovascular drugs is difficult; nonetheless, governmental regulatory agencies are likely to change the requirements for drug safety information. This article explores our recommendations for rethinking current regulatory policies, emphasizing the need for mandatory post-marketing surveillance registries and highlighting the exposures necessary to subserve the need for greater assessment of safety issue

Management of patients with heart failure in clinical practice: differences between men and women

Objectives: This study evaluated gender differences in clinical characteristics, treatment and outcome among patients with heart failure, and to what extent these differences are due to age and differences in left ventricular (LV) function. Although gender differences are observed among heart failure patients, few studies have been adequately powered to investigate these differences. Methods: A total of 8914 (out of 10 701) patients (47% women) from the Euro Heart Survey on Heart Failure with confirmed diagnosis of heart failure were included in the analyses. Results: Women were older (74.7 vs 68.3 years, p < 0.001), and less often had evidence of coronary artery disease (56% vs 66%, age-adjusted odds ratio (OR) 0.62; 95% CI 0.57 to 0.68). Women were more likely to have hypertension, diabetes, or valvular heart disease. Fewer women had an investigation of LV function (59% vs 74%, age-adjusted OR 0.67; 95% CI 0.61 to 0.74), and, among those investigated, fewer had moderate/severe left ventricular systolic dysfunction (44% vs 71%, age-adjusted OR 0.35; 95% CI 0.32 to 0.39). Drugs with a documented impact on survival, that is ACE-inhibitors and beta-blockers, were given less often to women, even in the adjusted analysis (OR 0.72; 95% CI 0.61 to 0.86 and OR 0.76; 95% CI 0.65 to 0.89, respectively). 12-week mortality was similar for men and women. Conclusions: Fewer women had an assessment of LV function, but, when investigated, women had better ventricular function. Women were less often treated with evidence-based drugs, even after adjustment for age and important clinical characteristics. Clinicians need to be aware of deficiencies in the treatment of women with heart failure and measures should be taken to rectify them