cardiovascular-agents and Dizziness

Serious adverse events (SAEs) from heart failure (HF) therapy are frequent; however, techniques to identify at-risk patients are inadequate. Furthermore, the relationship between SAEs, quality of life (QOL), and cardiac structure are unknown.. 151 symptomatic patients with systolic HF were followed for a mean of 10 months. In this post hoc analysis, treatment-related SAEs included acute renal failure, dizziness, hypo/hyperkalemia, hypotension, and syncope. At 1 year, 21 treatment-related SAEs occurred. No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided arm and the standard of care arm (P = .20). At baseline, patients who suffered SAEs were less likely to be receiving beta-blockers (85.7% vs 97.7%; P = .009) and had worse functional class and lower chloride levels. Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Questionnaire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period. Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction; patients in the highest risk quartile had the shortest time to first cardiovascular event (P = 0.01).. NT-proBNP-guided HF care is safe. Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling. A risk score to prospectively predict SAEs in aggressive HF management was developed.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Chronic Disease; Disease Management; Dizziness; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Quality of Life; Renal Insufficiency; Surveys and Questionnaires; Treatment Outcome

We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality.. Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at approximately 50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012).. FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.

Topics: Adult; Aged; Arthralgia; Biomarkers; Black or African American; Cardiovascular Agents; Cause of Death; Disease-Free Survival; Dizziness; Double-Blind Method; Drug Combinations; Heart Failure; Heart Transplantation; Hospitalization; Humans; Hydralazine; Hypotension; Isosorbide Dinitrate; Kaplan-Meier Estimate; Middle Aged; Mortality; Natriuretic Peptide, Brain; Nitric Oxide Donors; Proportional Hazards Models; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Vasodilator Agents

We tested the hypothesis that resolution versus persistence of symptomatic ischaemia and/or development of nausea/dizziness on the third day of loading with perhexiline maleate (PM), is correlated with perhexiline plasma concentrations after the standard loading phase in patients with acute coronary syndromes. Forty consecutive patients with either unstable angina pectoris or non-Q-wave myocardial infarction with persistent angina pectoris, despite maximal pharmacological therapy (other than PM), were studied. All patients received PM 400 mg/day for 3 days and 200 mg/day thereafter. On days 2 and 3 observers blinded to the 72-96 h plasma perhexiline concentration assessed the patient regarding episodes of angina and/or nausea/dizziness. On the third day of loading with PM, 12 patients experienced angina and 11 patients had nausea and/or dizziness. Plasma perhexiline concentrations at 72-96 h varied widely: mean 0.46 +/- 0.26 (range 0.11-1.77) microgram/ml. There was a relationship of borderline statistical significance between resolution of anginal symptoms and plasma perhexiline concentration > 0.15 microgram/ml (p = 0.055). There was a close relationship between emergence of nausea/dizziness with plasma perhexiline concentration > 0.06 microgram/ml (p < 0.01). We conclude that this study (a) suggests that PM exerts incremental antianginal effects over those of other antiischaemic agents in patients with acute coronary syndromes and (b) establishes that the development of nausea and/or dizziness in such patients is strongly predictive of accumulation of perhexiline beyond the therapeutic range of the drug.

Topics: Aged; Aged, 80 and over; Angina, Unstable; Calcium Channel Blockers; Cardiovascular Agents; Dizziness; Drug Monitoring; Female; Humans; Male; Middle Aged; Nausea; Perhexiline; Vasodilator Agents

Ranolazine is approved for patients with chronic stable angina but has not been formally studied in patients with refractory angina pectoris (RAP). Patients with RAP have limited therapeutic options and significant limitations in their quality of life. The Ranolazine Refractory Angina Registry was designed to evaluate the safety, tolerability, and effectiveness of ranolazine in RAP patients in order to expand treatment options for this challenging patient population. Using an extensive prospective database, we enrolled 158 consecutive patients evaluated in a dedicated RAP clinic. Angina class, medications, major adverse cardiac events including death, myocardial infarction, and revascularization were obtained at 12, 24, and 36 months. At 3 years, 95 (60%) patients remained on ranolazine. A ≥2 class improvement in angina was seen in 48% (38 of 80 patients with known Canadian Cardiovascular Society class) of those who remained on ranolazine. Discontinuation due to side effects, ineffectiveness, cost, and progression of disease were the principle reasons for discontinuation, but primarily occurred within the first year. In conclusion, ranolazine is an effective antianginal therapy at 3-year follow-up in patients with RAP and may reduce cardiac readmission.

Topics: Aged; Angina Pectoris; Cardiovascular Agents; Constipation; Deprescriptions; Diabetes Mellitus; Disease Progression; Dizziness; Drug Costs; Dyslipidemias; Edema; Female; Humans; Hypertension; Male; Medication Adherence; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Nausea; Ranolazine; Registries; Smoking; Treatment Failure; Treatment Outcome

Patient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process.. Concept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items.. During concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders.. Development of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program.

Topics: Aged; Aged, 80 and over; Cardiac Myosins; Cardiovascular Agents; Clinical Trials as Topic; Dizziness; Dyspnea; Edema; Fatigue; Female; Focus Groups; Heart Failure; Humans; Male; Middle Aged; Patient Reported Outcome Measures; Qualitative Research; Quality of Life; Sleep Initiation and Maintenance Disorders; United States; United States Food and Drug Administration; Urea

Adverse drug events (ADEs) are a substantial cause of hospital admissions. However, little is known about the incidence, preventability and severity of ADEs resulting in emergency department visits. To address this issue, we conducted a prospective survey in emergency departments of French public hospitals.. This study was performed over two periods of 1 week each, one in June 1999 and one in December 1999, in emergency departments of five university hospitals and five general hospitals throughout France. All patients aged>or=15 years presenting with medical complaints were included in the study. Trauma patients, those with gynaecological conditions and those with alcohol intoxication or intentional drug poisoning were excluded from the study. Each patient was assessed by two local emergency physicians to determine whether the visit was the result of an ADE. All medical records were subsequently validated by an independent group of medical lecturers in iatrogenic disorders.. Out of a total of 1937 patients consulting, 1562 were taking at least one drug during the previous week and were included for analysis; 328 (21%; 95% CI 19, 23) of these patients consulted an emergency physician because of an ADE. Patients with ADEs were older than those without (mean age 63.5 vs 54.8 years; p<0.0001). Furthermore, ADE patients were more likely to have a higher severity presentation than the non-ADE group (p=0.019). The number of drug exposures was significantly higher in patients with an ADE than in those without (mean number of medications 5.17 vs 3.82; p<0.0001). On multivariate analysis, only age and the number of medications taken were significantly associated with adverse events. In total, 410 drugs were incriminated in the occurrence of 328 ADEs. The most frequently incriminated drug classes were: (i) psychotropic agents (n=84; 20.5%); (ii) diuretics (n=48; 11.7%), anticoagulants (n=38; 9.3%) and other cardiovascular drugs (n=63; 15.4%); and (iii) analgesics, including NSAIDs (n=57; 13.9%). Preventability could be assessed in 280 of the 328 cases. In 106 cases (37.9%), the ADE was judged to be preventable.. ADEs leading to emergency department visits are frequent, and many are preventable, confirming that there is a need to develop prevention strategies.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Analgesics; Anticoagulants; Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System Agents; Diuretics; Dizziness; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Emergency Service, Hospital; Female; France; Gastrointestinal Diseases; Hospitals, General; Hospitals, University; Humans; Male; Middle Aged; Nervous System Diseases; Observer Variation; Prospective Studies; Time Factors