Diversity and Representation Among United States Participants in Amgen Clinical Trials.

OBJECTIVE: Describe the demographic profile of US participants in Amgen clinical trials over a 10-year period and variations across therapeutic areas, indications, and geographies. METHODS: Cross-sectional retrospective study including participants enrolled (2005-2020) in phase 1-3 trials completed between January 1, 2012 and June 30, 2021. RESULTS: Among 31,619 participants enrolled across 258 trials, one-fifth represented racial minority populations (Asian, 3%; Black or African American, 17%; American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, multiracial, each < 1%); fewer than one-fifth (16%) represented an ethnic minority population (Hispanic or Latino). Compared with census data, representation of racial and ethnic groups varied across US states. Across most therapeutic areas (bone, cardiovascular, hematology/oncology, inflammation, metabolic disorders, neuroscience) except nephrology, participants were predominantly White (72-81%). A similar proportion of males and females were enrolled between 2005 and 2016; male representation was disproportionately higher than female between 2016 and 2020. Across most medical indications, the majority of participants were 18-65 years of age. CONCLUSIONS AND RELEVANCE: While the clinical research community is striving to achieve diversity and proportional representation across clinical trials, certain populations remain underrepresented. Our data provide a baseline assessment of the diversity and representation of US participants in Amgen-sponsored clinical trials and add to a growing body of evidence on the importance of diversity in clinical research. These data provide a foundation for strategies aimed at supporting more equitable and representative research, and a baseline from which to assess the impact of future strategies to advance health equity.

Lipid Modification to Reduce Cardiovascular Risk in Secondary Prevention Patients with Special Emphasis on PCSK9 Inhibitor Requirement: An Analysis Based on Delphi Panel Approach.

OBJECTIVE: The aim of this study is to analyze the low-density lipoprotein cholesterol-lowering therapies in secondary prevention patients by analyzing their plasma low-density lipoprotein cholesterol levels, current treatment, considering their inadequate response to medications (as defined in current guidelines), and the requirement for a protein convertase subtilisin/kexin type 9 inhibitor. METHODS: Delphi panel is used to seek expert consensus of experienced 12 cardiologists. A questionnaire consisting of 6 main questions is used to reflect the opinion of the expert panelists on the practices of low-density lipoprotein cholesterol-lowering therapies of patients with high and very high cardiovascular risk. Patients with atherosclerotic cardiovascular disease are covered in this present analysis. RESULTS: According to expert opinion data, 18.6% of the patient population with atherosclerotic cardiovascular disease is estimated to have experienced recurrent vascular events. The current treatment of the patient population is 39.7% on high dose, 36.9% on low/moderate dose of statin, 13.1% on maximum tolerated dose statin+ezetimibe, and 1.2% on maximum tolerated dose statin+ezetimibe+protein convertase subtilisin/kexin type 9 inhibitor. The percentage of atherosclerotic cardiovascular disease patients with inadequate treatment response is estimated to be 20.2% in those using "maximum tolerated dose statin+ezetimibe." The proportion of patients who will need to be treated with a protein convertase subtilisin/kexin type 9 inhibitor increases as their low-density lipoprotein cholesterol levels rises from 9.1% in 70-99 mg/dL to 50.8% in ≥160 mg/dL for these patients. CONCLUSION: According to expert opinion, although a substantial proportion of patients with secondary prevention have not achieved low-density lipoprotein cholesterol goals, the use of protein convertase subtilisin/kexin type 9 inhibitors is very low. Since the questionnaire subject to panel discussion did not include any question elaborating the issue, the discrepancy between the recommendation of the related guidelines and Turkish practice needs further studies for the explanation.

[Evaluation of statin use on LDL cholesterol levels in Turkey: A systematic review]. / Türkiye'de statin kullaniminin LDL-kolesterol düzeyleri üzerine etkisinin degerlendirildigi sistematik derleme.

OBJECTIVE: The aim of this study was to examine and present the effect of statin treatment on the low-density lipoprotein (LDL) cholesterol level of patients in Turkey by evaluating the data of studies conducted in the country. METHODS: Manuscripts published between January 1, 2008 and December 31, 2017 with terms 'LDL' and 'TURK' in the title or abstract and reporting LDL cholesterol data of patients treated with statins were evaluated for inclusion in the study. From the initial search result a total of 1795 papers, 39 manuscripts with 63 study arms were selected for analysis and the data of 3486 patients were included. Descriptive analysis was used to assess the data. Weighted averages of the data were also calculated. RESULTS: The female/male ratio was 42/58. The mean age was 52.9±10.1 years. The proportion of patients with the recommended LDL cholesterol level of <70 mg/dL after treatment with statins was 15.3%;. In all, 10.2% of the patients who were prescribed a low-dose statin and 28.0% of those who were prescribed a high-dose statin had an LDL cholesterol of <70 mg/dL after treatment. Among patients who were being treated with statins for ≤2 months, 25.7% achieved an LDL cholesterol level of <70 mg/dL. Among those who were being treated with statins for 2-4 months and >4 months the proportion was 11.4% and 9.7%, respectively. The percentage of patients at the target level was 21.8%, 21.7%, 17.9%;, 8.6%, and 0.8% among those using atorvastatin, simvastatin, rosuvastatin, fluvastatin, and pravastatin, respectively. CONCLUSION: In Turkey, only 15% of the patients who had received statin therapy had a LDL cholesterol level of <70 mg/dL. Revision of the current treatment should be considered to reach the target levels recommended in the guidelines, especially for patients with high cardiovascular risk.

Renin-angiotensin-aldosterone system blockers and cardiovascular outcomes: a meta-analysis of randomized clinical trials.

OBJECTIVE: Hypertension is the most prevalent modifiable risk factor for cardiovascular (CV) and cerebrovascular morbidity and mortality. This study aimed to assess the effects of renin-angiotensin-aldosterone system (RAAS) blockade on CV outcomes. METHODS: This study was designed according to the Preferred Reporting Items for Systemic reviews and Meta-Analyses statement. Databases were searched for articles published as of December 2014. Two sets of studies were selected. One set included randomized clinical trials comparing RAAS blocker (angiotensin II receptor blocker [ARB] or angiotensin-converting enzyme inhibitor [ACEI]) with placebo or active treatment. Second set included head-to-head randomized clinical trials comparing an ARB with an ACEI. Studies in both sets had reported any CV outcome parameter or death, i.e., all-cause mortality, CV mortality, emergence of CV events, myocardial infarction, cerebrovascular event, stroke, heart failure, and hospitalization for heart failure. RESULTS: Fifty-four pairwise comparisons of 51 trials with 277,609 patients were included. Statistically significant differences in favor of RAAS blockers vs non-RAAS blockers (risk ratio [RR] ranging from 0.805 to 0.967) were observed in terms of most CV outcomes, including all-cause mortality, CV mortality, CV events, myocardial infarction, heart failure and stroke. ARBs and ACEIs were found to be completely comparable (RR ranging from 0.923 to 1.090, all non-significant). CONCLUSION: RAAS blockers are superior to medications other than RAAS blockers with respect to impact on CV outcomes in patients with hypertension. ARBs and ACEIs are comparable in terms of these outcomes.

Cost of heart failure management in Turkey: results of a Delphi Panel.

OBJECTIVE: To analyze health-related cost of heart failure (HF) and to evaluate health-related source utilization aiming to provide data on the economic burden of HF in actual clinical practice in Turkey. METHODS: The study used the Delphi process of seeking expert consensus of opinion including 11 cardiologists who are experienced in HF. The standardized questionnaire comprised items to reflect the opinion of the expert panelists on the distribution of the HF patients in terms of demographic and clinical characteristics and background disease states. Costs related to out-patient follow-up, in-patient follow-up, medications, and other therapies were also evaluated. RESULTS: 34.1% of the HF patients were in the age range of 60-69 years, and 62.3% were males. Coronary heart disease was the leading cause of HF (59.6%); 63.6% of the HF patients had reduced ejection fraction (rEF) and 42.3% were in New York Heart Association (NYHA)-II class. Approximately 75 % of the patients were followed up by a cardiology unit. The total annual visit number was estimated as 3.41. Approximately 32% of HF patients were hospitalized 1.64 times a year, for an average of 6.77 days each time. The total annual costs of all HF patients and HF-rEF patients were estimated as 1.537 TL and as 2.141 TL, respectively. CONCLUSION: The analysis demonstrating the magnitude of the economic impact of HF management on Turkey's healthcare system may help facilitate health and social policy interventions to improve the prevention and treatment of HF.

The most critical question when reading a meta-analysis report: Is it comparing apples with apples or apples with oranges?

OBJECTIVE: While the number of meta-analyses published has increased recently, most of them have problems in the design, analysis, and/or presentation. An example of meta-analyses with a study selection bias is a meta-analysis of over 160,000 patients in 20 clinical trials, published in Eur Heart J in 2012 by van Vark, which concluded that the significant effect of renin-angiotensin-aldosterone system (RAAS) inhibition on all-cause mortality was limited to the class of angiotensin-converting enzyme inhibitors (ACEIs), whereas no mortality reduction could be demonstrated with angiotensin receptor blockers (ARBs). Here, we aimed to discuss how to select studies for a meta-analysis and to present our results of a re-analysis of the van Vark data. METHODS: The data were re-analyzed in three steps: firstly, only ACEI/ARB-based studies (4 ACEI and 12 ARB studies) were included; secondly, placebo-controlled studies were excluded, and 10 studies left were analyzed; and thirdly, 2 studies that were retracted after the manuscript of van Vark had been published were excluded. The final analysis included 8 studies with ~65,000 patients (3 ACEI and 5 ARB studies). RESULTS: The hazard ratios for all-cause mortality and cardiovascular mortality were 0.992 (95% CI 0.899-1.095; p=0.875) and 1.017 (0.932-1.110; p=0.703) for the ACEI versus control group and 1.007 (0.958-1.059; p=0.778) and 0.967 (0.911-1.025; p=0.258) for the ARB versus control group in the first step. The results were similar in the second and third steps. CONCLUSION: The studies to be included in meta-analyses, particularly comparing ACEIs and ARBs, should be chosen carefully.

Efficacy and safety of valsartan/amlodipine single-pill combination in patients with essential hypertension (PEAK LOW).

OBJECTIVES: This study evaluated the efficacy as well as the safety and tolerability profile of low-dose valsartan/amlodipine (Val/Amlo) single-pill combination (SPC) (160/5 mg) in patients with essential hypertension in Turkey. STUDY DESIGN: Adult patients with essential hypertension [systolic blood pressure (SBP)>140 mmHg and/or diastolic blood pressure (DBP)>90 mmHg], who were on low dose Val/Amlo (160/5 mg) SPC before enrollment and gave informed consent, were accepted for this multi-centric observational study performed at 30 sites. The absolute changes in SBP and DBP from baseline were the primary efficacy outcomes. Safety assessments consisted of recording all adverse events. RESULTS: Of 381 patients enrolled, 327 completed the study; 39% were females. The mean age was 57.3±11.8 years. Median duration of hypertension was 38 months. Both SBP and DBP values showed reductions from 162.6±16.6 mmHg and 94.0±13.2 mmHg to 137.6±14.2 mmHg and 81.9±9.0 mmHg at 4th week and to 131.6±11.5 mmHg and 79.7±7.6 mmHg at 12th week, respectively. The control and response rates at the end of the study were 82.0% and 92.6%, respectively. Twelve patients (3.2%) experienced a total of 12 adverse events; there were no serious adverse events. The most common adverse event was edema (1.3%). Patient compliance was approximately 99%. CONCLUSION: Low-dose (160/5 mg) Val/Amlo SPC is efficacous and has a good tolerability and safety profile for the management of essential hypertension in Turkey.

Hypertension and valsartan.

Hypertension, which is pointed to be the most frequent cause of death in the World and in Turkey and defined by the World Health Organization as global health crisis and the prominent risk factor for cardiovascular diseases, is a problem threatening public health. Renin-angiotensin system (RAS) plays an important role in pathophysiology and in turn treatment of the disease. The drugs suppressing RAS are recommended both for monotherapy and combinations. Together with the blood pressure lowering effects and positive contributions of this group of drugs to the cardiovascular and renal process have been proved by clinical studies. In this review, the recent developments about the hypertension treatment were summarized and the place of valsartan molecule, being an angiotensin receptor blocker in hypertension treatment, was examined in the light of the studies in which the effectiveness, tolerability and safety of valsartan were evaluated.

Efficacy and safety of valsartan and amlodipine single-pill combination in hypertensive patients (PEAK study).

OBJECTIVES: This study was designed to assess the safety, compliance and efficacy of amlodipine (Aml) and valsartan (Val) single-pill combination (SPC) in a large hypertensive patient population. STUDY DESIGN: This is a non-interventional, observational, open label study conducted in 166 centers in Turkey with a 24-week follow-up period. RESULTS: Of the 1184 enrolled patients, two-thirds were female (62.2%). The mean age was 57.7±11.3 years, and 26.1% of the patients were older than 65 years. The majority of patients (82.3%) were overweight or obese. During the course of the study, 150 (12.7%) patients experienced a total of 174 adverse events (AEs). The overall mean (SD) compliance rate was determined to be 96.9 (0.2)%. The most commonly reported AE was edema, with a new-onset edema incidence of 6.7%. In the entire group, Aml/Val SPC significantly reduced both systolic and diastolic blood pressure (BP), with a reduction of 29.6±0.9 / 14.7±0.6 mmHg (for each, p<0.001). CONCLUSION: As a result of the low incidences of AEs and new-onset edema, the safety profile of Aml/Val SPC proved to be optimal. Aml/Val SPC reduced BP efficiently and met the needs of most patients to achieve the targets. Aml/Val SPC seems to be a beneficial option for effective BP control, which is a key factor influencing cardiovascular outcome.

The efficacy and safety of triple vs dual combination of angiotensin II receptor blocker and calcium channel blocker and diuretic: a systematic review and meta-analysis.

Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple combination of angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Medical literature between January 1990 and April 2012 was reviewed systematically and data from eligible studies were abstracted. Data were analyzed using random-effects models. Of the 224 studies screened, 7563 eligible patients from 11 studies were included. Triple combinations of ARBs (olmesartan or valsartan), CCBs (amlodipine), and diuretics (hydrochlorothiazide) at any dose provided more blood pressure reduction in office and 24-hour ambulatory measurements than any dual combination of these molecules (P<.0001 for both). Significantly more patients achieved blood pressure targets with triple combinations (odds ratio, 2.16; P<.0001). Triple combinations did not increase adverse event risk (odds ratio, 0.96; P=.426). Triple combinations at any dose seem to decrease blood pressure more effectively than dual combination of the same molecules without any remarkable risk elevation for adverse events. Further prospective studies evaluating the efficacy and safety of triple combinations, especially in the form of single pills, are required.