Pharmacology of new treatments for hyperkalaemia: patiromer and sodium zirconium cyclosilicate.

Hyperkalaemia is a life-threatening condition, resulting from decreased renal function or dysfunctional homoeostatic mechanisms, often affecting patients with cardiovascular (CV) disease. Drugs such as renin-angiotensin-aldosterone system inhibitors (RAASi) are known to improve outcomes in CV patients but can also cause drug-induced hyperkalaemia. New therapeutic options exist to enhance potassium excretion in these patients. To this aim, we reviewed pharmacological properties and available data on patiromer and sodium zirconium cyclosilicate for the treatment of hyperkalaemia. These agents have been shown in randomized trials to significantly reduce serum potassium in patients with hyperkalaemia on renin-angiotensin-aldosterone system inhibitors. Additional research should focus on their long-term effects/safety profiles and drug-drug interactions

Pharmacology of new treatments for hyperkalaemia: patiromer and sodium zirconium cyclosilicate.

Hyperkalaemia is a life-threatening condition, resulting from decreased renal function or dysfunctional homoeostatic mechanisms, often affecting patients with cardiovascular (CV) disease. Drugs such as renin-angiotensin-aldosterone system inhibitors (RAASi) are known to improve outcomes in CV patients but can also cause drug-induced hyperkalaemia. New therapeutic options exist to enhance potassium excretion in these patients. To this aim, we reviewed pharmacological properties and available data on patiromer and sodium zirconium cyclosilicate for the treatment of hyperkalaemia. These agents have been shown in randomized trials to significantly reduce serum potassium in patients with hyperkalaemia on renin-angiotensin-aldosterone system inhibitors. Additional research should focus on their long-term effects/safety profiles and drug-drug interactions

Hyperkalemia and Renin-Angiotensin-Aldosterone System Inhibitors Dose Therapy in Heart Failure With Reduced Ejection Fraction.

Renin-angiotensin-aldosterone system inhibitors (RAASi) are known to improve outcomes in patients who have heart failure with reduced ejection fraction (HFrEF). To reduce mortality in these patients, RAASi should be uptitrated to the maximally tolerated dose. However, RAASi may also cause hyperkalemia. As a result of this side-effect, doses of RAASi are reduced, discontinued and seldom reinstated. Thus, the therapeutic target needed in these patients is often not reached because of hyperkalemia. Also, submaximal dosing of RAASi may be a result of symptomatic hypotension, syncope, hypoperfusion, reduced kidney function and other factors. The reduction of RAASi dose leads to adverse outcomes, such as an increased risk of mortality. Management of these side-effects is pivotal to maximise the use of RAASi in HFrEF, particularly in high-risk patients

Monitoring of biomarkers in heart failure.

The role of biomarkers is increasingly recognized in heart failure (HF) management, for diagnosis, prognostication, and screening of high-risk patients. Beyond natriuretic peptides and troponins, the utility of novel, emerging biomarkers is less established. This document reflects the key points of a Heart Failure Association of the European Society of Cardiology (ESC) consensus meeting on biomarker monitoring in HF

The age of randomized clinical trials: three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid and diabetes trials.

Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiovascular (CV) therapy. The cornerstone of RCTs is the recording of hard clinical endpoints instead of surrogates. It is important to select an appropriate endpoint. Efficacy endpoints must be clinically relevant and can be hierarchically divided. A very interesting innovation in endpoint acquisition is the total event paradigm

Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events.

Awareness of racial/ethnic disparities represents a key challenge for healthcare systems that attempt to provide effective healthcare and to reduce existing inequalities in the use of and adherence to guideline-recommended cardiovascular drugs to improve clinical outcomes for cardiovascular disease (CVD). In this review, we describe important racial/ethnic differences between and within ethnic groups in the prevalence, risk factors, haemostatic factors, anti-inflammatory and endothelial markers, recurrence, and outcomes of CVD. We discuss important differences in the selection, doses, and response [efficacy and adverse drug reactions (ADRs)] in ethnically diverse patients treated with antithrombotics or lipid-lowering drugs. Differences in drug response are mainly related to racial/ethnic differences in the frequency of polymorphisms in genes encoding drug-metabolizing enzymes (DMEs) and drug transporters. These polymorphisms markedly influence the pharmacokinetics, dose requirements, and safety of warfarin, clopidogrel, and statins. This review aims to support a better understanding of the genetic differences between and among populations to identify patients who may experience an ADR or a lack of drug response, thus optimizing therapy and improving outcomes. The greater the understanding of the differences in the genetic variants of DMEs and transporters that determine the differences in the exposure, efficacy, and safety of cardiovascular drugs between races/ethnicities, the greater the probability that personalized medicine will become a reality

Psychosocial factors during the first year after a coronary heart disease event in cases and referents. Secondary Prevention in Uppsala Primary Health Care Project (SUPRIM)

<p>Abstract</p> <p>Background</p> <p>A large number of studies have reported on the psychosocial risk factor pattern prior to coronary heart disease events, but few have investigated the situation during the first year after an event, and none has been controlled. We therefore performed a case-referent study in which the prevalence of a number of psychosocial factors was evaluated.</p> <p>Methods</p> <p>Three hundred and forty-six coronary heart disease male and female cases no more than 75 years of age, discharged from hospital within the past 12 months, and 1038 referents from the general population, matched to the cases by age, sex and place of living, received a postal questionnaire in which information on lifestyle, psychosocial and quality of life measures were sought.</p> <p>Results</p> <p>The cases were, as expected, on sick leave to a larger extent than the referents, reported poorer fitness, poorer perceived health, fewer leisure time activities, but unexpectedly reported better social support, and more optimistic views of the future than the referents. There were no significant case-referent differences in everyday life stress, stressful life events, vital exhaustion, depressive mood, coping or life orientation test. However, women reported less favourable situations than men regarding stressful life events affecting others, vital exhaustion, depressive mood, coping, self-esteem, sleep, and symptom reporting, and female cases reported the most unfavourable situation of all groups.</p> <p>Conclusion</p> <p>In this first controlled study of the situation during the first year after a CHD event disease and gender status both appeared to be determinants of psychological well-being, with gender status apparently the strongest. This may have implications for cardiac rehabilitation programmes.</p

Physical distress is associated with cardiovascular events in a high risk population of elderly men

Background Self-reported health perceptions such as physical distress and quality of life are suggested independent predictors of mortality and morbidity in patients with established cardiovascular disease. This study examined the associations between these factors and three years incidence of cardiovascular events in a population of elderly men with long term hyperlipidemia. Methods We studied observational data in a cohort of 433 men aged 64–76 years from a prospective, 2 × 2 factorial designed, three-year interventional trial. Information of classical risk factors was obtained and the following questionnaires were administered at baseline: Hospital Anxiety and Depression Scale, Physical Symptom Distress Index and Life Satisfaction Index. The occurrence of cardiovascular death, myocardial infarction, cerebrovascular incidences and peripheral arterial disease were registered throughout the study period. Continuous data with skewed distribution was split into tertiles. Hazard ratios (HR) were calculated from Cox regression analyses to assess the associations between physical distress, quality of life and cardiovascular events. Results After three years, 49 cardiovascular events were registered, with similar incidence among subjects with and without established cardiovascular disease. In multivariate analyses adjusted for age, smoking, systolic blood pressure, serum glucose, HADS-anxiety and treatment-intervention, physical distress was positively associated (HR 3.1, 95% CI 1.2 – 7.9 for 3rd versus 1st tertile) and quality of life negatively associated (HR 2.6, 95% CI 1.1–5.8 for 3rd versus 1st tertile) with cardiovascular events. The association remained statistically significant only for physical distress (hazard ratio 2.8 95% CI 1.2 – 6.8, p < 0.05) when both variables were evaluated in the same model. Conclusion Physical distress, but not quality of life, was independently associated with increased risk of cardiovascular events in an observational study of elderly men predominantly without established cardiovascular disease. Trial Registration Trial registration: NCT0076401

2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC).

peer reviewe

The age of randomized clinical trials: three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid, diabetes, and antithrombotic trials.

This review article aims to explain the important issues that data safety monitoring boards (DSMB) face when considering early termination of a trial and is specifically addressed to the needs of clinical and research cardiologists. We give an insight into the overall background and then focus on the three principal reasons for stopping trials, i.e. efficacy, futility, and harm. The statistical essentials are also addressed to familiarize clinicians with the key principles. The topic is further highlighted by numerous examples from lipid trials and antithrombotic trials. This is followed by an overview of regulatory aspects, including an insight into industry–investigator interactions. To conclude, we summarize the key elements that are the basis for a decision to stop a randomized clinical trial (RCT)