Ohman, E. Magnus

Hypertension is the single most important modifiable risk factor for preventable disability and death worldwide and disproportionately affects socially disadvantaged populations. We face a paradox—blood pressure control is low and recent trends suggest it is even declining, despite the availability of inexpensive and effective therapies. A variety of barriers on the system, patient, and healthcare provider side hinder effective drug-based risk factor management. Clinical inertia represents a major barrier on the clinician side, as well as workload and limited education. Common barriers on the patient side include limited English proficiency, low health literacy, and nonadherence with misaligned incentives, limited resources, lack of structured clinical pathways, and reimbursement issues. New innovations in the field of RNA-targeted therapies and device-based interventions could prevent and potentially even cure diseases previously designated as chronic health conditions, such as hypertension. Such novel therapies could potentially overcome several major barriers to effective treatment, including nonadherence. Drug development of novel, long-acting treatments requires consideration of specific clinical trial design aspects, including safety collection, benefit: risk assessment, the development and assessment of novel, qualitative surrogate end points, such as time-in-therapeutic range, the use of representative trial settings as well as the definition of standard of care in placebo-controlled trials, which should be of reasonably high-quality allowing for credible evaluation of effectiveness. Here, we provide an overview on barriers to effective treatment and a framework for trials assessing novel treatments for cardiovascular disease risk factors, including early and broad implementation programs.

Abstract Objectives To evaluate the periprocedural characteristics and outcomes of patients supported with Impella 2.5 prior to percutaneous coronary intervention (pre‐PCI) versus those who received it after PCI (post‐PCI) in the setting of cardiogenic shock (CS) complicating an acute myocardial infarction (AMI). Background Early mechanical circulatory support may improve outcome in the setting of CS complicating an AMI. However, the optimal timing to initiate hemodynamic support has not been well characterized. Methods Data from 154 consecutive patients who underwent PCI and Impella 2.5 support from 38 US hospitals participating in the USpella Registry were included in our study. The primary end‐point was survival to discharge. Secondary end‐points included assessment of patients' hemodynamics and in‐hospital complications. A multivariate regression model was used to identify independent predictors for mortality. Results Both groups were comparable except for diabetes (P = 0.02), peripheral vascular disease (P = 0.008), chronic obstructive pulmonary disease (P = 0.05), and prior stroke (P = 0.04), all of which were more prevalent in the pre‐PCI group. Patients in the pre‐PCI group had more lesions (P = 0.006) and vessels (P = 0.01) treated. These patients had also significantly better survival to discharge compared to patients in the post‐PCI group (65.1% vs.40.7%, P = 0.003). Survival remained favorable for the pre‐PCI group after adjusting for potential confounding variables. Initiation of support prior to PCI with Impella 2.5 was an independent predictor of in‐hospital survival (Odds ratio 0.37, 95% confidence interval: 0.17–0.79, P = 0.01) in multivariate analysis. The incidence of in‐hospital complications included in the secondary end‐point was similar between the 2 groups. Conclusions The results of our study suggest that early initiation of hemodynamic support prior to PCI with Impella 2.5 is associated with more complete revascularization and improved survival in the setting of refractory CS complicating an AMI. (J Interven Cardiol 2014;27:1–11)

Background —A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation. Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed. The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States. Methods and Results —Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase–MB elevation were eligible for enrollment. Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States. Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours. Other medical therapies and revascularization strategies were at the discretion of the treating physician. Eptifibatide reduced the rate of the primary end point of death or myocardial infarction by 30 days from 15.4% to 11.9% ( P =0.003) among patients in the United States. The treatment effect was achieved early and maintained over a period of 6 months (18.9% versus 15.2%; P =0.004). Bleeding events were more common in patients receiving eptifibatide but were predominantly associated with invasive procedures. The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world. Conclusions —Platelet glycoprotein IIb/IIIa receptor blockade with eptifibatide reduces the incidence of death or myocardial infarction among patients treated for acute ischemic syndromes without ST-segment elevation within the United States.

Background— Outcomes in patients with mild to moderate renal function (RF) abnormalities presenting with acute coronary syndromes (ACS) are not well defined. Methods and Results— A convenience sample of 4 ACS trial databases including all enrolled patients was assessed to determine 30- and 180-day outcomes. The 4 trials were Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb, GUSTO-III, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A). Patients were stratified into ST-segment elevation (STE) and non–ST-segment elevation (NSE) groups and by the presence or absence of abnormal RF (creatinine clearance <70 mL/min). In the STE group, 7670 of 18 621 patients (41%) had abnormal RF. In the NSE group, 8152 of 19 304 (42%) had abnormal RF. Patients with abnormal RF were older, more often female, and more likely to have adverse baseline characteristics. They had higher mortality and higher mortality/nonfatal myocardial infarction (MI) at both 30 and 180 days, regardless of ST-segment status. Creatinine clearance was independently associated with risk of mortality (hazard ratio 0.79 in the STE group and 0.81 in the NSE group) and with risk of mortality/MI (hazard ratio 0.93) in the NSE group at 180 days. Conclusions— Patients presenting with ACS frequently have abnormal RF. Abnormal RF is a marker of adverse baseline clinical characteristics and is independently associated with increased risk of death and death/MI.