H2 Receptor Antagonists versus Proton Pump Inhibitors in Patients on Dual Antiplatelet Therapy for Coronary Artery Disease: A Systematic Review.

OBJECTIVES: Mitigating the gastrointestinal (GI) bleeding risks of dual antiplatelet therapy (DAPT) is a common clinical concern. While proton pump inhibitors (PPIs) remain the most effective therapy, their adverse events warrant considering alternatives, including Histamine 2 receptor antagonists (H2RAs). METHODS: We searched for randomized controlled trials in MEDLINE, EMBASE, PubMed, and Cochrane Central Register of Controlled Trials, published from 1980 to 2016. After screening, 10 trials were eligible. We compared PPIs to H2RAs in patients on DAPT in terms of 2 clinical and one laboratory outcomes; GI complications, major adverse cardiovascular events (MACE) and high on-treatment platelet reactivity (HTPR). Clinical and statistical inter-study heterogeneity was low for all 3 outcomes (I2 = 0%, p > 0.05 for all). RESULTS: Fixed effects meta-analysis suggested that PPIs were superior to H2RAs in preventing GI complications (OR 0.28, 95% CI 0.17-0.48) but with higher risk of HTPR (OR 1.28, 95% CI 1.030-1.60) though without a higher incidence of MACE (OR 0.99, 95% CI 0.55-1.77). CONCLUSIONS: PPIs are superior to H2RAs for gastroprotection in patients on DAPT. However, PPIs are associated with HTPR, with no significant difference demonstrated in MACE. Based on currently available data, the use of PPIs may be warranted in selected patients on DAPT deemed at risk for GI complications.

Importance of receptor regulation in the pathophysiology and therapy of congestive heart failure.

The available data indicate that the beta-adrenergic receptors that mediate positive inotropic responses undergo "down-regulation," a cellularly mediated decrease in surface receptor number, in congestive heart failure. This decrease in beta-adrenergic receptor number is proportional to the degree of myocardial dysfunction and the loss of contractility that occurs in congestive heart failure. It appears to be chamber-specific, occurring to the greatest degree in the most severely affected ventricular chamber, and is specific to the beta 1-adrenergic receptor subtype. Beta-adrenergic receptor down-regulation may be the result of the excessively high levels of plasma catecholamines seen in congestive heart failure, inasmuch as a similar phenomenon of beta-adrenergic receptor down-regulation is seen in animals treated with high doses of catecholamines. The specific down-regulation in cardiac beta receptors may be, in part, the cause of the decrease in myocardial function observed during long-term beta-adrenergic receptor stimulation, and an actual decrease in beta-adrenergic receptor number has been observed in myocardial tissue from patients with congestive heart failure. Down-regulation of beta receptors in congestive heart failure results in a decrease or loss of efficacy of beta-adrenergic receptor agonists on long-term administration. This is especially evident for partial agonists, which are more dependent on receptor number for their positive inotropic effects than full agonists. Although beta receptors are down-regulated in congestive heart failure, myocardial alpha 1-adrenergic receptors and histamine H2 receptors do not appear to be subject to this same regulatory process. Inasmuch as stimulation of both of these receptors results in a positive inotropic effect, further study should be given to the potential therapeutic utility of selective stimulation of myocardial alpha 1-adrenergic receptors and histamine H2 receptors in congestive heart failure. It is evident that the status of specific receptor subtypes in pathophysiologic states such as congestive heart failure must be considered when assessing the likelihood of success in treating patients with beta-adrenergic receptor agonists.

Adherence to proton pump inhibitors or H2-receptor antagonists during the use of non-steroidal anti-inflammatory drugs.

BACKGROUND: The efficacy of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) prescribed as prophylaxis for NSAID-related upper gastrointestinal (UGI) toxicity is dependent upon patient adherence. AIM: To describe patient adherence to prophylactically prescribed PPIs and H2RAs in the clinical setting. METHODS: We conducted a retrospective observational cohort study using the Integrated Primary Care Information Project database. The study population consisted of incident non-specific NSAID users prescribed a PPI or H2RA specifically as prophylaxis for NSAID-related UGI toxicity. Patients were classified as non-adherent if < 75% of days of NSAID use were covered by one of these agents, and as continuing users after discontinuation of NSAID use if they had a renewed prescription for these agents after their last NSAID prescription. RESULTS: The study cohort comprised 784 patients: 374 with H2RAs, 405 with PPIs, and 5 with both PPI and H2RA. Eighty-five percent of H2RA users and 7% of PPI users were prescribed these drugs at doses below the minimum recommended/effective dose for NSAID-associated gastroduodenal ulcer prophylaxis. Thirty-seven percent of patients were non-adherent. The lowest rate of non-adherence was associated with the first NSAID prescription (9%), increasing to 61% for patients with >/= 3 prescriptions. In a cohort of subjects who stopped their NSAID and were followed for up to 2 years (n = 711), there was significant persistent use of acid suppressive agents; 40% of patients had at least one additional prescription for the acid suppressive agent after stopping NSAIDs, and> 30% received enough drug to cover a period longer than 2 months after stopping their NSAID. CONCLUSIONS: The pattern of PPI and H2RA prescriptions, when prescribed as prophylactic strategy, does not correspond with the pattern of NSAID use. Physicians should consider the medical impact of non-adherence with dual therapies and the impact of prolonged use of GPAs on treatment cost.

Ambulatory intragastric pH monitoring: clinical laboratory to clinical practice.

Intragastric pH monitoring has become an important tool, used in the clinical laboratory to assess pharmacodynamic profiles of antisecretory agents. The technique is standardized, reproducible, and reliable. We have been able to compare antisecretory agents head-to-head, develop an understanding of interindividual variability in pH control with proton pump inhibitors, evaluate the role of H. pylori and its effect on intragastric pH, and gain insight into the potential role of genetic variation in cytochrome p450 status and its effect on pH control. These laboratory experiences can be used in clinical practice to aid in management of patients with gastroesophageal reflux disease.

The use of prophylactic gastroprotective therapy in patients with nonsteroidal anti-inflammatory drug- and aspirin-associated ulcer bleeding: a cross-sectional study.

BACKGROUND: Poor adherence to gastroprotective agents (GPAs) is common among users of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (ASA). There are little data on the utilization of GPAs among NSAID and ASA users complicated by ulcer bleeding. AIM: To study the utilization of GPA among NSAID and ASA ulcers before the onset of ulcer bleeding. METHODS: We conducted a cross-sectional study to determine the exposure to NSAIDs, ASA, and GPAs within 4 weeks before endoscopically confirmed ulcer bleeding. Sensitivity analysis was performed to study how improving adherence to GPA use would reduce the risk of ulcer bleeding in high-risk users. RESULTS: Between 2000 and 2009, 1093 and 2277 patients had NSAID- and ASA-associated ulcer bleeding respectively. The incidence of NSAID-associated ulcer bleeding declined by 40%, whereas that of ASA-associated ulcer bleeding increased by 46%. Thirty-nine per cent of NSAID users and 75% of ASA users belonged to high ulcer risk category. Although GPA prescription rate has increased over time, only 41.6% and 30.6% of high-risk NSAID and ASA users received GPAs before ulcer bleeding respectively. Sensitivity analysis showed that if GPAs could reduce bleeding risk by 50%, improving adherence would prevent up to 35% of ulcer bleeding in high-risk users. CONCLUSIONS: A substantial proportion of high-risk NSAID and ASA users had not received prophylaxis with gastroprotective agents before ulcer bleeding. These bleeding episodes may be preventable with better adherence to gastroprotective agent use.

Un nuevo Bloqueador H2 en el tratamiento de la Ulcera Duodenal

Se presenta un estudio doble ciego comparativo entre la famotidina bloqueador H2, la ranitidina y el placebo, para estudiar la cicatrización de la úlcera duadenal en 12 pacientes de edades comprendidas entre 21 y 61 años, 8 hombres, 4 mujeres quienes iniciaron su estudio con presencia de úlcera duodenal, endoscópica y fotográficamente identificada y que fueron observados a la 2a., 4a., 8a., 24a., y 48a. semanas, y en secuencia continuada durante 12 meses para confirmar la cicatrización permanente de la lesión. Los pacientes que han seguido la observación de tres años de seguimiento se mantuvieron curados de la úlcera identificada al iniciar el estudio. En el lapso mencionado no se presentaron efectos colaterales de ninguna especie tanto clínicos como biométricos, hecho significativo para el uso de la famotidina en el tratamiento de la úlcera duodenal