Sitagliptin and the risk of hospitalization for heart failure: A population-based study

Background

Saxagliptin was associated with an increased risk of hospitalization for heart failure (HHF) in diabetic patients with high cardiovascular risk. This study assessed the risk of HHF during an exposure to sitagliptin in general diabetic patients.

Methods

In Taiwan National Health Insurance research database, a study of the beneficiaries aged ≥ 45 years with diabetes treated with or without sitagliptin between March 2009 and July 2011 was conducted. Patients treated with sitagliptin were matched to patients never exposed to a dipeptidyl peptidase-4 (DPP-4) inhibitor by the propensity score methodology. The outcome measures were the first and the total number of HHF, and mortality for heart failure or all causes.

Results

A total of 8288 matched pairs of patients were analyzed. During a median of 1.5 years, the first event of HHF occurred in 339 patients with sitagliptin and 275 patients never exposed to a DPP-4 inhibitor (hazard ratio: 1.21, 95% confidence interval: 1.04–1.42, P = 0.017); all-cause mortality was similar (hazard ratio: 0.87, 95% confidence interval: 0.74–1.03, P = 0.109). The risk for HHF was proportional to exposure (hazard ratio: 1.09, 95% confidence interval: 1.06–1.11, P < 0.001 for every 10% increase in adherence to sitagliptin). Overall, there were 935 events of HHF, in which the association between the number of HHF and the adherence to sitagliptin was linear. The greatest total number of HHF occurred in the patients with the highest adherence.

Conclusions

The use of sitagliptin was associated with a higher risk of HHF but no excessive risk for mortality was observed.     

Cotreatment with the α-glucosidase inhibitor miglitol and DPP-4 inhibitor sitagliptin improves glycemic control and reduces the expressions of CVD risk factors in type 2 diabetic Japanese patients

Objective

In this study, we examined whether inhibition of postprandial hyperglycemia by combination therapy with two drugs for reducing postprandial hyperglycemia, i.e., α-glucosidase inhibitor miglitol and dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin, improves glycemic control and reduces the risk of cardiovascular disease (CVD) development.

Materials/Methods

We enrolled 32 type 2 diabetic Japanese patients with hemoglobin A1c (HbA1c) levels ranging from 6.9% to 10.5%, who had been treated for at least 2 months with 50 mg miglitol (t.i.d.) or 50 mg sitagliptin (q.d.). Following a monotherapy period with either miglitol (Group-M) or sitagliptin (Group-S) for 1 month, the patients were subjected to combination therapy with sitagliptin and miglitol for 3 months. Meal tolerance tests were performed at the end of the monotherapy and combination therapy.

Results

Combination therapy for 3 months after monotherapy reduced HbA1c (changes: Group-M: − 1.3% ± 0.7%, P < 0.001; Group-S: − 0.6% ± 0.5%, P < 0.001) and glycoalbumin levels and increased 1,5-anhydroglucitol concentrations in the blood. In the meal tolerance tests, circulating active glucagon-like peptide-1 levels were elevated in both groups, while active glucose-dependent insulinotropic polypeptide levels were reduced by combination therapy in the group with add-on miglitol therapy. The plasma protein concentrations of interleukin (IL)-8 and adhesion molecules (sE-selectin and sVCAM-1) were reduced by switching to the combination therapy, in particular with the add-on miglitol therapy.

Conclusions

Our results suggest that combination therapy with miglitol and sitagliptin improves glycemic control and reduces the circulating protein concentrations of IL-8, sE-selectin, and sVCAM-1 in type 2 diabetic Japanese patients.     

The dipeptidyl peptidase-4 inhibitor-sitagliptin modulates calcium dysregulation,inflammation, and PPARs in hypertensive cardiomyocytes

Background

Hypertension induces cardiac dysfunction, calcium (Ca^2 +) dysregulation, and arrhythmogenesis. Dipeptidyl peptidase (DPP)-4 inhibitors, an antidiabetic agent with anti-inflammation and anti-hypertension potential, may regulate peroxisome proliferator-activated receptors (PPARs)-α, -γ, and -δ and Ca^2 + homeostasis.

Objective

The purpose of this study was to investigate whether DPP-4 inhibitor, sitagliptin, can modulate PPARs and Ca^2 + handling proteins in hypertensive hearts.

Methods

A Western blot analysis was used to evaluate protein expressions of myocardial PPAR isoforms, tumor necrosis factor (TNF)-α, interleukin (IL)-6, sarcoplasmic reticulum ATPase (SERCA2a), Na⁺–Ca^2 + exchanger (NCX), ryanodine receptor (RyR), voltage-dependent Ca^2 + (CaV1.2), slow-voltage potassium currents (Kvs), angiotensin II type 1 receptor (AT1R), and receptor of advanced glycated end-products (RAGE) from Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and SHR treated with sitagliptin (10 mg/kg for 4 weeks). Conventional microelectrodes were used to record action potentials (APs) in the ventricular myocytes from each group.

Results

Compared to the control group, SHR had lower cardiac PPAR-α and PPAR-δ protein expressions, but had greater cardiac PPAR-γ levels, and TNF-α, IL-6, RAGE, and AT1R protein expressions, which were ameliorated in the sitagliptin-treated SHR. SHR had prolonged QT interval and AP duration with less SERCA2a and RyR, and greater CaV1.2 expressions, which were also attenuated in sitagliptin-treated SHR.

Conclusions

Sitagliptin significantly changed the cardiac electrophysiological characteristics and Ca^2 + regulation, which may have been caused by its effects on cardiac PPARs, proinflammatory cytokines, and AT1R.     

Efficacy of trimetazidine on functional capacity in symptomatic patients with stable exertional angina — The VASCO-angina study

Background/objectives

Trimetazidine (TMZ) is a metabolic agent of proven efficacy in improving myocardial ischemia and angina. VASCO, a randomised double-blinded, placebo-controlled trial, assessed anti-anginal efficacy and safety of standard and high dose of modified-release TMZ (70 mg/d and 140 mg/d) in symptomatic and asymptomatic patients with chronic ischemic heart disease receiving background atenolol 50 mg/d on exercise test parameters.The VASCO-angina study assessed the efficacy of the two doses of TMZ on total exercise duration (TED) and time to 1-mm ST segment depression (T1), in symptomatic patients with chronic stable angina receiving background atenolol treatment.

Methods and results

In the all cohort of chronic stable angina patients TMZ significantly improved TED compared to baseline and to placebo. Both doses of TMZ significantly increased TED (p = 0.0044 and p = 0.0338 for TMZ 140 mg/d and TMZ 70 mg/d, respectively). A greater TED improvement was observed in TMZ 140 mg/d than in TMZ 70 mg/d, although the difference was not significant. Amongst patients with limiting angina during exercise test, both doses of TMZ significantly improved both T1 and TED. No difference in serious adverse events was noted between TMZ and placebo.

Conclusions

The VASCO-angina gives evidence for the efficacy and tolerability of standard and high dose of TMZ in improving effort-induced myocardial ischemia and functional capacity in patients with chronic stable angina receiving background beta-blockers.     

Response of QT interval in methadone maintenance treated patients to the rapid changes in heart rate provoked by brisk standing: Comparison to healthy controls and patients with long QT syndrome

Background

Patients on methadone maintenance therapy are somehow similar to patients with congenital long QT syndrome (LQTS) because they have malfunction of potassium channels caused by a drug that cannot be easily discontinued. We tested patients on methadone therapy with the “stand-up” test, which has been shown to unravel pathologic QT-prolongation in congenital long-QT patients.

Methods

“Stand-up” test results of methadone-users, healthy volunteers and congenital LQTS patients were compared. Methadone serum levels and doses were collected. The prognostic value of the test was evaluated after 4 years of follow-up.

Results

The QT-response of methadone-users to the “stand-up” test resembled that of healthy volunteers more than the response of LQTS-patients. Differences in the QTc of methadone treated patients and controls, which were statistically significant at baseline, became no longer significant after standing. Within 52 months of follow-up, one patient had suffered unexplained death and one had documented ventricular tachycardia.

Conclusions

The QT-response of methadone-users to the “stand-up” test is similar to that of healthy volunteers, not to that of LQTS-patients.     

Pharmacokinetic and pharmacodynamic study of ipragliflozin in Japanese patients with type 2 diabetes mellitus: A randomized,double-blind,placebo-controlled study

Aims

Ipragliflozin is a novel and highly selective sodium–glucose transporter 2 (SGLT2) inhibitor that reduces plasma glucose levels by enhancing urinary glucose excretion in patients with type 2 diabetes mellitus (T2DM). We examined the pharmacokinetic and pharmacodynamic characteristics of two oral doses of ipragliflozin in Japanese patients with T2DM.

Methods

In this randomized, placebo-controlled, double-blind study, patients were treated with placebo, 50 mg or 100 mg ipragliflozin once daily for 14 days. Plasma and urine pharmacodynamic parameters were measured on Days −1 and 14, and pharmacokinetic parameters on Day 14. Pharmacodynamic characteristics included area under the curve (AUC) for plasma glucose and insulin for 0–3 h (AUC_0–3h) and 0–24 h (AUC_0–24h). Pharmacokinetic characteristics included AUC_0–24h, maximum ipragliflozin concentration (C_max), and time to maximum plasma ipragliflozin concentration (t_max).

Results

Thirty patients were enrolled; 28 were included in pharmacokinetic/pharmacodynamic analyses and 30 in safety analyses. Administration of 50 and 100 mg ipragliflozin significantly reduced fasting plasma glucose, as well as the AUC_0–3h and AUC_0–24h for plasma glucose relative to placebo. Both doses of ipragliflozin also reduced AUC_0–24h for insulin, body weight, and glycoalbumin, while urinary glucose excretion increased remarkably. C_max and AUC_0–24h were 1.7- and 1.9-fold higher, respectively, in the 100-mg group than in the 50-mg group.

Conclusions

Ipragliflozin increased urinary glucose excretion and improved fasting and postprandial glucose, confirming its pharmacokinetic/pharmacodynamic properties in Japanese patients with T2DM.     

Acute hemodynamic response of infused fasudil in patients with pulmonary arterial hypertension: A randomized,controlled, crossover study

Background

The Rho-kinase pathway has been shown to be involved in the pathogenesis of PAH. As yet, however, the acute effects of the Rho-kinase inhibitor fasudil have not been compared with established pulmonary selective vasodilators in patients with PAH. We compared the acute effects of intravenous fasudil with inhaled iloprost in patients with pulmonary arterial hypertension (PAH).

Methods

Using a crossover design, 50 patients with PAH (idiopathic PAH, PAH associated with repaired left-to-right cardiac shunts, or connective tissue disease) were randomized to iloprost inhalation (5 μg) and intravenous fasudil (30 mg over 30 min). Hemodynamic data were collected at baseline and during acute drug exposure.

Results

Comparable decreases were observed in mean pulmonary artery pressure (− 4.6 ± 4.3 mm Hg vs. − 4.8 ± 4.2 mm Hg) and pulmonary vascular resistance (− 3.0 ± 3.0 Wood U vs. − 2.2 ± 2.7 Wood U) with fasudil infusion and iloprost inhalation, respectively, during acute challenge. However, fasudil infusion resulted in a more pronounced increase in mean cardiac output and mixed venous oxygen saturation compared with iloprost inhalation (13.7 ± 17.1% vs. 6.9 ± 15.0%; p = 0.044 and 4.5 ± 5.3% vs. 2.7 ± 8.2%; p = 0.044, respectively). Whereas inhaled iloprost resulted in a non-significant increase in mean systemic arterial oxygen saturation (0.8 ± 3.6%), infused fasudil resulted in a non-significant reduction (− 0.6 ± 1.1%).

Conclusion

Infused fasudil improved pulmonary hemodynamics in patients with PAH without significant toxicity.     

Effect of sitagliptin monotherapy on serum total ghrelin levels in people with type 2 diabetes

Aim

Sitagliptin is not associated with weight gain and has neutral effects on body weight. It is unclear whether sitagliptin treatment alters serum ghrelin levels in people with type 2 diabetes.

Methods

Forty-four subjects with type 2 diabetes were randomly assigned to receive sitagliptin or medical nutrition therapy (MNT) for 12 weeks. Changes in anthropometric variables, glycemic control, insulin resistance, lipid parameters, and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment.

Results

Significant decreases in body weight and body mass index were observed over the entire study period in both treatment groups. Glycosylated hemoglobin and postprandial plasma glucose levels were statistically significant decreased in the groups receiving sitagliptin compared with baseline values (p = 0.021 and p = 0.021, respectively), while they were unchanged in the groups receiving MNT. There was a significant decrease in total ghrelin in the groups receiving sitagliptin (p = 0.04) compared with baseline values but not in the groups receiving MNT (p = 0.46) at the end of the 12 weeks.

Conclusions

In this study of patients with type 2 diabetes, treatment with sitagliptin was associated with a significant decrease in serum ghrelin levels. These results suggest that the neutral effect of sitagliptin on weight might be associated with the suppression of fasting serum ghrelin levels.     

Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized,controlled, clinical trial

Objective

To examine the effects of different coffee amounts on blood glucose and insulin concentrations of healthy volunteers, and to assess potential effect modification by sex and body mass index category.

Materials/Methods

Thirty-three volunteers [16♀/17♂, 16 normal-weight and 17 overweight/obese, 27.3 ± 7.2 (19–44) y] took part in this randomized, crossover study. Ιn the morning of each experimental day volunteers received a standardized meal along with 200 mL of water or instant coffee containing either 3 or 6 mg of caffeine/kg body weight. Blood samples were obtained and analyzed for glucose and insulin concentrations in the fasting state, immediately after meal/drink consumption and at standard time points for the next 3 h thereafter.

Results

Coffee delayed the rise of insulin in response to the standardized meal and the fall of glucose concentrations from its maximum levels in the entire study sample. Glucose incremental area under the curve (IAUC) was significantly different between interventions (P = .009) with both coffee amounts inducing a greater area compared to water. Secondary, subgroup analysis at the nominal level showed that this might be more evident among females (P_IAUC = .05) and overweight/obese participants (P_IAUC = .03). Furthermore, coffee, mainly the 6 mg dose, could be lowering insulin concentrations the first 30 min after its consumption compared to water in men and overweight/obese participants.

Conclusions

Coffee exerts an acute effect on postprandial glucose and insulin concentrations. This effect may be modified by sex and overweight/obese status. Future research is necessary to elucidate underlying mechanisms.     

Sitagliptin attenuates methionine/choline-deficient diet-induced steatohepatitis

Aims

Accumulating evidence suggests that inhibitors of dipeptidyl peptidase-4 (DPP-4), such as sitagliptin, may play an important role in the prevention of non-alcoholic steatohepatitis (NASH). This study was conducted to elucidate whether sitagliptin could prevent steatohepatitis by inhibiting pathways involved in hepatic steatosis, inflammation, and fibrosis.

Methods

C57BL/6 mice were fed a methionine/choline-deficient (MCD) diet with or without supplement with sitagliptin for 5 weeks. Liver and adipose tissue from mice were examined histologically and immunohistochemically to estimate the effect of sitagliptin on the development of NASH.

Results

Supplementation with sitagliptin resulted in significant improvement of MCD diet-induced fat accumulation in the liver. In addition, sitagliptin treatment lowered fatty acid uptake, expression of VLDL receptor and hepatic triglyceride content. Sitagliptin also effectively attenuated MCD diet-induced hepatic inflammation, endoplasmic reticulum (ER) stress, and liver injury, as evidenced by reduced proinflammatory cytokine levels, ER stress markers, and TUNEL staining. Expression of CYP2E1 and 4NHE were strongly increased by the MCD diet, but this effect was successfully prevented by sitagliptin treatment. Furthermore, sitagliptin significantly decreased levels of MCD diet-induced fibrosis-associated proteins such as fibronectin and α-SMA in the liver. Inflammatory and atrophic changes of adipose tissue by MCD diet were restored by sitagliptin treatment.

Conclusions

Sitagliptin attenuated MCD diet-induced hepatic steatosis, inflammation, and fibrosis in mice through amelioration of mechanisms responsible for the development of NASH, including CD36 expression, NF-κB activation, ER stress, CYP2E1 expression, and lipid peroxidation. Treatment with sitagliptin may represent an effective approach for the prevention and treatment of NASH.     

Effects of long-term omega-3 polyunsaturated fatty acid supplementation on paroxysmal atrial tachyarrhythmia burden in patients with implanted pacemakers: Results from a prospective randomised study

Background

Sino-atrial node disease and aging increase AF risk. We investigated if long-term fish oil supplementation reduces paroxysmal atrial tachycardia/fibrillation (AT/AF) burden in patients aged ≥ 60 years with sinoatrial node disease and dual chamber pacemakers.

Methods

Following a run-in period of 6 months (p1) where AT/AF burden was logged,78 patients were randomised to control or fish oil group(total omega-3 6 g/d) and AT/AF burden evaluated after 6 months(p2; 39 controls, 39 fish oil) and 12 months (p3; 39 controls; 18 fish oil). A subset of 21 fish oil patients crossed over to controls in the final 6 months (crossover group).

Results

Median AT/AF burden increased significantly in controls (1.5%, 3.2%, 4.3%, P < .001) but not in fish oil patients at 6 months (1.4% to 2%, P = .46) or those continuing for 12 months (1.5%, 0.98%, 1%, P = .16). Time to first episode of AT/AF > 1 min was not significantly different between the groups (P = .9). There was a rebound increase in AT/AF burden in p3 in cross over patients (2.2% to 5.8%, P = .01) reaching a level similar to controls (crossover vs. controls, 5.8% vs. 4.3%, P = .63) and higher than those who continued fish oil for 12 months (crossover vs. continued intake 5.8% vs. 1.2%, P = .02). Fish oil patients had shorter duration episodes of AT/AF with no difference in frequency compared to controls.

Conclusion

Long-term fish oil supplementation did not suppress AT/AF burden but may have attenuated its temporal progression related to aging and sinus node disease.     

Management of hyperglycemia associated with pasireotide (SOM230): Healthy volunteer study

Aims

Pasireotide, a multireceptor-targeted somatostatin analogue with efficacy in Cushing's disease and acromegaly, can affect glucose metabolism due to inhibition of insulin secretion and incretin hormone responses. A study was therefore conducted to evaluate different antihyperglycemic drugs in the management of pasireotide-associated hyperglycemia.

Methods

This was a 1-week, Phase I, open-label study. Healthy male volunteers were randomized to pasireotide 600 μg sc bid alone or co-administered with metformin 500 mg po bid, nateglinide 60 mg po tid, vildagliptin 50 mg po bid, or liraglutide 0.6 mg sc qd. An oral glucose tolerance test (OGTT) was performed on days 1 and 7 to evaluate effects on serum insulin, plasma glucose and glucagon levels. Safety/tolerability and pharmacokinetic effects were also evaluated.

Results

Ninety healthy male volunteers were enrolled (n = 18 per arm). After 7 days of treatment, plasma glucose AUC post-OGTT increased by 69% with pasireotide alone. The effect was reduced by 13%, 29%, 45% and 72% with co-administration of metformin, nateglinide, vildagliptin and liraglutide, respectively. On day 7, compared with pasireotide alone, the decrease in serum insulin was attenuated with nateglinide, metformin, liraglutide and vildagliptin co-administration (levels were 3%, 6%, 34% and 71% higher, respectively). Minimal changes in plasma glucagon were observed. Adverse events were consistent with the safety profiles of the drugs used.

Conclusions

Vildagliptin and liraglutide were most effective in minimizing pasireotide-associated hyperglycemia in healthy volunteers.     

Canagliflozin,a sodium glucose co-transporter 2 inhibitor,reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial

Objective

Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin.

Materials/Methods

Patients (N = 37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300 mg/placebo, (C) canagliflozin 300 mg/canagliflozin 300 mg, or (D) canagliflozin 300 mg/canagliflozin 150 mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion [UGE] expected for Treatments B–D). A mixed-meal tolerance test (MMTT) was given 20 minutes post-dose on Day 3 of each period.

Results

A single dose of canagliflozin 300 mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B–D. An additional dose of canagliflozin 300 mg (Treatment C), but not 150 mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC_0–2h, − 7.5% for B vs A; − 18.5% for C vs A; − 12.0% [P = 0.012] for C vs B), leading to modestly greater reductions in total glucose AUC_0–2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated.

Conclusions

These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg.     

Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: Potent antiviral activity but no clinical benefit if treatment is given late

Background

We evaluated efficacy and safety of sofosbuvir and daclatasvir ± ribavirin in liver transplant recipients with severe recurrent hepatitis C.

Methods

Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir ± ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12.

Results

Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400 mg/day + daclatasvir 60 mg/day, and 6 patients (50%) also received ribavirin 200–800 mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n = 2; week 4, n = 3) and was undetectable in all cases. Mean Child–Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed.

Conclusion

All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.     

Perioperative administration of enoximone and renal function after cardiac surgery: A propensity-matched analysis

Background

Perioperative administration of enoximone has been shown to improve hemodynamics, organ function, and inflammatory response. Aim of the present study is to evaluate the impact of enoximone on postoperative renal function after on-pump cardiac surgery.

Methods

A total of 3727 patients undergoing cardiac surgery at one Institution between May 2004 and November 2010 were reviewed. A propensity score was built and a 1:1 perfect matching was performed, providing two fairly comparable cohorts of 712 patients each, receiving or not enoximone after surgery. Renal function was evaluated by lower glomerular filtration rate (GFR) value reached postoperatively.

Results

Overall 30-day mortality rate was 4.3% (62/1424). Cumulative incidence of postoperative renal failure (RF) was 157/1424(11%), of which 99/1424(7%) needed renal replacement therapy. Mean lower postoperative GFR in patients who received or not enoximone was 63 ± 30.1 and 53.5 ± 26.1 ml/min/1.73 m² (p < 0.0001), respectively. At multivariable analysis age (OR2.75, p = 0.0004), diabetes (OR1.82, p = 0.006), preoperative GFR (OR3.81, p < 0.0001), preoperative cardiogenic shock (OR1.65, p = 0.004), previous cardiac surgery (OR2.12, p = 0.0002), type of intervention (OR1.96, p = 0.005), and enoximone (OR0.38, p = 0.001) were found to be independently associated with postoperative RF. Logistic regression analysis showed that the administration of enoximone (OR0.41, p = 0.0001), and of no inotropes (OR0.27, p < 0.0001) were protective vs. the occurrence of postoperative RF.

Conclusion

Patients perioperatively receiving enoximone showed a statistically significant better renal function after cardiac surgery.     

Résultats diagnostiques à court terme et pronostiques à long terme chez des patients avec syncopes inexpliquées : résultats d’un série menée en centre hospitalier

Objective

Evaluate the diagnostic and prognostic input of head-up tilt test in the exploration of unexplained syncope.

Method

Between January 2009 and December 2012, all patients undergoing a head-up tilt test for recurrent syncope were studied. Follow-up data were obtained using telephone interviews and medical record reviews.

Results

A head-up tilt test was realized in 77 patients (47.8 ± 20 years, 53% female) for an exploration of syncope. The tilt test elicited syncope or pre-syncope in 57 patients (74%). The positive response included vaso-vagal syncope in 53 patients and psychogenic syncope in 4 patients. After a mean follow-up of 32 ± 11 months (range 6–54 months), 90% of patients had not a recurrence of syncope. Of note, the incidence of recurrence was the same regardless of whether the patients had a positive (n = 5/48; 10%) or a negative head-up tilt test response (n = 2/19; 10%).

Conclusion

The tilt test has a certain diagnostic value in the exploration of unexplained syncope. Recurrence rate of syncope after a tilt test is low. However, our study suggests no correlation between head-up tilt test results and the likelihood of recurring syncope.     

Drug adherence and the incidence of coronary heart disease- and stroke-specific mortality among 218,047 patients newly prescribed an antihypertensive medication: A five-year cohort study

Background

Randomized trials have shown that optimal adherence to antihypertensive agents could protect against cardiovascular diseases, but whether adherence reduces cardiovascular deaths in community settings has not been explored so fully. This study evaluates the association between antihypertensive adherence and cardiovascular (coronary heart disease and stroke) mortality in the primary care settings.

Methods

From a territory-wide database in Hong Kong, we included all patients who were prescribed their first-ever antihypertensive agents in the years between 2001 and 2005 from the public healthcare sector. All patients were followed up for five years, and assigned as having poor (Proportion of Days Covered [PDC] < 40%), intermediate (40–79%), and high (≥ 80%) adherence to antihypertensive agents. The association between antihypertensive adherence and cardiovascular mortality was evaluated by using the Cox proportional hazard models.

Results

From a total of 218,047 eligible patients, 3825 patients (1.75%) died of cardiovascular disease within five years after having received their first-ever antihypertensive agents. The proportions of patients having poor, intermediate, and high medication adherence were 32.9%, 12.1%, and 55.0%, respectively. Higher adherence levels at PDC 40%–79% (HR = 0.46, 95% C.I. 0.41–0.52, p < 0.001) and ≥ 80% (HR = 0.91, 95% C.I. 0.85–0.98, p = 0.012) were significantly less likely to be associated with mortality than the poor adherence (PDC0.040) group.

Conclusions

Better antihypertensive adherence was associated with lower cardiovascular mortality. This highlights the need to promote adherence through strategies which have been proved to be effective in clinical settings.     

Racial susceptibility for QT prolongation in acute drug overdoses

Background and Purpose

QT prolongation independently predicts adverse cardiovascular events in suspected poisoning. We aimed to evaluate the association between race and drug-induced QT prolongation for patients with acute overdose.

Methods

This was a cross-sectional observational study at two urban teaching hospitals. Consecutive adult ED patients with acute drug overdose were prospectively enrolled over a two year period. The primary outcome, long-QT, was defined using standard criteria: QTc > 470 ms in females and > 460 ms in males. The association between race and drug-induced QT prolongation was tested, considering several confounding variables.

Results

In 472 patients analyzed (46% female, mean age 42.3), QT prolongation occurred in 12.7%. Blacks had two-fold increased odds of drug-induced QT prolongation (OR 2.01, CI 1.03–3.91) and Hispanics had 48% decreased odds of drug-induced QT prolongation (OR 0.52, CI 0.29–0.94).

Conclusions

We found significant racial susceptibility to drug-induced QT prolongation in this large urban study of acute overdoses.