Dual Therapy In Patients Research Articles

Safety and effectiveness of daclatasvir and asunaprevir dual therapy in patients with genotype 1 chronic hepatitis C: results from postmarketing surveillance in Japan.

Safety and effectiveness of daclatasvir (DCV)/asunaprevir (ASV) dual therapy were demonstrated in Japanese patients with chronic hepatitis C (CHC) genotype (GT) 1b in phase III studies. This postmarketing surveillance (PMS) was conducted to assess the safety and effectiveness of DCV/ASV in Japanese patients with GT-1 CHC treated in routine clinical practice. This PMS was conducted between September 2014 and February 2017 at 261 centers in Japan. Patients with GT-1 CHC with or without compensated cirrhosis starting DCV and ASV dual therapy were observed from treatment initiation until 24weeks after completing treatment. Safety and effectiveness assessments included incidence of adverse drug reactions (ADRs) and sustained viral response (SVR) rates at 24weeks (SVR24). Of 2820 patients (median age, 71.0years; ≥ 65years, 73.1%; female, 56.1%; with compensated cirrhosis, 39.1%) in the safety population, 726 (25.7%) experienced 1063 ADRs and 47 (1.7%) experienced 55 serious ADRs. Overall, 532 hepatic ADRs were reported; most hepatic ADRs occurred between > 4 and ≤ 12weeks after treatment initiation. Subgroup analysis showed a higher incidence of ADRs in female, elderly, underweight, and renal function-impaired patients. SVR24 and SVR at 12weeks (SVR12) were 87.3% (2216/2538) and 88.4% (2284/2584), respectively. Patients without (SVR12, 89.1%; SVR24, 87.9%) and with (SVR12, 87.3%; SVR24, 86.3%) compensated cirrhosis had similar SVR rates. Results from this large PMS indicate that DCV and ASV dual therapy is generally well tolerated and effective in routine clinical practice in Japanese patients with GT-1 CHC with or without compensated cirrhosis.

Another Look at Dual Therapy in Patients with Established Atherosclerosis

Despite the development of effective secondary-prevention therapies for individuals who have clinically apparent atherosclerosis, the residual risk of

Dual Therapy Appears Superior to Monotherapy for Low-Income Individuals With Newly Diagnosed Type 2 Diabetes.

Background: There are variable recommendations regarding initiating monotherapy or dual therapy in patients with newly diagnosed type 2 diabetes (T2D). Clear initial strategies are of particular importance in underserved settings where access to care and financial burdens are significant barriers. Objectives: To provide descriptive data of metabolic outcomes to therapy regimens for low-income individuals with newly diagnosed T2D placed on oral hypoglycemic agents (OAs). Methods: We conducted a retrospective chart review of low-income individuals with newly diagnosed T2D initiated on OAs. We provided descriptive data and then evaluated the effects of OA regimens (ie, mono-, dual-, transition [from mono to dual or vice versa] therapy) on hemoglobin A1c (A1c) (baseline to 12 months). Results: A total of 309 patients were included in the study. At 12 months, the mean decrease in A1c for the entire sample was −2.36% (9.37% to 7.01%). Patients prescribed dual therapy had a greater change of A1c compared to those taking monotherapy with metformin (−1.11%, P < .01). Patients who transitioned therapies did not differ in change of A1c compared to monotherapy. Conclusion: Initiation of dual therapy was superior to metformin monotherapy or transitioning therapies and may be preferred for low-income individuals with newly diagnosed T2D.

Efficacy and safety of triple versus dual antithrombotic therapy in atrial fibrillation and ischemic heart disease: a systematic review and meta-analysis.

The optimal antithrombotic regimen for patients with atrial fibrillation and ischemic heart disease remains unclear. Therefore, we aimed to compare the efficacy and safety of triple therapy (TT [an anticoagulant and 2 antiplatelet drugs]) with dual therapy (DAPT [2 antiplatelet drugs] or DT [an anticoagulant and a single antiplatelet drug]) in patients with atrial fibrillation and ischemic heart disease. We systematically searched the Cochrane Library, PubMed and Embase databases for all relevant studies up to August 2017. The overall risk estimates were calculated using the random-effects model. A total of 17 observational studies were included. Regarding the efficacy outcomes, no differences were observed between the triple therapy and the dual therapy for all-cause death, cardiovascular death, or thrombotic complications (i.e., acute coronary syndrome, stent thrombosis, thromboembolism/stroke, and major adverse cardiac and cerebrovascular events). Regarding the safety outcomes, compared with DAPT, TT was associated with increased risks of major bleeding (a relative risk of 1.96 [1.40–2.74]), minor bleeding (1.69 [1.06–2.71]) and overall bleeding (1.80 [1.23–2.64]). Compared wtih DT, TT was associated with a greater risk of major bleeding (1.65 [1.23–2.21]), but rates of minor bleeding (0.99 [0.56–1.77]) and overall bleeding (1.14 [0.76–1.71]) were similar. Overall, TT confers an increased hazard of major bleeding with no thromboembolic protection compared with dual therapy in patients with atrial fibrillation and ischemic heart disease.

Post-stroke epilepsy in Burkina Faso (West Africa)

Post-stroke epilepsy (PSE) is defined as “recurrent seizures following stroke with confirmed diagnosis of epilepsy”. Our objective was to describe the epidemiological, clinical and therapeutic PSE aspects at the Yalgado Ouedraogo Teaching Hospital, the main reference centre for neurological conditions in Burkina Faso. We conducted a retrospective study from January 2006 to December 2014. The data on thirty-two (32) cases of PSE was collected from a total of 1616 patients hospitalized for stroke, representing a rate of 1.98%. The patients' ages ranged from 25 to 77years old with a mean age of 58±10.39. There were 21 men and 11 women, with a gender ratio of 1.9. The time of occurrence of PSE ranged between 10 and 3600days (10years). The brain CT scan helped distinguish the different subtypes of stroke. Sixty-four percent (64%) of the cases experienced ischemic stroke and 36% of the cases cerebral hemorrhage. With regard to medical treatment, 23 patients received monotherapy, and 4 patients dual therapy. Exactly 96.87% of seizures were stabilized during the hospitalization period. PSE is a symptomatic type of epilepsy occurring during stroke sequelae. It is important not to lose sight of this before the occurrence of any focal or generalized seizure after a stroke.

A comparative prospective study to assess the clinical efficacy and safety of pantoprazole monotherapy versus pantoprazole and itopride dual therapy in patients with gastroesophageal reflux disease in a tertiary care hospital

Background: Gastroesophageal reflux disease (GERD) is a common chronic, relapsing condition that carries a risk of significant morbidity and potential mortality from resultant complications. Proton pump inhibitors (PPIs) remained as the main stay in the therapy of GERD but they do not have any role in increasing the tone of lower esophageal sphincter which is the main pathophysiology of GERD. In this regard addition of prokinetic agent like Itopride may be beneficial in improving the symptoms associated with GERD. So the present study has been taken to compare the healing rates of esophagitis and reduction in symptom scores associated with GERD between Pantoprazole monotherapy and Pantoprazole plus Itopride combination. Methods: 100 patients diagnosed with GERD were randomly assigned into two groups, Group A and Group B. Group A received tablet Pantoprazole 40 mg twice daily alone and group B received tablet Pantoprazole 40 mg twice daily and tablet Itopride 50 mg thrice daily 30 minutes before food for 4 weeks. The patients were followed up at the end of 4 weeks and were given the questionnaire to assess the FSSG scores. Endoscopy and FSSG scores were recorded and then the percentage of responders in both groups was compared. Results: Endoscopic evidence of healing of esophagitis was similar in both the groups, 72% in Group A and 74% in Group B. The symptom relief was significantly more in Pantaprozole plus Itopride group 74.5% (4.2±1.6) than Pantaprozole alone 62.5% (6.4±1.1) after 4 weeks (p < 0.001).The occurrence of side effects was less in group B compared to group A (22% vs 30%, p= 0.172). Conclusions: Pantoprazole and combination of Pantoprazole plus Itopride provide more effective endoscopic healing of esophagitis. Pantoprazole and Itopride combination is more efficacious in ameliorating the symptoms of GERD than Pantoprazole alone.

Pegylated Interferon/Ribavirin dual therapy in patients with chronic Hepatitis C: results of 323 cases

Objective: The combination of pegylated interferon-α (PEG-IFN) and ribavirin has become a mainstay in the treatment of chronic hepatitis C (CHC). We aimed to evaluate the efficacy of this treatment in patients with CHC, while considering new approaches. Methods: A total of 323 patients with CHC underwent PEG-IFN and ribavirin combination treatment from the 3 centers (2 in Ordu and 1 in Samsun provinces) in Middle Black Sea region between the years of 2003-2013. Results: Of the patients, 208 (67%) were female and had a mean age 54 ± 10 years (median: 54; 19-70). Genotyping was performed in 163 patients, and 161 patients (98.8%) revealed genotype 1. Sustained virologic response (SVR) and the end of treatment response rates ere 58.3% and 75.6%, respectively. In patients with rapid virological response, the SVR rate was 85.1%, whereas in patients with a HCV RNA level less than 800,000 IU/ml, the SVR rate was 71.2%. The SVR rates were found to be higher in patients who developed hypothyroidism, which was statistically significant (p = 0.03). The most frequent side effect was anemia, followed by thrombocytopenia, fatigue, and loss of appetite. Conclusion: Presently, PEG-IFN/ribavirin is still an option in the treatment of certain patient populations even after the consideration of newer treatment methods. J Microbiol Infect Dis 2015;5(4): 151-155 Key words: Pegylated interferon, ribavirin, therapy, hepatitis C

Esomeprazole and rabeprazole did not reduce antiplatelet effects of aspirin/clopidogrel dual therapy in patients undergoing percutaneous coronary intervention: a prospective, randomized, case–control study

Objectives: Controversy has been prompted based on drug interaction between proton pump inhibitors (PPIs) and aspirin/clopidogrel leading to weakened effects. However, whether such interaction was drug-specific or class effect remains controversial. This study predicted the impact of esomeprazole and rabeprazole on efficacy of dual antiplatelet therapy (DAPT).Methods: This study, involving 150 patients, evaluated the efficacy of DAPT upon concomitant use of esomeprazole (40 mg/d) or rabeprazole (20 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at day 1, day 3 and day 30 end points after initiation of DAPT.Results: No significance were observed by post-hoc analysis of treatment-by-period interaction in LTA value and VASP-PRI value when compared with non-PPI users, which suggests no carryover effect in both PPIs over the 30-day treatment period. Moreover, no statistical differences was in LTA or VASP-PRI value in esomeprazole group while rabeprazole group showed decreased in antiplatelet function of DAPT at the day 3 and day 30 end points.Conclusion: Although antiplatelet effect of DAPT were not affected upon concomitant use of both PPIs over the 30-day treatment period, esomeprazole exerts much more stable impact on antiplatelet effect than rabeprazole among respective end points.

Efficacy of dual therapy in patients &gt;65 years old with alanine transaminase flare during chronic hepatitis C genotype 2

Hepatitis C virus (HCV)-related chronic hepatitis is characterized by different clinical outcomes as well as by distinct biochemical and virological patterns. According to guidelines concerning dual therapy, high rates of sustained virological response (or HCV-RNA undetectable 24 weeks after the end of antiviral treatment) has been obtained in patients with persistent HCV infection, caused by genotype 2 (CHC G2). Dual therapy (pegylated interferon plus ribavirin) might be an useful strategy not only in the treatment of younger patients (≤65 years old, that is generally considered as age limit for the beginning of the antiviral treatment) but also of older patients (>65 years old) experiencing an alanine aminotransferase (ALT) flare (with value of ALT-alanine transaminase ≥400 U/L). In fact the progress of fibrosis can advance quicker exactly during the transaminase breakthrough. We report our experience in the treatment of two Italian patients with CHC G2, one of them was a never treated (naive) woman, whereas the other was a previously treated man with several co-morbidities. Both patients presented an excellent virological response to dual therapy despite unfavorable predictive factors, such as old age (>65 years), ALT flare and possible moderate hepatic fibrosis.

Efficacy and safety of telaprevir and boceprevir in patients with hepatitis C genotype 1: a meta-analysis

Two NS3/4A protease inhibitors (PIs), telaprevir and boceprevir, were recently approved in the United States. The primary objective was to compare the efficacy and safety of triple therapies including either PI to dual therapy in patients with chronic hepatitis C genotype 1; the secondary objective was to conduct subgroup analyses to make comparisons based on patients' race. Published and unpublished RCTs were selected if they: (i) had patients with chronic hepatitis C genotype 1, (ii) compared triple therapies (telaprevir or boceprevir + peg-interferon + ribavirin) and dual therapy (peg-interferon + ribavirin) and (iii) measured the outcome using sustained virologic response (SVR). A total of 4421 patients from 10 evaluated articles were included in the meta-analysis. Overall, triple therapy was significantly associated with a higher achievement of SVR than dual therapy: (i) telaprevir-based triple therapy in treatment-naïve patients (relative risk [RR]=1·62; 95% confidence interval [CI], 1·47-1·78), (ii) telaprevir-based triple therapy in treatment-experienced patients (RR=3·85; 95% CI, 3·03-4·90), (iii) boceprevir-based triple therapy in treatment-naïve patients (PR=1·70; 95% CI, 1·56-1·86) and (iv) boceprevir-based triple therapy in treatment-experienced patients (RR=2·98; 95% CI, 2·29-3·87). Although black and non-black patients demonstrated the higher rates of achieving SVR with triple therapy compared to dual therapy, the rates of SVR were still lower among black patients than among non-black patients. Patients on triple therapies had the significantly increased incidences of treatment discontinuation attributable to adverse events and serious adverse events when compared to dual therapy, especially treatment-experienced patients. Regarding achieving SVR, triple therapies including either PI are superior to dual therapy for both treatment-naïve and treatment-experienced patients.

PIN8 - Efficacy and safety of telaprevir and boceprevir in patients with hepatitis c genotype 1: A meta-analysis

Summary What is known and objective Two NS3/4A protease inhibitors (PIs), telaprevir and boceprevir, were recently approved in the United States. The primary objective was to compare the efficacy and safety of triple therapies including either PI to dual therapy in patients with chronic hepatitis C genotype 1; the secondary objective was to conduct subgroup analyses to make comparisons based on patients' race. Methods Published and unpublished RCTs were selected if they: (i) had patients with chronic hepatitis C genotype 1, (ii) compared triple therapies (telaprevir or boceprevir + peg-interferon + ribavirin) and dual therapy (peg-interferon + ribavirin) and (iii) measured the outcome using sustained virologic response (SVR). Results A total of 4421 patients from 10 evaluated articles were included in the meta-analysis. Overall, triple therapy was significantly associated with a higher achievement of SVR than dual therapy: (i) telaprevir-based triple therapy in treatment-naive patients (relative risk [RR] = 1·62; 95% confidence interval [CI], 1·47–1·78), (ii) telaprevir-based triple therapy in treatment-experienced patients (RR = 3·85; 95% CI, 3·03–4·90), (iii) boceprevir-based triple therapy in treatment-naive patients (PR = 1·70; 95% CI, 1·56–1·86) and (iv) boceprevir-based triple therapy in treatment-experienced patients (RR = 2·98; 95% CI, 2·29–3·87). Although black and non-black patients demonstrated the higher rates of achieving SVR with triple therapy compared to dual therapy, the rates of SVR were still lower among black patients than among non-black patients. Patients on triple therapies had the significantly increased incidences of treatment discontinuation attributable to adverse events and serious adverse events when compared to dual therapy, especially treatment-experienced patients. What is new and conclusions Regarding achieving SVR, triple therapies including either PI are superior to dual therapy for both treatment-naive and treatment-experienced patients.

Is there benefit in dual renin– angiotensin–aldosterone system blockade? No, yes and maybe: A guide for the perplexed

Since the initial discovery of Angiotensin converting enzyme inhibitors (ACEI) in the 1960s and the launch of Captopril as the first available for clinical use in the 1970s, there now exist three other classes of drugs that block the renin angiotensin aldosterone system (RAAS): the angiotensin II receptor blockers (ARB), aldosterone antagonists (AA) and direct renin inhibitors (DRI). With the proven efficacy of RAAS blockers as monotherapy in many arenas there has been considerable interest in the use of dual therapy combinations of these medications that target different points in the pathway. By potentially offering a more complete RAAS blockade with a commensurate enhanced clinical effect, the strong biological rationale for dual therapy has led to it being embraced by clinicians as a treatment option, for hypertension and nephroprotection in particular. However, the initial enthusiasm for this treatment has been tempered by the recent results from several large trials such as ONTARGET and ALTITUDE, which do not support a specific dual therapy approach. In contrast, there is supportive evidence for dual blockade of specific combinations in selected patient groups and data are lacking for others. In the wake of this complex contemporary evidence, the conundrum now faced by clinicians committed to individualised care is, for which patients dual therapy could still be of benefit. This review examines for the practising clinician the current 'state of play' for dual blockade of various combinations and a perspective on its use in cardio-renal disease and diabetic complications.

Comparative efficacy and safety of fenofibrate/pravastatin plus ezetimibe triple therapy and simvastatin/ezetimibe dual therapy in type 2 diabetic patients with mixed hyperlipidaemia and cardiovascular disease

This study was designed to compare the efficacy and safety of a fenofibrate/pravastatin 160/40 mg fixed-dose combination plus ezetimibe 10 mg triple therapy and simvastatin 20 mg plus ezetimibe 10 mg dual therapy in patients with type 2 diabetes, mixed hyperlipidaemia and cardiovascular disease. After a 6-week run-in period on simvastatin 20 mg, 273 patients with non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dl or low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dl were randomised to receive 12-week treatment with triple therapy or dual therapy, followed by a 12-week safety period during which all patients received the triple therapy. At week 12, similar significant decreases in non-HDL-C were observed with both treatments. The triple therapy has induced a greater decrease in triglycerides (between-treatment difference: -14.6%, p = 0.007) and the dual therapy a greater decrease in LDL-C (between-treatment difference: +5.3%, p = 0.05). Both treatments were generally well tolerated. The fenofibrate/pravastatin plus ezetimibe therapy improves the global atherogenic lipid profile in type 2 diabetic patients with mixed hyperlipidaemia.

Manidipine for Hypertension not Controlled by Dual Therapy in Patients with Diabetes Mellitus

Little is known about the effects of the calcium channel antagonist manidipine when it is added as a third drug in non-controlled hypertensive patients with diabetes mellitus receiving dual antihypertensive therapy. The aim of this study was to evaluate the response in terms of blood pressure (BP) and microalbuminuria when manidipine is administered to patients with type 2 diabetes and uncontrolled hypertension who are already being treated with a combination of a low-dose diuretic plus an ACE inhibitor or an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]). We also evaluated the effects of addition of manidipine on plasma fasting glucose, glycosylated haemoglobin (HbA(1c)), serum uric acid, the lipid profile, serum creatinine and creatinine clearance. This was a non-comparative, open-label study of hypertensive diabetic patients with systolic/diastolic BP >130/80 mmHg. All patients had been receiving treatment for ≥3 months with stable doses of a diuretic plus an ACE inhibitor or ARB. Manidipine 10 mg/day was added, increasing to 20 mg/day if the target BP was not reached after 3 months' treatment. The follow-up period was 6 months. Patient compliance was verified by tablet count. The doses of statins being taken by patients prior to commencement of the trial were not modified during the study. All patients were treated with oral antihyperglycaemic agents only; patients receiving insulin were excluded from the study. 136 patients were enrolled in the trial and completed the study; 41.9% of the patients were males, the mean ± SD age of the study population was 64.4 ± 12.3 years, and the mean ± SD body mass index was 30.2 ± 4.9 kg/m(2). The mean ± SD BP at baseline was 158.6 ± 15.6/86.7 ± 11.2 mmHg compared with 136.8 ± 12.0/78.0 ± 11.2 (-21.8/-8.7, respectively) mmHg at the end of the study period (p < 0.001). A total of 63.6% of the patients attained a BP of <140/90 mmHg and 20.9% attained a BP of <130/80 mmHg. The mean ± SD heart rate decreased from 75.1 ± 11.2 at baseline to 72.8 ± 11.2 beats/min at the end of the study (p = 0.06; not significant). Fifty percent (95% CI 41.6, 58.4) of the patients had microalbuminuria at baseline compared with 31.3% (95% CI 23.0, 39.6) at study end (p = 0.006). Reductions in mean ± SD fasting glucose levels (-10.2 ± 50.3 mg/dL; p < 0.05), HbA(1c) (-0.19 ± 0.97%; p = 0.05), total cholesterol (-11.9 ± 35.2 mg/dL; 95% CI -18.1, -5.8; p < 0.005), triglycerides (-10.8 ± 51.1 mg/dL; 95% CI -19.7, -1.8; p = 0.018) and low-density lipoprotein-cholesterol (-8.1 ± 27.7 mg/dL; 95% CI -13.2, -2.9; p = 0.002) were observed. No patients dropped out of the study because of adverse effects. The most frequent adverse effect encountered was malleolar oedema (9%). Manidipine added as the third drug to a renin-angiotensin system inhibitor plus a low dose of diuretic significantly reduces BP, improves renal function, has favourable effects on the lipid and glucose profiles, and reduces microalbuminuria in uncontrolled hypertensive patients with type 2 diabetes. Long-term trials are necessary to evaluate time-related effects.

Survival after the initiation of combination therapy in patients with pulmonary arterial hypertension: an Australian collaborative report

Several cellular pathways are implicated in the pathogenesis of pulmonary arterial hypertension (PAH) and attempts to arrest disease progression with a single drug would not be expected to succeed in the medium term. In clinical practice, combination therapy is often used in patients deteriorating on monotherapy, despite the absence of firm evidence from randomized controlled controls. From January 2005 to August 2009, 112 patients with World Health Organisation Functional Class (FC) II-IV PAH deteriorating on monotherapy received non-parenteral combination therapy at six Australian PAH expert hospitals. Combination therapy included bosentan, sitaxentan, ambrisentan, iloprost and sildenafil. Data were prospectively collected for survival status, 6-min walk distance, FC and echocardiographic parameters at the start of monotherapy through to commencement of combination therapy and at 6-monthly intervals thereafter. After varying periods of monotherapy (18.7±13.4onths), survival estimates on combination therapy were 88%, 71% and 61% for the additional 1, 2 and 3years respectively. Survival on dual therapy in patients with idiopathic PAH/familial PAH was 93% at 1year and 79% at 2years, and for scleroderma-related PAH, 72% at 1 year and 48% at year 2 after initiation of combination therapy. In survivors, dual therapy reversed the deterioration in FC, from 3.1±0.6 on monotherapy to 2.2±0.6 at 12months. Similarly, dual therapy improved 6-min walk distance from 316±119m to 406±129m at 12months, and sequential echocardiography demonstrated a fall in pulmonary artery systolic pressure and improved right ventricular function. Dual non-parenteral therapy appears safe and effective and should be considered for PAH patients who are deteriorating on monotherapy to improve long-term outcomes.

New players in the field of antiplatelet and anticoagulant therapy in coronary heart disease - current therapeutic issues and hot topics

The development of anticoagulants started in the 1930s with the discovery and availability of parenteral heparin. In the 1950s, oral vitamin K antagonists found their way into clinical therapeutics. Although both components are flawed with considerable limitations such as a narrow therapeutic window, an unpredictable anticoagulatory effect, drug-interactions and the necessity of continuous aPTT/INR-monitoring, they have been the only anticoagulants for prophylaxis and therapy of thromboembolic disorders for several decades [Alban, 2005]. The first step toward more predictable anticoagulatory activity of unfractionated heparin (UFH) was the development of low molecular weight heparins (LMWHs) in the 1980s. This family of heparins features a higher ratio of anti-Xa and anti-IIa activity, lower plasma protein interactions and renal elimination and, as a consequence, they do not require routine monitoring of their antithrombotic effect. Today, enoxaparin and dalteparin are the only LMWHs which are also indicated for use in patients with unstable angina/NSTEMI, STEMI with percutaneous coronary intervention (PCI) (enoxaparin) and in combination with aspirin for patients with unstable angina/NSTEMI (dalteparin) [Anderson et al. 2007]. Aspirin therapy is still a cornerstone of antiplatelet therapy in cardiovascular medicine since the early 1980s when the Veterans Administration Cooperative Study revealed significantly protective effects, reducing nonfatal myocardial infarction and the combined endpoint of death or myocardial infarction (MI), by 51% [Lewis et al. 1983]. Aspirin therapy in combination with P2Y12-inhibition with clopidogrel (which binds highly selectively to the P2Y12receptor on the surface of platelets and selectively blocks ADP-induced platelet aggregation) is today still the recommended platelet inhibitory treatment regimen for patients presenting with an acute coronary syndrome (ACS) and in those undergoing PCI and stent implantation [Anderson et al. 2007]. Although undoubtedly beneficial in reducing the risk for adverse thrombotic events in a broad range of cardiovascular patients, we are nowadays more and more recognizing several limitations to this treatment regimen: On the one hand, 15 40% of patients are poor responders to treatment, as evaluated by ADP-induced platelet aggregation and several trials show that such patients are at increased risk of stent thrombosis, MI and death [Wallentin, 2009]. On the other hand, the risk for bleeding is substantially increased by dual antiplatelet therapy. Assuming a baseline risk for major bleeding of 1.9% over a 13 month period based on the mean event rate in patients treated with aspirin alone in the 4 longer term clinical trials, an 80% increase in the odds of major bleeding is equivalent to an absolute risk increase of 1.5% [Bowry et al. 2008]. In other words, the number needed to treat (NNT) for 13 months to cause one additional major haemorrhage is only 66. It is assumed today that the use of dual therapy in patients with acute coronary syndrome (ACS), especially in the acute phase, has a favourable risk/benefit ratio, whereas in stable patients with cardiovascular disease, it is associated with an increased risk for bleeding [Eshaghian et al. 2007].

Comparison of Triple Antiplatelet Therapy Including Triflusal and Conventional Dual Therapy in Patients Who Underwent Drug-Eluting Stent Implantation

Triflusal is a derivative of acetylsalicylic acid but it exhibits different pharmacological and pharmacokinetic properties. The object of this study was to evaluate the efficacy of additional use of triflusal in patients who underwent drug-eluting stent implantation. First, we prospectively tested platelet function with a rapid platelet function analyzer (VerifyNow-Aspirin) in patients with stable angina (male, age, 61.6 +/- 8.3, body weight, 69.3 +/- 11.2 kg) who maintained dual (aspirin 100 mg and clopidogrel 75 mg per day, n = 23) or triple (aspirin 100 mg, clopidogrel 75 mg, and triflusal 300 mg per day, n = 23) therapy for more than one month. They were randomly assigned to a group. The triple group showed superior inhibition of arachidonic acid induced platelet aggregation compared to the dual group (420.2 +/- 47.7 ARU versus 465.0 +/- 71.2 ARU, P = 0.016). Second, we compared composite outcomes (death, myocardial infarction, and nonhemorrhagic stroke) after drug-eluting stent (DES) implantation between the dual (n = 1474) and triple (n = 433) groups in the prospective Seoul National University Hospital drug-eluting stent (SNUH-DES) cohort. The triple group had more current smokers, male patients, and patients with a previous history of revascularization. Also, the triple group underwent more complex interventions such as left main, chronic total occlusion, long lesion, and restenotic lesion than the dual group. In spite of their higher risk profiles, the triple group patients showed comparable composite outcomes (19 cases, 4.4%) to those of the dual group ones (41 cases, 2.8%) (P = 0.12). The triflusal-based triple antiplatelet therapy achieved superior platelet inhibition compared to the dual therapy ex vivo and it could be applied after complex intervention with DES.

Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation

Optimal antithrombotic/anticoagulation therapy in patients on chronic oral anticoagulation (OAC) undergoing drug-eluting stent (DES) implantation is unknown. We investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC. We included a series of 515 patients on OAC who underwent DES implantation between 2002 and 2007. Based on predefined clinical and echocardiographic criteria, 306 patients continued OAC (triple therapy) and 209 patients discontinued OAC (dual therapy) for the time they received antiplatelet therapy with clopidogrel and aspirin [stent-related antithrombotic treatment (SRAT)]. The primary end point was a composite of death, myocardial infarction, stent thrombosis or stroke. During SRAT the primary endpoint was observed in 13 patients in the group with triple therapy versus 15 patients in the group with dual therapy [Kaplan-Meier estimates 4.2% and 7.2%, odds ratio (OR) = 0.61, 95% confidence interval (CI) 0.29-1.28; P = 0.19]. At 2 years of follow-up, the primary endpoint was observed in 35 patients in the group with triple therapy versus 36 patients in the group with dual therapy (Kaplan-Meier estimates 14.1% and 18.0%, OR = 0.76, 95% CI: 0.48-1.21; P = 0.25). Two-year incidence of major bleeding was 1.4% (n = 4, triple therapy) versus 3.1% (n = 6, dual therapy) (P = 0.34). In patients on chronic OAC undergoing DES implantation, clinical and echocardiographic criteria help to define postprocedural antithrombotic/anticoagulation therapy. Based on these criteria, both a double antiplatelet therapy (clopidogrel plus aspirin) and a triple therapy (OAC plus clopidogrel plus aspirin) are associated with favourable safety and efficacy.

The Clinical and Economic Effects of Hemo-Clips for High-Risk Bleeding Ulcers: Are They Likely to Be Worth the Money?

Background: Data suggest that dual therapy with epinephrine and bipolar electrocoagulation is superior to epinephrine alone in high-risk bleeding peptic ulcers. In the last several years, however, mechanical hemostasis with endoscopic clipping devices has become increasingly popular. Yet, the added cost of widespread use of clips can only be justified if they also provide added benefit to patients by reducing ulcer rebleeding risk. The purpose of this study was to quantify the minimum incremental reduction in ulcer rebleeding risk needed to make a triple therapy approach with epinephrine, bipolar electrocoagulation, and clipping, cost-effective by traditional standards (<$50,000 per life-year saved). Methods: A simple mathematical model was developed to compare triple therapy to traditional dual therapy for high-risk bleeding peptic ulcers. The published literature was used to estimate risks, benefits, and costs. The model assumed that: (1) the rebleeding risk for high-risk lesions was 12% (range 5%-20%); (2) the risk of mortality from rebleeding was 12% (5%-20%); (3) the added cost of clip-based therapy was $600 per endoscopy ($300-$900); and, (4) the cost of ulcer rebleeding was $4000 ($1,000-$20,000). We calculated the minimum incremental relative risk reduction (RRR) required for triple therapy to cost less than $50,000 per life-year saved (LYS). Results: In the base-case analysis, the cost-effectiveness threshold (<$50,000 per LYS) for the triple therapy approach was achieved at a RRR for rebleeding of 5% or greater. In sensitivity analysis, this result proved to be sensitive to the overall rebleeding risk and the mortality from rebleeding, though the RRR of triple therapy required to meet the cost-effectiveness threshold remained ≤10% even in the worst-case scenario. Conclusions: To meet traditional criteria for cost-effectiveness, triple therapy need only demonstrate a small incremental reduction in rebleeding risk over traditional dual therapy. In the future, adequately powered studies should compare triple therapy to dual therapy in patients with high-risk bleeding peptic ulcers.