Aspirin

Method precision was tested by preparing model solutions corresponding to sample solution of dosage 150 mg ASA and 40 mg GLY (active substances and excipients)—sample solution preparation was described in “Methods” section. Solutions were spiked with salicylic acid at the concentrations which were equivalent to 0.005%, 0.05% and 0.30% with respect to acetylsalicylic acid content in a sample. Three replicates were prepared for each concentration level. The analysis was performed in duplicate by Analyst 1 at the same day and using the same HPLC system to evaluate intra-day precision. For inter-day precision Analyst 2 performed analysis on a different day, using different HPLC system. %Found of salicylic acid, standard deviations in groups of results, %RSD as well as intra-day and inter-day variance were calculated.

The VIAMI-trial was conducted to investigate the differences in clinical outcome between an invasive and a conservative strategy in patients with demonstrated viability in the infarct-area. The expected event rate in the viability positive group was estimated to be 35 percent. To demonstrate with a power of 80% (α = 0.05, two-sided) that PCI leads to a 50% reduction in event rate in the invasive group compared to the conservative group, 200 patients would be needed in each group.
As a formal stopping rule for the study the following was used: if one of the treatment strategies appeared significantly superior at interim analysis (p ≤ 0.01), the study would be stopped. Interim analysis was performed each time another 100 patients were included.
Baseline descriptive data are presented as a mean ± standard deviations (SD). Differences in clinical and echocardiographic variables are assessed by unpaired Student's t-test. Differences between proportions are assessed by chi-square analysis; a Fisher's exact test is used when appropriate. Event-free survival curves are computed with the Kaplan-Meier method, and the differences between these curves are tested with a log-rank test. The Cox proportional hazards regression analysis was used to estimate the treatment effect as hazard ratio (HR) with 95% confidence intervals. Besides the "crude" effects, adjustments were made for DM, hypertension, hypercholesterolemia, current smoking, family history of CAD (model a), clinical history (angina, myocardial infarction, PCI or CABG) and medication use at baseline (aspirin, beta-blocker, Ca-inhibitor, statins, ACE-I and AT II antagonist) (model b) and for all covariates (model c).
All analyses were performed on an intention-to-treat basis. Outcome per-protocol was also evaluated, since this would reflect the true influence of PCI on clinical outcome. Because after randomization there was a median waiting-time of two days before a revascularization procedure was performed inevitably some events occurred. In the per-protocol analysis these events are excluded from analysis, because they occurred before the by protocol demanded intervention. To make a fair comparison between the two groups in the per-protocol analysis we also excluded the events in the conservative group occurring during the first two days after randomization. All analyses were performed with the use of SPSS software, version 16.0 (SPSS, Inc., Chigago, Illinois).

The IraPEN's preventive actions are expected to reduce cardiovascular events. The relative risks (RRs) of these preventive actions and the medications that are used in the program were obtained from meta-analyses or randomized clinical trials (RCTs). By multiplying or adding up the RRs of different medications, there is a risk of effect overestimation, and a correction was made by using the formula below wherever multiple interventions were involved:
This equation has been developed based on a study that compared the effect of controlling the risk factors separately vs. controlling all of them simultaneously (15 (link)).
Based on the field interviews, it was clear which medications are used for each index cohort. Almost in all cases, angiotensin-converting enzyme (ACE) inhibitors are the first choice for hypertension treatment. Enalapril is the most prescribed one as monotherapy. Thiazides (diuretics) are the second choice followed by beta-blockers. In case the hypertension is not controlled by monotherapy instead of increasing the dose, the second drug is added. As recommended by guidelines, small doses of various classes of antihypertensive medications are more useful than a high dose of one (16 ). In general, the combination of ACE inhibitors and thiazide is the most common one. This pattern is aligned with Joint National Committee (JNC8) guidelines. Statins are prescribed for hyperlipidemia treatment. Among statins, Atorvastatin is the choice as it is one of the most potent ones. For diabetes, Metformin is started and increased to the maximum dose (2 g) and then the second medication that is Glibenclamide is added. Due to its potential harm and insufficient evidence of its efficacy, Aspirin was not recommended for primary prevention by PEN protocols. Therefore, Aspirin is not used in IraPEN as well. Here are the list of medications and their daily dosages which are used in IraPEN:
The unit price of each of these medications was derived from the Iranian Annual Pharma Statistics file. For the calculation of the intervention's effects, it is assumed that the adherence of individuals to the treatment is 100%. Table 3 lists the RRs of different interventions (medications) for CHD and stroke.

Retention times of the analytes were measured with Shimadzu HPLC system on the CHIRALPAK®HAS stationary phase (50 × 3 mm, 5 μm, Chiral Technologies, DAICEL Group, Europe SAS, France). The mobile phase A consisted of 50 mM aqueous ammonium acetate buffer (pH 7.4) and phase B of 2-propanol according to Valko et al.^{65 (link)} Analysis was performed at prolonged 1 mL min⁻¹ flow rate in the linear gradient. Retention capacity factors (k′) were calculated by using DMSO or a substance with 0% HAS binding for systems' dead time (R_t0). The system was calibrated by injecting the reference compounds: acetylsalicylic acid (CAS 69-72-7), betamethasone (CAS 378-44-9), budesonide (CAS 5133-22-3), carbamazepine (CAS 298-46-4), cimetidine (CAS 51481-61-9), ciprofloxacin (CAS 85721-33-1), indomethacin (CAS 53-86-1), isoniazid (CAS 54-85-3), metronidazole (CAS 443-48-1), nicardipine (CAS 55985-32-5), nizatidine (CAS 76963-41-2) and warfarin (CAS 81-81-2) obtained from Sigma-Aldrich, diclofenac (CAS 15307-86-5) from EMD Chemicals Inc., flumazenil (CAS 78755-81-4) from ABX and ketoprofen (CAS 22071-15-4) from LKT Labs. The logarithmic capacity factors of the references' Rt (log(k′)) on the HSA column were plotted against the %PPB values from literature. The slope and the intercept were used to convert the log(k′) of the compounds (6a, c, f, h, m–o) to %PPB using the regression equation.^{66 (link)}