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Evidence Extractions Evidence Extractions Question: What is the clinical /cost effectiveness of standard antianginal drugs (nicorandil) for the management of angina? Grading: 1++ High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias Ulvenstam G;Diderholm E;Frithz G;Gudbrandsson T;Hedback B;Hoglund C;Moelstad P;Perk J;Sverrisson JT; Antianginal and anti-ischemic efficacy of nicorandil compared with nifedipine in patients with angina pectoris and coronary heart disease: a double-blind, randomized, multicenter study Ref ID 15934 1992 Study Type Randomised Controlled Trial Funding Not reported. Number of participant N=58 (n=29 Nicorandil, n=29 Nifedipine) Inclusion/Exclusion Patients <76 years old with a history of typical effort induced angina pectoris relieved Criteria by nitroglycerin or rest were eligible for inclusion in the study. Patients with a recent MI<3 months), unstable angina, angina at rest, or vasospastic angina were excluded from the study, as were patients with uncontrolled hypertension. Also excluded were patients with ECG tracings disturbing the evaluation of the ST segment and patients with congestive heart failure, a history of exercise-induced arrhythmia, concomitant medication with digitalis, antiarrhythmics, and anti anginal dugs (e.g. B-Blockers, Calcium channel blockers, vasodilators, nitrates). Patient Characteristics 54 of the randomised patients were men (mean age, 62. Years; range 42-64 years), and four were women (mean age, 60.3 years, range49-70 years). History of cardiovascular disease CVD: Nicorandil (n=29) vs. Nifedipine (n=29) Myocardial infarction: 13vs. 6 Cardiac failure: 1 vs. 1 Bypass surgery: 3 vs. 1 Cerebrovascular disease: 1 vs.0 Peripheral vascular disease: 3 vs. 2 Hypertension: 6 vs. 4 The pre-treatment of coronary heart disease, which occurred before entry in to pre- phase of the trial, ranged from no treatment except for nitroglycerin to triple therapy with a combination of B-Blockers, calcium antagonists, and long acting nitrates. Recruitment Not reported. Setting Interventions/ Test/ Nicorandil 10mg b.i.d for first 4 weeks. During the last 4 week period, the dose of Factor being Nicorandil was increased to 20 mg b.i.d. Total 8 weeks treatment. investigated Comparisons Nifedipine 20 mg b.i.d for first 8 weeks. Length of Study/ At 4 weeks and at the end of 8 weeks of treatment (i.e. immediately after the Follow-up treatment) Outcome measures Exercise duration (min), time to onset of angina pectoris (min), time to 1 mm ST studied depression, ST depression on maximal work load (mm), weekly anginal attack rate, adverse events. Results At 4 weeks : Weekly anginal attack rate: Nicorandil (n=26 vs. nifedipine (n=24) [Mean±SD] 2.6± 3.6 vs. 7.0±12.2 Exercise duration (min): nicorandil (n=25) vs. nifedipine (n=23) [mean±SE] 10. ±0.56vs. 10.6±0.55 Time to onset of angina pectoris (min): nicorandil (n=23) vs. nifedipine (n=22) [mean±SE] 7.4±0.64 vs. 7.8 ±0.60 Time to 1mm ST depression (min) : nicorandil (n=23) vs. nifedipine (n=20) [mean±SE] 7.8 ±0.54 vs.7.0 ±0.60 ST depression on maximal identical work load (mm) : nicorandil (n=24) vs. nifedipine (n=20) [mean±SE] 1.9±0.17 vs. 1.8±0.17 At 8 weeks: Weekly anginal attack rate: Nicorandil (n=27) vs. nifedipine (n=23) [Mean±SD] 2.1±2.1 vs. 7.4±15.0 Exercise duration (min): nicorandil (n=25) vs. nifedipine (n=23) [mean±SE] 11.4±0.64 vs. 10.4±0.51 Time to onset of angina pectoris (min): nicorandil (n=23) vs. nifedipine (n=22) [mean±SE] 8.7±0.74 vs. 7.6 ±0.57 Time to 1mm ST depression (min) : nicorandil (n=23) vs. nifedipine (n=20) [mean±SE] 8.0 ±0.66 vs.6.4±0.50 ST depression on maximal identical work load (mm) : nicorandil (n=24) vs. nifedipine (n=20) [mean±SE] 1.9±0.18 vs. 1.7±0.17 Safety and adverse Adverse events: effects 4 patients in the nicorandil group dropped out due to adverse events (one because of acute MI and 3 because of headaches in combination with other symptoms of vasodilatation). Two patients in the nifedipine group dropped due to adverse events (one because of atrial fibrillation with high ventricular response and one because of vertigo, palpitations and nausea), and one patient dropped out because of poor compliance. Adverse events: Nicorandil (n=29) vs. nifedipine (n=29) Cardiovascular symptoms due to vasodilatation (symptoms such as dizziness, flush, ankle oedema, reported most frequently): 4 vs. 9 Headache: 13 vs. 9 Miscellaneous events (infections, gastrointestinal events, muscular or skeletal pain) : 6 vs. 5 No adverse events: 11 vs. 11 Does the study Yes. In the nicorandil group, an improvement was noted with the 20 mg dose answer the question? compared with the 10mg dose, but no significant differences were noted between the nicorandil and nifedipine groups after either treatment. Symptoms caused by peripheral vasodilatation were commonly reported in the nifedipine group. Effect due to factor in study? Consistency of results with other studies? Directly applicable to guideline population? Internal Validity Allocation concealment and ITT not reported. Grading: 1+ Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias Chatterjee T;Fleisch M;Meier B;Eber A; Comparison of the antiischaemic and antianginal effects of nicorandil and amlodipine in patients with symptomatic stable angina pectoris: The SWAN study Ref ID 3629 1999 Study Type Randomised Controlled Trial Funding Not reported Number of participant N=121 (N=57 in nicorandil group and N=64 in Amlodipine group). Inclusion/Exclusion Patients aged 18-80 years with symptomatic stable angina were screened for Criteria enrolment in the study. Eligible patients had a history of stable angina for ≥ 3 months and CHD confirmed by a history of myocardial infarction or a positive angiogram (>50% stenosis of a main coronary artery). Exclusion criteria included: myocardial infarction, invasive coronary intervention, unstable angina, angina at rest or vasospastic angina within the last 3 months; hypertension with supine diastolic blood pressure (DBP) >105 mmHg; electrocardiogram (ECG) recordings not allowing a evaluation of the ST segment; manifest congestive heart failure (New York Heart Association class 3-4); peripheral arterial obstructive disease or any other exercise test limiting disease; cardiac valvular disease with haemodynamic or clinical consequences; supine systolic blood pressure (SBP) <100 mmHg or DBP <70 mmHg; postural hypotension (>20% decrease in SBP after 1 min standing); and severe concomitant disease. Female patients were to be postmenopausal or surgically sterile. Patient Characteristics Characteristic: Nicorandil (N=57); Amlodipine (N=64) Gender (male: female): 44: 13; 53:11 Age (years): 62±9; 62±9 Bodyweight (Kg): 76±12; 76±10 No. of anginal attacks/week: 4.3±4.1; 4.4±5.5 Duration of history of angina pectoris (months): 51±69; 57±64 No. of patients with previous history of MI: 14; 26 No. of units of nitroglycerin required for immediate relief: 1.9±2.9; 1.6±2.4 Exercise tolerance test parameters Time to onset of 0.1 Mv ST-depression (min): 4.7±0.3; 5.1±0.3 Time to onset of anginal pain (min): 5.2±0.3; 5.6±0.3 Total exercise duration (min): 6.7±0.3; 7.3±0.4 ST-segment depression (Mv): -0.17±0.01; -0.17±0.01 Recruitment Participants recruited from 25 centres in Austria (n=11) and Switzerland (n=14). Setting Hospital centre Interventions/ Test/ Intervention is Nicorandil 10 mg bd orally.Depending on the patient’s clinical Factor being condition, study medication was either maintained at the same dosage for the investigated remainder of the study or increase after 2-4 weeks to nicorandil 20 mg bd. Dose titration: The percentage of patients following the high dosage regimen was similar in the nicorandil and amlodipine groups (50% and 43.5%, respectively at the end of the study). Comparisons Comparison is is Amlodipine 5 mg od orally. Depending on the patient’s clinical condition, study medication was either maintained at the same dosage for the remainder of the study or increased after 2-4 weeks to amlodipine 10 mg od. Length of Study/ The patients were followed up for 8 weeks. Follow-up Outcome measures Primary and Sec. endpoints not specified. studied Outcome measures: Exercise tolerance test using an upright bicycle, patients recorded no. of anginal attacks/day and the no. of nitroglycerin tablets, quality of life (4 variable questionairre), adverse events. Results Exercise tolerance tests (ETT): Nicorandil (n=56) Parameter: Baseline; 2 weeks; 8 weeks (mean±SEM) Time to onset of 0.1 mv ST-segment depression (min): 4.7±0.3; 5.0±0.3; 5.1 ±0.3 Time to onset of anginal pain (min): 5.2±0.3; 6.1±0.3*; 6.1±0.4* Total exercise duration (min): 6.7±0.3; 7.2±0.3*; 7.2±0.4* ST-segment depression at maximal identical workload (mv):-0.17±0.01; -0.14±0.01*; - 0.13±0.01* Amlodipine (n=62) Parameter: Baseline; 2 weeks; 8 weeks (mean±SEM) Time to onset of 0.1 mv ST-segment depression (min): 5.1±0.3; 6.0±0.4*; 5.7±0.3* Time to onset of anginal pain (min): 5.6±0.3; 6.6±0.3*; 7.0±0.4* Total exercise duration (min):7.3±0.4; 7.9±0.4*; 7.9±0.3* ST-segment depression at maximal identical workload (mv):-0.17±0.01; -0.12±0.01*;- 0.12±0.01* *indicates that the difference to baseline was statistically significant.
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