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A Practitioner Based Evaluation of Nicorandil on Symptoms and Quality of Life in Patients with Chronic Stable Angina Pectoris

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A Practitioner Based Evaluation of Nicorandil on Symptoms and Quality of Life in Patients with Chronic Stable Angina Pectoris Journal of Clinical and Basic Cardiology An Independent International Scientific Journal Journal of Clinical and Basic Cardiology 2001; 4 (2), 149-152 A Practitioner Based Evaluation of Nicorandil on Symptoms and Quality of Life in Patients with Chronic Stable Angina Pectoris Kiowski W, Riebenfeld D Homepage: www.kup.at/jcbc Online Data Base Search for Authors and Keywords Indexed in Chemical Abstracts EMBASE/Excerpta Medica Krause & Pachernegg GmbH · VERLAG für MEDIZIN und WIRTSCHAFT · A-3003 Gablitz/Austria ORIGINAL PAPERS, CLINICAL CARDIOLOGY Nicorandil in Angina Pectoris Patients in General Practice J Clin Basic Cardiol 2001; 4: 149 A Practitioner Based Evaluation of Nicorandil on Symptoms and Quality of Life in Patients with Chronic Stable Angina Pectoris W. Kiowski1, D. Riebenfeld2 Nicorandil is an antianginal agent with unique pharmacological properties combining a nitrate-like action with vasodilation through opening of ATP-potassium channels. The antianginal effects of nicorandil have been carefully studied in mostly small, comparative trials but its usefulness outside of the setting of clinical trials is less well studied. We investigated the antianginal effects (patient diary for angina episodes and nitroglycerin consumption for immediate pain relief) of nicorandil in 200 patients (46 % females, 71.4 ± 9.9 years) followed by 56 primary care physicians in general practice. Nicorandil was started at 2 × 10 mg and, increased after 3 weeks to 2 × 20 mg, if tolerated and judged necessary, for a total of 12 weeks. Nicorandil was given as monotherapy in 22 % and in combination with beta-blockers, calcium antagonists or long-acting nitrates in 78 % of patients. An assessment of quality of life was performed at baseline and at week 12. Nicorandil was withdrawn in 14 patients (7 %) because of headache and/or flushing and in 10 patients because of acute illnesses unrelated to therapy or administrative reasons. After 12 weeks, nicorandil resulted in small but statistically significant (p < 0.05) decreases of systolic (–5.0 ± 14.3 mmHg) and diastolic (–2.4 ± 8.6 mmHg) blood pressure and heart rate (–1.9 ± 9.0 bts/min). Weekly anginal episodes and nitroglycerin consumption decreased markedly by –5 ± 6.3 and –5.6 ± 8.5 (p < 0.001) and ratings of quality of life improved for all aspects (p < 0.001). Both patients and physicians rated efficacy and tolerability in 80 to 90 % as excellent or good and 169 out of 174 patients opted for long-term nicorandil therapy after 12 weeks. Thus, nicorandil given alone or in combination proved to be highly efficacious and well tolerated in patients with chronic stable angina pectoris followed by their private physicians in general practice. J Clin Basic Cardiol 2001; 4: 149–152. Key words: nicorandil, angina pectoris, quality of life icorandil is an antianginal agent with unique pharma- with chronic stable angina pectoris agreed to participate in this N cological properties. On the one hand, it induces vascu- open label, 12 weeks trial that was approved by the local ethics lar smooth muscle relaxation by stimulation of guanylyl cy- committees. Exclusion criteria were a recent (< 3 months) clase leading to a nitrate-like action due to increased intracel- myocardial infarction and known intolerance to nicorandil. lular cyclic guanosine monophosphate levels [1]. On the After obtaining written informed consent patients were other hand, it results in hyperpolarization of vascular smooth instructed in the use of diaries to record the frequency of an- muscle cell membrane by opening of ATP-sensitive potas- gina pectoris episodes and the number of acutely acting ni- sium (KATP) channels [2, 3], which, in turn, leads to closing troglycerin preparations required for pain relief. In addition, of calcium (Ca2+) channels, a reduction in intracellular Ca2+ an attempt was made to assess patients’ quality of life using a concentration and venous and arterial vasodilation [4–8]. Al- scale of 1 (best) to 5 (worst) for the following questions: “How though nicorandil has a nitrate-like action there is good evi- is your general well being?”; “How is your physical capac- dence that opening of KATP channels contributes signifi- ity?”; “How is your endurance during strenuous physical cantly to its vasodilatory properties [3]. Trials in patients with work?”; and “How much are you bothered by angina pectoris chronic stable angina pectoris have demonstrated that nico- in daily life?”. Patients were asked to fill out the question- randil, 10–20 mg twice daily, is effective and well tolerated naire at the end of each week. Moreover, at the end of the and has a similar antianginal and antiischaemic efficacy as study, patients were asked to judge the efficacy and tolerabil- compared to nitrates [9, 10], beta-adrenoreceptor blockers ity of nicorandil as excellent, good, moderate, or poor and [11–13] and calcium channel blockers [14–16]. Interestingly, physicians were asked to perform the same rating. despite its nitrate-like action clinical tolerance does not ap- Following the baseline visit, patients were started on open pear to be a problem [10, 17, 18]. Although, therefore, the label nicorandil 2 × 10 mg daily and were scheduled for a fur- value of nicorandil is undoubted in patients with chronic sta- ther visit three weeks later. Concomitant therapy was contin- ble angina pectoris, there is little information about practica- ued. If tolerated and/or judged clinically necessary, nicorandil bility of its use outside of controlled trials. This aspect is im- was increased after three weeks to 2 × 20 mg daily. Down portant, as results obtained in controlled trials, often per- titration to 2 × 5 mg daily was allowed in case of adverse ef- formed in specialized centers, need not necessarily reflect ef- fects. Patients were scheduled for a final visit after 12 weeks ficacy and acceptance by patients and physicians in general when they were given the option to continue nicorandil. practice. Accordingly, we investigated efficacy, tolerability At each visit, seated casual blood pressure (sphygmomano- and acceptance of nicorandil therapy for treatment of angina meter), heart rate (radial pulse) and body weight were meas- pectoris in patients treated in general practice. ured. Patients and Methods Statistics Paired t-test was used to analyse changes as compared to The study was conducted in the offices of 56 general practi- baseline. Results are presented as means ± standard devia- tioners and internists in Switzerland. Two hundred patients tion and proportions as percentages. Received April 11th, 2001; accepted June 28th, 2001. For full list of investigators see appendix From the 1Division of Cardiology, University Hospital, 2Medical Department, Merck (Schweiz) AG, Zürich, Switzerland Correspondence to: Prof. W. Kiowski, MD, Division of Cardiology, University Hospital, CH-8091 Zürich, Switzerland; e-mail: [email protected] For personal use only. Not to be reproduced without permission of Krause & Pachernegg GmbH. Homepage Journal of Clinical and Basic Cardiology: http://www.kup.at/JClinBasicCardiol ORIGINAL PAPERS, CLINICAL CARDIOLOGY J Clin Basic Cardiol 2001; 4: 150 Nicorandil in Angina Pectoris Patients in General Practice Results Table 1. Patient characteristics Age (years) 71.4 ± 9.9 Patient characteristics Male/female (%) 54 / 46 Baseline patient characteristics are given in Table 1. Patients Current/previous smoker (%) 14 / 19.5 were elderly and mildly to moderately symptomatic with a Angina pectoris NYHA class II/III (%) 74.5 / 25.5 history of prior myocardial infarction on average 7.85 ± 7.9 Duration of angina pectoris (years) 4.29 ± 5.2 Previous myocardial infarction (%) 29.5 years earlier in approximately 30 %, coronary artery bypass Percutaneous coronary intervention (%) 12.5 grafting 7.2 ± 4.4 years earlier in 13.5 %, and percutaneous Coronary artery bypass grafting (%) 13.5 coronary intervention 3.8 ± 3.4 years earlier in 12.5 % of the β-blockers (%) 44.0 patients. Only 14 % of patients were current smokers and Calcium antagonists (%) 26.0 antihypertensive drugs other than beta-blockers and calcium Long acting nitroglycerin preparations (%) 29.5 antagonists were used in approximately one fourth. Diabetes Molsidomine (%) 9.5 Platelet inhibitors (%) 39.0 mellitus was infrequent with 6.5 % of patients using oral hy- HMG-CoA reductase inhibitors (%) 9.6 poglycaemic drugs and only one patient using insulin. Beta- ACE-inhibitors, angiotensin receptor antagonists, diuretics (%) 26.5 blockers were used most frequently, followed by long-acting Oral hypoglycaemic drugs (%) 6.0 nitroglycerin preparations, calcium antagonists and mol- sidomine. Forty six percent of the pa- tients received one, 24 % two, and 8 % Table 2. Haemodynamic and antianginal effects of nicorandil three antianginal agents. Twenty two Nicorandil Nicorandil Baseline percent of patients used nitroglycerin 3 weeks 12 weeks tablets or sprays only for pain relief. In- Systolic blood pressure (mmHg) 141.8 ± 18.5 137.4 ± 17.9* 136.5 ± 16.4** terestingly, only 40 % received a platelet Diastolic blood pressure (mmHg) 82.3 ± 9.1 80.3 ± 9.7 79.8 ± 8.7 inhibitor and only 10 % an HMG-CoA Heart rate (bts/min) 72.8 ± 9.9 72.0 ± 9.7 71.2 ± 8.6* reductase inhibitor. In 27 patients, Weight (kg) 74.5 ± 13.4 74.4 ± 13.4 74.0 ± 13.7 nicorandil replaced other antianginal Angina pectoris episodes (per week) 6.3 ± 6.4 2.6 ± 3.3** 1.3 ± 2.1** therapy (beta-blockers in three, calcium Nitroglycerin consumption (per week) 6.6 ± 8.9 2.5 ± 3.5** 1.0 ± 1.7** channel blockers in 4, and long-acting * p < 0.05, ** p < 0.001 nitrates in 20 patients), mostly because of adverse effects of these therapies. Table 3. Rating of nicorandil by physicians and patients Patient disposition during study Physicians Patients During the 12 weeks of follow up, 24 patients discontinued Efficacy (%) nicorandil. In 14 of them (7 %), adverse effects (headaches – excellent 44.8 42.1 and/or flush in 13, gastrointestinal disturbances in 1 patient(s)) – good 40.6 42.6 led to withdrawal of nicorandil within the first three weeks.
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