ANGIOLOGY T3ie Journal
of Vascular Diseases
Physical Training and Antiplatelet Treatment in Stage II Peripheral Arterial Occlusive Disease: Alone or Combined? Elmo Mannarino, M.D., F.I.C.A. Leonella Pasqualini, M.D. Salvatore Innocente, M.D. Vito Scricciolo, M.D. Antonio Rignanese, M.D. and Giovanni Ciuffetti, M.D., F.I.C.A. PERUGIA, ITALY
Abstract The efficacy of physical training alone or combined with antiplatelet therapy (dipyridamole and aspirin) was studied in 30 patients with stage II peripheral arterial occlusive disease (PAOD). Patients were randomly allocated to one of the following groups: Group A— dipyridamole 75 mg three times daily and aspirin 330 mg once daily: Group B— physical exercise; Group C—physical exercise and dipyridamole 75 mg three time daily and aspirin 330 mg once daily. After six months’ treatment the pain-free walking time (PFWT) and the maximum walking time (MWT) improved significantly (p < 0.05) in all three groups. In group A the PFWT lengthened by 35% (from 101.00 ± 34.56 to 137.32 ± 40.50 s) and the MWT by 38% (from 150.34 ± 55.60 to 207.26 ± 60.67 s); in group B the PFWT lengthened by 90% (from 90.65 ± 40.54 to 171.45 ± 55.60 s) and the MWT by 86% (from 145.39 ± 60.50 to 270.63 ± 63.61 s). When physical exercise was associated with drugs as in group C, the PFWT lengthened by 120% (from 89.51 ± 43.89 to 196.72 ±51.73 s) and the MWT by 105% (from 160.43 ± 59.84 to 329.05 ± 63.96 s). No significant variations were observed at any stage of the study in the ankle/arm pressure ratio at rest and after standard treadmill exercise, in the plethysmographic rest and peak flows, or in the transcutaneous oxygen pressure in basal conditions and in its half recovery time after an induced ischemia. The results confirm the benefits of regular exercise in stage II PAOD patients but suggest
they
may be enhanced
From the Angiology Section, 2nd Dept. Internal Medicine, Presented at the 32nd Annual Meeting of the International
by antiplatelet therapy.
University of Perugia, Perugia, Italy College of Angiology, Toronto, Canada, June,
513
Downloaded from ang.sagepub.com at Purdue University on June 26, 2015
1990
514
Introduction
Nowadays the best conservative treatment for stage II peripheral arterial occlusive disease (PAOD) is based on the correction of any eventual risk factors such as smoking, hyperlipidemia, and diabetes and on regular physical exercises Indeed these measures have been shown to increase the walking capacity in patients with intermittent claudication by doubling or even trebling their walking distances.’-&dquo; Controlled studies have, on the other hand, shown that stage II PAOD patients also benefit from hemodilution and from pharmacologic treatment such as the administration of antiplatelet agents, anticoagulants, and rheologically active drugs.’4-’8 Antiplatelet drugs, in particular, dipyridamole associated with aspirin, seem to improve the walking capacity in these patients and slow the progression of occlusive diseases It remains to be seen whether antiplatelet agents are as efficacious as physical exercise in improving walking capacity and whether combining pharmacologic treatment with physical exercise would be more beneficial than physical training alone. Bearing this in mind we designed a trial to evaluate the efficacy of physical training, by itself or combined with dipyridamole and aspirin, in patients affected by stage II PAOD, adopting the pain-free walking time (PFWT) and the maximum walking time (MWT) as clinical end points. We also wanted to see whether the clinical improvement was associated with variations in the usual instrumental parameters used to assess ischemic damage. These included the ankle/arm pressure ratio, the plethysmographic rest and peak flows, and the transcutaneous oxygen pressure (TcP02) values. Materials and Methods
Thirty stage II PAOD patients (20 men, 10 women, average age sixty-three ± five range forty-eight to seventy-five years) were recruited to the study. The clinical diagnosis of PAOD was confirmed by Doppler (ankle/arm pressure ratio 0.80) and angiographic findings. All the patients had been suffering for at least two years from intermittent claudication, which appeared after they walked less than 300 meters and which had been stable in the previous three months, when the pain-free walking times had varied by less than 20070. No patient had a case history of angina pectoris, recent myocardial infarction, or stroke or had undergone vascular surgery or percutaneous angioplasty in the preceding six months. Patients affected by impaired cardiac or lung functions; major liver, kidney, or metabolic diseases; infections; or cancer were excluded. Peptic ulcer constituted another criterion for exclusion since aspirin is not indicated in these cases. In the three months prior to the beginning of the study and during the six month study period, hypertension, diabetes, and/or hyperlipidemia were controlled, when present, by the best pharmacologic treatment available. Before entering the study all patients stopped smoking and all antiplatelet, anticoagulant, rheologically active or vasoactive agents were suspended. Ten patients were then randomized to each of the following three groups and were treated for six months with:
Downloaded from ang.sagepub.com at Purdue University on June 26, 2015
515
Clinical details
Abreviations: sten
=
of the 30 Stage
stenosis,
sup
=
TABLE I II PAOD Patients Admitted to the
superior,
fem
=
femoral, ocel
=
Study
occlusion
-pharmacologic therapy (dipyridamole 75 mg three times daily and aspirin 330 mg daily) (Group A) -a physical training program (Group B) -the same physical training program plus pharmacologic treatment (dipyridamole 75 mg three times daily and aspirin 330 mg daily) (Group C) No significant differences emerged in sex, age, or the distribution of risk factors and concomitant diseases in the three groups, which were also homogeneous in the localization of vascular stenosis and occlusions according to angiographic findings (Table I). The six-month physical training program our patients underwent included one-hour daily exercises carried out at home every day and twice a week under supervision in our Outpatient Department as described in our previous study.’3 The home training program was an hour’s walk in the open air scheduled as follows: .
week 1: 500 meters in twenty minutes week 2: 1000 meters in forty minutes ~ week 3: 2000 meters in sixty minutes. This was to be carried out on flat ground at a regular pace (about 60 paces per minute). Patients were to halt at the first sign of pain and then start off again when again when it passed. The distance covered in an hour was measured by means of a pedometer. As an alternative to the daily walk, patients could choose an exercise program designed to exercise postural muscles with specific exercises for the lower extremities such as raising and lowering them, flexing and extending, and making lateral foot movements. The twice weekly exercise session in the Outpatient Department was designed to monitor the progress made at home and to encourage and motivate the patients. It included movements designed to exercise total motor coordination: slow walk, quick march, hopping, jogging, and following a fixed itinerary; isometric and isotonic gymnastics to exercise the lower extremity muscles in the standing, sitting, supine, and prone positions with the selective involvement of muscles distal to the vascular occlusion. ~ ~
Downloaded from ang.sagepub.com at Purdue University on June 26, 2015
516 The following tests were performed before the study was begun and after the first, third, and sixth months: · Standard treadmill test (12 °/2km/hr/5 minutes); the painfree walking time (time in seconds from starting treadmill exercise to the appearance of pain) and the maximum walking time (time in seconds from beginning to end of treadmill exercise) were registered. ~ Doppler velocimetry, ankle/arm pressure ratio before and after exercise. ~ Strain-gauge plethysmography evaluated the basal calf muscle flow (rest flow: mL/ 100 mL/min) and the maximum muscle blood flow after an ischemia was induced by applying a cuff to the lower third of the thigh and inflating it to a pressure of 240 mmHg held for three minutes (peak flow: mL/100 mL/min). o Transcutaneous oxygen pressure (mmHg) was determined on the dorsum of the foot at the first intermetarsal space in basal condition and after an induced ischemia; the socalled half-recovery time (the time taken to recuperate half the decrease from basal values caused by the ischemia) was then taken . 21 Students t test for paired data was used for the statistical analysis of the results. Data were analyzed longitudinally (intragroup) and cross-sectionally (intergroup) with only p < 0.05 being considered significant and reported here.
Results
Group
A
After six months’
225 mg dipyridamole and 330 mg aspirin per day, a significant (p < 0.05) increase in PFWT ( + 35 Vo) was observed in the 10 patients (from 101.00 ± 34.56 to 137.32 ± 40.50 (Fig. 1). The MWT increased by 3807o from 150.34 ± 55.60 to 207.26 ± 60.67 (p < 0.05) (Fig. 2). No significant variations were observed in the ankle/arm pressure ratio, in the plethysmographic rest and peak flows, or in the TcPC2 values (Table II).
Group
therapy with
B
physical training the average PFWT significantly increased in these patients by 90070, lengthening from 90.65 ± 40.54 to 171.45 ± 55.60 (p
of Vascular Diseases
Physical Training and Antiplatelet Treatment in Stage II Peripheral Arterial Occlusive Disease: Alone or Combined? Elmo Mannarino, M.D., F.I.C.A. Leonella Pasqualini, M.D. Salvatore Innocente, M.D. Vito Scricciolo, M.D. Antonio Rignanese, M.D. and Giovanni Ciuffetti, M.D., F.I.C.A. PERUGIA, ITALY
Abstract The efficacy of physical training alone or combined with antiplatelet therapy (dipyridamole and aspirin) was studied in 30 patients with stage II peripheral arterial occlusive disease (PAOD). Patients were randomly allocated to one of the following groups: Group A— dipyridamole 75 mg three times daily and aspirin 330 mg once daily: Group B— physical exercise; Group C—physical exercise and dipyridamole 75 mg three time daily and aspirin 330 mg once daily. After six months’ treatment the pain-free walking time (PFWT) and the maximum walking time (MWT) improved significantly (p < 0.05) in all three groups. In group A the PFWT lengthened by 35% (from 101.00 ± 34.56 to 137.32 ± 40.50 s) and the MWT by 38% (from 150.34 ± 55.60 to 207.26 ± 60.67 s); in group B the PFWT lengthened by 90% (from 90.65 ± 40.54 to 171.45 ± 55.60 s) and the MWT by 86% (from 145.39 ± 60.50 to 270.63 ± 63.61 s). When physical exercise was associated with drugs as in group C, the PFWT lengthened by 120% (from 89.51 ± 43.89 to 196.72 ±51.73 s) and the MWT by 105% (from 160.43 ± 59.84 to 329.05 ± 63.96 s). No significant variations were observed at any stage of the study in the ankle/arm pressure ratio at rest and after standard treadmill exercise, in the plethysmographic rest and peak flows, or in the transcutaneous oxygen pressure in basal conditions and in its half recovery time after an induced ischemia. The results confirm the benefits of regular exercise in stage II PAOD patients but suggest
they
may be enhanced
From the Angiology Section, 2nd Dept. Internal Medicine, Presented at the 32nd Annual Meeting of the International
by antiplatelet therapy.
University of Perugia, Perugia, Italy College of Angiology, Toronto, Canada, June,
513
Downloaded from ang.sagepub.com at Purdue University on June 26, 2015
1990
514
Introduction
Nowadays the best conservative treatment for stage II peripheral arterial occlusive disease (PAOD) is based on the correction of any eventual risk factors such as smoking, hyperlipidemia, and diabetes and on regular physical exercises Indeed these measures have been shown to increase the walking capacity in patients with intermittent claudication by doubling or even trebling their walking distances.’-&dquo; Controlled studies have, on the other hand, shown that stage II PAOD patients also benefit from hemodilution and from pharmacologic treatment such as the administration of antiplatelet agents, anticoagulants, and rheologically active drugs.’4-’8 Antiplatelet drugs, in particular, dipyridamole associated with aspirin, seem to improve the walking capacity in these patients and slow the progression of occlusive diseases It remains to be seen whether antiplatelet agents are as efficacious as physical exercise in improving walking capacity and whether combining pharmacologic treatment with physical exercise would be more beneficial than physical training alone. Bearing this in mind we designed a trial to evaluate the efficacy of physical training, by itself or combined with dipyridamole and aspirin, in patients affected by stage II PAOD, adopting the pain-free walking time (PFWT) and the maximum walking time (MWT) as clinical end points. We also wanted to see whether the clinical improvement was associated with variations in the usual instrumental parameters used to assess ischemic damage. These included the ankle/arm pressure ratio, the plethysmographic rest and peak flows, and the transcutaneous oxygen pressure (TcP02) values. Materials and Methods
Thirty stage II PAOD patients (20 men, 10 women, average age sixty-three ± five range forty-eight to seventy-five years) were recruited to the study. The clinical diagnosis of PAOD was confirmed by Doppler (ankle/arm pressure ratio 0.80) and angiographic findings. All the patients had been suffering for at least two years from intermittent claudication, which appeared after they walked less than 300 meters and which had been stable in the previous three months, when the pain-free walking times had varied by less than 20070. No patient had a case history of angina pectoris, recent myocardial infarction, or stroke or had undergone vascular surgery or percutaneous angioplasty in the preceding six months. Patients affected by impaired cardiac or lung functions; major liver, kidney, or metabolic diseases; infections; or cancer were excluded. Peptic ulcer constituted another criterion for exclusion since aspirin is not indicated in these cases. In the three months prior to the beginning of the study and during the six month study period, hypertension, diabetes, and/or hyperlipidemia were controlled, when present, by the best pharmacologic treatment available. Before entering the study all patients stopped smoking and all antiplatelet, anticoagulant, rheologically active or vasoactive agents were suspended. Ten patients were then randomized to each of the following three groups and were treated for six months with:
Downloaded from ang.sagepub.com at Purdue University on June 26, 2015
515
Clinical details
Abreviations: sten
=
of the 30 Stage
stenosis,
sup
=
TABLE I II PAOD Patients Admitted to the
superior,
fem
=
femoral, ocel
=
Study
occlusion
-pharmacologic therapy (dipyridamole 75 mg three times daily and aspirin 330 mg daily) (Group A) -a physical training program (Group B) -the same physical training program plus pharmacologic treatment (dipyridamole 75 mg three times daily and aspirin 330 mg daily) (Group C) No significant differences emerged in sex, age, or the distribution of risk factors and concomitant diseases in the three groups, which were also homogeneous in the localization of vascular stenosis and occlusions according to angiographic findings (Table I). The six-month physical training program our patients underwent included one-hour daily exercises carried out at home every day and twice a week under supervision in our Outpatient Department as described in our previous study.’3 The home training program was an hour’s walk in the open air scheduled as follows: .
week 1: 500 meters in twenty minutes week 2: 1000 meters in forty minutes ~ week 3: 2000 meters in sixty minutes. This was to be carried out on flat ground at a regular pace (about 60 paces per minute). Patients were to halt at the first sign of pain and then start off again when again when it passed. The distance covered in an hour was measured by means of a pedometer. As an alternative to the daily walk, patients could choose an exercise program designed to exercise postural muscles with specific exercises for the lower extremities such as raising and lowering them, flexing and extending, and making lateral foot movements. The twice weekly exercise session in the Outpatient Department was designed to monitor the progress made at home and to encourage and motivate the patients. It included movements designed to exercise total motor coordination: slow walk, quick march, hopping, jogging, and following a fixed itinerary; isometric and isotonic gymnastics to exercise the lower extremity muscles in the standing, sitting, supine, and prone positions with the selective involvement of muscles distal to the vascular occlusion. ~ ~
Downloaded from ang.sagepub.com at Purdue University on June 26, 2015
516 The following tests were performed before the study was begun and after the first, third, and sixth months: · Standard treadmill test (12 °/2km/hr/5 minutes); the painfree walking time (time in seconds from starting treadmill exercise to the appearance of pain) and the maximum walking time (time in seconds from beginning to end of treadmill exercise) were registered. ~ Doppler velocimetry, ankle/arm pressure ratio before and after exercise. ~ Strain-gauge plethysmography evaluated the basal calf muscle flow (rest flow: mL/ 100 mL/min) and the maximum muscle blood flow after an ischemia was induced by applying a cuff to the lower third of the thigh and inflating it to a pressure of 240 mmHg held for three minutes (peak flow: mL/100 mL/min). o Transcutaneous oxygen pressure (mmHg) was determined on the dorsum of the foot at the first intermetarsal space in basal condition and after an induced ischemia; the socalled half-recovery time (the time taken to recuperate half the decrease from basal values caused by the ischemia) was then taken . 21 Students t test for paired data was used for the statistical analysis of the results. Data were analyzed longitudinally (intragroup) and cross-sectionally (intergroup) with only p < 0.05 being considered significant and reported here.
Results
Group
A
After six months’
225 mg dipyridamole and 330 mg aspirin per day, a significant (p < 0.05) increase in PFWT ( + 35 Vo) was observed in the 10 patients (from 101.00 ± 34.56 to 137.32 ± 40.50 (Fig. 1). The MWT increased by 3807o from 150.34 ± 55.60 to 207.26 ± 60.67 (p < 0.05) (Fig. 2). No significant variations were observed in the ankle/arm pressure ratio, in the plethysmographic rest and peak flows, or in the TcPC2 values (Table II).
Group
therapy with
B
physical training the average PFWT significantly increased in these patients by 90070, lengthening from 90.65 ± 40.54 to 171.45 ± 55.60 (p
