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IVANČICA PAVLIČEVIĆ ; Department of Family Medicine, Split University School of Medicine, Split, Croatia
MARION KUZMANIĆ ; Department of Family Medicine, Split University School of Medicine, Split, Croatia
MIRJANA RUMBOLDT ; Split University School of Medicine, Split, Croatia
ZVONKO RUMBOLDT ; Split University School of Medicine, Split, Croatia

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Background: Nonsteroidal anti-inflammatory drug (NSAID) side effects can impair quality of life in patients with osteoarthritis. Due to its particular mechanism of action, paracetamol might bypass these negative effects.
Objectives: To determine both the role of paracetamol in the treatment of osteoarthritis patients and optimal combination of antihypertensives
and antirheumatics for these patients.
Methods: A prospective clinical trial in a family practice included 110 treated hypertensives aged over 55 years: 50 controls and 60 also taking NSAIDs for osteoarthritis. This 3-month study compared two antihypertensives, lisinopril/hydrochlorothiazide fixed combination and amlodipine, with two NSAIDs, ibuprofen and piroxicam, and with paracetamol. Following clinical work-up and NSAID discontinuation for at least 3 days (run-in period of only 3-7 days), osteoarthritis subjects were randomized to 1-month periods of ibuprofen (400-600 mg t.i.d.) or piroxicam (10-20 mg o.d.) with one month of paracetamol (1000 mg t.i.d.) in the middle as a “wash-out” interval, continuing the prescribed amlodipine (5-10 mg o.d.) or lisinopril/hydrochlorothiazide fixed drug
combination (10/6.25-20/12.5 mg o.d.), while control subjects (hypertensives with no osteoarthritis) were just keeping their antihypertensive therapy. Blood pressure was measured with standard mercury sphygmomanometer and with an automatic device, in standing, sitting and supine position. The intensity of arthritic pain (on a visual analogue scale from 1 to 10, where 0 means “no pain” and 10 “the worst pain you may imagine”) and the patient’s quality of life estimate (on a visual analogue scale from 1 to 10, where 0 means “general condition excellent” and 10 “the worst possible”) were recorded.
Results: Blood pressure control was unchanged in the amlodipine group across the study periods and impaired in the lisinopril/
hydrochlorothiazide group during either ibuprofen or piroxicam, but not during paracetamol. In the amlodipine ± ibuprofen subgroup, the reduction of the average pain intensity score throughout the study was significant (2=8.250; df 3; P=0.037). In the lisinopril/hydrochlorothiazide ± piroxicam subgroup, the assessed quality of life differed significantly (2=9.716; df 3; P=0.018),
while in the amlodipine ± ibuprofen and amlodipine ± piroxicam subgroups the changes were marginal (2=6.936; df 3; P=0.072
and 2=7.146; df 3; P=0.065, respectively).
Discussion: In our trial, paracetamol had analgesic efficacy similar to ibuprofen and only marginally inferior to piroxicam. The analgesic effect of ibuprofen, piroxicam and paracetamol was more pronounced in amlodipine than in the lisinopril/hydrochlorothiazide subgroups. The quality of life was reported to be worse with NSAIDs than with paracetamol, presumably due to dyspeptic problems. Although during the paracetamol phases, the quality of life was slightly improved, the difference was statistically nonsignificant because of the small samples and insufficiently sensitive scale.
Conclusion: Analgesic efficiency of paracetamol is comparable to that of ibuprofen and is marginally inferior to piroxicam. Only paracetamol did not interfere with the antihypertensive effects of lisinopril/ hydrochlorothiazide combination. Piroxicam and ibuprofen markedly blunt the effects of antihypertensive drugs while paracetamol is almost inert in this sense. Lisinopril/hydrochlorothiazide combination is much more affected by this interaction than amlodipine. Because of less side effects and better tolerability, paracetamol is the analgesic of choice for hypertensive patients with osteoarthritis, needed prolonged pain relief. The second choice drugs are narcotic analgesics (e.g., tramadol). Small doses of NSAIDs can eventually be added with concomitant prescription of gastroprotective agents.


NSAIDs; paracetamol; osteoarthritis; arterial hypertension; quality of life

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