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The FDA has approved two drugs for intermittent claudication: pentoxifylline (Trental)($24) and cilostazol (Pletal)($120). Pentoxifylline is thought to involve red blood cell deformability as well as a reduction in fibrinogen concentration, platelet adhesiveness and whole blood viscosity. Cilostazol is a potent, reversible, phosphodiesterase III inhibitor. The inhibition of phosphodiesterase allows for the increased availability of cyclic adenosine monophosphate (cAMP). cAMP mediates many agonist-induced platelet inhibitory, vasodilatory and vascular antiproliferative responses. Ginkgo biloba, available as an over-the-counter extract, provides symptom relief comparable to pentoxifylline. Two European agents, naftidrofuryl and buflomedil, also have efficacy that is reported to be similar to pentoxifylline. Policosanol ($6-10) has been found to reduce symptoms of claudication. Amino acids, certain peptides and prostaglandins may have a therapeutic role. Drug treatment of intermittent claudication. Jacoby D, Mohler ER. University of Pennsylvania. Drugs. 2004;64(15):1657-70. Pletal causes lots of side-effects including headaches, palpitations, edema, dizzness, and diarrhea, while Trental's side-effects are more modest and policosanol without side-effects. The carnitines also look good. They work by improving mitochondrial functioning. They are available without a prescription. The cost is $8 per month when purchased by the kilo in powder form or $40-$100 per month in 500 tablets. Padma-28, a Tibetan remedy mixture, also has been found of benefit in 3 DB studies. Ticlopidine (Ticlid)($108) is a platelet aggregation inhibitor used for patients at risk for strokes due to transient ischemic attacks, transient monocular blindness, or minor strokes. It did no better than policosanol in a head-to-head study. Carnitines: L-Carnitine Helps: In a DB PC crossover study of 20 patients receiving 2 g/d found distance walked increased from 170 feet to 300 feet. Brevetti, Circ 4/88 Carnitines: Propionyl-L-Carntine Helped: PLC helps increase the citric energy cycle in ischemic muscle and it increases pyruvate dehydrogenase activity. In a DB phase III study of peripheral artery disease, patients taking 1-3 g/day improved their maximum walking distance. Wiseman, Drugs Aging 3/98; Helped patients only with inability to walk 250 feet. J Am Coll Cardiol 1999 Nov 1;34(5):1618-24 Carnitines: Propionyl-L-carnitine Helped in 2 Studies: In a DB PC study, PLC did not help patients with a basal max walking distance of over 250 meters but helped those who were more impaired. Naples, Am J Cardiol ’97;79:777; PLC was also found of benefit in a DB PC study of 112 patients. Brevetti, Italy, J Am Coll Cardiol ‘95;26:1411 Padma 28 Helped Intermittent Claudication in 3 DB Studies: In a 4-month DB PC study of 36 patients with intermittent claudication, those who received two tablets bid containing 340 mg of a dried herbal mixture composed according to an ancient lamaistic preparation (Padma 28) had a significant increase in the pain-free walking distance from 52 m to 86 m; P < 0.05) and in the maximal walking distance from 115 m to 227 m (P < 0.05). The placebo group showed no improvement. A botanical compound, Padma 28, increases walking distance in stable intermittent claudication. Drabaek H, Mehlsen J, et al. Frederiksberg Hospital, Denmark. Angiology. 1993 Nov;44(11):863-7. Similar results are reported from a DB PC Polish study of 50 patients. There was also a decrease in the index of blood platelets aggregation, a drop in the level of cholesterol, triglycerides, total lipids, beta lipoproteins, and an increase in ++alpha lipoproteins. Ann Acad Med Stetin. 1991;37:191-202. The first study was a 48 patient DB PC German study with similar results. Schweiz Med Wochenschr. 1985 Jun 1;115(22):752-6. It reduced atherosclerotic plaques in rabbits. Arch Immunol Ther Exp (Warsz). 1992;40(5-6):291-5. Policosanol Helped in Small Study: Policosanol also has an antiplatelet effect. In a 28-patient, 20-week DB PC study after a 4-week baseline, those on policosanol 10 mg or ticlopidine 250 mg tablets twice daily did equally well. Walking distances in a treadmill, policosanol significantly increased the initial claudication distance from 162.1 to 273.2 m and the absolute (ACD) from 255.8 to 401.0 m. Ticlopidine also raised ICD (166.2 to 266.3 m) and ACD (252.9 to 386.4 m). Policosanol, but not ticlopidine, (p < 0.05) modestly increased the ankle/arm pressure ratio. Policosanol lowered (p < 0.001) LDL-C (30.2%), TC (16.9%), and TC/HDL-C (33.9%), increased HDL-C (+31.7%), and left triglycerides unchanged. Ticlopidine did not affect the lipid profile. Policosanol induced modest reductions (p < 0.01) of fibrinogen levels compared with baseline and ticlopidine. Three ticlopidine patients (21.4%) withdrew, only 1 owing to a serious adverse event (unstable angina). Effects of policosanol and ticlopidine in patients with intermittent claudication: a double-blinded pilot comparative study. Castano G, Mas R, Gamez R, Fernandez L, Illnait J. Havana City, Cuba. Angiology. 2004 Jul-Aug;55(4):361-71. Ticlid Very Expensive Stroke Preventative; Not Cost Effective: Ticlopidine (Ticlid) is a platelet aggregation inhibitor used for patients at risk for strokes due to transient ischemic attacks, transient monocular blindness, or minor strokes. In two very large, industry-funded studies of 4,142 patients, at 250 mg twice a day, it slightly lowered the risk for a stroke by 4% (18% vs. 14%) over a five year period of time compared to aspirin and by 6% (24% vs. 18%) when compared to placebo when given to stroke victims over a three year period. The generic costs $108 per month at Walgreens. This means that it costs $160,000 per stroke actually prevented in medication cost alone when compared to aspirin. That‘s a huge amount of money. The cost is so high because 24 out of 25 patients taking the medicine won’t be helped by it. Ticlid can have a number of serious side-effect affecting the white and red blood cells. |