Gemfibrozil for CAD in Men with Low Levels of High Density Lipoprotein Cholesterol
Up to 30% of patients with coronary disease have a low level of HDL as their primary abnormality, with normal levels of LDL cholesterol. Clinical trials have generally focused upon persons with elevated LDL cholesterol and have proven that lowering LDL below 130 with pharmacotherapy reduces major cardiac events.
The Veterans Affairs HDL Cholesterol Intervention Trial Study Group investigated treatment with gemfibrozil in men with low HDL (< 40 mg/dL) and normal LDL (< 140 mg/dL); all men had proven coronary heart disease (n = 2531).
On average, treatment lasted about five years. Treatment was associated with a 22% relative risk reduction in cardiac events, designated as combined incidence of nonfatal MI and fatality due to coronary heart disease. The combination of death from coronary heart disease, nonfatal MI, and stroke was also reduced 24%. These effects were achieved with a mean reduction in cholesterol of 4%, triglyceride 31%, and a 6% increase in HDL. Treatment had no effect on LDL in these patients, with baseline LDL less than 140.
The only common side effect attributed to gemfibrozil was dyspepsia, for which there was a placebo-subtracted frequency of 6%. All other measured adversities were equivalent for the active treatment and placebo group.
This study concludes that for patients whose primary lipid abnormality is low HDL, secondary preventive treatment with gemfibrozil reduces MI and death from coronary heart disease.
Rubin HB, et al. N Engl J Med 1999; 341:410-418.
Contact Lens- Associated Microbial Keratitis
Most of the 28 million contact lens wearers in the United States use them for cosmetic reasons as an alternative to spectacles for correcting refractive errors, as opposed to the small number (3%) who use them for treatment of ocular surface diseases or aphakia. Microbial keratitis, which may result in permanent corneal scarring or perforation, with subsequent permanent visual loss, is the most dreaded complication of contact lens wear. It is usually due to bacteria, though fungi and acanthamoebae have also been implicated.
For this study, a prospective population study was done among all ophthalmologists in the Netherlands (n = 440), who were asked to report all cases of microbial keratitis seen over a 90-day period in 1996. During this interval, 111 cases of keratitis were identified.
Extended wear soft contact lens (1-2 week disposables) users were almost 20 times as likely to incur microbial keratitis as users of daily-wear rigid gas-permeable lens users. Even daily-wear soft lenses were more than three times more likely to suffer microbial keratitis than rigid gas-permeable lens users. In this trial, Serratia and Pseudomonas aeruginosa were the most commonly isolated bacteria; only one case of acanthamoeba was identified, and there were no fungal infections. Less than half of all cases had any pathogen recoverable from culture.
Infections resulted in five hospitalizations, requiring one excimer laser corneal scar excision and three cases of corneal transplantation due to visual impairment from scar. The patient with acanthamoeba progressed to visual impairment resulting in near-blindness.
Cheng and colleagues note that overnight use of lenses was the primary risk factor for corneal infection and should hence be discouraged. In this population, rigid gas-permeable lenses were associated with the least risk of microbial keratitis.
Cheng KH, et al. Lancet 1999;354: 181-185.
ACE-Inhibition in Nondiabetic Nephropathies
Prevention of overt nephropathy by treatment of proteinuria with ACE inhibitors is well established for patients with diabetes. A 1997 trial of ACE inhibitor therapy (ramipril) for hypertensive nondiabetic patients with significant nephropathy (protein excretion > 3 g/d) was so successful that the trial was stopped early. Another subgroup of this same population, consisting of persons with more modest levels of proteinuria (between 1-3 g proteinuria daily) was the subject of this investigation.
Study participants (n = 175) were normotensive or hypertensive and had persistent proteinuria. After a median of 31 months treatment with the ramipril, significantly fewer treated patients progressed to end stage renal failure or to overt proteinuria. Patients with the lowest baseline renal function (GFR 45 mL/min or less) demonstrated the greatest therapeutic benefits. As anticipated, the decline in renal function in this study was that of the preceding trial that had included more severe proteinuria. Overall, patients with proteinuria cut their risk of progression to end stage renal failure and severe proteinuria in half.
Ruggenenti and colleagues note that since proteinuria greater than 3 g/24/h heralds rapid progression of renal deterioration, clinicians should aim to forestall this degree of proteinuria. They also suggest that the commonplace practice of withholding ACE inhibitors in severe renal failure for fear of further failure or hyperkalemia is not justified.
Ruggenenti P, et al. Lancet 1999;354: 359-364.