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Statin Toxicity in HIV+ & Elderly
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106249/
Toxicity
Toxicity associated with discontinuing statin therapy occurred rarely (in 6.4% of cases), with similar rates across the 3 commonly used statins: 6.1% for pravastatin, 7.3% for atorvastatin, and 5.3% for rosuvastatin. Among the 44 patients who experienced toxicities, 15 (2.2% of all study participants) had potentially serious toxicity and 29 (4.3%) had symptomatic toxicity. An elevation in CPK level (with or without a decline in renal function) was the most common potentially serious toxicity followed by elevations in liver enzymes. Five patients had CPK-level elevations between 1000 and 10,000 U/L (4 on pravastatin, 1 on rosuvastatin), and 1 had an elevation >10,000 U/L (on atorvastatin). Among 29 patients with symptomatic toxicity, the most common symptoms were myalgias/arthralgias (62%), gastrointestinal symptoms (21%), and fatigue (7%). Overall, 49 patients (7.2%) discontinued statins without any laboratory abnormalities or symptoms reported in the medical record. The rate of discontinuation for unknown reasons was similar across the 3 statins.
Toxicity
Adverse events associated with statins among individuals without HIV infection are uncommon [31]. Most reports of toxicity in HIV-infected persons included small numbers of patients [13, 15, 27, 32] or did not compare the effects of statins [15, 21, 27]. In contrast to data for laboratory toxicities, data for symptomatic toxicity such as myalgia are rarely collected and reported [16, 32]. We found low toxicity rates associated with statin discontinuation that did not vary across the 3 commonly used statins. The rate of CPK elevations was lower than that reported previously [6], despite our use of a very low cutoff point for CPK elevations to increase sensitivity. This may reflect more limited use of simvastatin. Furthermore, CPK elevations may occur even in the absence of statins and often are asymptomatic.
A number of drug interactions with statins have been described that may increase toxicity risk among HIV-infected individuals [33]. Until recently, pravastatin and rosuvastatin were thought to be safer than other statins because the metabolism of these statins did not utilize the cytochrome P450 (CYP450) 3A4 enzyme system influenced by many antiretroviral medications. However, recent studies have demonstrated increased plasma levels (expressed as area under the plasma concentration–time curve [AUC] and maximum concentration [Cmax] values) of these statins associated with particular antiretroviral medications [25, 34] (For a table of selected examples of these associations, see Supplementary Appendix Table 1). These increased levels may be the result of inhibition of the organic anion transporting polypeptide (OATP) 1B1 that facilitates statin uptake into the liver [22]. The disposition of pravastatin and rosuvastatin may be more dependent than other statins on OATP1B1. Consistent with this theory, a study found that atazanavir-ritonavir was associated with increased rosuvastatin levels. This finding led the authors to conclude that the maximum dose of rosuvastatin with atazanavir-ritonavir should be 10–20 mg, similar to current recommendation of a maximum rosuvastatin dose of 10 mg when used with lopinavir-ritonavir [34]. Although increased statin levels may enhance the effectiveness of the drugs, this benefit may come with the expense of enhanced toxicity. To date there are no known interactions between rosuvastatin and NNRTIs [22].
There is another study published showing more adverse events in older HIV+ taking statins but right now I can’t find it. Still these publications particularly the one immediately below give pause to concern of increased toxicities in older HIV+ who already may have predisposition with CK elevations, muscle wasting etc. And liver toxicity.
Significant association between statin-associated myalgia and vitamin D deficiency among treated HIV-infected patients.....Myalgia was significantly more likely to occur in older patients (mean age, 58.6 vs. 52.5 years; P = 0.041)......RESULTS - the baseline vitamin D deficiency is usually predictive of a persistent vitamin D deficiency at the moment of muscle toxicity occurrence.......Muscle toxicity was reported by 100 patients (18.3%),.....Of the 100 study participants who developed muscle toxicity, 10% occurred in 34.2 days, 25% in 153.7 days, 50% in 412.7 days, 75% in 674.2 days, and 90% in 1815.7 days. Muscle toxicity led to discontinuation of statin treatment in 68 out of the 100 patients (68%)....and there were 44 discontinuations (44%) because of muscle toxicity within the first 12 months of therapy.....Particularly, discontinuation occurred in 23 out of 42 patients (54.8%) with myalgia, 20 out of 33 (60.1%) with creatine kinase elevation, and 25 out of 25 (100%) with creatine kinase elevation and myalgia. Nine out of the 32 patients who continued statin treatment had their statin dose lowered and seven patients were switched to another statin (pravastatin in four cases and fluvastatin in three cases).....Baseline characteristics were similar between patients who experienced muscle toxicity and those who tolerated statin treatment with the exception of age, 25-hydroxyvitamin D concentration, and total duration of statin therapy. Myalgia was significantly more likely to occur in older patients (mean age, 58.6 vs. 52.5 years; P = 0.041).....The prevalence of comorbidities was similar between persons who developed muscle toxicity and those who did not with the exception of history of myalgia. In fact, a history of muscle pain was reported in a significantly higher percentage of cases among patients who experienced myalgia (69%) and creatine kinase elevation and myalgia (44%) than in those who tolerated the statin treatment (11%; P = 0.022 and 0.037,.....Older patients (age ≥ 60 years), patients with history of myalgia, patients with a low baseline serum concentration of 25-hydroxyvitamin D (<30 ng/ml), and patients with a long duration of statin treatment (>24 months) were significantly more likely to develop myalgia while taking atorvastatin or rosuvastatin in association with cART (Fig. 2). At the same time, patients with history of myalgia and patients with a low baseline serum concentration of 25-hydroxyvitamin D (<30 ng/ml) were significantly more likely to develop creatine kinase elevation and myalgia while taking atorvastatin or rosuvastatin in association with cART. There were no factors significantly associated with the occurrence of isolated creatine kinase elevation.....The pathogenetic mechanism leading to a more frequent occurrence of myositis and myalgia in patients treated with statins and with a low vitamin D concentration is debated still today.
The favorable effect of the vitamin D supplementation on the statin intolerance represented by muscle pain was evaluated by an observational, prospective study including 150 patients unable to tolerate one or more statins because of myositis or myalgia and with low serum concentration of vitamin D (<32 ng/ml). After 3 weeks of vitamin D supplementation (50 000 units twice a week) without statins, statins were restarted. After a median follow-up of 8.1 months, the serum vitamin D level normalized in the 78% of patients and the 87% of study participants were free of myositis/myalgia and tolerated the statins well [28]. Another observational study assessed 146 patients intolerant to two or more statins because of myalgia or myopathy and found to have a low serum vitamin D concentration (<32 ng/ml). The enrolled patients were treated with a vitamin D2 supplementation (50 000 to 100 000 units a week) and followed up for 24 months. The median vitamin D level rose from 23 to 55 ng/ml after a 24-month follow-up and the serum concentration normalized in 91% of the enrolled patients. On rechallenge with statins while on vitamin D supplementation, after 24 months 95% of the previously statin-intolerant study participants were free of myalgia and myopathy, so the muscle toxicity was safely resolved by the vitamin D supplementation [29].
Ending Statins May Not End Associated Muscle Pains
Skeletal muscle toxicity associated with raltegravir-based combination anti-retroviral therapy in HIV-infected adults
Controversy Over Statins for Older Patients/New AHA Guidelines
"Taking statins may not prolong life in older adults, but it may certainly improve the quality of life" for people who might otherwise become disabled by heart attacks of strokes, said Dr. Antonio Gotto Jr., one of the authors of the analysis and dean emeritus of Weill Cornell Medical College.
As in many studies of this kind, the incidence of side effects associated with statin use was not reported. "This data is very well guarded," and without it the clinical picture is incomplete, said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, Medical Center and editor-in-chief of JAMA Internal Medicine.
"I see elderly patients every week who tell me they couldn't get out of bed, they had terrible diarrhea, they were walking around in a fog after they started taking statins, and when they stopped the medications those feelings went away," Dr. Redberg said.
According to her summary of the evidence for using statins to prevent heart disease, heart attacks will be prevented in only one or two of every 100 healthy people with high cholesterol who take the medications for up to five years, while one person will develop diabetes. Meanwhile, it is worth noting that "older people are much more vulnerable to the side effects of medications," she said, and there's some evidence that "low cholesterol seems to be associated with higher mortality at an older age."
Experts agree that more high quality evidence is needed about statin use in seniors without existing heart disease. Pending that, it seems this debate isn't going to be resolved any time soon. As ever, consult with a doctor before starting or discontinuing any medication.
Statins for the Elderly - efficacy ??
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