Carol Stanford

Clinical Outcomes by Race in Hypertensive Patients With and Without the Metabolic Syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

BACKGROUND Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcomes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an alpha-blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril). METHODS A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 418 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women. RESULTS Significantly higher rates of heart failure were consistent across all treatment comparisons in those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.18-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 [1.09-1.40] and 1.10 [1.02-1.19], respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 [1.19-1.58] and 1.18 [1.08-1.30], respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [1.07-1.76] for the lisinopril-chlorthalidone comparison, and RR, 1.49 [1.09-2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS also had higher rates of end-stage renal disease (RR, 1.70 [1.13-2.55]) with lisinopril compared with chlorthalidone. CONCLUSIONS The ALLHAT findings fail to support the preference for calcium channel blockers, alpha-blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants.

Progression of Kidney Disease in Moderately Hypercholesterolemic, Hypertensive Patients Randomized to Pravastatin Versus Usual Care: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

BACKGROUND Dyslipidemia is common in patients with chronic kidney disease. The role of statin therapy in the progression of kidney disease is unclear. STUDY DESIGN Prospective randomized clinical trial, post hoc analyses. SETTING & PARTICIPANTS 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) stratified by baseline estimated glomerular filtration rate (eGFR): less than 60, 60 to 89, and 90 or greater mL/min/1.73 m(2). Mean follow-up was 4.8 years. INTERVENTION Randomized; pravastatin, 40 mg/d, or usual care. OUTCOMES & MEASUREMENTS Total, high-density lipoprotein, and low-density lipoprotein cholesterol; end-stage renal disease (ESRD), eGFR. RESULTS Through year 6, total cholesterol levels decreased in the pravastatin (-20.7%) and usual-care groups (-11.2%). No significant differences were seen between groups for rates of ESRD (1.36 v 1.45/100 patient-years; P = 0.9), composite end points of ESRD and 50% or 25% decrease in eGFR, or rate of change in eGFR. Findings were consistent across eGFR strata. In patients with eGFR of 90 mL/min/1.73 m(2) or greater, the pravastatin arm tended to have a higher eGFR. LIMITATIONS Proteinuria data unavailable, post hoc analyses, unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range, statin drop-in rate in usual-care group with small cholesterol differential between groups. CONCLUSIONS In hypertensive patients with moderate dyslipidemia and decreased eGFR, pravastatin was not superior to usual care in preventing clinical renal outcomes. This was consistent across the strata of baseline eGFR. However, benefit from statin therapy may depend on the degree of the cholesterol level decrease achieved.

Cardiovascular risk assessment: addition of CKD and race to the Framingham equation

BACKGROUND/AIMS The value of the Framingham equation in predicting cardiovascular risk in African Americans and patients with chronic kidney disease (CKD) is unclear. The purpose of the study was to evaluate whether the addition of CKD and race to the Framingham equation improves risk stratification in hypertensive patients. METHODS Participants in the ALLHAT were studied. Those randomized to doxazosin, older than 74 years, and those with a history of coronary heart disease were excluded. Two risk stratification models were developed using Cox proportional hazards models in a two-thirds developmental sample. The first model included the traditional Framingham risk factors. The second model included the traditional risk factors plus CKD, defined by estimated glomerular filtration rate categories, and stratification by race (black vs non-black). The primary outcome was a composite of fatal coronary heart disease, nonfatal myocardial infarction, coronary revascularization, and hospitalized angina. RESULTS There were a total of 19,811 eligible subjects. In the validation cohort, there was no difference in C-statistics between the Framingham equation and the ALLHAT model including CKD and race. This was consistent across subgroups by race and sex and among those with CKD. One exception was among Non-Black women where the C-statistic was higher for the Framingham equation (0.68 vs 0.65, P = .02). In addition, net reclassification improvement was not significant for any subgroup based on race and sex, ranging from -5.5% to 4.4%. CONCLUSION The addition of CKD status and stratification by race does not improve risk prediction in high-risk hypertensive patients.

Pravastatin and cardiovascular outcomes stratified by baseline eGFR in the lipid-lowering component of ALLHAT

Background/Aims: The role of statins in preventing cardiovascular outcomes in patients with chronic kidney disease (CKD) is unclear. This paper compares cardiovascular outcomes with pravastatin vs. usual care, stratified by baseline estimated glomerular filtration rate (eGFR). Methods: Post-hoc analyses of a prospective randomized open-label clinical trial; 10,151 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) were randomized to pravastatin 40 mg/day or usual care. Mean follow-up was 4.8 years. Results: Through Year 6, total cholesterol declined in pravastatin (–20.7%) and usual-care groups (–11.2%). Use of statin therapy in the pravastatin group was 89.8% (Year 2) and 87.0% (Year 6). Usual-care group statin use increased from 8.2% (Year 2) to 23.5% (Year 6). By primary intention-to-treat analyses, no significant differences were seen between groups for coronary heart disease (CHD), total mortality or combined cardiovascular disease; findings were consistent across eGFR strata. In exploratory “as-treated” analyses (patients actually using pravastatin vs. not using), pravastatin therapy was associated with lower mortality (HR = 0.76 (0.68 – 0.85), p < 0.001) and lower CHD (HR = 0.84 (0.73 – 0.97), p = 0.01), but not combined cardiovascular disease (HR = 0.95 (0.88 – 1.04), p = 0.30). Total cholesterol reduction of 10 mg/dl from baseline to Year 2 was associated with 5% lower CHD risk. Conclusions: In hypertensive patients with moderate dyslipidemia, pravastatin was not superior to usual care in preventing total mortality or CHD independent of baseline eGFR level. However, exploratory “as-treated” analyses suggest improved mortality and CHD risk in participants using pravastatin, and decreased CHD events associated with achieved reduction in total cholesterol. Potential benefit from statin therapy may depend on degree of reduction achieved in total and LDL-cholesterol and adherence to therapy.

Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment

Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician’s guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.

Pityriasis Rosea-Like Drug Eruptions

Pityriasis rosea is an acute, mild, self-limited papulosquamous skin disease of uncertain etiology. The disease is characterized by the initial presence of a salmon-pink oval patch or plaque deemed the “herald patch.” This is followed by the widespread eruption of oval macules, papules, and plaques whose long axis follows the lines of cleavage, resulting in the characteristic “Christmas tree” or “fir tree” distribution. A skin eruption very similar to this presentation has been reported to be caused by several drug categories and whose recovery depends on the discontinuation of the drug. These drug categories include NSAIDS, ACE inhibitors, vaccinations, mood stabilizers, barbiturates, and antihistamines. The idiopathic disease may sometimes be distinguished from the drug eruption by characteristics of presentation and duration.

Lichen Planus Drug Reactions

Lichen planus is a common chronic, inflammatory, autoimmune mucocutaneous disease. The lesions of lichen planus are most notably described using the six Ps: planar (flat-topped), purple, polygonal, pruritic, papules, and plaques. These characteristic lesions are often covered by the lacy, reticular, white lines known as Wickham striae. The exact etiology of this disease is unknown, however an immune- mediated pathology is well documented in the literature. A mucocutaneous eruption very similar to the idiopathic lichen planus presentation has been reported to be caused by several drug categories and whose recovery depends on the discontinuation of the drug. These drug categories include NSAIDS, ACE inhibitors, antimicrobials, and antiarthritics. The idiopathic disease can be distinguished from the drug eruption by characteristics of presentation and duration.

Erythema Multiforme and Drug Reactions

Erythema multiforme (EM) is an acute, immune-mediated mucocutaneous condition that characteristically presents with acrally distributed targetoid lesions. The disease is often self-limited, and treatment is frequently unnecessary. Although many factors have been associated with EM, the study of EM remains difficult due to various inconsistencies in terminology. Herpes simplex virus (HSV) causes the vast majority of EM cases, but drugs and Mycoplasma pneumoniae are also described in the literature. EM-like drug reactions are likely of different pathogenesis than herpes-associated EM. Drug reactions are frequently implicated in more serious disease, such as Stevens-Johnson syndrome, which can show papules and plaques that are targetoid lesions of EM. Thus, making the clinical distinction between EM and its more severe counterparts is crucial.

Acne and Drug Reactions

Acne vulgaris is a chronic disease of the pilosebaceous follicle and it is characterized by any combination of open comedones, closed comedones, pustules, cysts, and scarring of varying severity. Factors which promote the development of acne are: increased sebum production, which is influenced by endogenous androgens; ductal hypercornification; abnormal follicular keratinization; colonization of the pilosebaceous ducts by Propionibacteria acnes; inflammation; and genetic predisposition. While the majority of acne cases are hormone-dependent juvenile acne, a subset of cases are drug induced, which is defined as the development of an acneiform eruption occurring after medication intake. Several classes of drugs are associated with acneiform eruptions and include: corticosteroids, neuropsychotherapeutic drugs, antituberculosis drugs, immunomodulating drugs, and targeted therapy in the field of oncology. Discontinuation of the drug will lead to recovery from the acneiform eruption, but is rarely mandatory, given the benign nature of acne. The idiopathic disease can be distinguished from the drug eruption by characteristics of presentation, unusual age on onset, unusual location of the lesions, and resistance to conventional acne therapy.