1.
Comparison of 80 versus 10 mg of atorvastatin on occurrence of cardiovascular events after the first event (from the Treating to New Targets [TNT] trial).
LaRosa, JC, Deedwania, PC, Shepherd, J, Wenger, NK, Greten, H, DeMicco, DA, Breazna, A, ,
The American journal of cardiology. 2010;(3):283-7
Abstract
Analyses of randomized clinical trials are usually restricted to examination of time to first event. However, because many patients have multiple events, this approach precludes much potentially useful clinical and economic data. To assess the effect on overall disease burden in the Treating to New Targets (TNT) study, we evaluated the effect of treatment with atorvastatin 80 versus 10 mg in the period after the occurrence of a first cardiovascular event. In TNT, 10,001 patients with stable coronary heart disease received double-blind therapy with atorvastatin 80 or 10 mg and were followed for 4.9 years. Post hoc time-to-event analysis was used to estimate separate hazard ratios for time to any first, second, third, fourth, and fifth recurrent cardiovascular events. During TNT, 3,082 patients had a first recurrent cardiovascular event, with 1,516, 698, 345, and 197 developing second, third, fourth, and fifth recurrent events, respectively. In patients receiving atorvastatin 80 mg, the relative risk of a first recurrent event was significantly decreased compared to those receiving atorvastatin 10 mg. Significant benefit with the 80-mg dose was also observed for second, third, fourth, and fifth recurrent events. Similar findings were recorded in 5,854 patients with type 2 diabetes mellitus and/or metabolic syndrome and in 3,809 patients > or = 65 years of age compared to younger patients. In conclusion, treatment with atorvastatin 80 mg continued to significantly decrease the risk of any cardiovascular event over time compared to atorvastatin 10 mg in patients who had survived previous events. In TNT, analyses limited to the primary end point significantly underestimated the decrease in total cardiovascular disease burden achieved by intensive low-density lipoprotein cholesterol lowering.
2.
ALLHAT findings revisited in the context of subsequent analyses, other trials, and meta-analyses.
Wright, JT, Probstfield, JL, Cushman, WC, Pressel, SL, Cutler, JA, Davis, BR, Einhorn, PT, Rahman, M, Whelton, PK, Ford, CE, et al
Archives of internal medicine. 2009;(9):832-42
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Abstract
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is reevaluated considering information from new clinical trials, meta-analyses, and recent subgroup and explanatory analyses from ALLHAT, especially those regarding heart failure (HF) and the association of drug treatment with new-onset diabetes mellitus (DM) and its cardiovascular disease (CVD) consequences. Chlorthalidone was superior to (1) doxazosin mesylate in preventing combined CVD (CCVD) (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.13-1.27), especially HF (RR, 1.80; 95% CI, 1.40-2.22) and stroke (RR, 1.26; 95% CI, 1.10-1.46); (2) lisinopril in preventing CCVD (RR, 1.10; 95% CI, 1.05-1.16), including stroke (in black persons only) and HF (RR, 1.20; 95% CI, 1.09-1.34); and (3) amlodipine besylate in preventing HF, overall (by 28%) and in hospitalized or fatal cases (by 26%). Central independent blinded reassessment of HF hospitalizations confirmed each comparison. Results were consistent by age, sex, race (except for stroke and CCVD), DM status, metabolic syndrome status, and renal function level. Neither amlodipine nor lisinopril was superior to chlorthalidone in preventing end-stage renal disease overall, by DM status, or by renal function level. In the chlorthalidone arm, new-onset DM was not significantly associated with CCVD (RR, 0.96; 95% CI, 0.88-2.42). Evidence from subsequent analyses of ALLHAT and other clinical outcome trials confirm that neither alpha-blockers, angiotensin-converting enzyme inhibitors, nor calcium channel blockers surpass thiazide-type diuretics (at appropriate dosage) as initial therapy for reduction of cardiovascular or renal risk. Thiazides are superior in preventing HF, and new-onset DM associated with thiazides does not increase CVD outcomes.