If you want to make the best use out of autoload with an APC cache don't use spl_autoload. It uses relative paths and thus will perform a stat even with apc.stat=0 (either that, or it doesn't work at all).
Instead make a custom function and use require/include with an absolute path (register it with spl_autoload_register).
Do NOT use *_once functions or a relative path. This will fail harder than spl_autoload.
Also avoid using file_exists and is_file. This will also perform a stat.
Why are stats bad? Because they access the file system. PHP does have a stat cache that helps, but it defeats the purpose of apc.stat = 0.
It's also good to keep in mind that it's good to keep your custom autoload function simple. This is my Loader class:
public static function registerAutoload()
return spl_autoload_register(array(__CLASS__, 'includeClass'));
public static function unregisterAutoload()
return spl_autoload_unregister(array(__CLASS__, 'includeClass'));
public static function includeClass($class)
require(PATH . '/' . strtr($class, '_\\', '//') . '.php');
Also want to point out that APC does an optimization with require/include (not *_once) with relative paths if require/include is done in the global scope (and isn't conditional). So it would be a good idea to explicitly include files you know you're going to use on every request (but don't use *_once). You could, for example, add a "registerProfiledAutoload" to the above class and keep track of what you're including to help you determine what you could explicitly include (during development, not production). The key is try not to make heavy use out of autoload.
If you must use relative paths and don't care about having to lower-case your file-names then spl_autoload works great.